Synthesis and antiviral activity of benzimidazolyl- and triazolyl-1,3,5-triazines

A novel series of 1,3,5-triazine analogs was successfully synthesized through conjugation with benzimidazole or 1,2,4-triazole derivatives via a methylenethio linker. The new analogs were in vitro evaluated against HSV-1 in Vero cells; among these analogs, two compounds exhibited good effect in inhibiting HSV-1 replication (for compound 5p: EC₅₀ = 3.5 μg/ml, SI = 358; for compound 5r: EC₅₀ = 5.0 μg/ml, SI = 300) in comparison to acyclovir.     

Mortality in bullous pemphigoid: A systematic review and meta‐analysis of standardized mortality ratios

There are inconsistent data on mortality rates in patients with bullous pemphigoid (BP). Trends in mortality in BP throughout the years are yet to be established. The aim of the present study was to study the mortality in BP patients relative to the general population and to estimate trends in standardized mortality over the past 30 years. We performed a systematic review and meta‐analysis of observational studies in Medline, Embase and Scopus (1823–2017). Reference lists of included studies were also searched for eligible studies. Quality of evidence was assessed using the Newcastle–Ottawa Scale (NOS). A meta‐analysis was performed using random‐effects models to estimate pooled standardized mortality ratios (SMR) with 95% confidence intervals (CI). Meta‐regression models were used to investigate the secular trends in SMR. Ten studies were included covering the period 1960–2015 (1736 patients, 746 deaths). Pooled all‐cause SMR was 3.6 (95% CI, 2.6–5.0). There was no trend in all‐cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04–0.08; P = 0.545). In conclusion, there is a 3.6‐fold increased mortality among patients with BP as compared with the age‐matched general population. The excess mortality in BP has not changed significantly over the past 30 years.     

Scalene Muscle Injections for Neurogenic Thoracic Outlet Syndrome: Case Series

Abstract: Scalene muscle injections are used to confirm the diagnosis of neurogenic thoracic outlet syndrome and predict the response of patients to surgery. We performed a retrospective study to determine if relief of pain was related to brachial plexus blockade in these patients. Methods: We reviewed the charts of 12 patients who had anterior and middle scalene muscle injections, for neurogenic thoracic outlet syndrome, between April 2009 and September 2010. The injections were performed under ultrasound guidance wherein 2 to 5 mL of 0.25% bupivacaine was injected into the belly of the anterior and scalene muscles. The following were noted: (1) sites of preprocedure pain; (2) volume injected into each of the anterior and middle scalene muscles; (3) presence of numbness after injection; and (4) presence and duration of pain relief. Results: All 12 patients had relief of their pain. Six of the twelve patients developed numbness, which ranged from blockade of the C4‐5, C6‐7, and C4‐T1 dermatomes. In the patients who developed numbness, there was no relationship between the duration of numbness and the duration of pain relief or the location of numbness and the location of pain relief. Conclusions: The relief from scalene muscle injections in patients with neurogenic thoracic outlet syndrome is not related to blockade of the brachial plexus. ?     

Local endometrial injury and IVF outcome: a systematic review and meta-analysis

A systematic review was conducted of the influence of local endometrial injury (LEI) on the outcome of the subsequent IVF cycle. MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI Conference Proceedings, ISRCTN Register and Meta-register were searched for randomized controlled trials to October 2011. The review included all trials comparing the outcome of IVF treatment in patients who had LEI in the cycle preceding their IVF treatment with controls in which endometrial injury was not performed. The main outcome measures were clinical pregnancy and live birth rates. In total, 901 participants were included in two randomized (n = 193) and six non-randomized controlled studies (n = 708). The quality of the studies was variable. Meta-analysis showed that clinical pregnancy rate was significantly improved after LEI in both the randomized (relative risk, RR, 2.63, 95% CI 1.39–4.96, P = 0.003) and non-randomized studies (RR 1.95, 95% CI 1.61–2.35, P < 0.00001). The improvement did not reach statistical significance in the one randomized study which reported the live birth rate (RR 2.29, 95% CI 0.86–6.11). Robust randomized trials comparing a standardized protocol of LEI before IVF treatment with no intervention in a well-defined patient population are needed.The endometrium is the lining of the womb where the embryo implants. Endometrial surface injury is a simple office procedure. We reviewed the literature to find out if performing endometrial surface injury before an IVF treatment cycle improves its outcome. Our review found that when endometrial surface injury was performed before an IVF treatment cycle, there was a significant improvement in the outcome of that treatment cycle. We recommend this question is addressed in a well-conducted randomized study to confirm the findings of our review.     

Clinical characteristics and outcome of children stung by scorpion

Scorpion envenomation is a health problem in children in tropical and subtropical regions. The aim of this study was to evaluate demographic and clinical characteristics as well as outcomes in referred children to Assiut University Children Hospital during the year 2012 with a history of scorpion sting. The medical files of these patients were reviewed retrospectively for demographic data, time and site of biting, and clinical manifestations. Laboratory investigations of the patients were reviewed for complete blood count (CBC), liver function tests, creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), arterial blood gases, and serum electrolytes. Results showed 111 children with a history of scorpion sting; 69 males and 42 females with a median age of 5 years. Out of the studied patients, 53.2 % were classified as class III of clinical severity with recorded pulmonary edema in 33.3 %, cardiogenic shock in 46.8 %, and severe neurological manifestations in 22.8 %. Twelve patients (10.8 %) were classified as class II with mild systemic manifestations, and 36 % of the patients were classified as class I with only local reaction. Outcomes of these patients were discharge without sequelae in 55.8 %, discharge with sequelae in 26.1 %, and death in 18.1 %. Conclusion: more than half of stung children had a severe clinical presentation and about one fifth died. Aggressive treatment regimens are recommended for such patients to improve the outcome.     

Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies,an in-depth review

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.