Antibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus Vaccine.

Ebolaviruses Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) cause human disease with high case fatality rates. Experimental monovalent vaccines, which all utilize the sole envelope glycoprotein (GP), do not protect against heterologous ebolaviruses. Human parainfluenza virus type 3-vectored vaccines offer benefits, including needle-free administration and induction of mucosal responses in the respiratory tract. Multiple approaches were taken to induce broad protection against the three ebolaviruses. While GP consensus-based antigens failed to elicit neutralizing antibodies, polyvalent vaccine immunization induced neutralizing responses to all three ebolaviruses and protected animals from death and disease caused by EBOV, SUDV, and BDBV. As immunization with a cocktail of antigenically related antigens can skew the responses and change the epitope hierarchy, we performed comparative analysis of antibody repertoire and Fc-mediated protective mechanisms in animals immunized with monovalent versus polyvalent vaccines. Compared to sera from guinea pigs receiving the monovalent vaccines, sera from guinea pigs receiving the trivalent vaccine bound and neutralized EBOV and SUDV at equivalent levels and BDBV at only a slightly reduced level. Peptide microarrays revealed a preponderance of binding to amino acids 389 to 403, 397 to 415, and 477 to 493, representing three linear epitopes in the mucin-like domain known to induce a protective antibody response. Competition binding assays with monoclonal antibodies isolated from human ebolavirus infection survivors demonstrated that the immune sera block the binding of antibodies specific for the GP glycan cap, the GP1-GP2 interface, the mucin-like domain, and the membrane-proximal external region. Thus, administration of a cocktail of three ebolavirus vaccines induces a desirable broad antibody response, without skewing of the response toward preferential recognition of a single virus.IMPORTANCE The symptoms of the disease caused by the ebolaviruses Ebola, Bundibugyo, and Sudan are similar, and their areas of endemicity overlap. However, because of the limited antigenic relatedness of the ebolavirus glycoprotein (GP) used in all candidate vaccines against these viruses, they protect only against homologous and not against heterologous ebolaviruses. Therefore, a broadly specific pan-ebolavirus vaccine is required, and this might be achieved by administration of a cocktail of vaccines. The effects of cocktail administration of ebolavirus vaccines on the antibody repertoire remain unknown. Here, an in-depth analysis of the antibody responses to administration of a cocktail of human parainfluenza virus type 3-vectored vaccines against individual ebolaviruses was performed, which included analysis of binding to GP, neutralization of individual ebolaviruses, epitope specificity, Fc-mediated functions, and protection against the three ebolaviruses. The results demonstrated potent and balanced responses against individual ebolaviruses and no significant reduction of the responses compared to that induced by individual vaccines.

Effects of terlipressin infusion on blood loss and transfusion needs during liver resection: A randomised trial.

BACKGROUND: Blood loss and perioperative blood transfusion requirements affect the long-term survival after liver resection for malignant tumours. Terlipressin is a synthetic vasopressin analogue with relative specificity for the splanchnic circulation where it causes vasoconstriction with subsequent reduction of blood loss during abdominal surgeries. We tried to examine the impact of terlipressin on blood loss and blood transfusion needs during liver resection. METHODS: In this randomised, double-blind placebo-controlled trial 84 patients scheduled for major liver resections were randomly assigned to receive either terlipressin at the onset of surgery as an initial bolus dose of (1 mg over 30 minutes) followed by a continuous infusion of 2 µg/kg/h throughout the procedure (Terlipressin group) or the same volume and rate of 0.9% saline (Placebo group).The primary outcome was the amount of intra-operative blood loss. RESULTS: The mean (SD) of the amount of intra-operative blood loss was 1351 (887) in the terlipressin group versus 1892 (889) mL in the placebo group (P = 0.006). Thirteen (30%) patients received blood transfusion in the terlipressin group compared with t27 (64.2%) in the placebo group (P = 0.002) with a statistically significant difference in the median (range) number of the transfused units of packed RBCs [0 (0-5) units and 1 (0-6) units in the two groups respectively; P = 0.001]. CONCLUSION: Terlipressin infusion during major liver resection was associated with less bleeding compared to placebo. More studies are required to confirm our results especially in patients with normal portal pressure.

Pathological Extramural Venous Invasion in High-stage Urothelial Carcinoma of the Bladder has Shorter Locoregional Recurrence-free Survival.

Extramural venous invasion is an independent prognostic factor in colorectal cancers; the pathological identification of extramural venous invasion in bladder cancer remains unclear. By focusing on high-stage urothelial carcinoma of the bladder, we provide insights into the pathological identification of extramural venous invasion in this particular clinical context. Clinical and demographic details and pathological reports were extracted from electronic medical records. Histological sections were reviewed for the pathological identification of extramural venous invasion. Statistical analysis was done using SPSS version 23 software. Survival analysis was done using Kaplan-Meier method. In patients with available follow-up data, 62% (n = 21) exhibited pathologically evidenced extramural venous invasion, whereas 38% (n = 13) did not. The extramural venous invasion positive group showed trends toward more advanced and pathological staging and a higher occurrence of extra-nodal extension. Positive margins were more frequent in the extramural venous invasion positive group (33%) compared to the extramural venous invasion negative group (8%). However, these differences were not statistically significant. Notably, all instances of recurrence were in the extramural venous invasion positive group of patients. The extramural venous invasion positive group of patients showed a significantly shorter locoregional recurrence-free survival (P-value of 0.045). However, extramural venous invasion did not emerge as a significant factor in univariate analyses for recurrence-free survival. These findings highlight the potential role of extramural venous invasion as a prognostic factor in bladder cancer but underscore the need for further research with larger cohorts to confirm its significance.

Evaluation of the Cutting Seton Technique in Treating High Anal Fistula.

Objectives Fistula-in-ano is a common condition that negatively affects the quality of life of its sufferers. A high anal fistula poses a significant challenge for surgeons due to its proximity to the anorectal ring and the potential risk of incontinence rather than recurrence. Many modalities have been used in a justified search for a satisfactory cure for the condition, but the seton remains a mainstay of surgical treatment. Therefore, the rationale of this study is to assess the outcome of treating a high anal fistula using the cutting seton technique in a hospital in Al Madinah, Saudi Arabia. The evaluation is intended through a retrospective analysis of patients' outcomes, comparing its effectiveness to similar articles. Methods This is a retrospective study that includes 50 patients with high anal fistulas who were treated with a cutting seton at the National Guard Hospital over a four-year period (2019-2022). Information obtained from medical records included clinical and demographic data. The data collected during the study was compiled and statistically analyzed using the SPSS Statistics version 26.0 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp.). A p-value of <0.05 was considered statistically significant. Results A total of 50 patients with high anal fistula treated with a cutting seton were included: 82% were males and 18% were females, with 66% below 45 years of age. Approximately 92% had inter-sphincteric fistulas, and only 28% had a recurrent fistula. Almost all patients (98%) had an MRI done before surgery. Around 70% of patients were completely cured, 26% had minor complications, 8% of the operated patients experienced mild incontinence, and only one recurrence (2%). Conclusion The cutting seton is still a valid modality in treating patients with a high anal fistula, as it is considerably safe, effective, and yields good outcomes. Standard preoperative assessment and thorough surgical techniques are cornerstones for achieving a satisfactory outcome.

Flow Cytometric Findings in Primary Effusion Lymphoma: A Report of Two Cases.

Primary effusion lymphoma (PEL) is a rare B-cell lymphoma that usually occurs in the setting of HIV infection, and it is associated with Human Herpesvirus-8 (HHV-8). Diagnosis of PEL is usually established in cell centrifuge, cell block, or tissue examination, and there are few reports describing flow cytometry findings in PEL. We report two male patients (a 34-year-old and a 56-year-old) with a history of HIV infection. The first patient presented with ascites and abdominal pain, and the second patient presented with chest pain and parapneumonic pleural effusion. Cavitary fluid examination showed large pleomorphic neoplastic lymphoid cells with plasmablastic morphology. Flow cytometry analysis of the neoplastic lymphocytes showed increased forward scatter and side scatter with intermediate to a high level of CD38 expression. In one patient, lymphoma cells showed bright CD45 expression with dim expression of CD19 and kappa light chain. There was no significant expression of CD20 or any T/NK cell markers in either case. Immunohistochemistry for CD30 was positive in one patient. Immunohistochemistry for HHV-8 and in situ hybridization for Epstein-Barr virus-encoded small RNAs (EBER) was positive on cell blocks in both cases, consistent with the diagnosis of primary effusion lymphoma. PEL should be considered in the differential diagnosis of CD20-negative hematopoietic neoplasms, and flow cytometry may provide helpful clues for the diagnosis of PEL as part of the workup for pleural effusion with cytologically malignant cells.

Removal of hazardous azopyrazole dye from an aqueous solution using rice straw as a waste adsorbent: Kinetic, equilibrium and thermodynamic studies.

In this research, activated carbonmade from rice straw (ACRS) was synthesized simply by a low cost and nontoxic procedure and used for the adsorption of hazardous azopyrazole dye. The effect of different variables in the batch method as a function of solution pH, contact time, concentration of adsorbate, adsorbent dosage and temperature were investigated and optimal experimental conditions were ascertaine. Surface modification of ACRS using scanning electron microscopy (SEM) was obtained. More than 75% removal efficiency was obtained within 75min at adsorbent dose of 0.5g for initial dye concentration of 30-100mgL(-1) at pH 3. The experimental equilibrium data were tested by the isotherm models namely, Langmuir and Freundlich adsorption and the isotherm constants were determined. The kinetic data obtained with different initial concentration and temperature were analyzed using a pseudo-first-order and pseudo-second-order equations. The activation energy of adsorption was also evaluated and found to be +13.25kJmol(-1) indicating that the adsorption is physisorption. The thermodynamics of the adsorption indicated spontaneous and exothermic nature of the process. The results indicate that ACRS could be employed as low-cost material for the removal of acid dyes from aqueous solution.