Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6–3.1 months and a Disease Control Rate (DCR) of 21.4–41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75–81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge.

Heavy menstrual bleeding (HMB) is a common clinical condition affecting adolescent and adult women and compromising their quality of life. Primary hemostasis disorders, affecting platelet plug formation, can be the underlying cause of HMB. They comprise a heterogeneous group of diseases with Von Willebrand disease (VWD) being the most commonly diagnosed; other disorders in this group that have been linked to HMB include (a) Glanzmann thrombasthenia, (b) Bernard–Soulier syndrome, (c) Hermansky–Pudlak syndrome, (d) immune thrombocytopenia (ITP), and (e) Ehlers–Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Diagnosing these diseases can be challenging, as the basic laboratory investigations can be within the normal range. Thus, identification of specific clinical features and a thorough hematologic workup can be very important, providing the correct diagnosis. Proper diagnosis of the underlying disorder is important, as management may vary accordingly. Although disease-specific management guidelines exist for some of these disorders such as VWD and ITP, due to the rarity of most primary hemostasis disorders, the best approach for the management of HMB in these women remains elusive. The goal of this study was to create an informative, comprehensive review of the primary hemostasis disorders that have been linked to HMB. This study provides a summary of the basic published information regarding epidemiology, pathophysiology, clinical phenotype, diagnosis, and treatment of HMB in those diseases and serves as a reference guide for further reading.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as predictors for severe COVID-19 outcomes. The aim of the present study is to identify prognostic cut-off values of NLR and PLR for intubation and death in hospitalized COVID-19 patients, with or without immunosuppression. From June 2021 to December 2022, we retrospectively analyzed 393 consecutively admitted COVID-19 patients, who were divided in two cohorts according to immunosuppression status (hematological malignancy and/or autoimmune condition vs. non-immunocompromised), using a propensity score-matching in 1:2 ratio. Higher NLR and PLR values were observed on days 1 and 4 for severe COVID-19, irrespective of immunosuppression status. NLR on day 1 >5.06 and day 4 >6.40 (p < 0.001), as well as PLR on day 1 >262.2 and day 4 >217.3 (p = 0.003), were associated with a greater probability for intubation. Similarly, a higher probability for death was found in the subset of patients with NLR on day 1 >4.82 (p < 0.001) and day 4 >6.41 (p < 0.001) and PLR on day 1 >229 (p = 0.009) and day 4 >205.4 (p = 0.003). Both PLR and NLR exhibited consistently higher negative predictive values (NPVs) (>93%) compared to positive predictive values (PPVs) for intubation and death. NLR and PLR displayed strong prognostic potential in hospitalized COVID-19 patients regarding intubation and death, irrespective of immunosuppression status, thus the surveillance of these biomarkers may help clinicians identify high-risk COVID-19 patients at an early stage.

Background: Since child abuse and neglect (CAN) is prevalent worldwide, medical students should acquire basic knowledge, skills, and confidence in identifying and addressing CAN. Although significant educational efforts have been previously described, none has focused on using participatory methods to teach medical students CAN. Purpose: To: 1) develop a participatory educational workshop in CAN for medical students, 2) gather, train, and establish a peer-to-peer teaching group, and 3) assess the effectiveness of the workshop in gain of knowledge and improvement of self-confidence for participants. Methods: A two-hour workshop was created with role-playing, the use of mannikins and peer-to-peer teaching. A 15-item knowledge and a 9-item self-confidence questionnaire were used before, right after, and six months after each workshop. Results: Nine workshops in two academic pediatric departments with a total attendance of 300 6th year medical students were conducted. For the 69 students who completed the questionnaires at all three times, there were statistically significant gains in knowledge right after (p < .001) and six months after (p < .0001) the workshops. Similarly, self-confidence increased right after (p < .0001) and six months after (p < .001) the workshops. Self-selection bias testing indicated that these 69 students who completed all three questionnaires were representative of those who completed the pre-testing and the testing right after. Conclusions: We successfully established a peer-to-peer teaching group to conduct nine participatory workshops that improved the participants’ knowledge and self-confidence in CAN. This feasible and novel active learning approach may help address inadequacies in medical curricula.

Lung cancer (LC) is a serious health problem worldwide. Survival outcomes have improved over time due to the widespread use of novel therapeutic agents, including immune checkpoint inhibitors (ICIs). Endocrine immune-related adverse events (e-irAEs) are common in LC patients treated with ICIs. We performed a retrospective study of patients with LC who received treatment with ICIs at a tertiary referral center between January 2014 and October 2023. In total, 983 LC patients were included in the study. E-irAEs presented at a median time of 4.1 months and included hypothyroidism (15.6%), hyperthyroidism (4.3%), adrenal insufficiency (0.4%), hypophysitis (0.4%), and diabetes mellitus (0.2%). These toxicities were not related to the duration of treatment or the type of ICIs. Most (97.6%) e-irAEs were mild (grade 1–2). Median overall survival (OS) was higher in LC patients who experienced e-irAEs (31.6 months) compared to those who did not (10.8 months). The difference remained statistically significant in the 3-month (HR: 0.42) and 6-month landmark analysis (HR: 0.51). The OS advantage was observed in both patients with NSCLC (HR: 0.36) and SCLC (HR: 0.27). Additional research is needed to validate the role of e-irAEs as an independent predictor of survival outcomes in patients with LC.

Clotting Factor deficiencies are rare disorders with variations in clinical presentation and severity of symptoms ranging from asymptomatic to mild to life-threatening bleeding. Thus, they pose a diagnostic and therapeutic challenge, mainly for the primary health care providers, general practitioners, and gynecologists who are more likely to first encounter these patients. An additional diagnostic challenge arises from the variable laboratory presentations, as PT, PTT, and BT are not always affected. The morbidity is higher among women of reproductive age since Abnormal Uterine Bleeding–specifically Heavy Menstrual Bleeding–is one of the most prevalent manifestations of these disorders, and in some cases of severe deficiencies has led to life-threatening episodes of bleeding requiring blood transfusions or even immediate surgical intervention. Physician awareness is important as, in the case of some of these disorders–i.e., Factor XIII deficiency–prophylactic treatment is available and recommended. Although uncommon, the potential for rare bleeding disorders and for hemophilia carrier states should be considered in women with HMB, after more prevalent causes have been excluded. Currently, there is no consensus on the management of women in these instances and it is reliant on the physicians’ knowledge.