Relationship of Right Ventricular Size and Function with Respiratory Status in Duchenne Muscular Dystrophy

The relationship between pulmonary function and right ventricle (RV) in Duchenne muscular dystrophy (DMD) has not been evaluated. Using cardiac magnetic resonance (CMR), we describe the relationship of RV size and function with spirometry in a DMD cohort. Fifty-seven boys undergoing CMR and pulmonary function testing within 1 month at a single center (2013–2015) were enrolled. Comparisons of RV ejection fraction (RVEF) and end-diastolic volume index (RVEDVI) were made across categories of percent forced vital capacity (FVC%), and relationships were assessed. Mean age was 15.5 ± 3.5 years. Spirometry and CMR were performed within 3.9 ± 4.1 days. Median FVC% was 92.0 % (67.5–116.5 %). Twenty-three (40 %) patients had abnormal FVC% (<80 %) of which 13 (57 %) had mild (FVC% 60–79 %), 6 (26 %) had moderate (FVC% 40–59 %), and 4 (17 %) had severe (FVC <40 %) reductions. Mean RVEF was 58.3 ± 3.7 %. Patients with abnormal FVC% were older and had lower RVEF and RVEDVI. Both RVEF and RVEDVI were significantly associated with FVC% (r = 0.31, p = 0.02 and r = 0.39, p = 0.003, respectively). In a large DMD cohort, RVEF and RVEDVI were related to FVC%. Worsening respiratory status may guide monitoring of cardiac function in these patients.     

Incidence and risk factors of bacterial infections in children following autologous hematopoietic stem cell transplantation: Single‐center experience from Jordan

Bacterial infection is a serious sequela following AHSCT; however, limited data are available regarding pediatric recipients, especially in developing countries. We retrospectively analyzed the incidence and risk factors of bacterial infections during the first 100 days after AHSCT in children at KHCC in Amman, Jordan between January, 2005 and September, 2013. A total of 65 patients were identified, with median age of four yr (1–17). Forty‐seven patients (72.3%) had solid tumors and 18 (27.7%) had lymphoma. Bacterial infections were documented in 33 patients (50%), with a total of 63 episodes. Gram‐negative infection (57.1%) was more prevalent than Gram‐positive infection (38%). The risk of bacterial infections was higher among patients less than five yr of age (p = 0.028) and those who developed hypogammaglobulinemia requiring IVIG replacement (p = 0.001). Patients with solid tumors developed more bacterial infections compared to patients with lymphoma (p = 0.0057). No deaths were attributed to bacterial infection. Bacterial infection rate is high among recipients of AHSCT in Jordan with Gram‐negative bacteria being the most common.     

Prevalence and risk factors of clopidogrel non-response among Saudi patients undergoing coronary angiography

Objectives:

To estimate the prevalence of clopidogrel non-response and identify its risk factors among Saudi patients.

Methods:

This cross-sectional study was conducted at Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia between January and June 2013, to assess the degree of platelet inhibition using the VerifyNow assay (Accumetrics, San Diego, CA, USA) after receiving clopidogrel standard loading dose. Clopidogrel resistance was defined as ≤15% platelet inhibition or >213 P2Y12 reaction units (PRU).

Results:

Three hundred and four patients were included in the study. The mean age was 60.3 ± 11.4 years, and 73% were males. Clopidogrel doses were 300 mg (57%), 600 mg (27%), and 75 mg (16%). All patients used aspirin (81 mg in 94%). Approximately 66% (200/304) showed in vitro clopidogrel non-response, 54% had low platelet inhibitions, and 61% had high post-loading PRU. Using multivariate regression analysis that included all significant characteristics; only diabetes (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.30-4.27, p=0.005) and higher preloading PRU (OR: 2.39, 95% CI: 1.40-4.11, p=0.002) remained significantly associated with higher clopidogrel non-response while myocardial infarction (OR: 0.34, 95% CI: 0.15-0.81, p=0.014) remained significantly associated with lower clopidogrel non-response. The associations of morbid obesity and diuretics use with higher clopidogrel non-response were slightly attenuated.

Conclusion:

Our findings indicate a high rate of clopidogrel in-vitro non-response among Saudi patients undergoing coronary angiography.Platelets play a critical role in the pathogenesis of atherothrombotic diseases such as coronary artery disease (CAD). The rupture of atherosclerotic plaques initiates a complex process of platelet adhesion, activation, and aggregation.1 Recently, clopidogrel and aspirin were the cornerstones of oral antiplatelet therapy for preventing ischemic events of atherothrombotic disease such as myocardial infarction and stroke.2,3 Clopidogrel was shown to be even more effective than aspirin in preventing such events of atherothrombotic disease.4 Clopidogrel is a prodrug and the active metabolite is generated by the cytochrome P450 system.5 The active metabolite acts by inhibiting platelet aggregation in response to adenosine diphosphate (ADP) through binding and blocking the platelet P2Y12 receptors.5 Variability in individual responsiveness to the antiplatelet effects of clopidogrel may lead to the occurrence of thromboembolic events despite regular antiplatelet therapy.6,7 This may be clinically translated into poor procedural and long-term morbidity and mortality outcomes.8,9 The prevalence of clopidogrel non-response (resistance) is highly variable in different studies and populations. A review10 estimated the non-response rate to range from 4-30%. This variability is partly caused by the lack of standard definition and the different assessment methods of clopidogrel non-response.11,12 A number of studies examined the patients characteristics associated with clopidogrel non-response but failed to identify any, probably due to small sample sizes and the presence of multiple confounding factors.13-15 Although, approximately 84% of Saudi patients admitted with acute coronary syndrome are treated with clopidogrel,16 there is lack of estimates of clopidogrel non-response and the associated risk factors in this population. The objective of the current study was to estimate the prevalence of clopidogrel non-response and to identify its risk factors among Saudi patients undergoing coronary angiography at a specialized cardiac center in Kingdom of Saudi Arabia (KSA).     

Immunohistological analysis of immune cells in blistering skin lesions

BACKGROUND: Bullous skin lesions are characterised by the presence of intraepidermal or subepidermal bullae. Although inflammatory cell infiltrate is a constant feature in these lesions, their immunophenotypic characterisation is still incomplete. AIM: To determine whether the development of bullous skin diseases is associated with changes in the inflammatory cell infiltrate. Materials and methods: 34 cases representing lesions with both intraepidermal and subepidermal bullae were examined using immunoperoxidase staining methods and antibodies targeting antigens for histiocytes (CD68), B cells (CD20+), T cells (CD3+), T cells with cytotoxic potential (T cell intracellular associated antigen, TIA1+) and activity (granzyme B, GRB+). The adjacent normal skin (lesions) and an additional five cases of normal skin were also examined (controls). RESULTS: The transition from normal skin to lesional skin (lesions with intraepidermal and subepidermal bullae) was associated with a significant increase (p< or =0.05) in the density of total inflammatory cell infiltrate, CD68+ cells, CD3+ T lymphocytes, CD20+ B lymphocytes, TIA1+ -resting cytotoxic T cells and GRB+ T cells with cytotoxic activity. CONCLUSIONS: The increase in inflammatory cell infiltrate during the transition from normal to lesional skin may reflect the presence of an increased antigenicity of the lesional cells or a response to some basement membrane components. CD68+ and CD3+ cells, especially the resting cytotoxic ones, achieved numerical dominance in these lesions. Cell-mediated immunity seems to have critical role in the development of these lesions.     

Locally delivered antimicrobials in the management of periodontitis: a critical review of the evidence for their use in practice

Plaque bacteria are the primary initiators of periodontal disease in susceptible persons and therapy is largely based on mechanical bacterial biofilm disruption. Patients' response to periodontal treatment is unpredictable and periodontal stability is not always achieved. Locally delivered antimicrobials (LDAs) may be used as adjuncts to mechanical therapy in treatment of recalcitrant deep (> or = 5mm), active, non-responding sites, providing the patient's oral hygiene is adequate. Their use as a monotherapy cannot be justified. The literature reveals that LDAs are safe and that they achieve statistically significant, yet clinically modest, gains in clinical attachment and reductions in pocket depths. Clinical Relevance: It has been suggested that LDAs may improve the clinical outcome in the treatment of recurrent and refractory cases of periodontitis when used as an adjunct to scaling and root surface instrumentation. This paper examines and discusses the evidence.     

Cheesy material on macroscopic on-site evaluation after endoscopic ultrasound-guided fine-needle biopsy: Don't miss the tuberculosis

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is an excellent investigation to diagnose pancreatic lesions and has shown high accuracy for its use in pathologic diagnosis. Recently, macroscopic on-site evaluation (MOSE) performed by an endoscopist was introduced as an alternative to rapid on-site cytologic evaluation to increase the diagnostic yield of EUS-FNB. The MOSE of the biopsy can estimate the adequacy of the sample directly by the macroscopic evaluation of the core tissue obtained from EUS-FNB. Isolated pancreatic tuberculosis is extremely rare and difficult to diagnose because of its non-specific signs and symptoms. Therefore, this challenging diagnosis is based on endoscopy, imaging, and the bacteriological and histological examination of tissue biopsies. This uncommon presentation of tuberculosis can be revealed as pancreatic mass mimicking cancer. EUS-FNB can be very useful in providing a valuable histopathological diagnosis. A calcified lesion with a cheesy core in MOSE must be suggestive of tuberculosis, leading to the request of the GeneXpert, which can detect Mycobacterium tuberculosis deoxyribonucleic acid and resistance to rifampicin. A decent diagnostic strategy is crucial to prevent unnecessary surgical resection and to supply conservative management with antitubercular therapy.     

Genetic polymorphisms in NQO1 and SOD2: Interactions with smoking,schistosoma infection,and bladder cancer risk in Egypt

BackgroundBladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.MethodsWe assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%.ResultsWater pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86–10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97–6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21–5.84]) than among the former (OR [CI 95%] = 1.86 [1.33–2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32–8.38]).ConclusionOur findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.     

Prevalence of Orthohantavirus-Reactive Antibodies in Humans and Peri-Domestic Rodents in Northern Ethiopia

In 2012, Tigray orthohantavirus was discovered in Ethiopia, but its seasonal infection in small mammals, and whether it poses a risk to humans was unknown. The occurrence of small mammals, rodents and shrews, in human inhabitations in northern Ethiopia is affected by season and presence of stone bunds. We sampled small mammals in two seasons from low- and high-density stone bund fields adjacent to houses and community-protected semi-natural habitats in Atsbi and Hagere Selam, where Tigray orthohantavirus was first discovered. We collected blood samples from both small mammals and residents using filter paper. The presence of orthohantavirus-reactive antibodies in blood was then analyzed using immunofluorescence assay (human samples) and enzyme linked immunosorbent assays (small mammal samples) with Puumala orthohantavirus as antigen. Viral RNA was detected by RT-PCR using small mammal blood samples. Total orthohantavirus prevalence (antibodies or virus RNA) in the small mammals was 3.37%. The positive animals were three Stenocephalemys albipes rats (prevalence in this species = 13.04%). The low prevalence made it impossible to determine whether season and stone bunds were associated with orthohantavirus prevalence in the small mammals. In humans, we report the first detection of orthohantavirus-reactive IgG antibodies in Ethiopia (seroprevalence = 5.26%). S. albipes lives in close proximity to humans, likely increasing the risk of zoonotic transmission.     

Early detection of subclinical lower limb enthesopathy by ultrasonography in patients with psoriasis: Relation to disease severity

BackgroundEntheseal involvement is a frequent and distinctive feature of psoriatic arthritis (PsA). It is detected clinically but lacks sensitivity and reliability. Musculoskeletal ultrasound (MSUS) is an important tool for accurate detection of enthesitis.Aim of the workTo determine the frequency and distribution of subclinical entheseal abnormalities at lower limbs using MSUS in patients with psoriasis for early detection of PsA, and to evaluate its relation to disease severity.Patients and methods80 patients with psoriasis were studied. Psoriasis Area and Severity Index (PASI) was assessed. High-resolution MSUS assessment of quadriceps, patellar and Achilles tendons, and plantar fascia entheses was performed. Glasgow Ultrasound Enthesitis Scoring System (GUESS) was assessed.ResultsThe median (interquartile range; difference between 75th and 25th quartile) age of the patients was 46(26.3) years and were 42 males. The disease duration was 9(12) years, PASI was 10.9(18.9), and GUESS 6(4). Nail dystrophy was found in 48(60%). Clinical enthesitis was found in 15(18.8%) patients; MSUS revealed lower limb enthesopathy in at least one enthesis in 76(95%) patients, and abnormality in 421 of 800 entheses (52.6%). Distal insertion of the patellar tendon was the most frequently involved (68.8%). GUESS significantly correlated with the age, body mass index (BMI), and PASI.ConclusionPsoriasis is associated with a relevant frequency of asymptomatic entheseal abnormalities. MSUS is a valuable, simple, and noninvasive tool in early detection of enthesopathy in psoriatic patients, especially in the presence of older age, high BMI, and high PASI as potential parameters for detection of psoriatic enthesitis.