Subcutaneous versus intravenous nivolumab for renal cell carcinoma.

BACKGROUND: The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and health care efficiencies. PATIENTS AND METHODS: CheckMate 67T (NCT04810078) was a phase III, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20 000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). The primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis [time-averaged serum concentration over the first 28 days (Cavgd28), and minimum steady-state serum concentration (Cminss); noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios (GMR) ≥0.8]. Objective response rate (ORR) was a key secondary endpoint powered for noninferiority [noninferiority threshold: lower boundary of 95% CI of relative risk of ORR (subcutaneous versus intravenous nivolumab) ≥0.60]. RESULTS: Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of Cavgd28 and Cminss was 2.098 (90% CI 2.001-2.200) and 1.774 (90% CI 1.633-1.927), respectively. After 8 months of minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI 19.0%-30.0%) versus 18.2% with intravenous nivolumab [95% CI 13.6%-23.6%; relative risk: 1.33 (95% CI 0.94-1.87)]. Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar. CONCLUSIONS: Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.

Dielectric relaxation and molecular interactions study of saccharides in aqueous solutions.

Time domain reflectometry (TDR) technique has been extensively used to study dielectric relaxation and solution properties of carbohydrates. Using TDR techninque, complex permittivity spectra of monosaccharides (d-fructose and d-xylose) and disaccharides (d-maltose monohydrates) were obtained in the frequency range of 10 MHz-50 GHz at various concentrations and temperatures. The static dielectric constant (ε0), dielectric constant at high frequency (ε∞), relaxation time (τ) and relaxation time distribution parameter (ß) extracted from the complex permittivity spectra using least squares fit method. The values of static dielectric constant were also verified by LCR meter by dielectric measurement in the frequency range of 20Hz to 2 MHz at 25 °C. The relaxation behavior of aqueous solutions of monosaccharides and disaccharides has been illustrated by using Cole-Davidson model. Activation enthalpy (ΔH), entropy (ΔS) and Kirkwood correlation factor have been determined to study extent of hydrogen bonding. This data might be useful in pharmaceutical, food processing industry and in solubility prediction method in aqueous solution.

Psychological and professional impact of COVID-19 lockdown on French dermatologists: Data from a large survey.

AIM: To evaluate the extent to which COVID-19-related lockdown affected dermatologists. METHODS: An anonymous online survey was proposed to all French dermatologists and dermatology residents to assess the impact of COVID-19 lockdown on their professional activity, their level of stress and their psychological state, as well as their coping strategies. RESULTS: Exactly 800 dermatologists completed the survey. The respondents noted changes in behaviour in their professional and personal environment. The number of cancelled or rescheduled appointments was very high, with a huge financial impact for private practitioners. Stigmatisation was also reported. Anxiety and a feeling of increased stress were very frequent. Increased substance use was also reported. CONCLUSION: The impact of the COVID-19 pandemic and lockdown was significant for French dermatologists, with risks to their own health, profound changes in their practice, and financial and psychological impact, but also the development of new consultation and evaluation strategies to improve their work-life balance.

Acidophilic actinobacteria synthesised silver nanoparticles showed remarkable activity against fungi-causing superficial mycoses in humans.

Superficial mycoses are limited to the most external part of the skin and hair and caused by Malassezia sp., Trichophyton sp. and Candida sp. We report extracellular biosynthesis of silver nanoparticles (AgNPs) by acidophilic actinobacteria (SF23, C9) and its in vitro antifungal activity against fungi-causing superficial mycoses. The phylogenetic analysis based on the 16S rRNA gene sequence of strains SF23 and C9 showed that they are most closely related to Pilimelia columellifera subsp. pallida GU269552(T). The detection of AgNPs was confirmed by visual observation of colour changes from colourless to brown, and UV-vis spectrophotometer analysis, which showed peaks at 432 and 427 nm, respectively. These AgNPs were further characterised by nanoparticle tracking analysis (NTA), Zeta potential, Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The FTIR analysis exhibited the presence of proteins as capping agents. The TEM analysis revealed the formation of spherical and polydispersed nanoparticles in the size range of 4-36 nm and 8-60 nm, respectively. The biosynthesised AgNPs were screened against fungi-causing superficial mycoses viz., Malassezia furfur, Trichophyton rubrum, Candida albicans and C. tropicalis. The highest antifungal activity of AgNPs from SF23 and C9 against T. rubrum and the least against M. furfur and C. albicans was observed as compared to other tested fungi. The biosynthesised AgNPs were found to be potential anti-antifungal agent against fungi-causing superficial mycoses.

Survey of meticillin-resistant Staphylococcus aureus policies in UK eye departments.

The purpose of this study was to investigate meticillin-resistant Staphylococcus aureus (MRSA) screening and decolonisation practices for patients undergoing routine cataract surgery in ophthalmology departments across the UK. A postal questionnaire survey of all ophthalmology departments in the UK was carried out, with 75 of 152 (49.3%) questionnaires returned. Sixty-three percent of units had a departmental MRSA policy. Preoperative MRSA screening was performed in 50 (66.7%) units, three of which screened all preoperative patients and the remainder performed selective screening. The proportion of patients screened for MRSA ranged from 0 to 100%, with a median of 2% and a mean of 9.9% (95% confidence interval: 3.5-16.2%). Overall, 65.3% of respondents felt that their departmental policy was reasonable, although there was considerable dissatisfaction and confusion, with comments identifying lack of evidence and the need for guidelines applicable to day-case cataract surgery. The survey demonstrates significant inconsistencies in preoperative MRSA screening practice in ophthalmology departments throughout the UK. Current recommendations from the Department of Health suggest that day-case ophthalmology patients do not require routine screening, although the implication appears that high risk patients continue to do so. Further investigation is required to ascertain the scientific validity of these recommendations.

Meningitis: an unusual cause of pneumocephalus.

Pneumocephalus, characterized by the presence of air in the cranium is frequently caused by trauma and surgery. Meningitis is a very rare cause of pneumocephalus. Here we report a patient who had meningitis as a cause for his pneumocephalus. This patient was diagnosed to have pneumocephalus on CT scan study and was treated with antibiotics to which he responded well, and the repeat CT scan done after two weeks showed normal study.

Comparison of Pilcher bag technique with standard suprapubic prostatectomy.

A total of 930 cases of open prostatectomies done at Lenox Hill Hospital from 1965 to 1974 are reviewed. The Pilcher bag technique utilized in 830 cases is compared with 100 cases of suprapublic prostatectomy with suturing of the bladder neck. Operating time, intra- and postoperative blood transfusions, hospital stay, and complications are compared. Operative time and intra- and postoperative blood loss are significantly less with the Pilcher bag technique.

Successful reimplantation of the penis using microvascular techniques.

The second case of traumatic amputation of the proximal shaft of the penis is reported. Microvascular techniques were used for direct anastomoses of the dorsal arteries of the penis. The apparent advantage of immediate restoration of arterial blood supply to the corpora and skin with a reduced amount of skin slough is evident.