Introduction:Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise.Objective:The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis.Materials and Methods:It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A – terbinafine 500 mg for 2 weeks, Group B – terbinafine 500 mg for 4 weeks, and Group C – terbinafine 500 mg for 6 weeks.Results:Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% (n = 169) patients showed very good response. In Group B, out of 211 patients, 92% (n = 194) of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% (n = 30) patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients.Conclusion:Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

Current strategies for the production of therapeutic mAbs include the use of mammalian cell systems to recombinantly produce Abs derived from mice bearing human Ig transgenes, humanization of rodent Abs, or phage libraries. Generation of hybridomas secreting human mAbs has been previously reported; however, this approach has not been fully exploited for immunotherapy development. We previously reported the use of transient regulation of cellular DNA mismatch repair processes to enhance traits (e.g., affinity and titers) of mAb-producing cell lines, including hybridomas. We reasoned that this process, named morphogenics, could be used to improve suboptimal hybridoma cells generated by means of ex vivo immunization and immortalization of antigenspecific human B cells for therapeutic Ab development. Here we present a platform process that combines hybridoma and morphogenics technologies for the generation of fully human mAbs specific for disease-associated human antigens. We were able to generate hybridoma lines secreting mAbs with high binding specificity and biological activity. One mAb with strong neutralizing activity against human granulocyte-macrophage colony-stimulating factor was identified that is now considered for preclinical development for autoimmune disease indications. Moreover, these hybridoma cells have proven suitable for genetic optimization using the morphogenics process and have shown potential for large-scale manufacturing.

Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in critically ill Coronavirus disease 2019 (COVID-19) patients. Here, we present high-dimensional profiling of blood and respiratory samples in severe COVID-19 patients to examine the association between cell-linked molecular features and mortality outcomes. Peripheral transcriptional profiles by single-cell RNAseq based deconvolution of immune states are associated with COVID-19 mortality. Further, persistently high levels of an interferon signaling module in monocytes over time leads to subsequent concerted upregulation of inflammatory cytokines. SARS-CoV-2 infected myeloid cells in the lower respiratory tract upregulate CXCL10 , leading to a higher risk of death. Our analysis suggests a pivotal role for viral infected myeloid cells and protracted interferon signaling in severe COVID-19.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection presents with varied clinical manifestations, ranging from mild symptoms to acute respiratory distress syndrome (ARDS) with high mortality. Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in severe COVID-19. We performed high-dimensional cellular and molecular profiling of blood and respiratory samples from critically ill COVID-19 patients to define immune cell genomic states that are predictive of outcome in severe COVID-19 disease. Critically ill patients admitted to the intensive care unit (ICU) manifested increased frequencies of inflammatory monocytes and plasmablasts that were also associated with ARDS not due to COVID-19. Single-cell RNAseq (scRNAseq)-based deconvolution of genomic states of peripheral immune cells revealed distinct gene modules that were associated with COVID-19 outcome. Notably, monocytes exhibited bifurcated genomic states, with expression of a cytokine gene module exemplified by CCL4 (MIP-1β) associated with survival and an interferon signaling module associated with death. These gene modules were correlated with higher levels of MIP-1β and CXCL10 levels in plasma, respectively. Monocytes expressing genes reflective of these divergent modules were also detectable in endotracheal aspirates. Machine learning algorithms identified the distinctive monocyte modules as part of a multivariate peripheral immune system state that was predictive of COVID-19 mortality. Follow-up analysis of the monocyte modules on ICU day 5 was consistent with bifurcated states that correlated with distinct inflammatory cytokines. Our data suggests a pivotal role for monocytes and their specific inflammatory genomic states in contributing to mortality in life-threatening COVID-19 disease and may facilitate discovery of new diagnostics and therapeutics.

<p class="abstract"><strong>Background:</strong> A newer itraconazole formulation i.e., super bioavailable itraconazole has been launched recently in India which is claimed to overcome all the pharmacokinetic challenges faced with conventional itraconazole. The present retrospective data analysis was undertaken to evaluate the effectiveness and safety of super bioavailable itraconazole in comparison with conventional itraconazole in the treatment of dermatophytosis in Indian patients.</p><p class="abstract"><strong>Methods:</strong> The present multi-centric, retrospective data analysis was done at 12 dermatological centers across India from July 2020 to December 2020. Medical records of patients of dermatophytosis, who were prescribed with either super bioavailable itraconazole 50 mg twice daily for four weeks or conventional itraconazole 100 mg twice daily for four weeks were included in the study.<strong></strong></p><p class="abstract"><strong>Results:</strong> 56% patients (n=30) in super bioavailable itraconazole group achieved complete clearance of their symptoms (cured) compared to only 34% patients (n=17) in conventional itraconazole group and this difference was statistically significant (p=0.02). Significantly more patients achieved complete clearance of their lesions in super bioavailable itraconazole-37 patients (69%) compared to conventional itraconazole group-25 patients (49%) at the end of 4 week therapy (p=0.04). The difference in total symptom score (∆TSS) in super bioavailable itraconazole group was more (5.81) as compared to conventional itraconazole group (4.75) (p=0.09). Both the treatment were well tolerated.</p><p class="abstract"><strong>Conclusions:</strong> From the findings of the present study, super bioavailable itraconazole was more effective with similar safety profile as compared to conventional itraconazole in the treatment of dermatophytosis.</p>