Association of Inflammatory Markers With Disease Progression and the Severity of COVID-19.

Introduction In December 2019, there was a massive outbreak of viral pneumonia, which had a high case fatality rate. Genetic sequencing of the virus showed similarity with severe acute respiratory syndrome coronavirus (SARS-CoV). It was later named novel coronavirus 2019 while the disease it caused was given the nomenclature of COVID-19. This deadly pneumonia outbreak was declared a pandemic by the World Health Organization (WHO). Aim To derive the strength of the correlation between blood levels of various inflammatory markers with the severity of COVID-19 pneumonia in patients affected with novel coronavirus 2019. Materials and methodology A prospective study was conducted on 300 confirmed cases of COVID-19 infection from August 2020 to July 2021 in SSG Hospital, Vadodara. Diagnosis of patients as confirmed cases of COVID-19 infection was done according to the WHO interim guidance for COVID-19. Their inflammatory markers were done for this study. All COVID-19-positive patients who had given negative consent for enrollment were excluded from the study. Patients were classified based on the severity of acute respiratory distress syndrome (ARDS). Comprehensive medical record information, encompassing biodata, clinical symptoms, comorbidities, and laboratory investigations, was systematically collected. Patients were given the standard treatment protocol as per guidelines. Patients were subjected to detailed investigations comprising complete blood counts and inflammatory markers like C-reactive protein (CRP), lactate dehydrogenase (LDH), serum ferritin, and D-dimer. Patients were further investigated by chest X-ray (posteroanterior view) or high-resolution computed tomography of the thorax. Results A total of 300 confirmed cases of COVID-19 infection were included in this study. Most of them were males (52%) with a mean age of 51 years and 48% were females with a mean age of 55 years. The majority of patients (40%) did not have ARDS, 23.3% of patients had mild, 16.7% of patients had moderate, and 20% of patients had severe ARDS. Higher CRP levels, serum ferritin, and serum D-dimer were significantly associated with the severity of COVID-19 infection as compared to those having no symptoms (p < 0.05). Increased levels were associated with severe clinical manifestations of COVID-19. The sensitivity of CRP is 69% and specificity is 100% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of ferritin is 88% and specificity is 81% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of D-dimer is 94% and specificity is 89% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of LDH is 93% and specificity is 84% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. Conclusions Current evidence from our study showed that higher levels of inflammatory markers such as CRP, LDH, D-dimer, and ferritin are associated with the severity of COVID-19 in terms of ARDS and thus could be used as significant prognostic factors of the disease. These indicators might support clinical decisions to identify high fatality cases and poor diagnosis in the initial admission phase.

Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma.

In the pivotal study ECHELON-1, brentuximab vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A + AVD) demonstrated superior efficacy compared with bleomycin + AVD for the treatment of advanced-stage classic Hodgkin lymphoma (cHL). However, there are minimal available data regarding the frequency of dose reductions or omission of BV during curative therapy and the potential impact on patient outcomes. In a real-world analysis, we retrospectively reviewed the characteristics and outcomes of 179 patients with stage III or IV cHL treated with frontline A + AVD from January 2010 to April 2022. Treatment consisted of up to 1.2 mg/kg of BV and standard dose AVD IV on days 1 and 15 of each 28-day cycle for up to 6 cycles. At the time of treatment, the median patient age was 37 years, and a high-risk International Prognostic Score was observed in 46% of patients. Overall, 91% of patients received 6 cycles of AVD; 55% of patients did not receive the intended cumulative dose of BV (CDB); 28% of patients received two-thirds or less than the planned CDB. At a median follow-up time of 27.4 months (95% confidence interval [CI], 24.8-29), the median progression-free survival (PFS) was not reached, and the 12-month PFS was 90.3% (95% CI, 85.9-95.0). The impact of CDB on PFS was not significant (P = .15), nor was high CDB significantly associated with increased adverse events. In real-world experience, A + AVD is a highly effective treatment for patients with advanced-stage cHL, including for patients with prominent dose reductions of BV.

High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study.

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.

Clinical efficacy of PARP inhibitors in breast cancer.

BRCA1 and BRCA2 are key tumor suppressor genes that are essential for the homologous recombination DNA repair pathway. Loss of function mutations in these genes result in hereditary breast and ovarian cancer syndromes, which comprise approximately 5% of cases. BRCA1/2 mutations are associated with younger age of diagnosis and increased risk of recurrences. The concept of synthetic lethality led to the development of PARP inhibitors which cause cell cytotoxicity via the inhibition of PARP1, a key DNA repair protein, in cells with germline BRCA1/2 mutations. Although still poorly understood, the most well-acknowledged proposed mechanisms of action of PARP1 inhibition include the inhibition of single strand break repair, PARP trapping, and the upregulation of non-homologous end joining. Olaparib and talazoparib are PARP inhibitors that have been approved for the management of HER2-negative breast cancer in patients with germline BRCA1/2 mutations. This review article highlights the clinical efficacy of PARP inhibitors in patients with HER2-negative breast cancer in early and advanced settings.

Combined ultrasound cavitation and persulfate for the treatment of pharmaceutical wastewater.

In recent years industrialization has caused magnificent leaps in the high profitable growth of pharmaceutical industries, and simultaneously given rise to environmental pollution. Pharmaceutical processes like extraction, purification, formulation, etc., generate a large volume of wastewater that contains high chemical oxygen demand (COD), biological oxygen demand, auxiliary chemicals, and different pharmaceutical substances or their metabolites in their active or inactive form. Its metabolites impart non-biodegradable toxic pollutants as a byproduct and intense color, which increases ecotoxicity into the water, thus this requires proper treatment before being discharged. This study focuses on the feasibility analysis of the utilization of ultrasound cavitation (20 kHz frequency) together with a persulfate oxidation approach for the treatment of complex pharmaceutical effluent. Process parameters like pH, amplitude intensity, oxidant dosage were optimized for COD removal applying response surface methodology-based Box-Behnken design. The optimum value observed for pH, amplitude intensity and oxidant dosage are 5, 20% and 100 mg/L respectively with 39.5% removal of COD in 60 min of fixed processing time. This study confirms that a combination of ultrasound cavitation and persulfate is a viable option for the treatment of pharmaceutical wastewater and can be used as an intensification technology in existing effluent treatment plants to achieve the highest amount of COD removal.

Molecular Landscape of Small Bowel Adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a rare malignancy, with lower incidence, later stage at diagnosis, and poor overall prognosis compared to other cancers of the gastrointestinal tract. Owing to the rarity of the disease along with the paucity of high-quality tissue samples and preclinical models, little is known about the molecular alterations characteristic of SBA. This is reflected by the fact that the clinical management of SBA is primarily extrapolated from colorectal cancer (CRC). Recent advances in genomic profiling have highlighted key differences between these tumors, establishing SBA as a molecularly unique intestinal cancer. Moreover, comprehensive molecular analysis has identified a relatively high incidence of potentially targetable genomic alterations in SBA, predictive of response to targeted and immunotherapies. Further advances in our knowledge of the mutational and transcriptomic landscape of SBA, guided by an increased understanding of the molecular drivers of SBA, will provide opportunities to develop novel diagnostic tools and personalized therapeutic strategies.

Efficacy and safety of low-dose heparin in hemodialysis.

INTRODUCTION: The dose of unfractionated heparin (UFH) administered during hemodialysis (HD) varies widely. This prospective study evaluated the safety and efficacy of UFH dose de-escalation. METHODS: Sixty-six prevalent patients on HD receiving UFH per standard-dose protocol (load dose [LD] 50-75 units/kg, maintenance dose [MD] 500-1000 units/hour) had heparin prescription converted to low-dose protocol (start LD 15 units/kg and MD 500 units/hour; dose adjusted in small increments based on assessments of extracorporeal blood circuit). Coagulation parameters, dialysis adequacy, dialyzer clotting, anemia management, and dialyzer reuse rates were compared based on the heparin protocol. FINDINGS: Mean(SD) UFH dose per HD session, before and after protocol conversion, was 6178(2644) and 2913(1116) units, respectively (P < 0.0001). This corresponded to LD 52.1(16.6) units/kg and MD 615(207) units/hour with standard-dose protocol, and LD 18.3(6.5) units/kg and MD 505(27) units/hour with low-dose protocol (P < 0.0001). Mid and postdialysis aPTT was 55.3(31.2) and 35.1(7.8) seconds before, and 37.3(12.9) and 31.5(5.3) seconds after conversion (P = 0.007 and 0.003, respectively); no significant changes in D-dimer levels occurred. Low-dose UFH was associated with a small increase in URR and spKt/V (73.0 and 1.54) compared with dialysis clearance on standard-dose UFH (71.2 and 1.48, respectively, P = 0.02). Weekly dose of ESA decreased by 2388 units postconversion (P = 0.03), while hemoglobin levels and the weekly dose of intravenous iron did not change (P = 0.16 and 0.78). A small rise in the rate of moderate dialyzer clotting at the end of HD was noted with low-dose UFH (5.7% vs. 7.5%, P = 0.002); the rate of severe dialyzer clotting events did not change (P = 0.91). No change in the dialyzer reuse rate was noted (18.5 vs. 17.0 treatments, P = 0.26). DISCUSSION: Low-dose heparinization did not compromise dialysis adequacy and permitted ESA dose reduction. Our findings suggest that in prevalent patients on HD, UFH dose of 15-20 units/kg loading and 500 units/hour maintenance was medically safe and effective.