Short term effects of periodontal therapy on inflammatory markers in patients with type-2 diabetes

Objectives:

To evaluate the influence of periodontal therapy on glycosylated hemoglobin and fasting blood glucose and serum levels of interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) in chronic periodontitis (CP) patients with type-2 diabetes mellitus (T2DM) and in controls.

Methods:

A total of 30 periodontal patients, 15 of which were systemically healthy (control group), and 15 were T2DM patients (test group) were included in this study. This prospective study was carried out at Istanbul University, Istanbul, Turkey between February 2011 and December 2013. Plaque index, gingival index, bleeding on probing, periodontal probing depth, and clinical attachment level were assessed and recorded at baseline, one, and 3 months after therapy. Serum samples were collected at the same time-points and analyzed using Luminex assay for the levels of IL-4, IL-6, IL-8, IL-10, and TNF-α. The change in the metabolic control was also monitored.

Results:

All clinical parameters were significantly improved after the periodontal therapy in both groups (p<0.001). Glycosylated hemoglobin levels were decreased; however, the difference was not significant (p>0.05). Fasting blood glucose levels were decreased one month after therapy, and increased at 3 months. Patients with T2DM had significantly higher levels of circulating IL-8 at each time point, and TNF-α (p<0.05) at baseline. The IL-4 and IL-10 levels were decreased at one month after therapy (p>0.05).

Conclusion:

Periodontal therapy has limited impact on the serum levels of IL-4, IL-6, IL-8, IL-10, and TNF-α. Metabolic control levels were not influenced by periodontal therapy.Chronic periodontitis (CP) is an infectious disease resulting in inflammation in periodontal tissues, progressive attachment, and bone loss. Chronic periodontitis is the most common type of periodontitis, and its prevalence and severity increases with age.1 Microbial dental plaque is the main etiological agent; however, progression from gingivitis to periodontitis is associated with host response and immunity. Presence of systemic disease such as diabetes, stress, and genetic factors are among the factors related to host response.2 Bone loss occurs with the influence of local factors, which are expressed from inflammatory mediators. Interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6 are the cytokines favoring bone loss around the teeth. It has been reported that patients with chronic periodontitis present with increased systemic inflammation and raised levels of various inflammatory markers compared with healthy controls.3 The local tissue produces inflammatory cytokines, as well as elevates their systemic circulating levels. Type-2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism. Defects in insulin secretion (b-cell dysfunction), insulin action (insulin resistance), or both cause T2DM.4 Type-2 diabetes is regarded as a low-grade inflammatory disease because some inflammatory cytokines are involved in the mechanism. Functions of specific immune system cells are impaired in patients with DM. Diabetes mellitus causes dysfunction in the adhesion, chemotaxis, and phagocytosis capacity of neutrophils. As a result, they cannot kill periodontopathogens, and cannot destroy their toxins resulting in the destruction of periodontal tissues,5-7 which may explain in part the increased incidence of periodontitis among diabetic patients. The glycosylated hemoglobin (HbA1c) levels reflect the glycemic level over the previous one to 3 months. Whether periodontal therapy reduces HbA1C levels in periodontitis patients remains controversial.8-14 In patients with periodontitis, diabetes is associated with elevated levels of several cytokines and other mediators in serum, saliva, and gingival crevicular fluid (GCF). It was reported that monocytes in peripheral blood of patients with DM produce higher amounts of TNF-α when encountered with Porphyromonas gingivalis.15The TNF-α, which is a pro-inflammatory cytokine was first reported by Hotamisligil et al16 to cause insulin-resistance. The TNF-α produced by the adipose tissues acts as a risk factor for periodontal disease; likewise, TNF-α produced due to periodontal inflammation may be an additional risk factor influencing insulin sensitivity.17 The TNF-α, IL-6, resistin, and other pro-, and anti-inflammatory cytokines activate intracellular pathways, which causes the development of insulin resistance and T2DM.18 Interleukin-4 reduces secretion of IL-1, IL-6, and TNF-α from monocytes.19 It was reported by a series of studies that patients with diabetes have a lower concentration of GCF IL-4 compared with healthy subjects.20-22 It was indicated that periodontal therapy reduces serum IL-6 concentration significantly in patients with CP.23 Interleukin-8 is a chemo attractive proinflammatory cytokine that affects neutrophil migrations in thetissue and circulation. Interleukin-1β and TNF-α has a role on IL-8 production.24 Substantial data has been accumulated on metabolic measures and serum levels of cytokines on T2DM patients with periodontitis. A systematic review has shown that non-surgical periodontal treatment results in a mean reduction in HbA1C of 0.36% (95% confidence interval [CI]: 0.19-0.54) at 3 months.25 However, the results from different reports are not consistent to demonstrate the potential effects of non-surgical periodontal therapy on Hba1C and specific cytokines in T2DM patients with CP.9-14We hypothesized that non-surgical periodontal therapy will reduce the levels of proinflammatory cytokines, HbA1c, and fasting blood glucose (FBG) levels in T2ßDM patients with CP, and this group of patients can benefit from periodontal therapy, as well as non-diabetics. Thus, the aim of this study was to evaluate the influence of periodontal therapy on HbA1C and FBG and serum levels of IL-4, IL-6, IL-8, IL-10, and TNF-α in CP patients with T2DM and in controls.     

Does social support affect development of cognitive dysfunction in individuals with diabetes mellitus?

Objectives:

To determine cognitive functions and perceived social support (SS) among individuals with diabetes mellitus (DM), and the effects of SS on the development of cognitive dysfunction (CD).

Methods:

This cross-sectional study was conducted in 121 patients with DM presenting at the Endocrinology Clinic of Cumhuriyet University Health Services Application and Research Hospital, Sivas, Turkey between April and June 2014. Data were collected utilizing the “Patient Assessment Form”, “Standardized Mini Mental State Examination (SMMSE)”, and “Multidimensional Scale of Perceived Social Support (MSPSS)”.

Results:

The mean score obtained for DM patients from the SMMSE was 21.55±5.7, with 65.3% found to have cognitive impairment. The total mean score of the participants for MSPSS was considered moderate (66.61±14.42). There was a significant positive correlation between cognitive function and SS (r=0.273, p=0.002). It was determined that individuals with CD had low levels of perceived SS, and that insufficient support from families and significant others contributed to the development of CD (p=0.008).

Conclusion:

In this study, it was determined that the cognitive function of individuals with DM was impaired and would improve as the perception of SS increased, and that perceived SS would affect the development of CD. Therefore, health professionals can contribute to the improvement of cognitive function of individuals with DM by facilitating the use of SS sources.The prevalence of diabetes mellitus (DM), a major public health problem affecting people’s quality of life - physically, mentally, socially, and economically,1 is on the rise in Turkey and the whole world. While 8.4% of the adult population suffers from DM worldwide, this rate is approximately 15% in Turkey.2 Diabetes mellitus leads to damage in a variety of tissues and organs over time. In the literature, DM is reported to impair cognitive functions due to damages it causes to the central nervous system.3 Cognitive function can be impaired in individuals with DM due to abnormalities in insulin secretion and glucose metabolism.4,5 Good cognitive function in diabetic individuals is important, since it facilitates metabolic control and treatment management.6 Therefore, early detection of cognitive impairment, and the implementation of effective treatment and coping methods will help people with DM to fulfill their professional and social activities, and thus, will facilitate management of the disease.7 One of the factors that affect diabetic individuals’ compliance with the treatment of DM and health outcomes is the perceived social support (SS). To manage the disease, an individual with DM needs the support of family and other individuals in the social environment, which he/she is in.8 The literature states that adequate SS will help a person to change his/her negative health behaviors, to increase his/her effectiveness, and to gain more control over his/her emotional state.9 The presence of SS in diabetic individuals affects their healthy eating habits’ compliance with treatment,8,10 and self-care processes specific to DM.11,12 In addition, the presence of perceived SS may be particularly useful in coping with difficulties likely to occur due to treatment.13 Cognitive dysfunction (CD) is a complication considered in the background in individuals with DM.7 Social support facilitates adaptation to treatment, and thus, reduces the likelihood of the development of complications.8,10 In the literature, there are studies investigating the effect of diabetic individuals’ perception of SS on metabolic parameters10,14 and other complications of DM.15 This study was conducted to determine the cognitive function and perceived SS among individuals with DM, and the effect of SS on the development of CD. This study may help determine whether SS provided for individuals with DM has an effect on cognitive functions such as attention, registration, and recall. A higher perceived SS is thought to positively contribute to the regulation of blood glucose levels, and thus, to prevent the deterioration of cognitive function caused by DM.     

Lack of association between the insulin receptor substrates-1 Gly972Arg polymorphism and type-2 diabetes mellitus among Saudis from Eastern Saudi Arabia

Objectives:

To investigate the association between the insulin receptor substrate-1 (IRS1) Gly972Arg polymorphism and type-2 diabetes mellitus (T2DM) among Saudis from Eastern Saudi Arabia.

Methods:

This study was conducted between May and December 2014 at King Fahad Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia. In a case-control study design, a total of 143 subjects (age range: 35-73 years) comprising 74 healthy controls and 69 patients with T2DM were examined. Blood samples were collected from subjects and subjected to genomic DNA extraction and chemical analysis. The IRS1 Gly972Arg polymorphism was then genotyped using the standard polymerase chain reaction-restriction fragment length polymorphism technique.

Results:

Eight out of 74 (10.8%) of the control group carried at least one copy of the mutated allele. The frequency (8.7%) of the IRS1 variant was also found in the diabetic group. Logistic regression analysis showed an adjusted odds ratio of 1.04, 95% confidence interval 0.28 - 3.95, and a p-value of 0.94.

Conclusion:

We failed to find any association between the IRS1 Gly972Arg polymorphism and T2DM.Diabetes mellitus (DM) is a major medical and public health concern worldwide. In 2014, it has been estimated that there were 382 million sufferers of diabetes worldwide.1 The prevalence of diabetes in Saudi Arabia is 23.9%, which is among the highest in the gulf area and the world.1,2 Type-2 diabetes mellitus (T2DM) represents approximately 90-95% of all diabetes cases.3 Type-2 diabetes mellitus is characterized by high blood glucose due to the inability of body cells to respond to insulin, a phenomenon known as insulin resistance.4 The genetic factors behind the insulin resistance are not well-understood and are under intensive research. Insulin is a metabolically important peptide hormone secreted from ß-cells of the pancreas in response to high blood glucose. Insulin signaling starts with binding of the insulin molecule to its cognate membrane insulin receptor (IR). This binding triggers conformational changes in the juxtamembrane intracellular region of the receptor causing autophosphorylation of certain tyrosine residues. The activated receptor then phosphorylates and activates a family of intracellular effector proteins known as insulin receptor substrates 1 to 4 (IRS-1 to 4).5 These activated proteins then interact with the regulatory subunit (p85) of the enzyme phosphatidylinositol (PI) 3-kinase causing glucose transporter-4 (Glut-4) translocation to the cell membrane to increase glucose uptake.6 In this signaling pathway, IRS1 seems to play a major role as suggested by IRS1 knockout mice studies.7 Additionally, several polymorphisms in the IRS1 gene were associated with insulin resistance, obesity, and T2DM.8,9 The single nucleotide polymorphism (SNP) (rs1801278) in the IRS1 gene causing an amino acid substitution where glycine (GGG) is replaced by arginine (AGG) at codon 972 was first described by Almind et al.10 It is the most widely studied candidate of the IRS1 gene variants by testing its association with insulin resistance and T2DM.11 However, the association of this polymorphism with the development of T2DM has not been consistent around the world. In a study focusing on Mexican participants, Burguete-Garcia et al8 found that the IRS1 Gly972Arg variant was significantly associated with T2DM. Another study that also focused on Mexican population similarly found a significant association between Gly972Arg variant and genetic susceptibility to T2DM.12 A study on Indian population from Hyderabad also reported significant association with T2DM.13 A meta-analysis study conducted in 2009 of 30 studies had shown that there was no significant association between the IRS1 Gly972Arg variant and T2DM.11 In addition, previous studies also reported no association between the IRS1 Gly972Arg polymorphism and T2DM.14-18 There is no report on the frequency of this polymorphism and its association with T2DM in the Eastern Province of Saudi Arabia. Thus, the aim of the current work is to examine the association between the IRS1 Gly972Arg polymorphism with T2DM among Saudis.     

Diagnostic efficacy of random albumin creatinine ratio for detection of micro and macro-albuminuria in type 2 diabetes mellitus

Objectives:

To compare a less cumbersome random albumin creatinine ratio (RACR) with 24-hour urinary albumin excretion (UAE) for detection of renal damage in patients with type 2 diabetes mellitus (T2DM).

Methods:

This retrospective study performed between March 2013 and June 2014 at the Department of Pathology, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia included 122 patients (mean age 54±15, 104 females and 18 males) with T2DM. Urine albumin levels of <30 mg/g was considered normal, from 30-300 mg/g considered as micro-albuminuria, and over 300 mg/g considered as macro-albuminuria.

Results:

Concordance between the 2 assays was observed in 114 (93.4%) samples. The sensitivity of RACR assay was 100%, specificity was 91.3% with a positive predictive value (PPV) of 95%, and a negative predictive value (NPV) of 100% in micro-albuminuria range. For macro-albuminuria, RACR had a sensitivity of 100%, specificity of 94.1% with PPV of 94% and NPV of 100%. Receiver operating characteristic (ROC) curves analysis cut-off values of 40 mg/g-300 mg/g for micro- and >300 mg/g for macro-albuminuria revealed 100% sensitivity, 97.5% specificity, 95% PPV, and 100% NPV for micro-albuminuria, and 100% sensitivity, 94% specificity, 76% PPV, and 100% NPP for macro-albuminuria. The area under the curve for micro-albuminuria was 100% and 98.2% for macro-albuminuria.

Conclusion:

Performance of RACR was comparable to 24 hour UAE assay particularly in excluding renal damage in T2DM.Diabetes related chronic kidney disease (CKD) is among the serious micro-vascular complications of type 2 diabetes mellitus (T2DM), and is a leading cause of end-stage renal disease.1 Between 30-40% of patients with diabetes develop CKD that manifests as albuminuria, or decreased glomerular filtration rate.2-4 The prevalence of diabetes-related CKD is increasing alongside the prevalence of diabetes all over the world.5 Micro-albuminuria is a term used for a relatively small amount of albumin excretion in urine in the early stages of CKD in diabetics. This may progress to overt proteinuria in 20-40% of diabetics in 10 years culminating in end-stage renal disease in approximately 20% of patients.6,7 The presence of diabetes, irrespective of new-onset, or previously diagnosed diabetes poses a 2.5 fold increased risk of albuminuria.8 Screening for micro-albuminuria early in the disease particularly in T2DM is, therefore, critical in salvaging kidneys as it is a potentially reversible form of kidney injury.9 The gold standard for assessment of albuminuria is the estimation of albumin concentration in a urine sample collected over 24-hours as the outcome will not be affected by the variations in protein excretion during the day.10,11 This procedure, however, has several limitations, such as sample collection errors on part of the patient, poor compliance, extended duration of sample collection, and is not cost effective.12-14 Since the excretion of creatinine and protein remains constant if the glomerular filtration is stable15 measurement of protein to creatinine in a spot, or random urine sample would not be affected by the variations in protein and albumin excretion in urine samples.16 Measurement of random urine albumin creatinine ratio (RACR) has been evaluated in a number of studies demonstrating a close relationship with 24-hour protein excretion.17,18 The existing data, however, falls short of certainty with which RACR might be used to rule in, or rule out proteinuria. This study was performed to assess the performance of RACR against the gold standard estimation of 24-hour urinary albumin excretion (UAE) for detection of micro-albuminuria in Saudi patients with T2DM.     

Effects of 12-month, 2000IU/day vitamin D supplementation on treatment na?ve and vitamin D deficient Saudi type 2 diabetic patients

Objectives:

To determine whether 12-month, 2000IU/day vitamin D supplementation cardiometabolically improves treatment naïve type 2 diabetes mellitus (T2DM) Saudi patients with vitamin D deficiency.

Methods:

This 12-month interventional study was conducted at primary health centers in 5 different residential areas in Riyadh, Saudi Arabia between January 2013 and January 2014. Forty-five Saudi T2DM patients were enrolled. Baseline anthropometrics, glycemic, and lipid profiles were measured and repeated after 6 and 12 months. All subjects were provided with 2000IU vitamin D supplements for one year.

Results:

Vitamin D deficiency at baseline was 46.7%, 31.8% after 6 months, and 35.6% after 12 months, indicating an overall improvement in the vitamin D status in the entire cohort. Insulin and homeostatic model assessment-insulin resistance (HOMA-IR) after 12 months were significantly lower than a 6 months (p<0.05), but comparable to baseline values. Mean levels of triglycerides increased overtime from baseline (1.9±0.01 mmol/l) to 12 months (2.1±0.2 mmol). This modest increase in serum triglycerides was parallel to the insignificant decrease in circulating high-density lipoprotein -cholesterol levels.

Conclusion:

Twelve-month vitamin D supplementation of 2000IU per day in a cohort of treatment naïve Saudi patients with T2DM resulted in improvement of several cardiometabolic parameters including systolic blood pressure, insulin, and HOMA-IR. Further studies that include a placebo group are suggested to reinforce findings.Diabetes mellitus (DM) is a major public health problem worldwide. The population of people with DM is on the rise secondary to an aging and urbanized population as well as an increasing prevalence of risk factors such as obesity and physical inactivity.1 In the Kingdom of Saudi Arabia (KSA) alone, the most-recent age-adjusted prevalence of type 2 diabetes mellitus (T2DM) was reported to be 31.6% in adults, considered among the highest in the Gulf region.2 Type 2 diabetes mellitus among Saudis results from the interaction between a genetic predisposition, behavioral, and environmental risk factors, which can manifest as early as pre-teens.3 This is alarming since the long-term cost of diabetes can be crippling to any health care system as there are many associated health problems, including: increased risk of coronary heart disease, eye problems, nerve damage, foot, and kidney problems.4 Vitamin D insufficiency, defined as serum 25-hydroxyvitamin D levels <50 nmol/l (25-OH-D), is also common in patients with T2DM.5 Using this arbitrary definition, it has been estimated that one billion people worldwide have either vitamin D deficiency or insufficiency.6 In KSA, there is an abundance of local literature pointing to an increased prevalence of vitamin D deficiency.7,8 Taken together, current evidence suggests a link between vitamin D deficiency and progression of T2DM, but results are not consistent and therefore the beneficial effects of vitamin D correction among T2DM patients with vitamin D deficiency remains controversial.9,10 Given that patients with T2DM are at higher risk for cardiometabolic complications, this study aims to determine whether vitamin D status improvement through dietary means improves the cardiometabolic profile of treatment naïve T2DM Saudi patients with vitamin D deficiency.     

Frequency and associated risk factors of recurrent diabetic ketoacidosis among Saudi adolescents with type 1 diabetes mellitus

Objectives:

To explore the frequency and associated risk factors of recurrent diabetic ketoacidosis (RDKA) among Saudi adolescents with type 1 diabetes mellitus (T1DM).

Methods:

A cross-sectional study was conducted among 103 T1DM adolescents (aged 13-18 years, 57 males) who were hospitalized for diabetic ketoacidosis (DKA) between January 2013 and May 2014 at Prince Sultan Military Medical City (PSMMC), Riyadh, Kingdom of Saudi Arabia. The respondents were purposively, conveniently selected, and interviewed using a structured Arabic questionnaire including clinical information and demographics.

Results:

Fifty-six participants had experienced one episode of DKA, 41 had 2 episodes, and 6 had ≥3 episodes. Compared with adolescents who had hemoglobin A1c (HbA1c) ≤9, mean difference in RDKA was found among adolescents with >9 HbA1c. Similarly, adolescents who stopped insulin and those with lipodystrophy at the injection site had a higher frequency of RDKA. Discontinuing insulin (67%) was the major reason for RDKA followed by infection (31%). Among adolescents who discontinued insulin treatment, 31 (46.3%) gave no reason for stopping, 25 (37.3%) reported feeling sick, 7 (10.4%) gave a combination of reasons, and 4 (6%) reported a lack of supplies or other reasons. Regression analysis revealed that a higher HbA1c level and the presence of lipodystrophy were independent risk factors for RDKA.

Conclusion:

The frequency of RDKA was significantly greater in the T1DM adolescents with a higher HbA1c level, lipodystrophy, and those who had discontinued insulin treatment. Comprehensive multidisciplinary diabetes education should be offered to control modifiable risk factors in these patients.According to the latest report by the International Diabetes Federation, Saudi Arabia is listed as third among the top 10 countries with the highest prevalence rates of diabetes (3.6 million cases of diabetes).1 While type 2 diabetes dominates in great numbers, type 1 diabetes mellitus (T1DM) remains an imperative issue. Over the last 3 decades, the incidence rate of T1DM is growing in Saudi Arabia,2 and the prevalence of T1DM in Saudi Arabian children and adolescents is 109.5 per 100,000.3 It is well established that adolescents diagnosed with T1DM, face several lifestyle changes and the risk of facing debilitating and life-threatening complications, such as diabetic ketoacidosis (DKA).4,5 Diabetic ketoacidosis is a recurrent problem with acute complications and is the most common cause of death in adolescents with T1DM.5,6Diabetic ketoacidosis is an acute metabolic complication of diabetes characterized by the triad of hyperglycemia, acidosis, and ketosis that take place in the presence of very low levels of effective insulin action.7 In some cases, DKA may be the first indication of previously undiagnosed diabetes, but it may often occur in those who already have diabetes as a result of a variety of causes, such as poor compliance with insulin therapy.8,9 Further, studies stated that infection is the important precipitating cause for DKA worldwide, occurring in 30-50% of cases. Vomiting, dehydration, confusion, deep gasping breathing, and occasionally coma are typical symptoms of DKA. Many studies reported that DKA is the leading cause of mortality in children with T1DM, and is associated with increased morbidity and health care expenditure.10,11 Longitudinal studies also indicate that 20% of pediatric patients account for 80% of all admissions for DKA, and the incidence of DKA peaks during the adolescent period.12Research shows that recurrent diabetic ketoacidosis (RDKA) rates are dependent on medical services and socioeconomic circumstances of the adolescents.13 Effective treatment of DKA requires frequent monitoring of patients, replacement of electrolyte losses, modification of hypovolemia and hyperglycemia, and careful search for the precipitating cause. As most DKA cases occur in patients with a known history of diabetes, this acute metabolic complication can be preventable by the education of patients, healthcare professionals, and the general public and frequent self measured blood glucose.14,15Compared with the developed countries, the dearth of research currently available on the frequency, associated risk factors of RDKA, as well as the socio-demographic properties of RDKA certainly warrants concern, particularly the lack of appropriate studies in this specified area in Saudi Arabia. Hence, we conducted this study to investigate the frequency and associated risk factors of RDKA among Saudi adolescents with T1DM.     

Electrophysiologic pattern and prevalence of subclinical peripheral neuropathy in children and adolescents with type I diabetes mellitus in Iran

Objectives:

To evaluate electrophysiologic pattern of subclinical diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) based on nerve conduction study.

Methods:

In this cross sectional study, 40 children and adolescents (62.5% female with mean age of 12.73 ± 0.43 years) with T1DM for at least 5 years attending the Pediatrics Clinics. Tabriz University of Medical Sciences, Tabriz, Iran, between 2014 and 2015 were recruited. Demographic and laboratory findings were recorded and all patients underwent clinical neurological examination and electrophysiologic studies.

Results:

According to electrophysiologic studies, DPN was found in 57.5% of patients including early stage of neuropathy (15%), mild sensory axonal neuropathy (25%), mild sensory motor axonal neuropathy (10%), and moderate sensory motor axonal neuropathy (7.5%). Age, duration of diabetes, fasting blood sugar, and glycosylated hemoglobin levels had no significant difference between patients with and without DPN. Reduced deep tendon reflexes were observed in the upper limb (30%) and lower limb (47.5%) of patients, which were both significantly higher in DPN patients (upper limb [p=0.03] and lower limb [p=0.04]). The most frequent electrophysiologic findings were unobtainable H-reflex, low amplitude sural, and median sensory responses.

Conclusion:

Subclinical DPN is a common complication found in children and adolescents with TIDM and peripheral sensory axonal neuropathy is the most frequent type. Nerve conduction study is recommended for early detection of DPN and prevention of its progress.Type 1 diabetes mellitus (T1DM) is the most common chronic endocrine disease in childhood, which is usually diagnosed among children, adolescents, and young adults.1 Children and adolescents are at higher risk of long term complications due to the longer period of T1DM.2 Diabetic peripheral neuropathy (DPN) is a major complication of T1DM with significant morbidity and mortality in adulthood. The DPN involves impairment of the large and/or small nerve fibers, and can be diagnosed by various methods.2,3 Sensory, motor, or autonomic nerves can be involved, often coexisting, but it is usually sensory dominant with eventual involvement of te\hemotor nerve fibers.4,5 Abnormalities of nerve conduction are common findings in children with diabetes and the highest prevalence for DPN is found in children and adolescents with poor glycemic control and longer duration of diabetes.5,6 Once symptoms appear, there are few effective therapeutic strategies;7 thus, early identification of DPN, especially in children and adolescents is crucial to prepare appropriate measures to prevent its development.8,9 Nerve conduction studies (NCS) are the most common method for the diagnosis of DPN and its sequelae.10 It is also possible that patients have subclinical neuropathy long before occurrence of clinically evident neuropathy.11 However, few studies have evaluated the subclinical neuropathy in these patients, and also the prevalence of early stages of DPN among children and adolescents is not well-known. In this study, we evaluated the frequency of different degrees of subclinical DPN in children and adolescents with T1DM and its possible related factors among children visiting the Tabriz Children Hospital. This hospital is the main referral center for disease of children in the north-west of Iran and our results can be applied to all the population.     

Management of rhino-orbital mucormycosis

Mucormycosis is an uncommon acute invasive fungal infection that affects immunocompromised patients. It progresses rapidly and has poor prognosis if diagnosed late. Early detection, control of the underlying condition with aggressive surgical debridement, administration of systemic and local antifungal therapies, hyperbaric oxygen as adjunctive treatment improves prognosis and survivability.Mucormycosis also known as zygomycosis and phycomycosis is an uncommon, opportunistic, aggressive fatal fungal infection caused by fungi of the order Mucorales, frequently among immunocompromised patients. This fungal infection begins from the sinonasal mucosa after inhalation of fungal spores; the aggressive and rapid progression of the disease may lead to orbital and brain involvement.1-4 In the past, the mortality rate of the rhino-cerebral type was 88%, but recently the survival rate of rhino-cerebral mucormycosis averages 21-73% depending on the circumstances.1 Mucormycosis is classified according to anatomical site into rhino-cerebral, which is the most common, central nervous system, pulmonary, cutaneous, disseminated, and miscellaneous.1,2,4-6 The rhino-orbito-cerebral is the most common form of mucormycosis.3 The most common predisposing factor is uncontrolled diabetes mellitus (DM), especially when the patient has a history of ketoacidosis, these species thrive best in a glucose rich and acidic environment.3,4,6,7 Immunosuppressive drugs such as steroids, neutropenia, acquired immune deficiency syndrome, dialysis patients on deferoxamine, malnutrition, hematologic malignancy, and organ transplant patients are also at risk of affection by the fungi.1,4-7 This case report describes a case of rhino-orbital mucormycosis affecting a diabetic female with good prognosis and satisfactory healing. Our objective in presenting this particular case is to emphasize that early diagnosis and proper management leads to good prognosis and high survivability.     

A call-to-action from the feedM.E. Middle East study group: Use of a screen-intervene-supervene strategy to address malnutrition in healthcare

Up to 50% of hospitalized patients worldwide are malnourished or at risk of malnutrition. Guidelines recommend nutritional screening of all patients on hospital admission. Results from studies of hospitalized patients show that screening, with follow-up nutritional assessment and care when indicated, can improve patients’ clinical outcomes and reduce healthcare costs. Despite compelling evidence, attention to nutritional care remains suboptimal in clinical settings worldwide. The feedM.E. Global Study Group developed a simple, stepwise Nutrition Care Pathway to facilitate best-practice nutrition care. This pathway guides clinicians to screen patients’ nutritional status on hospital admission or at initiation of care; intervene promptly with nutrition care when needed; and supervene or follow-up routinely with adjustment and reinforcement of nutrition care plans. The feedM.E. Middle East Study Group seeks to extend this program to our region. We advise clinicians to adopt and adapt the Nutrition Care Pathway, bringing quality nutrition care to everyday practice.Up to 50% of hospitalized patients are reported to be at risk of malnutrition or actually malnourished.1,2 Clinical studies in healthcare settings worldwide have shown that disease-related malnutrition is exceedingly common,3-7 especially in older patients.8,9 The prevalence of disease-related malnutrition-nutritional inadequacy with an inflammatory component10 is similarly high in hospitals of both emerging and industrialized nations. This prevalence remains as high now as it was a decade ago in almost every country.11-14 Patients with poor nutritional status are susceptible to disease progression and complications, and their recovery from illness or injury is often prolonged.1,15,16 A key barrier to best-practice nutrition care is limited hospital resources; clinicians report that too little time and not enough money constrain staff training on how to recognize and treat malnutrition.17,18While educational training and nutrition interventions have financial costs, so do the consequences of malnutrition. Disease-related malnutrition increases costs of care due to higher rates of complications (infections, pressure ulcers, falls) longer hospital stays, and more frequent readmissions.19-28 By contrast, clinical study results show that attention to nutrition care during hospitalization can improve patients’ health outcomes and cut healthcare costs.29-39 Nutrition planning and follow-up nutrition care can also provide both health and financial paybacks, whether the patient is living in the community, preparing for surgery, or ready to be discharged from the hospital.40-43 Yet disease-related malnutrition continues to be overlooked and under-treated.Despite compelling evidence of benefits from nutrition care29,30,32,34-38 and clearly-stated nutrition care guidelines,43-46 nutrition interventions for people with disease-related malnutrition still fall far short of best-practice.3,4,47 To address this shortfall, clinicians worldwide have issued a “call-to-action” for increased recognition of nutrition’s role in improving patient outcomes.42,48-50 To take action, clinical nutrition experts from Asia, Europe, the Middle East, and North and South America formed the feedM.E. (Medical Education) Global Study Group and put together a working program to increase awareness and improve nutrition care around the world.1 The global feedM.E initiative introduced the mantra “screen, intervene, and supervene” to cue the steps of a straightforward Nutrition Care Pathway.1 To support the feedM.E. global educational initiative, we formed a feedM.E. Middle East Study Group, which includes nutrition leaders from Egypt, Saudi Arabia, Turkey, and the United Arab Emirates (Open in a separate windowIn our current article, we the members of the feedM.E. Middle East Study Group emphasize the screen-intervene-supervene strategy for nutrition care, which is further defined for incorporation into practice as a Nutrition Care Pathway. For Middle East healthcare, we advise that this pathway can be adapted to meet cultural differences in different Middle East countries, and can be followed for patients in the community, in the hospital, and after discharge to home or to long-term care centers.

Malnutrition in the Middle East

Countries of the Middle East region are highly diverse in ecology (green valleys and dry yellow deserts), political structures (republics, monarchies), government stability or instability (conflicts, civil wars, unrest), and economic status (world’s richest and poorest countries). This diversity creates marked differences in the health and nutritional status of people in regional populations.51 In some cases, rapid urbanization and social development have occurred in the absence of economic growth.51 For adults in the Middle East and worldwide, malnutrition is often related to sickness, which includes people with limited physical or mental function. Disease-related malnutrition occurs in people of all ages and circumstances but is notably common in older people.9 Disease-related malnutrition is evident at hospital admission, during hospitalization, and in the periods before admission and after discharge. With all these influences, the prevalence of disease-related malnutrition varies widely across the Middle East; from 6% to 58% of hospitalized patients are malnourished or at risk of malnutrition (52

Table 2

Reports of hospital- and community-based malnutrition prevalence in Middle East countries.Open in a separate window

Malnutrition predicts poor health outcomes

Poor nutrition is a predictor of poor outcomes, as shown by results of a large multicenter collaboration including hospitals in 3 countries of the Middle East (Lebanon, Egypt, and Libya) and 9 countries in Europe.53 This prospective study enrolled 5,051 patients; of these, 33% of patients were found to be ‘at risk’ of malnutrition (NRS 2002 score). The proportion of ‘at risk’ patients generally reflected the severity of the underlying illness or injury in the population studied. For patients in the Middle East, risk for malnutrition by hospital department was: internal medicine (11%), oncology (37%), surgery (55%), and intensive care (97%).53 Patients ‘at risk’ had significantly more complications, longer lengths of hospital stay, and higher rates of mortality.53 Further, of those who were discharged, fewer ‘at risk’ patients were discharged to home, and more were sent to nursing homes or to other hospital care sites, as compared with patients who were adequately nourished.53

Malnutrition is under-treated

Even when nutrition problems are identified, studies have found that such problems are not adequately treated. In one Middle Eastern study, 34 Turkish hospitals from 19 cities contributed data from 29,139 patients.54 On admission, 15% of patients were found to be at nutritional risk; risk was highest in intensive care unit patients (52%). Of those identified to be ‘at nutritional risk’ in this study, only around half received nutrition intervention.54 Studies carried out in Australian and European hospitals reported similar shortfalls in treating malnutrition or reaching nutritional targets.3,47

Nutrition care improves outcomes and lowers costs

Nutrition interventions, including food fortification or oral nutrition supplements (ONS), tube-fed enteral nutrition, and parenteral nutrition, are recognized to have significant clinical and economic benefits across patient groups and in different settings. Specifically, nutrition interventions were associated with fewer in-hospital complications,30 reduced pressure ulcer incidence,37 achievement of higher functional status in recovery,30 improved quality of life,34,55 and reduced risk of mortality,56 as shown by results of randomized and controlled trials and by meta-analyses. Nutrition interventions to prevent or treat disease-related malnutrition also show resource savings; reports have shown reduced length of hospital stay,57 fewer readmissions,38,55 and lowered hospital-related costs.35,36 Few studies have considered cost of hospital-based malnutrition in Middle East countries. However, a recent survey of neurologists from 8 tertiary centers in Turkey examined current practice related to treatment of patients recovering from strokes.58,59 The researchers determined that the overall one-year costs of care were higher for malnourished patients compared to those who were adequately-nourished ($5201 versus $3618; p=0.09). Of the total costs, oral nutrition supplements (ONS) costs were $868 in patients with malnutrition and $501 in patients without malnutrition, whereas all others costs were $4334 and $3117. Investment in ONS as treatment for malnutrition was thus supported as a way to decrease the cost of illness.

Malnutrition definition

For caregivers to provide best-practice nutrition care, it is important to be aware of the current definition of malnutrition. Malnutrition is now recognized as 3 clinical syndromes, which are characterized by underlying illness or injury and varying degrees of inflammation.10 These malnutrition syndromes are: 1) starvation-related malnutrition, namely, a form of malnutrition without inflammation; 2) chronic disease-related malnutrition, namely, nutritional inadequacy associated with chronic conditions that impose sustained inflammation of a mild-to-moderate degree; and 3) acute disease- or injury-related malnutrition, namely, undernutrition related to conditions that elicit marked inflammatory responses. Inflammation is a component of underlying disease in several chronic disease states, such as kidney disease and heart failure and thus increases the risk of malnutrition,60 even among patients who are overweight or obese.61 Most severe acute health crises such as severe infection, surgery, burn injury, or sepsis are associated with marked inflammation, which contributes to and intensifies risk for severe malnutrition.60 Adult undernutrition was further described as a condition characterized by 2 or more of 6 criteria: unintentional weight loss, inadequate energy intake, loss of muscle mass, loss of subcutaneous fat, fluid accumulation, and functional decline (for example, decreased hand-grip strength).62

The feedM.E. Nutrition Care Pathway

The feedM.E. Global Study Group recently introduced screen-intervene-supervene as a guide for delivering prompt and complete nutrition care (Appendix 1A).1 We members of the feedM.E. Middle East Study Group support this overall strategy, and we advise the use of the Nutrition Care Pathway to bring this strategy to everyday practice. To facilitate broad use of the Nutrition Care Pathway throughout the Middle East, we provide versions in Turkish and Arabic (Appendix 1 B and ​andCC). For complete uptake, specific aspects of nutrition care may need adjustments to meet country-to-country cultural differences to accommodate disparate lifestyles, food availability, and genetic factors, as was the case with a diabetes nutrition program.63,64

Nutrition Care Pathway: screen for malnutrition risk

Screening patients for malnutrition on admission to the hospital is now a standard of care. In the Middle East, we advise that routine nutrition screening is likewise appropriate in rehabilitation facilities, long-term care centers, and community healthcare settings. To determine nutritional risk, we advise screening with (1) the 2 Malnutrition Screening Tool (MST) questions65,66 and (2) a quick clinical decision on whether the patient’s illness or injury carries risk for malnutrition.10In the Middle East, as is the case elsewhere, admitting nurses are often the first contacts for patients, and we suggest that nurses conduct the initial screen for nutritional risk. If risk is found, we advise immediate intervention with nutrition advice, an increase in the quantity or protein density of food, and/or use of protein-containing oral nutrition supplements. With risk recognition, particularly when the patient is unable to take food orally, refer to a trained clinician (dietitian, nutrition specialist) for further assessment and specific treatment.

Nutrition Care Pathway: intervene with targeted nutrition

The intervention portion of the Nutrition Care Pathway includes assessment of nutritional status, diagnosis of malnutrition, and implementation of treatment. For nutrition assessment, the SGA is widely used for most adults,67 and the MNA is used for older persons;68 other tools are available.52 To facilitate malnutrition diagnosis and help standardize malnutrition care, experts from A.S.P.E.N. and the Academy of Nutrition and Dietetics (AND) defined specific criteria for malnutrition diagnosis.62 Guidelines support prompt intervention, namely, targeted nutrition therapy within 24 to 48 hours of admission.43-46 Implementation of treatment involves decisions on how much to feed, how and when to feed, and what to feed, as discussed in detail for the feedM.E. global initiative.1

Nutrition Care Pathway: supervene

The next step of the Nutrition Care Pathway is to supervene, or follow-up with continuing attention to meeting nutrition needs. Individuals receiving nutrition therapy should also be monitored regularly to ensure feeding tolerance and adequate supplies of energy with sufficient protein, vitamins, and minerals.69 For those patients who are initially well-nourished, rescreening should occur at regularly determined intervals, especially when clinical status changes.70 An effective nutrition plan considers multiple aspects of care.43 It requires that the patient have cognitive competence, social and functional abilities, and economic access to food; alternatively, some patients need a caregiver and other social support programs to meet their needs. The nutrition plan should be prepared for and discussed with the patient, modified as needed to meet personal and cultural preferences, and include ongoing measures/assessment of the patient’s nutritional status.To ensure best-practice nutrition care in the Middle East, we recommend continued efforts to prevent and treat malnutrition among patients who have been discharged from the hospital into long-term care centers or into the community. Such efforts include nutrition education for the patient or their caregivers and individualized dietary advice on the use of food enrichment and/or oral nutrition supplements. We also emphasize the importance of routine rescreening for malnutrition risk. We call on regional and local health authorities to endorse nutritional risk assessment as an integral part of routine medical care.In conclusion, attention to nutrition is fundamental to good clinical practice. As members of the feedM.E. Middle East Group on nutrition in healthcare, we call healthcare providers in our region to action. To do so, we recommend use of the Nutrition Care Pathway that includes 3 key steps: screen always, intervene promptly when needed, and supervene or follow-up routinely. Because of wide socioeconomic differences among Middle Eastern countries, we recognize that feedM.E. global strategies may need to be adapted to meet country-specific needs, and we propose testing pilot models for feedM.E. training in each country.     

Intestinal lymphangiectasia in children: A favorable response to dietary modifications

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification.Intestinal lymphangiectasia (IL) is a rare1-4 benign disease characterized by focal or diffuse dilation of the mucosal, submucosal, and subserosal lymphatics.2,5 In addition to being an important cause of protein losing enteropathy (PLE),6 IL is frequently associated with extraintestinal lymphatic abnormalities.5 Depending on the underlying pathology IL can be classified as primary or secondary disease.1,2,4,5 Primary IL (PIL) probably represents a congenital disorder of mesenteric lymphatics.1,3 The IL can be secondary to diseases like constrictive pericarditis, lymphoma, sarcoidosis, and scleroderma.1 A secondary disorder should always be ruled out before labeling IL as primary, this is by testing for proteinuria, rheumatic, neoplastic, and parasitic infection.1,3 Recently, a functional form of PIL with typical endoscopic and pathological findings but without clinical symptoms has been reported.3 The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction.1,2,4 Palliative treatment with lifelong dietary modification is the most effective and widely prescribed therapy.6 Limiting the dietary fat intake reduces chyle flow and therefore, protein loss.1 Once protein level is within the normal range, recurrence of enteric protein loss can be prevented by total parenteral nutrition (TPN) and medium chain triglycerides (MCT).1 In cases of secondary IL, treating the underlying primary disorder may be curative.2 Although the therapeutic approach for this disorder have gained a lot of attention lately, few studies have considered the therapeutic effects, nutritional condition, and long-term results in PIL patients.4 Here, we report 2 patients with PIL who were diagnosed by endoscopy and biopsy, and showed positive response to dietary modifications. We present these particular cases to highlight the effect of dietary modifications on the clinical status of patients with IL.     

X-ray repair cross-complementing protein 1 and 3 polymorphisms and susceptibility of breast cancer in a Jordanian population

Objectives:

To elucidate the contribution of x-ray repair cross-complementing (XRCC) protein 1 399Gln, XRCC3 241M, and XRCC3-5’-UTR polymorphisms to the susceptibility of breast cancer (BC) in a Jordanian population.

Methods:

Forty-six formalin fixed paraffin embedded tissue samples from BC diagnosed female patients, and 31 samples from the control group were subjected to DNA sequencing. Samples were collected between September 2013 and December 2014.

Results:

The XRCC1 Arg399Gln genotype did not exhibit any significant correlation with the susceptibility of BC (odds ratio [OR]=1.45, 95% confidence interval [CI]: 0.60-3.51) (p=0.47). Likewise, XRCC3 M241T genotype did not show significant correlation with BC (OR=2.02, 95% CI: 0.50-8.21) (p=0.40). However, distribution of XRCC3-5’UTR (rs1799794 A/G) genotype showed a significant difference between the patient and control group (OR=0.73, 95% CI: 0.06-8.46) (p=0.02).

Conclusion:

The XRCC3-5’UTR (rs1799794) G allele frequency was higher in cancer patients while XRCC1 (rs25487) and XRCC3 (rs861539) did not show any significant correlation with susceptibility of BC in the selected Jordanian population. Contribution of other environmental factors should be studied in future works, as well as the response of cancer therapy.Breast cancer (BC) incidence in Jordan has been estimated at 1,237 cases in 2012, with a prevalence of 4,260 cases over 5 years, and mortality rate up to 426 cases.1 Genetic predisposition contributes to less than 10% of BC cases, which raises a demand for further research into new genetic markers of BC risks.2 Fewer than 5% of BC cases have been found to be mutated at breast cancer 1 (BRCA1) early onset and BRCA2 genes, and approximately 40% of familial BC families have been identified for genetic predisposition.3 Unfortunately, mammalian cells are habitually exposed to genotoxic agents, such as ionizing radiation that can lead to DNA damage. Many double strand break,4 and single strand break (SSB) repairing proteins have been identified including DNA repair protein homolog, or RAD tecombinase, or x-ray repair cross-complementing (XRCC)s family proteins.5 Deficiency in repairing system might contribute to cancer development due to the loss of genetic integrity and genome instability.6 Mutation in DNA repair proteins is very rare.7 Therefore, many studies have been conducted to evaluate the role of allelic polymorphisms in DNA repair genes involved in cancers development.8,9 Genetic polymorphisms in DNA repair genes XRCC1, and XRCC3 have been screened to find an association with the risk of BC.10-12 Studies have demonstrated an association between XRCC1 and XRCC3 polymorphisms, and certain cancers subsuming colorectal cancer,13 lung cancer,14 pancreatic cancer,15 head and neck cancer,16 gastric cancer,17 esophageal cancer,18 melanoma skin cancer,19 oral squamous cell carcinomas,20 lung cancer risk,21 bladder cancer,22 and BC.23 Furthermore, a meta-analysis study supported the contribution of XRCC1 Arg399Gln polymorphism in susceptibility of BC in the American population.24 On the other hand, no relationship has been found between XRCC1 and XRCC3 polymorphisms and the risk of BC,25 lung cancer,26 bladder cancer,27 prostate cancer,28 lung cancer risk,29 cutaneous malignant melanoma,30 furthermore, it may decrease the risk for myeloblastic leukemia31 and non-melanoma skin cancer.32 Alcoholism, abortion, and non-breast feeding have been associated with increased risk of BC with contribution of XRCC1 399Gln and XRCC3 T241M polymorphisms.11 Moreover, family history,12 age group,33 polycyclic aromatic hydrocarbon-DNA adducts, fruit and vegetable and antioxidant intake, and non-smokers have been suggested to be associated with the risk of BC in interaction with XRCC1 or XRCC3 polymorphisms.34 The aim of the current study was to elucidate the contribution of XRCC1 399Gln, XRCC3 241M and XRCC3-5’-UTR polymorphisms in the susceptibility of BC in the Jordanian population. This study is intended to establish a reference point for future single nucleotide polymorphism (SNP) studies in the Jordanian population, which may contribute to the development of a national cancer database.     

Pemphigus and pregnancy: Analysis and summary of case reports over 49 years

Pemphigus is a group of immune-mediated bullous disorders, which often cause fragile blisters and extensive lesions of the skin or mucous membranes, such as in the mouth. This disease could be life-threatening in some cases. During pregnancy, its condition will become more complicated due to the change in the mother’s hormone level and the effect of drug therapy on both the mother and her fetus. Thus, it will be more difficult to identify the clinical manifestations and to establish the treatment plan. In this article, we present a comprehensive review of pemphigus and pregnancy by analyzing 47 cases of pemphigus reported between 1966 and 2014, with diagnosis before or during pregnancy. The aim of this study is to make a comprehensive review of pemphigus and pregnancy, provide organized and reliable information for obstetricians, dermatologists, physicians, and oral medicine specialists.Pemphigus is characterized by widely distributed bullae and erosions on the skin and mucosa membranes. There are mainly 3 types of pemphigus: Pemphigus vulgaris (PV), Pemphigus foliaceus (PF), and other variants of pemphigus.1,2 The pathogenesis of pemphigus is associated with autoantibodies directed against transmembrane glycoproteins of desmosomes, which causes steric hindrance to homophilic adhesion of desmogleins, and results in the formation of Dsg1-depleted desmosomes in PF and Dsg3-depleted desmosomes in PV.3,4 Pemphigus usually affects the elderly, and genetics play an important role in predisposition.5,6 Pemphigus could involve one or more mucosae, while PV often shows extensive lesions of the oral mucosa.7,8 When it occurs in pregnancy, the condition becomes more complex.9 Early diagnosis and individually adjusted therapy are needed to avoid any risk for mother or child.10 The purpose of this article is to make a comprehensive review of the pemphigus and pregnancy, and provide organized and reliable information for clinicians.

Basic demographics

The existing reseasrch is mainly focused on case reports and retrospective studies. References were retrieved by an electronic search strategy “(pemphigus [MeSH Terms]) AND pregnancy [MeSH Terms] Filters: Case Reports” on PubMed, and a total of 62 cases were reviewed. Of the 62 cases, 14 were excluded based on abstract, which indicated discussion about gestational pemphigoid, and 7 were excluded because they were non-English. Finally, we included 41 relevant case reports according to their titles and abstracts. These 41 case reports between 1966 and 2014 involved 47 women identified with pemphigus before (n=21 cases) or during pregnancy (n=26 cases). These cases of pemphigus and pregnancy have been reported in different populations, Asia, Europe, and North America, with more than in Africa, South America, and Oceania (Figure 1). A recent study from the United Kingdom has suggested an incidence of PV of 0.68 cases per 100,000 persons per year. The incidence varies in different areas, being more common in the Near and Middle East than in Western Europe and North America.11-14Open in a separate windowFigure 1Regional distribution of 47 cases of pemphigus and pregnancy between 1966 and 2014.We analyzed the characteristics of 21 patients with pemphigus diagnosed before pregnancy. Among them, 71.4% were diagnosed as PV, 19% as PF, 4.8% as Pemphigus vegetans, while the remaining was indefinite. The age of onset of pemphigus was generally 20-42 years old (mean age 27.35±5.73), with a mean interval of 3.16±2.11 years between disease onset and pregnancy. The pemphigus course was characterized by exacerbation (61.9%), improvement (9.5%), and remaining stable (28.6%) during the pregnancy. The newborn status is meaningful for our conclusion. The incidence of neonatal pemphigus was as high as 57.1% (including 38.1% of PV and 19% of PF). In contrast, the percentage of healthy neonates was only 33.3%, which may be considered to be publication bias (15-31

Table 1

Characteristics of 21 patients with pemphigus diagnosed between 1966 and 2013.Open in a separate windowIt seems to be quite a rare phenomenon that pregnancy as a triggering factor of PV seems to be quite a rare phenomenon.13 4,14,19,32-52

Table 2

Characteristics of 26 patients with pemphigus diagnosed during pregnancy between 1966 and 2013.Open in a separate window

Effects on the mother

If a pregnant woman becomes sick (such as pemphigus), she is more likely to suffer from disorders of the neuroendocrine system and immune system due to the state of high pressure.53 According to the current study, the mother’s condition may exacerbate, enter into remission, or remain stable during the pregnancy.54 The disease is aggravated most likely during the first, second trimester, and postpartum, then is relived during the third trimester.15 This may be due to the increased level of endogenous corticosteroid hormone chorion and subsequent immunosuppression.40,55 Although some literature reports the postpartum flare of pemphigus due to the rapid drop of corticosteroid hormones levels, the postpartum status in our study was optimistic, only 2 cases (9.5%) of pemphigus diagnosed before pregnancy and 8 cases (30.8%) of pemphigus diagnosed during pregnancy exacerbated after delivery.19,56 However, some patients with pemphigus during pregnancy may not show any obvious changes, especially those patients in remission.9,15

Effects on the mode of delivery

Goldberg et al32 and Fainaru et al14 indicated that the trauma of vaginal delivery can result in extension and deterioration of the wound. In a cesarean section, patients who receive long-term steroid therapy will increase the risk, and the disease itself, and corticosteroid therapy may complicate wound healing. Therefore, delivery by cesarean section is the absence of additional benefits. Except for obstetric contraindications, vaginal delivery is recommended. Although it is a potential risk that local blisters may result in passive transfer of antibodies to the fetus through the breast milk, breastfeeding is not contraindicated.

Effects on the pregnancy outcome

Pregnancy outcome includes live birth, stillbirth, spontaneous abortion, and induced abortion.57 Pemphigus vulgaris in pregnancy may result in abortion, fetal growth retardation, intrauterine death, premature delivery, and in approximately 30% neonatal PV of the newborns.58 In this article, we will discuss the 3 most common outcomes of pemphigus in pregnancy: normal fetal outcome, neonatal pemphigus, and stillbirth.

Normal fetal outcome

Most of the patients with pemphigus can give birth to a normal full-term, healthy newborn through vaginal delivery or cesarean section, depending on the collaborative efforts of the dermatologist and obstetrician.56 In our study, although there were only 7 (33.3%) healthy neonates from the cases with pemphigus diagnosis before pregnancy, we considered it likely to be an underestimate due to the less frequent reports of successful deliveries than that of neonatal adverse outcomes.

Neonatal pemphigus

Neonatal pemphigus is a rarely reported transitory autoimmune blistering disease. It is clinically characterized by transient flaccid blisters and erosions on the skin and rarely on the mucous membranes.17 The disease can be self-healing at 2-3 weeks without special treatment, and does not have long-term clinical significance. No new vesicles or bullae appears in the newborn after birth. Neonatal PV has never been reported to persist beyond the neonatal period and progress to adult disease.17,34,35,39 Neonatal pemphigus is mainly due to the transplacental transmission of antibodies, and only a very small amount of immunoglobulin G (IgG) is synthesized by the neonate itself.36,59 Pemphigus IgG is found both in the fetal circulation and fixed to the fetal epidermis in a characteristic intercellular distribution, while IgA, IgM, IgE, and IgD generally do not participate in the passive transport.60 Contrary to PV, PF in pregnant women rarely leads to neonatal skin lesions.61 The absence of skin disease in the newborns may be due to low transfer of IgG4 autoantibodies through the placenta, and the “immunosorbent” effect of the placenta to contain desmosomes and desmogleins.62-65 This is because to the distribution and cross-compensation of the pemphigus antigens desmoglein 3 and 1 in neonatal and adult skin or mucosa are different.60

Stillbirth

In the literature, the rate of stillbirth in pemphigus during pregnancy was reported to range from 1.4-27%.18,33,56,66 In contrast to the high percentage of some previous observations, pregnancy ended in stillbirth in only one case (4.8%) of pemphigus diagnosed before pregnancy and 2 cases (7.7%) of pemphigus diagnosed during pregnancy in our study. The occurrence of stillbirth emphasizes the management problems encountered when a pemphigus patient becomes pregnant.56,66No relevance has been indicated between maternal treatment regimen and fetal outcome.38,67 Instead of particular medications, adverse pregnancy outcomes seem to be correlated more closely to poor maternal disease control, higher maternal serum, and umbilical cord blood antibody titers.38

Treatment options

Almost all types of pemphigus patients experience severe worsening of the disease after delivery if there is a lack of treatment during pregnancy (n=66). Treatment is often required to control both maternal diseases and fetal outcomes.68 The current study suggested that standard therapy gives priority to systemic glucocorticoids, alone or in combination with other immunosuppressive agents such as immunosuppressant, intravenous immunoglobulin (IVIg) or plasmapheresis.15,32,69 If the disease worsens during the first trimester, a medical termination of pregnancy may be considered, and if it happens during the second and third trimester, application of corticosteroids is a safe treatment.20 The treatment of pemphigus patients diagnosed during pregnancy is similar to the treatment before pregnancy.38

Glucocorticoids

The use of systemic steroids is considered safe in pregnancy, and glucocorticoid remains the first-line agent for treatment with low dosages when patients are mildly ill.70 Some corticosteroids such as prednisone (FDA pregnancy category B), featured with a fast action and high pharmacological effect, can be safely used as immunosuppressive drugs during pregnancy as they do not readily cross the placenta. Prednisone is the safest drug compared with other less used glucocorticoids such as dexamethasone and betamethasone.71,72 The dose of prednisone/prednisolone should be reduced to the lowest effective dose, and standardized doses are still experimental.15,19,32,56

Immunosuppressants

Immunosuppression of steroid-sparing agents are needed when pemphigus has to be controlled by larger doses of medications. Azathioprine is the most widely used steroid-sparing agent for pemphigus.73,74 Cyclosporine is believed to be less effective in the treatment of pemphigus, but it is the safest corticosteroid-sparing agent in pregnancy.38,69 Mycophenolatemofetil, cyclophosphamide, and methotrexate are strongly discouraged or even contraindicated in pregnancy.38,72

Intravenous immunoglobulin

There is moderate evidence suggestive of an effective and safe effect of IVIg as an auxiliary therapy in pregnancy patients with pemphigus.75-77 Therefore, when pregnancy is associated with significant medical problems or disease states, clinicians may need to consider using IVIg early.78

Plasmapheresis

Plasmapheresis is a useful alternative immunosuppressive therapy in pregnancy, which can be used as adjuvant therapy, combined with systemic corticosteroids, reducing the dosage of glucocorticoid treatment.21In conclusion, the patients may suffer from pemphigus before or during pregnancy. The condition of pemphigus and pregnancy can interact with each other and make the treatment and prognosis of these diseases more complicated, presenting challenges for the clinician. Pregnancy may precipitate or aggravate pemphigus, and new born babies of such patients may have a normal outcome or neonatal pemphigus, or, rarely, a stillbirth. Current treatment of pemphigus coexisting with pregnancy priorities systemic glucocorticoids, alone or in combination with other immunosuppressive agents such as immunosuppressants, IVIg or plasmapheresis. The number of reported cases of pemphigus in pregnancy is too small to predict the change of conditions for an individual patient. In summary, pemphigus and pregnancy is still an indistinct area that needs collaborative work by obstetricians, dermatologists, neonatologists, endocrinologists, and oral medicine specialists, to establish a mechanism of multi-disciplinary treatment.     

A cross-sectional study of anxiety and marital quality among women with breast cancer at a university clinic in western Saudi Arabia

Objectives:

To examine relationship between the quality of marital relationship and anxiety among women with breast cancer (BC) in the Kingdom of Saudi Arabia (KSA).

Methods:

This cross-sectional study recruited a consecutive series of 49 married women with BC seen in the Al-Amoudi Breast Cancer Center of Excellence at King Abdulaziz University, Jeddah, KSA in early 2013. Participants completed the Hospital Anxiety and Depression Scale, Spouse Perception Scale, and Quality of Marriage Index forms, and answered questions on demographic and cancer characteristics.

Results:

Anxiety symptoms indicating “possible” anxiety disorder were present in 10.4% and “probable” anxiety disorder in 14.6% (25% total). No significant relationship was found between the quality of marital relationship and anxiety symptoms (B=-0.04, standard error=0.05, t=-0.81, p=0.42). Anxiety was primarily driven by low education, poor socioeconomic status, and young age.

Conclusion:

Anxiety symptoms are prevalent among married women with BC seen in a university-based clinic in the KSA. Further research is needed to determine whether a diagnosis of BC adversely affects marital relationship, and whether this is the cause for anxiety in these women.Breast cancer (BC) is the most common cause of cancer death in women worldwide,1 and the Kingdom of Saudi Arabia (KSA) is no exception.2 Breast cancer has become a particular problem in Arab countries due to its late stage at presentation and its increased occurrence among young women.3 Both during and after treatment, even if the cancer goes into remission, concerns regarding recurrence, effect on the marital relationship, and frequent medical visits for monitoring, often result in high levels of anxiety (including post-traumatic stress-like symptoms).4-8 Anxiety and other mood symptoms are not benign in women with BC, as they are associated with increased mortality and cancer recurrence.9,10Studies in Western countries (United States, Canada, England, Australia, and Germany) indicate a prevalence of significant anxiety ranging from 4-45% in BC patients, depending on anxiety measure, cutoff score, geographical region, and time since diagnosis11-14 (compared with 15-37% of cancer patients in general with anxiety during the first year after diagnosis).15 The most commonly used measure of anxiety symptoms in BC patients is the Hospital Anxiety and Depression Scale (HADS), which assesses for “possible” and “probable” anxiety disorder (with a sensitivity and specificity of approximately 80%).12,16,17 Using this measure, the prevalence of “probable” anxiety disorder in BC patients ranges from 2-23% and “possible” anxiety disorder is present in an additional 19-22% (21-45% combined).11,13,18 Although factors that increase risk of anxiety in women with BC are poorly understood, a few studies largely from Western countries report more symptoms in younger persons and Caucasians, immigrants, those with lower education, later disease stage, and lower social support.8,11,13,19 In one of the few studies from an Eastern country,20 anxiety levels among BC patients from Bangkok, Thailand, were significantly higher among those with poor problem solving skills, more pain and fatigue, and poorer family functioning. Although research is limited almost entirely to the US and other Western countries, studies indicate that support from a spouse (especially emotional support) improves the adjustment of women to BC,21-25 and may even impact survival.26 Not all studies, however, report that having a marital partner buffers against the stress of BC.27,28 The demands of caregiving, the effects of BC and its treatments on sexual relationship, and coping with psychological changes in a BC patient can all lead to lower well-being in a spouse, and decrease his ability to provide support.24 Our exhaustive review of the literature uncovered several studies that have examined the prevalence of emotional reactions to BC in the Middle East, finding that 19-73% of women had significant anxiety symptoms.22,29-34 In those studies, anxiety was associated with poorer physical functioning, the presence of metastatic disease, higher education, lower social support, duration of marriage, and spouse’s level of anxiety. With regard to KSA, there has been a significant increase in the incidence of BC, which occurs at a younger age than in Western countries.35 A recent review of research on coping with BC, however, revealed not a single study from KSA.36 Our review identified only 2 studies37,38 that examined the prevalence or correlates of anxiety in Saudi cancer patients (none specifically in BC), and only one study39 that examined attitudes of Saudi males toward BC. The first study examined anxiety in 30 hospitalized patients with cancer (9 with BC) at the King Khalid National Guard Hospital in Jeddah, KSA.37 Researchers found that anxiety symptoms assessed by the Hamilton Anxiety Scale were significantly higher in cancer patients compared with 39 patients with a range of chronic illnesses; 3 patients with cancer (10%) had a clinical diagnosis of generalized anxiety disorder based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The second study examined non-pain symptoms in 124 cancer patients (27% with BC) at King Faisal Specialist Hospital in Riyadh, KSA.38 The most frequently reported non-pain symptoms were fatigue (80%), loss of appetite (72%), dry mouth (69%), and anxiety (61%). Finally, researchers examined attitudes toward BC among males accompanying female patients to outpatient clinics at King Abdulaziz Hospital in Jeddah, KSA. When men were asked what they would do if their wives were diagnosed with BC, 9.4% said they would leave their wives.39Given the current knowledge gap on this subject in KSA, we decided to: 1) determine the prevalence of anxiety symptoms in married women seen in an urban-based university outpatient clinic in Jeddah; 2) identify the correlates of anxiety symptoms (especially marital quality [MQ]); and 3) determine whether the relationship between MQ and anxiety differed between Saudi nationals and immigrants. We hypothesized that anxiety symptoms would be prevalent, that higher MQ would be strongly and inversely related to anxiety symptoms, and that this relationship would be particularly strong in women who were Saudi nationals (where cultural factors might have the most influence).     

Molecular mechanisms of anti-hyperglycemic effects of Costus speciosus extract in streptozotocin-induced diabetic rats

Objectives:

To investigate the mechanisms of the anti-hyperglycemic effect of Costus speciosus (C. speciosus) root ethanolic extracts (CSREt) by assessing its action on insulin synthesis and glucose catabolic enzyme gene expression and activities in streptozotocin (STZ) diabetic rats.

Methods:

This study was carried out at the Biochemical Laboratory, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt between July and August 2013. Sixty male albino rats (120 ± 20 g weight, and 6 months old) were used and divided into 6 groups (n=10). Two groups served as diabetic and nondiabetic controls. Four groups of STZ diabetic animals were given oral C. speciosus (CSREt) in doses of 200, 400, and 600 mg/kg body weight, and 600 µg/kg body weight of the standard drug glibenclamide for 4 weeks.

Results:

The CSREt 400 and 600 mg/kg body weight induced a decrease in blood glucose and an increase in serum insulin level, glucokinase (GK), aldolase, pyruvate kinase (PK), succinate dehydrogenase (SDH), and glycogen synthase activities in addition to a higher expression level of insulin, insulin receptor A (IRA), GK, PK, SDH, and glucose transporting protein.

Conclusion:

The C. speciosus has anti-hyperglycemic activity. It induces insulin secretion and release from cells, as well as stimulates the tissue’s insulin sensitivity leading to an increase of the tissues’ glucose uptake, storage, and oxidation.Diabetes mellitus (DM) may be defined as a state of chronic hyperglycemia caused by either relative, or absolute deficiency in the level of blood insulin.1 A huge number of people in the world suffer from diabetes; the alarming increase in incidence of DM makes it a serious health problem.2 The persistent hyperglycemia in diabetic patients is the inducer of DM complications, such as coronary artery disease, hyperlipidemia, cerebrovascular disease, blindness, renal failure, neurological complications, limb amputation, and premature death.3 The current available anti-diabetic drugs may have some limitations and side effects, therefore, the growing trend for DM treatment was directed to the use of natural agents, such as medicinal herbs.4 Medicinal plants have always been a part of human culture, and up to 80% of the world population relies on this system for some aspects of primary health care. A large number of folkloric plants are still in use as herbal therapies in the Kingdom of Saudi Arabia, among them is Costus speciosus (C. speciosus [Koenig]).5 The C. speciosus has a very wide distribution in India as a diabetic controller, usually diabetic patients eat one leaf daily to keep their blood glucose low.6 The Hexane extract of rhizome possess anti-hyperglycemic and hypo-lipidemic activity,7 reverses diabetes and its complications,8 improves hepatic antioxidant enzyme activity, affects neurotransmitters and monoamine oxidase activity,9 anti-inflammatory and antipyretic properties,10 and significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity.11 The C. speciosus has a huge content of spirostanol glycosides, and furostanol glycoside 26-O-beta-glucosidase (F26G), which has hypoglycemic effects.5 The mechanism of the anti-hyperglycemic action of C. speciosus was not clearly studied, therefore the objective of this work was to investigate on a molecular level, the possible mechanisms of anti-hyperglycemic action of C. speciosus by monitoring its effects on the gene expression and activities of glycolytic enzymes in streptozotocin (STZ)-diabetic male rats.     

Cardiac lymphangioma presenting as intrapericardial cystic mass

Cystic lymphangioma usually confined to head and neck is a well-recognized tumor that occurs during childhood. However, a cardiac lymphangioma is exceptionally uncommon and a particularly rare form of disease. We report a case of cystic lymphangioma arising from the right ventricular wall, and presenting as pericardial mass in a young female, who presented with a history of exercise intolerance in the form of breathlessness on exertion and palpitations. The management of such a case was a difficult task; however, she underwent near total resection of the mass, and is doing well for the last 2 years.Cardiac tumors are rare but potentially curable form of heart disease with incidence ranging from 0.0017-0.33% at autopsy. A high index of clinical suspicion is necessary for diagnosis as these tumors have protean manifestations that mimic a variety of other cardiac and noncardiac diseases.1,2 Most (>80%) of these tumors are benign, and myxoma is by far the most common. Myxoma constitutes approximately 50% of all benign cardiac tumors in adults, but only a small percentage of such tumors in children. Rhabdomyoma is the most common benign tumor in children, and accounts for 40-60% of cases. Other benign cardiac tumors include fibromas, lipomas, hemangiomas, papillary fibroelastomas, cystic tumors of the atrioventricular node, and paragangliomas. The remaining 20% of primary cardiac tumors are malignant, and are usually described as sarcomas.3 Cystic lymphangioma, usually confined to head and neck, is a well-recognized benign tumor that occurs during childhood. However, a cardiac lymphangioma is exceptionally uncommon and a particularly rare form of cardiac disease, and is considered to be a malformation that arises from sequestration of lymphatic tissue that fails to communicate normally with the rest of the lymphatic system.1,4,5 Cardiac lyphangiomas most frequently occur in the pericardial space, sometimes compressing adjacent structures; a chylous pericardial effusion may be present.6,7 The presentation in most cases is usually but not necessarily dramatic or acute, and the type of symptoms depends on the site and degree of involvement, ranging from syncope or palpitations to arrhythmia, or congestive heart failure.4,5 All imaging studies can provide information regarding the anatomic details of the mass, however to obtain final diagnosis and treatment, patient’s need surgical exploration and resection of the mass as was seen in our case.1,4,5 The objective in presenting this particular case is to highlight its atypical clinical picture and diagnostic uncertainty until surgical exploration.     

Clinical utility of dabigatran in United Arab Emirates: A pharmacovigilance study

Objectives:

To provide early data regarding clinical utility of dabigatran in Al-Ain, United Arab Emirates (UAE).

Methods:

This was an ethics approved retrospective cross sectional study. We retrieved a total of 76 patients who were using dabigatran from September to December 2014 in the Cardiology Clinic at Al-Ain Hospital, Al-Ain, UAE. The primary analysis was designed to test the frequency of bleeding events (rate) with dabigatran 75, 110, and 150 mg.

Results:

The mean age ± standard deviation of cohort was 67.9 ± 1.5 years (range; 29-98 years), composed of males (52.6%) with mean age of 66.3 ± 1.7 years, and females (47.4%) with mean age of 69.6 ± 1.1 years. The highest age group was those between 61-80 years (60.5%). Most comprised the age strata of ≤75 years (73.7%). The main indication for dabigatran use was atrial fibrillation. The rate of bleeding with dabigatran was 18/76 (23.7%), and melena was the leading cause of bleeding 8/76 (10.7%). The hospitalization rate was 67.1%, dabigatran withdrawal rate was 0.01%, and mortality rate was 6.5%. The cohort had exhibited incidences of minor bleeding with one fatal major bleeding, high co-morbidities, admission, and readmission, which was not directly linked to dabigatran. We did not identify any relation of death due to dabigatran.

Conclusion:

Dabigatran is a suitable alternative to warfarin obviating the need for repetitive international normalized ratio monitoring, however, it may need plasma drug monitoring.Atrial fibrillation (AF) is the most common cardiac arrhythmia that affects 1-1.5% of population worldwide.1 Atrial fibrillation prevalence increases with age, and rises from 0.7% in those between 55-59 years to 17.8% in those ≥85 years. Nearly 85% of patients with AF are aged >65 years old.2 The lifetime risk for the development of AF as demonstrated in the Framingham study was one in 4 for men and women aged ≥40 years,3 which pose certain concerns in countries with aging populations.4,5 In addition to this, hospitalization related to AF is alarmingly increasing.6 The risk of stroke in patients with AF is 5 folds, and systemic thromboembolism is 3 folds.7,8 Banerjee, et al9 has deployed stroke prevention score in patients with AF, however, the predictive value is of less magnitude. The European Society of Cardiology set estimation of stroke risk in patients with AF as per CHA₂DS₂-VASc score to determine the recommendation for initiating an oral anticoagulant,10 whereas in patients with CHA₂DS₂-VASc ≥2, HAS-BLED score can be used to assess the risk of bleeding, and commencement of anticoagulant.11Warfarin (vitamin K antagonist [VKA]) has proven efficacy in reducing the risk of stroke in patients with AF, however, it poses high bleeding incidences, emergency hospitalizations, unpredictable therapeutic effect, and multiple international normalized ratio (INR) tests leading to many limitations in its clinical utility.12 Novel oral anticoagulants (NOACs) are proved as effective anticoagulants in prevention of stroke in patients with AF. Novel oral anticoagulants were preferred in non-valvular AF, and do not require coagulation monitoring, however, strict adherence to approved indication is highly warranted.13 Dabigatran (Pradaxa^®), a competitive inhibitor of thrombin was approved in October 2010 by the United States of America Food and Drug Administration to reduce the risk of stroke, and systemic embolism in patients with non-valvular AF.14 A systematic review incorporated 6 economic reviews from diverse healthcare systems (USA, Canada, and United Kingdom) utilizing different economic models. It has suggested the benefit of dabigatran in patients with high-risk of stroke, high-risk of intra-cerebral hemorrhage, or suboptimal use of warfarin. The review outlined concerns on tolerability of dabigatran, adherence issues, and adverse consequences.15In comparison with warfarin, dabigatran 150 mg has shown low rates of stroke, and systemic embolism (dabigatran p<0.001 for superiority). However, both drugs exhibited comparable rates of major hemorrhage.16-18 Greater fatal, and non fatal bleeding events were reported with dabigatran than warfarin.19,20 A recent (2015) retrospective Medicare data analysis study20 on dabigatran’s safety highlighted that the incidence of bleeding was higher than with warfarin (33% versus 27%), major bleeding (9% versus 6%), and gastrointestinal bleeding (17% versus 10%). Intracranial hemorrhage occurred more often with warfarin than dabigatran (1.8% versus 0.6%).20 It has been documented that risks of major bleeding from dabigatran is high for patients with chronic kidney disease, and in African Americans.20 The Randomized Evaluation of Long-term Anticoagulant Therapy: Dabigatran versus warfarin-RE-LY studies18 have showed similar risk of bleeding with warfarin versus dabigatran in patients with non-valvular AF. This dictated the importance of age sub-group analysis in studies. In real clinical practice, patients from different countries may have more co-morbid conditions than those in the RE-LY study.21 The current available data around bleeding incidences from dabigatran is relevant to populations with diverse characteristics. Revealing the clinical utility of dabigatran in our Emirati population may demonstrate different perspectives. Therefore, we intend to provide early data around the clinical utility of dabigatran in United Arab Emirates (UAE) Emirati population.