Acute rheumatic fever diagnosis and management: Review of the global implications of the new revised diagnostic criteria with a focus on Saudi Arabia

Rheumatic fever (RF) is a common cause of acquired heart disease in children worldwide. It is a delayed, nonsuppurative, autoimmune phenomenon following pharyngitis, impetigo, or scarlet fever caused by group A β-hemolytic streptococcal (GAS) infection. RF diagnosis is clinical and based on revised Jones criteria. The first version of the criteria was developed by T. Duckett Jones in 1944, then subsequently revised by the American Heart Association (AHA) in 1992 and 2015. However, RF remains a diagnostic challenge for clinicians because of the lack of specific clinical or laboratory findings. As a result, it has been difficult for some time to maintain a balance between over- and underdiagnosis of RF cases. The Jones criteria were revised in 2015 by the AHA, and the main modifications were as follows: the population was subdivided into moderate- to high-risk and low risk; the concept of subclinical carditis was introduced; and monoarthritis was included as a feature of musculoskeletal inflammation in the moderate- to high-risk population. This review will highlight the major changes in the AHA 2015 revised Jones criteria for pediatricians and general practitioners.     

Parathormone,vitamin D and the risk of atrial fibrillation in older adults: A prospective study

Background & aimsVitamin D and parathormone (PTH) have been associated with cardiovascular outcomes, but their impact on atrial fibrillation (AF) onset is still unclear. We explored the influence of serum 25-hydroxyvitamin D (25[OH]D) and PTH on AF risk in older adults.Methods and resultsData come from 2418 participants enrolled in the Progetto Veneto Anziani study. Serum 25(OH)D and intact PTH were measured using radioimmunoassay and two-site immunoassay, respectively. The associations between 25(OH)D, PTH and adjudicated AF cases over 4-years were explored by Cox regression.Over the follow-up, 134 incident cases of AF were assessed. The incidence rate of the sample was 13.5 (95%CI 11.4–15.9) per 1000 person-years, and was higher among those with high PTH levels (high: 16.4 [95%CI 11.3–24.0] per 1000 person-years), especially when associated to low 25(OH)D (20.3 [95%CI 12.9–32.3] per 1000 person-years). At Cox regression, only high PTH was significantly associated to an increased risk of AF (HR = 1.90, 95%CI 1.27–2.84). A marginal significant interaction (p = 0.06) was found between 25[OH]D and PTH concentrations in influencing AF risk. When exploring the risk of AF for combined categories of 25(OH)D and PTH, we found that those with high PTH and low 25(OH)D levels had an AF risk twice as high as that of people with normal values (HR = 2.09, 95%CI 1.28–3.42).ConclusionThe risk of AF may be increased by high PTH levels, especially when associated with 25(OH)D deficiency. The identification and treatment of high PTH or vitamin D deficiency may thus contribute to lower the risk of AF.     

Mediterranean alcohol-drinking pattern,low to moderate alcohol intake and risk of atrial fibrillation in the PREDIMED study

Background and aimsThere is ongoing controversy about the effect of a low to moderate alcohol consumption on atrial fibrillation (AF). Our aim is to assess the association between adherence to a Mediterranean alcohol drinking pattern and AF incidence.Methods and resultsA total 6527 out of the 7447 participants in the PREDIMED trial met our inclusion criteria. A validated frequency food questionnaire was used to measure alcohol consumption. Participants were classified as non-drinkers, Mediterranean alcohol drinking pattern (MADP) (10–30 g/d in men and 5–15 g/day in women, preferably red wine consumption with low spirits consumption), low-moderate drinking (<30 g/day men y and < 15 g/day women), and heavy drinking. We performed multivariable Cox regression models to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) of incident AF according to alcohol drinking patterns. After a mean follow up of 4.4 years, 241 new incident AF cases were confirmed. Alcohol consumption was not associated to AF incidence among low-moderate drinkers (HR: 0.96; 95%CI: 0.67–1.37), adherents to MADP (HR: 1.15 95%CI: 0.75–1.75), or heavy drinkers (HR: 0.92; 95%CI: 0.53–1.58), compared with non-drinkers.ConclusionsIn a high cardiovascular risk adult population, a Mediterranean alcohol consumption pattern (low to moderate red wine consumption) was not associated with an increased incidence of AF.Clinical trialsURL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.     

Different prognosis of patients with esophageal carcinoma with M1a and regional node involvement

Background and purposeBased on the 6th edition of the American Joint Commission on Cancer (AJCC) staging system for esophageal squamous cell carcinoma (ESCC), M1a node involvement was classified as regional node involvement in the revised 7th/8th edition. However, the clinical significance of M1a node involvement is unclear. Thus, we analyzed the prognostic value of M1a node involvement in patients with ESCC after definitive concurrent chemoradiotherapy (CCRT).Materials and methodsIn total, 188 patients with ESCC had M0 disease according to the 7th/8th edition AJCC. We reclassified 31 (16.5%) of these patients as having M1a disease according to the 6th edition. After definitive CCRT, we compared baseline characteristics between the two groups and analyzed the rates of responders and recurrence. Finally, we compared prognoses according to overall survival (OS), disease-specific OS, and disease-free survival (DFS).ResultsAmong 31 patients reclassified to have M1a disease, 21 (67.7%) had supraclavicular lymph node metastasis and 10 (32.3%) had celiac lymph node metastasis. The number of responders was significantly lower for M1a disease based on univariate (p = 0.004) and multivariate (p = 0.011) analyses. Significantly lower survival rates were observed in individuals with M1a disease (median OS, 16.4 vs. 42.7 months; 5-year OS, 10.8% vs. 41.2%).ConclusionsM1a node involvement should be differentiated from regional node involvement.     

Comparison and correlation of fibrosis stage assessment by collagen proportionate area (CPA) and the ELF panel in patients with chronic liver disease

BackgroundFibrosis progression is the common consequence of most chronic liver diseases.AimsTo evaluate the performance of Collagen Proportionate Area (CPA) and ELF using Ishak’s score in patients with chronic liver diseases.MethodsRetrospective analysis of medical data from patients on whom a liver biopsy was performed as part of the diagnostic assessment. CPA was calculated by using digital image analysis and then compared with Ishak and ELF scores.Results143 patients (84 men (59%); mean age 48.8 ± 12.8 years) were evaluated. Patients were mainly affected by viral hepatitis (92 HCV and 8 HBV). CPA and ELF values increased with worsening Ishak stage (P < 0.001) and their median values were significantly different among Ishak stages (P < 0.001). There was a significant correlation between CPA and ELF (r = 0.5). In AUROC analysis, CPA and ELF had similar diagnostic accuracy in identifying cirrhosis, but CPA had higher diagnostic accuracy than ELF in identifying significant or absent fibrosis. High ELF scores were observed in non-cirrhotic patients who suffered non-liver related deaths.ConclusionsThis study demonstrated that CPA and ELF values successfully identified patients with advanced fibrosis or cirrhosis, thus confirming the role of ELF as a clinical method for non-invasive assessment of fibrosis stage in chronic hepatitis.     

Hazards of pulse steroid use in a cohort of Egyptian lupus nephritis patients

BackgroundPulse methylprednisolone is a tool for rapid immunosuppression in systemic lupus erythematosus (SLE) patients with life-threatening manifestations.Aim of the workTo assess the effect of the frequent use of high-dose pulse steroids on renal response and to detect any associated hazards in lupus nephritis (LN) patients with a disease duration >3 years.Patients and methodsMedical records of 90 Egyptian LN patients were revised every 6 months for the preceding 3 years. Patients’ examination was followed-up every 6 months for another year. Disease damage and activity (SLEDAI) indices were assessed; criteria for renal response evaluated, relevant laboratory investigations performed, and history of steroid therapy reported.ResultsThe patients mean age was 30.1 ± 8.3 years, 75 were females (83.3%) and 15 males (16.7%), mean SLEDAI was 7.6 ± 6.9 and damage index was 0.38 ± 0.95. All were on treatment with steroids and immunosuppressives. Those receiving frequent pulse-steroids (n = 71) had a significantly higher proteinuria and both significantly correlated throughout the study course (p < 0.001). A higher pulse-steroid dose was associated with poor renal response (p < 0.001). There was a significantly higher damage index in those receiving pulse compared to those not (p < 0.001). The cumulative steroid dose was significantly higher in patients with renal damage (n = 18), with cerebrovascular accident (n = 5) and with avascular necrosis of the hip (n = 8) than those without (p = 0.001, p = 0.047 and p = 0.001).ConclusionRepeated “pulse” steroid was associated with higher renal damage and deleterious effect on central nervous system and bone. The abuse of “pulse” steroid therapy should be avoided.     

Clinical Impact of Diabetes Mellitus on Short-Term Outcomes andIn-Hospital Mortality of Cardiac Mechanical Support with Left Ventricular Assist Device (LVAD): A Retrospective Study from a National Database

BackgroundCardiac support with left ventricular assist devices (LVAD) is a growing field. LVAD are increasingly used for patients with advanced congestive heart failure. Multiple studies have evaluated the outcomes of cardiac support with LVAD in patients with and without diabetes mellitus (DM), yet we still have conflicting results. This study aimed to assess the clinical impact of diabetes mellitus on patients undergoing cardiac support with LVAD.MethodsDiabetic patients who underwent mechanical support with LVAD between 2011 and 2014 were identified in the National Inpatient Sample (NIS) database using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The primary outcome was the effect of diabetes mellitus on inpatient mortality. Secondary outcomes were the impact of diabetes on other immediate post-LVAD complications and the cost of hospitalization. Multivariable logistic regression models analysis was performed to address potential confounding.ResultsAfter adjusting for patient-level and hospital-level characteristics, diabetic patients who underwent cardiac support with LVAD have no significant increase in in-hospital mortality (OR: 0.79, 95% CI (0.57–1.10), p = 0.166), post-LVAD short-term complications and cost of hospitalization (OR: 0.97, 95% CI (0.93–1.01), p = 0.102).ConclusionCardiac mechanical support with LVAD implantation is feasible and relatively safe in patients with diabetes and stage-D heart failure as a bridge for transplantation or as destination therapy for patients who are not candidates for transplantation. However, further trials and studies using bigger study sample and more comprehensive databases, need to be conducted for a stronger and more valid evidence.     

Intracranial hypertension,nephritis and serositis complicating unexpected pregnancy in a lupus patient

Background: Systemic lupus erythematosus (SLE) flare in pregnancy is challenging. The simultaneous occurrence of intracranial hypertension (IH) is unusual and raises the possibility of being a presentation of neuropsychiatric SLE. Aim of the work: We here discuss the presentation and management of a complicated case of lupus associated with IH, lupus nephritis (LN) and serositis in unplanned pregnancy. Case presentation: A 26-year old SLE patient presented 10 weeks pregnant with marked pleural effusion, hypertension, grade V papilledema, impaired renal functions, proteinuria (2.2 g/24 h), high anti-double stranded deoxyribonucleic acid and consumed complement (C3). Renal biopsy revealed LN (class IV and V). MRI brain demonstrated features consistent with IH and perimetry revealed early optic nerve affection. Ultrasound-guided pleurocentesis and relieving lumbar puncture were performed. Pulse methylprednisolone and cyclosporine A (CsA) (2 mg/kg/day) were provided. Acetazolamide was added to manage the IH and meticulous control of BP was achieved. In 2 weeks renal functions, proteinuria and papilloedema improved. The patient gave birth via vaginal delivery at full term to a normal healthy boy. On follow-up after delivery, proteinuria ranged from 100 to 300 mg/24 h with normal renal functions and fundus. The patient was maintained on CsA, hydroxychloroquine and tapering doses of steroids with no relapses. Conclusion: Pregnant SLE cases presenting with IH, LN and serositis are challenging concerning the management of SLE activity. IH may be a sign of lupus activity and its resolution coincides with the control of the flare. Lower dose CsA is potentially effective in treating LN in pregnancy with no reported side effects.     

Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study

BackgroundNovel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM).MethodsA prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up.Main findingsThe composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38–6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40– 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers.ConclusionsPatients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.     

Impaired enhancement of insulin action in cultured skeletal muscle cells from insulin resistant type 2 diabetic patients in response to contraction using electrical pulse stimulation

AimsSkeletal muscle insulin resistance is a characteristic feature of type 2 diabetes. The aim of this study was to examine the effect of contraction on insulin action using electrical pulse stimulation (EPS) in cultured skeletal muscle cells from insulin resistant type 2 diabetic patients.MethodsSkeletal muscle cell cultures were established from 6 insulin resistant type 2 diabetic subjects and age and BMI matched non-diabetic control subjects. Day 7 differentiated myotubes were treated with or without EPS for 16 h, after which glucose uptake and AS160 phosphorylation were measured in the presence or absence of insulin.ResultsIn control myotubes, EPS resulted in increased phosphorylation of AMPKThr¹⁷² (vs no EPS; p < 0.01), and this was associated with increased glucose uptake (p < 0.05). Insulin in the absence of EPS increased glucose uptake and AS160Thr⁶⁴² phosphorylation, and both effects were significantly enhanced by prior EPS. In the absence of EPS, AMPK activation was significantly increased (p < 0.01) in the diabetic vs control myotubes. Despite a comparable degree of AMPK activation following EPS, the action of insulin on glucose uptake (p < 0.05) and AS160Thr⁶⁴² phosphorylation (p < 0.001) was decreased in the diabetic vs control myotubes.ConclusionEPS mediated AMPK activation enhances the effect of insulin on glucose uptake and AS160Thr⁶⁴² phosphorylation in control myotubes replicating key metabolic benefits of exercise on insulin action in man. Conversely, insulin mediated glucose uptake and AS160Thr⁶⁴² phosphorylation remain significantly decreased in diabetic vs control myotubes despite a comparable degree of AMPK activation following EPS.     

Glucometabolic characteristics and higher vascular complication risk in Korean patients with type 2 diabetes with non-albumin proteinuria

ObjectiveWe investigated the clinical relevance of non-albumin proteinuria (NAP) in Korean patients with type 2 diabetes (T2D).Research design and methodsWe enrolled 883 T2D patients who had both their urinary albumin-to-creatinine ratio (uACR) and protein-to-creatinine ratio (uPCR) measured. We classified the patients into non-proteinuria (NP; uPCR <150 mg/g and uACR <30 mg/g), isolated NAP (iNAP; uPCR ≥150 mg/g and uACR <30 mg/g), and albuminuria (uACR ≥30 mg/g) groups. The associations between uPCR, uACR, and several indices of glucose metabolism were investigated.ResultsThe glucometabolic pathophysiology of iNAP (96 [10.9%]) group was more associated with a decrease in homeostatic model assessment (HOMA)-beta value (aOR 1.89 [95% CI, 1.21–2,96]) than with an increase in HOMA-insulin resistance (aOR 1.29 [95% CI, 0.83–2.01]). uPCR ≥150 mg/g was also found to have more consistent and stronger association with vascular complications than uACR ≥30 mg/g (aOR 1.44 [95% CI, 1.03–2.02] vs. 1.26 [95% CI, 0.89–1.79]).ConclusionsThe nephropathy of iNAP may be mainly attributed to decreased beta cell function. Furthermore, uPCR might be a more sensitive urinary biomarker than uACR for the detection of vascular complications in T2D patients.