Pediatric valve replacement, 15 years experience in Oman

Background Despite improving surgical techniques, treatment of heart valve disease in children remains controversial. Somatic growth and adequate anticoagulation are of concern when children undergo valve replacement. We conducted this study to evaluate the performance of valves in this age group. Methods 42 children under the age of 13 years who underwent valve replacement were included in this study. Totally, 50 valves were implanted in 42 patients: 48 were mechanical prostheses, two were bioprosthetic both in pulmonary position. 37 (74%) valves were implanted in mitral position, 10 (20%) in aortic position, 1 (2%) in tricuspid position and 2 (4%) in pulmonary position. Preoperatively, 14 (33,3%) patients were in New York Heart Association (NYHA) class IV, while 27 (64.2%) were in NYHA class III. Results There were 2 (4.7%) hospital deaths and 2 (4.7%) late deaths while 2 (4.7%) patients were lost to follow up. The mean follow up period was 9.4 yrs. 35 (83.3%) patients are in NYHA Class I and free of all medications except warfarin. 3 (7.1%) patients have undergone 5 successful pregnancies. The median INR was 2.23. Major thrombo-embolic episode occurred in 1 (2.3%) patient. Conclusions In view of the problems of sizing, anticoagulation and need for re-operation at an early age, there is a reluctance to replace valves in children. This study shows that despite these problems, valve replacement can be undertaken safely and successfully in children, when repair has failed or not technically feasible.     

West Nile virus preferentially transports along motor neuron axons after sciatic nerve injection of hamsters

Prior findings led us to hypothesize that West Nile virus (WNV) preferentially transports along motor axons instead of sensory axons. WNV is known to undergo axonal transport in cell culture and in infected hamsters to infect motor neurons in the spinal cord. To investigate this hypothesis, WNV was injected directly into the left sciatic nerve of hamsters. WNV envelope-staining in these hamsters was only observed in motor neurons of the ipsilateral ventral horn of the spinal cord, but not in the dorsal root ganglion (DRG). To evaluate the consequence of motor neuron infection by WNV, the authors inoculated wheat germ agglutinin—horseradish peroxidase (WGA-HRP) 9 days after WNV sciatic nerve injection, and stained the spinal cord and the DRG for HRP activity 3 days later. The degree of HRP-staining in DRG was the same in WNV- and sham-infected animals, but the HRP-staining in the motor neuron in the ventral horn was considerably less for WNV-infected hamsters. To investigate the mechanism of WNV transport, hamsters were treated with colchicine, an inhibitor of membranous microtubule-mediated transport. The intensity of the WNV-stained area in the spinal cord of colchicine-treated hamsters at 6 days after WNV infection were significantly reduced (P≤.05) compared to the placebo-treated hamsters. These data suggest that WNV is preferentially transported through the motor axons, but not the sensory axons, to subsequently infect motor neurons and cause motor weakness and paralysis.     

Uterine carcinosarcomas and grade 3 endometrioid cancers: evidence for distinct tumor behavior

OBJECTIVE: To compare the clinical behavior and outcome of uterine carcinosarcomas and grade 3 endometrioid carcinomas. METHODS: Data on patients with grade 3 endometrioid adenocarcinomas and uterine carcinosarcomas, from 1988 to 2004, was obtained from the Surveillance, Epidemiology, and End Results database. Mortality was analyzed using Cox proportional hazards models. Survival analysis was performed with the Kaplan-Meier method and log rank test. RESULTS: The cohort included 8,986 women with 5,024 (56%) grade 3 endometrioid carcinomas and 3,962 (44%) uterine carcinosarcomas. Women with uterine carcinosarcomas were older (aged 70 years compared with 66 years; P<.001) and more often nonwhite (23% compared with 15%; P<.001). These women presented with more advanced disease (stage III/IV 41% compared with 31%; P<.001). Multivariable analysis demonstrated that uterine carcinosarcoma histology, advanced age, nonwhite race, and advanced stage were independent predictors of poor survival. Cancer-specific mortality was 45% lower in women with grade 3 endometrioid carcinomas (hazard ratio 0.55; 95% confidence interval [CI] 0.5-0.6). The 5-year cancer-specific survival was lower for women with uterine carcinosarcoma for each disease stage. Survival for stage IC was 38% (95% CI 33-45%) for uterine carcinosarcoma compared with 68% (95% CI 63-73%) for grade 3 endometrioid carcinoma. For stage III, survival was 22% (95% CI 19-26%) for uterine carcinosarcoma compared with 45% (95% CI 41-49%) for grade 3 endometrioid carcinoma. CONCLUSION: Carcinosarcomas present at more advanced stage and have worse survival than grade 3 endometrioid carcinomas. Carcinosarcomas may represent a distinct biologic entity. LEVEL OF EVIDENCE: II.     

Butyrate Hastens Restoration of Barrier Function after Thermal and Detergent Injury to Rat Distal Colon in Vitro

Background: Epithelial migration restores barrier function after superficial injury to any mucosa. The present study aimed to determine whether butyrate, important to colonic epithelial physiology in diverse ways, influences restoration of barrier function in the injured rat colon. Methods: Rat distal colon was transiently exposed in vitro to heat (55°C for 10 sec) or to detergent (deoxycholic acid, 7.5 mM, for 15 min), and tissue damage was verified histologically. Epithelial barrier function was assessed, in colon tissue mounted in Ussing chambers, by measuring electric resistance and passive serosa-to-mucosa fluxes of ²²Na and of ¹⁴C PEG 4000 under voltage clamp conditions. Studies were done in the absence and presence of 25 mM butyrate in the bathing solutions. Results: Heat exposure induced superficial epithelial damage, and the electric resistance decreased significantly. This was accompanied by increase in flux of­¹4C PEG and increased passive flux of 22Na. Electric resistance was significantly higher, and PEG flux significantly lower, in tissues bathed with butyrate. Exposure to deoxycholic acid also induced superficial epithelial damage, reduced tissue electric resistance, and increased passive flux of Na and PEG. Electric resistance was significantly higher, and PEG flux significantly lower, in injured tissues bathed in butyrate, than in injured tissues bathed in butyrate-free solution. The effect of butyrate on restoration of electric resistance towards normal was seen in colon both from adult rats and from younger rats that were 2 or 6 weeks old. Conclusions: Butyrate enhanced restoration of mucosal barrier function in rat distal colon in response to heat and detergent injury.     

False Discovery Rates for Rare Variants From Sequenced Data

The detection of rare deleterious variants is the preeminent current technical challenge in statistical genetics. Sorting the deleterious from neutral variants at a disease locus is challenging because of the sparseness of the evidence for each individual variant. Hierarchical modeling and Bayesian model uncertainty are two techniques that have been shown to be promising in pinpointing individual rare variants that may be driving the association. Interpreting the results from these techniques from the perspective of multiple testing is a challenge and the goal of this article is to better understand their false discovery properties. Using simulations, we conclude that accurate false discovery control cannot be achieved in this framework unless the magnitude of the variants' risk is large and the hierarchical characteristics have high accuracy in distinguishing deleterious from neutral variants.     

Haploidentical Hematopoietic Stem Cell Transplantation in Leukemia’s: Experience from a Cancer Center in India

There has been a surge in haploidentical hematopoietic stem cell transplantation (HSCT) in India recently. However, there is a paucity of data on haploidentical HSCT from India. The report is an analysis of data of haploidentical HSCT performed at our center. Analysis of patients with acute leukemia or chronic myeloid leukemia who underwent haploidentical HSCT during 2014–2019 was performed. The graft versus host disease (GVHD) prophylaxis was post-transplant Cyclophosphamide with Mycophenolate-mofetil and Cyclosporine. All patients were transfused peripheral blood stem cells from donors. Overall survival (OS) was calculated using the Kaplan–Meier method. Twenty-one patients underwent haploidentical HSCT. Fourteen-patients were males. The median age of patients was 15 years. Fludarabine with total body irradiation was the most common conditioning regimen (n = 15, 71.4%). The median duration for neutrophil and platelet engraftment was 14 days. Cumulative incidence of acute and chronic GVHD was 19%, and 38% respectively. The median follow-up was 26 months and the two-year OS was 38%. Twelve (57%) patients died during the study period, 8 patients (38%) died from transplant-related mortality (TRM), and 4 from disease relapse. Sepsis was the cause of death in six of the eight TRM. Nine out of 21 patients (42.8%) are leukemia-free on follow-up. Haploidentical HSCT is a promising modality of treatment in patients who have no suitable matched donors. Though the TRM remains high, good disease control was achieved in 42.8% of patients. Multi-drug resistant bacterial infection remains a challenge in performing haploidentical HSCT in developing countries.     

A modified olanzapine-based anti-emetic regimen for the control of nausea and vomiting in patients receiving weekly cisplatin

International Journal of Clinical Pharmacy - Background There is limited data on specific antiemetic protocols for control of chemotherapy-induced nausea/vomiting (CINV) caused by weekly cisplatin...     

Burkitt's lymphoma of maxillary gingiva: A case report

Burkitt's lymphoma(BL) is an aggressive form of nonHodgkin's B-cell lymphoma with three variants namely endemic, sporadic, and immunodeficiency-associated types. It is endemic in Africa and sporadic in other parts of the world. While the endemic form is widely reported to occur in early childhood and commonly involves the jaw bones, the sporadic form typically presents as an abdominal mass. This presentation reports a rare case of sporadic form of BL clinically manifesting as a generalized gingival enlargement in an immunocompetent adult male which demonstrated an aggressive behavior. The patient reported with a prominent anterior gingival swelling of 6 mo duration which slowly enlarged in size and associated with multiple lymph node involvement. Microscopic examination of the lesion using H, E and immunohistochemical diagnosis confirmed the diagnosis as BL. The patient succumbed to the disease before any therapy could be instituted. Since a wide array of causes can be attributed to gingival enlargements, it is necessary to consider malignancies as one of the important differential diagnosis so as to facilitate the need for appropriate diagnosis and prompt treatment.