Subsequent chemotherapy with paclitaxel plus cetuximab-based chemotherapy following immune checkpoint inhibitor in recurrent or metastatic squamous cell carcinoma of the head and neck

BackgroundImmune checkpoint inhibitors (ICIs) are essential in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the overall response rate (ORR) is limited to 10-20%, and subsequent chemotherapy is critical to maximizing the subjects’ prognosis.MethodsWe retrospectively reviewed 59 patients with R/M SCCHN treated with paclitaxel+cetuximab (PE)-based chemotherapy (PCE, paclitaxel+carboplatin+cetuximab; or PTX+Cmab, paclitaxel+cetuximab) following disease progression after either pembrolizumab or nivolumab monotherapy.ResultsOf 59 patients, 15 were treated with pembrolizumab, with an ORR of 13.3%, and the remaining 44 with nivolumab, with an ORR of 11.4%. All patients in the pembrolizumab cohort had platinum-sensitive disease. Following ICI treatment, 19 patients were treated with PCE and the remaining 40 with PTX+Cmab. PE-based chemotherapy induced favorable and prompt tumor shrinkage even in cases where ICI was not effective, with a median change in the summed dimensions of target lesions of -43.4%, resulting in an ORR of 62.7%. Median time to response was 1.8 months. The patients in the pembrolizumab cohort appeared to have a numerically higher response rate than those receiving nivolumab (80.0% vs. 56.8%). For the 59 patients, progression-free survival and overall survival, calculated from the initiation of PE-based chemotherapy, were 4.6 months and 17.1 months, respectively. Grade ≥3 adverse events occurred in 40.7%, and no treatment-related death was observed.ConclusionPE-based chemotherapy following ICI is encouraging for its robust antitumor efficacy in R/M SCCHN

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate

Background We aimed to demonstrate the biochemical characteristics of vitamin B6–dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate and pyridoxal in the cerebrospinal fluid. Methods Using our laboratory database, we identified patients with vitamin B6–dependent epilepsy and extracted their data on the concentrations of pyridoxal 5′-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5′-phosphate concentrations. Results We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5′-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5′-phosphate concentrations were low in patients with vitamin B6–dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6–dependent epilepsy, suggestive of pyridoxal 5′-phosphate deficiency in the brain. Conclusions Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5′-phosphate deficiency in the brain in vitamin B6–dependent epilepsy than low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5′-phosphate homeostasis protein deficiency, which does not have known biomarkers

Interferência da solução de armazenamento na superfície do implante dentário

Implants with hydrophilic surfaces have been to better maintain surface integrity compared to hydrophobic surfaces. This underscores the importance of surface hydrophilicity in enhancing implant stability during the osseointegration period, especially in challenging bone conditions. Despite the benefits associated with hydrophilic surfaces, it is essential to understand the limitations and optimal methods for achieving and maintaining surface hydrophilicity. This study aims to spectroscopically differentiate the aqueous substances used by Straumann® and assess variations in surface wettability of dry Singular® implants before and after immersion in the aqueous substance. Material and Methods: Dental implant samples were divided into two groups: Group 1 (n=6) comprised SLActive Straumann® implants, commercialized in an aqueous medium, and Group 2 (n=4) consisted of dry Singular® implants. Wettability evaluations were conducted initially, followed by immersion of dry implants in the aqueous solution of SLActive Straumann® implants. After 180 days, samples were reevaluated to observe changes in surface wettability, the analysis was employed to analyze the aqueous substance. Wettability analysis was performed using the contact angle technique. Data analysis involved tabulation and application of the Shapiro Wilk test for normality verification, followed by paired t-tests for wettability analysis. Spectroscopic analysis revealed significant similarities among the samples, with characteristic peaks indicating the presence of water molecules. Contact angle measurements indicated a statistically significant reduction after immersion in the aqueous medium, transitioning the surface from hydrophobic to hydrophilic. Most analyzed samples exhibited high water concentrations, indicating the presence of water as the primary component. The saline solution showed potential for improving osseointegration by reducing contact angles, suggesting enhanced wettability. Classification of surface wettability indicated a shift from hydrophobic to hydrophilic after immersion in the aqueous medium, aligning with previous studies on SLActive surfaces. Our study demonstrates that immersion in an aqueous medium alters implant surface wettability, regardless of surface treatment.Os implantes com superfícies hidrofílicas têm mantido melhor a integridade da superfície em comparação com superfícies hidrofóbicas. Isto sublinha a importância da hidrofilicidade da superfície no aumento da estabilidade do implante durante o período de osseointegração, especialmente em condições ósseas desafiadoras. Apesar dos benefícios associados às superfícies hidrofílicas, é essencial compreender as limitações e os métodos ideais para alcançar e manter a hidrofilicidade da superfície. Este estudo tem como objetivo diferenciar espectroscopicamente as substâncias aquosas utilizadas pela Straumann® e avaliar variações na molhabilidade superficial de implantes Singular® secos antes e após imersão na substância aquosa. Material e Métodos: As amostras de implantes dentários foram divididas em dois grupos: Grupo 1 (n=6) composto por implantes SLActive Straumann®, comercializados em meio aquoso, e Grupo 2 (n=4) composto por implantes Singular® secos. Avaliações de molhabilidade foram realizadas inicialmente, seguidas de imersão dos implantes secos na solução aquosa dos implantes SLActive Straumann®. Após 180 dias, as amostras foram reavaliadas para observar alterações na molhabilidade superficial, a análise foi empregada para analisar a substância aquosa. A análise de molhabilidade foi realizada pela técnica do ângulo de contato. A análise dos dados envolveu tabulação e aplicação do teste de Shapiro Wilk para verificação de normalidade, seguido de testes t pareados para análise de molhabilidade. A análise espectroscópica revelou semelhanças significativas entre as amostras, com picos característicos indicando a presença de moléculas de água. As medidas do ângulo de contato indicaram uma redução estatisticamente significativa após a imersão no meio aquoso, fazendo a transição da superfície de hidrofóbica para hidrofílica. A maioria das amostras analisadas apresentou altas concentrações de água, indicando a presença de água como componente primário. A solução salina mostrou potencial para melhorar a osseointegração, reduzindo os ângulos de contato, sugerindo maior molhabilidade. A classificação da molhabilidade da superfície indicou uma mudança de hidrofóbica para hidrofílica após imersão no meio aquoso, alinhando-se com estudos anteriores em superfícies SLActive. Nosso estudo demonstra que a imersão em meio aquoso altera a molhabilidade da superfície do implante, independentemente do tratamento de superfície

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements