Early discontinuation of immune checkpoint inhibitor therapy prior to disease progression in patients with metastatic non-small cell lung cancer: a survival analysis.

Introduction: Limited survival data are available for patients with metastatic non-small cell lung cancer (mNSCLC) who stop immune checkpoint inhibitor therapy (ICI) early for reasons other than progression of disease (POD), such as immune-related adverse events (irAEs). Methods: We conducted a retrospective observational study of all patients with mNSCLC treated with ICIs, with or without combination chemotherapy, at 3 Mayo Clinic sites between 2011 and 2022. Separate analyses were conducted at 6- and 12-month intervals. Patients who discontinued ICI due to POD prior to these time points were excluded from the analysis. Results: A total of 246 patients with stage IV NSCLC used ICIs. Patients were then excluded if they had experienced POD prior to 6 or 12 months, resulting in 81 and 63 patients, respectively, for each timepoint. Sixty-four patients continued treatment beyond 6 months and were found to have longer progression-free survival (PFS) compared to the 17 patients who discontinued treatment (22.8 months vs 11.8 months, P =1.1E-04), as well as a significant increase in overall survival (OS) (33.9 months vs 14.4 months, P =7.2E-08). Forty patients continued treatment beyond 12 months and had longer PFS compared to the 23 patients that discontinued treatment (27.9 months vs 14.8 months, P =1.1E-04), as well as a significant increase in OS (39.7 months vs 18.0 months, P =2.0E-07). The most common reason for ICI discontinuation was irAEs. Other common reasons for stopping ICI were non-irAEs and stable disease. At both time points, 12 patients continued or restarted ICI after experiencing an irAE, and 2 patients experienced recurrent/new grade 1-2 irAEs. More patients continued/rechallenged with ICI after experiencing an irAE in the groups that continued ICI compared to those that discontinued ICI. Conclusions: Patients with mNSCLC and no POD who continued ICI beyond 6 months and 12 months, experienced significantly increased PFS and OS compared to patients who discontinued ICI, with larger increases in those who continued ICI past 12 months. Oncology providers should discuss the survival benefits of continuing ICI and offer support to overcome obstacles to continuation of treatment, if possible, particularly management of grade 1 and 2 irAEs.

Acute Compartment Syndrome of the Thigh After Contusion in a Football Player.

Acute compartment syndrome of the thigh is an exceptionally uncommon condition that can have severe consequences if not promptly and effectively treated. A 19-year-old man presented to our emergency department with severe and progressive pain in his left thigh after sustaining a direct trauma during a football game 24 hours prior. Compartment pressure was assessed, confirming the diagnosis of compartment syndrome arising from a sizable intramuscular hematoma without detection of any other contributing factors. Fasciotomy incisions were closed using the shoelace technique with excellent functional results. This case highlights the importance of high suspicion and intra-compartmental pressure measurement to diagnose this condition accurately.

The role of immunotherapy sensitizers and novel immunotherapy modalities in the treatment of cancer.

The importance of the immune system in the response against cancer has always been a subject of intense investigation. The advent of immune checkpoint inhibitors has transformed the landscape of oncologic treatments, while expanding the understanding of this disease's pathophysiology. Consequently, many therapies are being investigated, with interventions directed at different steps and pathways of the immune response. Relevantly, immunotherapy sensitizers have arisen as approaches focused on the synergistic effects of immunotherapy combination, or the combination of immunotherapy and other treatment modalities, such as chemotherapy or radiation therapy. Concomitantly, novel immunotherapy modalities are also in development. Approaches focusing from the tumor intrinsic pathways to the tumor microenvironment and ex-vivo interventions, such as CAR-T cell therapies and tumor-infiltrating lymphocytes are important examples. Although many of those interventions were initially envisioned as standalone options, their combination has demonstrated promising results in early-phase in vitro studies and clinical trials. The possibility of coupling different immunotherapy modalities, as well as with other techniques, further strengthen the concept of sensitizers, allowing for deeper and more robust responses in cancer treatment. This review aims to present an overview of the concepts of these sensitizing mechanisms that are the basis for the synergistic effects of immunotherapy combination, or the combination of immunotherapy and a multitude of therapeutic strategies. Novel immunotherapy modalities are also presented, focusing on the potential of combining them with sensitizer interventions. Understanding the complexity underlying these principles may be the key for future breakthroughs and improved patient outcomes.

Comparing Anticoagulation Strategies for Venous Thromboembolism Associated With Active Cancer: A Systematic Review and Meta-Analysis.

Background: Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE). Objectives: The aim of this study was to assess the efficacy and safety of DOACs in patients with active cancer. Methods: Literature searches were conducted in PubMed, Embase, and Cochrane Central in November 2022. Randomized controlled trials investigating anticoagulation strategies (vitamin K antagonists, parenteral anticoagulation [eg, low-molecular weight heparin], and DOACs) for VTE in patients with active cancer were identified for network meta-analysis. The outcomes included recurrent VTE, recurrent pulmonary embolism, recurrent deep venous thrombosis, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and a composite outcome of major bleeding or CRNMB. Pooled HRs and 95% CIs were estimated using either the HR or relative risk provided from each study. Random-effects models were used for all the analyses. Results: Seventeen randomized controlled trials involving 6,623 patients with active cancer were included. No significant differences were found among the DOACs for efficacy outcomes (recurrent VTE, pulmonary embolism, and deep venous thrombosis). In terms of major bleeding, apixaban was similarly safe compared with dabigatran and rivaroxaban but was associated with a decreased risk compared with edoxaban (HR: 0.38; 95% CI: 0.15-0.93). Regarding CRNMB, edoxaban was similarly safe compared with apixaban but was associated with a decreased risk compared with rivaroxaban (HR: 0.31; 95% CI: 0.10-0.91). Compared with parenteral anticoagulation, apixaban was associated with a reduced risk for recurrent VTE (HR: 0.60; 95% CI: 0.38-0.93) without increasing bleeding, edoxaban was associated with an increased risk for major bleeding or CRNMB (HR: 1.35; 95% CI: 1.02-1.79), and rivaroxaban was associated with an increased risk for CRNMB (HR: 3.76; 95% CI: 1.43-9.88). Conclusions: DOACs demonstrate comparable efficacy but exhibit different safety profiles. Apixaban may confer an antithrombotic benefit without an increased risk for bleeding, distinguishing it from other contemporary anticoagulation strategies in patients with active cancer and VTE.

Brain Wearables: Validation Toolkit for Ear-Level EEG Sensors.

EEG-enabled earbuds represent a promising frontier in brain activity monitoring beyond traditional laboratory testing. Their discrete form factor and proximity to the brain make them the ideal candidate for the first generation of discrete non-invasive brain-computer interfaces (BCIs). However, this new technology will require comprehensive characterization before we see widespread consumer and health-related usage. To address this need, we developed a validation toolkit that aims to facilitate and expand the assessment of ear-EEG devices. The first component of this toolkit is a desktop application ("EaR-P Lab") that controls several EEG validation paradigms. This application uses the Lab Streaming Layer (LSL) protocol, making it compatible with most current EEG systems. The second element of the toolkit introduces an adaptation of the phantom evaluation concept to the domain of ear-EEGs. Specifically, it utilizes 3D scans of the test subjects' ears to simulate typical EEG activity around and inside the ear, allowing for controlled assessment of different ear-EEG form factors and sensor configurations. Each of the EEG paradigms were validated using wet-electrode ear-EEG recordings and benchmarked against scalp-EEG measurements. The ear-EEG phantom was successful in acquiring performance metrics for hardware characterization, revealing differences in performance based on electrode location. This information was leveraged to optimize the electrode reference configuration, resulting in increased auditory steady-state response (ASSR) power. Through this work, an ear-EEG evaluation toolkit is made available with the intention to facilitate the systematic assessment of novel ear-EEG devices from hardware to neural signal acquisition.

Características Sócio-comportamentais, o Conhecimento Sobre o Exame Citopatológico e os Resultados Citológicos de Usuárias do Serviço Único de Saúde / Socio-behavioral characteristics, Knowledge about the Cytopathological Examination and the Cytological Results of Users of the Unique Health Service

Objetivos: Analisar, por meio de estudo de coorte transversal, a associação entre as características sociodemográficas-comportamentais, o conhecimento sobre o exame citopatológico e o resultado citológico das mulheres atendidas no Centro de Saúde da Família (CSF) da Vila Mutirão, em Goiânia, Goiás. Métodos: As pacientes incluídas no estudo atendidas responderam um questionário sobre o conhecimento a respeito do exame citopatológico, características sociodemográficas e comportamentais. Os dados coletados foram inseridos em um banco de dados no Microsoft® Excel 2010 e utilizado o Software R i386 versão 3.6.3. Para validação das associações foi utilizado o teste do Qui-quadrado (x²), com nível de significância de 5% (p<0,05). Resultados: Das 64 participantes, 96,8% possuem escolaridade até o ensino fundamental. Dessas, 65,5% afirmam ser pardas, a maioria com renda familiar menor que dois salários mínimos, indicando 53,1%. Cerca de 78,0% possuem vida sexualmente ativa, sendo 54,7% iniciado após os 16 anos, 49,2% apresentavam mais de dois parceiros sexuais. Sobre o conhecimento do citopatológico, 93,8% tem o conhecimento, entretanto 89,9% não o realizam na periodicidade adequada. A microbiota lactobacilar foi a mais frequente com 60,93%. Mulheres que faziam uso de cigarros há mais de 10 anos tiveram maior frequência de microbiota não lactobacilar no exame citopatológico com significante associação (p=0,0065). Conclusões: O estudo reforça a importância da necessidade de criação estratégica de medidas educativas e de saúde pública, além de programas de educação sexual e sobre a importância da realização do exame citopatológico e sua periodicidade.

Basal cell carcinoma of the vulva: A rare presentation of a common disease / Carcinoma de células basales de la vulva: una presentación rara de una enfermedad común

Abstract Background Basal cell carcinoma (BCC) is the most common skin malignancy, representing 75 % of non-melanoma skin cancers. BCC of the vulva is a very rare disease, accounting for only 2 to 3% of vulvar malignancies and less than 1% of all BCC. In the majority of cases occurs in postmenopausal women and usually presents as an asymptomatic lesion. However, itching, pain, bleeding and a sensation of a lump may occur. Clinical case We present the case of a 82-year old patient with a BCC located in the vulva. On physical examination, the patient had a lesion with elevated borders and central ulceration on the vulva, near the right side of the clitoris, measuring 2x2 cm, without any suspicious inguinal lymph nodes on physical examination and ultrasonography of the inguinal region. Excision of the lesion with safety margins was performed. She remains asymptomatic without signs of local recurrence or metastases 24 months after surgery. Conclusion El BCC por lo general ocurre en mujeres mayores y generalmente se presenta como una lesión asintomática. el examen físico y la biopsia son esenciales para el diagnóstico. La cirugía con márgenes libres es el tratamiento de elección. Aunque tiene un buen pronóstico, las recurrencias locales son comunes.

Resumen Antecedentes: El carcinoma de células basales es la neoplasia maligna más común de la piel, representa 75% de los cánceres de piel no melanoma. El carcinoma de células basales de la vulva es muy raro: representa de 2 a 3% de las neoplasias malignas de la vulva y menos de 1% de todos los carcinomas de células basales. En la mayoría de los casos ocurre en mujeres posmenopáusicas y casi siempre se manifiesta como una lesión asintomática, aunque puede causar picazón, dolor, sangrado y la sensación de un nudo. Caso clínico: Paciente de 82 años, con carcinoma de células basales de localización vulvar. En el examen físico se encontró una lesión con bordes elevados y ulceración central en la vulva, cerca del lado derecho del clítoris, de 2 x 2 cm, sin ganglios linfáticos inguinales sospechosos en el examen físico ni en la ecografía de la región inguinal. Se realizó la escisión de la lesión con márgenes de seguridad. Veinticuatro meses después de la cirugía la paciente permanece asintomática, sin signos de recurrencia local o metástasis. Conclusión: El carcinoma de células basales suele aparecer en mujeres mayores y generalmente se presenta como una lesión asintomática; el examen físico y la biopsia son esenciales para el diagnóstico. La cirugía con márgenes libres es el tratamiento de elección. Aunque tiene un buen pronóstico, las recurrencias locales son comunes.

Estimulação magnética transcraniana e aplicabilidade clínica: perspectivas na conduta terapêutica neuropsiquiátrica / Transcranial magnetic stimulation and clinical applicability: perspectives in neuropsychiatric therapeutics

Estimulação magnética transcraniana (EMT) é uma técnica conhecida desde o começo dos anos 90 e que atualmentetem ganhado destaque devido a sua segurança e possível aplicabilidade para tratar diversas patologias neuropsiquiátricas refratárias. A fim de clarificar os possíveis usos da EMT e suas variações no campo da clínica como forma de tratamento, procedemos à revisão da literatura selecionando os artigos nas áreas em que a técnica de EMT já tem sido largamente utilizada,a saber: AVC, Dor, Doença de Parkinson e Depressão. Essas doenças possuem elevada morbidade, possuindo grandesimplicações na qualidade de vida devido ao elevado grau de incapacidade associado e ao fato de ainda carecerem de métodos terapêuticos totalmente eficientes. Nesse contexto, a EMT emerge como ferramenta promissora, apresentando bons resultados, os quais fornecem margem para aplicações diretas na prática clínica. É necessário, todavia, o desenvolvimento de mais estudos randomizados, para se padronizar e aperfeiçoar as abordagensdessa técnica no tratamento de tais patologias...

Transcranial Magnetic Stimulation (TMS) is a technique that emerged in the 90s and has currently become recognized for its safety and potential applicability in the treatment of neuropsychiatry diseases. To clarify the possible uses of TMS and its variations in the clinical scope as a treatment, weproceeded a literature review selecting articles in the areas where the technique of TMS has already been widely used: Stroke, Pain, Parkinson’s Disease and Depression. These diseases have high morbidity, with large implications for the quality of life due to the high degree of disability and the fact that we still lack of fully efficient therapeutic methods. In this context, EMT emerges as a promising tool with amazing results, which provide scope for direct applications in clinical practice. However, the developmentof more randomized studies is necessary, in order to standardizeand improve the approaches of this technique in the treatment of such pathologies...