Endocrine Immune-Related Adverse Events Are Independent Predictors of Survival in Patients with Lung Cancer.

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.

Efficacy and Safety of Tinzaparin Thromboprophylaxis in Lung Cancer Patients with High Thromboembolic Risk: A Prospective, Observational, Single-Center Cohort Study.

BACKGROUND: The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk. METHODS: This was a non-interventional, single-arm, prospective cohort study of lung cancer patients who received thromboprophylaxis with Tinzaparin 10.000 Anti-Xa IU in 0.5 mL, OD, used in current clinical practice. Enrolled ambulatory patients signed informed consent. Anti-Xa levels were tested. RESULTS: In total, 140 patients were included in the study, of which 81.4% were males. The histology of the tumor was mainly adenocarcinoma. Lung cancer patients with high thrombotic risk based on tumor, patient, treatment, and laboratory-related factors were enrolled. Only one patient experienced a thrombotic event (0.7%), and 10 patients had bleeding events (7.1%), including only one major event. Anti-Xa levels measured at 10 days and 3 months did not differ significantly between patients who developed hemorrhagic events and those who did not (p = 0.26 and p = 0.32, respectively). CONCLUSION: Thromboprophylaxis with an intermediate Tinzaparin dose in high thrombotic-risk lung cancer patients is a safe and effective choice for the prevention of VTE.

Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors following Disease Progression or Relapse.

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.

Eligibility for screening with low-dose CT in a real-world cohort of patients with lung cancer in Greece: A brief report.

INTRODUCTION: NELSON and NLST prompted the implementation of lung cancer screening programs in the United States followed by several European countries. This study aimed to assess the sensitivity of different screening criteria among patients with lung cancer in Greece and investigate reasons for ineligibility. METHODS: We performed a retrospective analysis on patients with lung cancer referred to the largest referral center in Athens, Greece, between June 2014 and May 2023. The proportion of patients who would meet the updated USPSTF and NLST criteria was compared to the corresponding proportion of the Greek population over 15 years of age. RESULTS: Out of 2434 patients with lung cancer, 77.4 % (N = 1883) would meet the updated USPSTF criteria, and 58.9 % (N = 1439) would meet the NLST criteria at diagnosis; the corresponding proportions for the Greek population over 15 years would be 13.8 % and 8.2 %, respectively. Ineligible patients were more likely to be female, former or never-smokers, have adenocarcinoma histology, and have driver mutations (p < 0.001). CONCLUSIONS: Although the updated USPSTF criteria demonstrated good sensitivity, a substantial proportion of patients with lung cancer would still not be eligible for screening. Future studies to shape a comprehensive screening strategy should focus on the incorporation of additional risk factors for lung cancer, including air pollution and individual genetic susceptibility.

The Burden of COVID-19 in Adult Patients With Hematological Malignancies: A Single-center Experience After the Implementation of Mass-vaccination Programs Against SARS-CoV-2.

BACKGROUND/AIM: Despite the widespread mass-vaccination programs worldwide and the continuing evolution of COVID-19 therapeutics, the burden of SARS-CoV-2 infection in patients with hematological malignancies (HM) remains elusive. The aim of the present study was to assess the clinical characteristics, outcomes and therapeutic strategies applied in HM patients hospitalized during the post-vaccine period in Greece. PATIENTS AND METHODS: From June 2021 to October 2022, 60 HM patients with COVID-19 were retrospectively analyzed. Exploratory end-points included the incidence of intubation, probability of recovery, mortality, and duration of remdesivir (RDV) administration. RESULTS: Overall, mechanical ventilation (MV) was required for five patients and crude mortality was 8.3%. HM of lymphocytic origin (p=0.035) and obesity (p=0.03) were the main determinants of the risk of intubation and among several laboratory markers, only LDH>520 IU/l was proven to be an independent MV predictor (p=0.038). The number of co-existing comorbidities (p=0.05) and disease severity on admission (p<0.001) were found to rule the probability of recovery, and dexamethasone was associated with worse prognosis, particularly in patients with mild/moderate COVID-19. RDV was administered to the entire cohort, of whom 38 were managed with an extended course. In the multivariate analysis, patients with HM of lymphocytic origin were more likely to receive RDV for more than five days (p=0.002). CONCLUSION: Our study emphasizes the frailty of HM patients, even in the era of Omicron-variant predominance, and underlines the need to optimize therapy.

Primary Hemostasis Disorders as a Cause of Heavy Menstrual Bleeding in Women of Reproductive Age.

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.

Clotting Factor Deficiencies as an Underlying Cause of Abnormal Uterine Bleeding in Women of Reproductive Age: A Literature Review.

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.

Efficacy of Tocilizumab in Severely Ill COVID-19 Patients With Rapid Respiratory Deterioration: A Single Center Experience During the Third Pandemic Wave in Greece.

BACKGROUND/AIM: Immunomodulatory therapy with Tocilizumab (TCZ), a monoclonal antibody against interleukin-6 receptor-alpha, has been endorsed by the World Health Organization and other major regulatory bodies, as part of the standard-of-care therapy for severe or critical COVID-19 cases despite discordant trial outcomes. The aim of the present study was to report the experience of our center regarding TCZ routine use in severely ill COVID-19 patients who were hospitalized during the third pandemic wave in Greece. PATIENTS AND METHODS: From March 2021 to December 2021, we retrospectively analyzed COVID-19 patients with radiological findings of pneumonia and signs of rapid respiratory deterioration that were treated with TCZ. The primary outcome included the risk of intubation or/and death in TCZ-treated patients compared to matched controls. RESULTS: TCZ administration was neither predictive of intubation and/or death [OR=17.5 (95% CI=0.47-652.2; p=0.12)] or associated with fewer events (p=0.92) in multivariate analysis. CONCLUSION: Our single-center real-life experience is in line with recently published research, revealing no benefit from TCZ routine use in severely or critically ill patients with COVID-19.

Effectiveness of full (booster) COVID-19 vaccination against severe outcomes and work absenteeism in hospitalized patients with COVID-19 during the Delta and Omicron waves in Greece.

AIM: We estimated vaccine effectiveness (VE) of full (booster) vaccination against severe outcomes in hospitalized COVID-19 patients during the Delta and Omicron waves. METHODS: The study extended from November 15, 2021 to April 17, 2022. Full vaccination was defined as a primary vaccination plus a booster ≥ 6 months later. RESULTS: We studied 1138 patients (mean age: 66.6 years), of whom 826 (72.6 %) had ≥ 1 comorbidity. Of the 1138 patients, 75 (6.6 %) were admitted to intensive care unit (ICU), 64 (5.6 %) received mechanical ventilation, and 172 (15.1 %) died. There were 386 (33.9 %) fully vaccinated, 172 (15.1 %) partially vaccinated, and 580 (51 %) unvaccinated patients. Unvaccinated patients were absent from work for longer periods compared to partially or fully vaccinated patients (mean absence of 20.1 days versus 12.3 and 17.3 days, respectively; p-value = 0.03). Compared to unvaccinated patients, fully vaccinated patients were less likely to be admitted to ICU [adjusted relative risk (ARR: 0.49; 95 % CI: 0.29-0.84)], mechanically ventilated (ARR: 0.43; 95 % CI: 0.23-0.80), and die (ARR: 0.57; 95 % CI: 0.42-0.78), while they were hospitalized for significantly shorter periods (ARR: 0.79; 95 % CI: 0.70-0.89). The adjusted full VE was 48.8 % (95 % CI: 42.7 %-54.9 %) against ICU admission, 55.4 % (95 % CI: 52.0 %-56.2 %) against mechanical ventilation, and 22.6 % (95 % CI: 7.4 %-34.8 %) against death. For patients with ≥ 3 comorbidities, VE was 56.2 % (95 % CI: 43.9 %-67.1 %) against ICU admission, 60.2 % (95 % CI: 53.7 %-65.4 %) against mechanical ventilation, and 43.9 % (95 % CI: 19.9 %-59.7 %) against death. CONCLUSIONS: Full (booster) COVID-19 vaccination conferred protection against severe outcomes, prolonged hospitalization, and prolonged work absenteeism.

Creation and evaluation of a participatory child abuse and neglect workshop for medical students.

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.