Immune checkpoint inhibitors such as pembrolizumab, ipilimumab, and nivolumab, now FDA-approved for use in treating several types of cancer, have been associated with immune-related adverse effects. Specifically, the antibodies targeting the programmed-cell death-1 immune checkpoint, pembrolizumab and nivolumab, have been rarely reported to induce the development of type 1 diabetes mellitus. Here we describe a case of a patient who developed antibody-positive type 1 diabetes mellitus following treatment with pembrolizumab in combination with systemic chemotherapy for metastatic adenocarcinoma of the lung. We will also provide a brief literature review of other rarely reported cases of type 1 diabetes presenting after treatment with pembrolizumab and nivolumab, as well as discussion regarding potential mechanisms of this adverse effect and its importance as these drugs continue to become even more widespread.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for lung cancer in recent years. These strategies consist of neutralizing antibodies against negative regulators of immune function, most notably cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1), thereby impeding the ability of tumor cells to escape immune surveillance. Though ICIs have proven a significant advance in lung cancer therapy, overall survival rates remain low, and lung cancer continues to be the leading cause of cancer-related death in the United States. It is therefore imperative to better understand the barriers to the efficacy of ICIs, particularly additional mechanisms of immunosuppression within the lung cancer microenvironment. Recent evidence suggests that regulatory T-lymphocytes (Tregs) serve as a central mediator of immune function in lung cancer, suppressing sterilizing immunity and contributing to the clinical failure of ICIs. Here, we provide a comprehensive summary of the roles of Tregs in lung cancer pathobiology and therapy, as well as the potential means through which these immunosuppressive mechanisms can be overcome.

Pelvic squamous cell carcinoma of unknown primary origin has been described in several case reports of female patients. However, there have been no published reports describing male patients with pelvic squamous cell cancer of unknown primary origin. Our case describes a 52-year-old man who presented with right buttock pain, rectal urgency, and constipation. His physical examination demonstrated tenderness to palpation around his gluteal folds. Computed tomography scan of his abdomen and pelvis demonstrated a large mass in his retroperitoneum. The mass was determined to be squamous cell carcinoma of unknown primary origin. Additionally, the patient had small nodules in his right lower lung lobe and right hepatic lobe. The patient was treated with concomitant chemoradiation, including cisplatin and intensity-modulated radiation therapy, followed by carboplatin and paclitaxel. The patient achieved partial remission, in which he remained one year after his presentation. Our case is consistent with the literature which suggests that squamous cell carcinoma of unknown primary origin occurring outside of the head and neck region may have a more favorable prognosis than other carcinomas of unknown primary origin. Further studies are necessary to determine the most appropriate work-up, diagnosis, and optimal treatment strategies.

Introduction: Presently, programmed death ligand 1 is the most commonly used biomarker to predict response to immune checkpoint inhibitors (ICIs) in NSCLC. Owing to its several limitations, there is continuous search for more precise and reliable markers. Frameshift mutations by insertion or deletion (fsindels) are suggested to induce more immunogenic tumor-specific neoantigens, conferring better response to ICIs. Positive correlation of fsindels with ICI response has been studied in melanoma and renal cell carcinoma. We investigated the implication of fsindels in the clinical outcomes and immune landscape of patients with NSCLC treated with ICIs. Methods: We utilized The Cancer Genome Atlas data set to analyze tumor mutational burden, neoantigen burden, and immune landscape in relation to fsindel status. In addition, utilizing the clinical data from 122 patients treated with ICIs, we evaluated the influence of fsindels on disease response rates and survival outcomes. Results: A positive correlation between fsindel burden and tumor mutational burden and activated CD4/CD8 T-cell infiltration was shown. Presence of fsindels was also associated with significant prolongation of progression-free survival in patients treated with ICIs (median 6.2 versus 2.7 months [p ¼ 0.01]). In addition, significant differences in the overall response rates (26% versus 12% [p ¼ 0.04]) and disease control rates (68% versus 48% [p ¼ 0.02]) were observed in patients with fsindels. Conclusion: Our findings suggest that fsindels may have a predictive role for ICI response in NSCLC.

Objective To determine whether postpartum haemorrhage (PPH) is associated with cardiovascular disease (CVD), including cerebrovascular and ischaemic heart disease beyond the peripartum period. Design Population‐based cohort study. Setting Merged databases of the Korea National Health Insurance (KNHI) claims, National Health Screening Examination and National Health Screening Program for Infants and Children. Population Women who gave birth in 2007 in the Republic of Korea and who were tracked through to 2015 for the occurrence of CVD. Methods Patients were identified and the occurrences of PPH and transfusion were determined using the KNHI claims database. The occurrence of CVD was tracked through 2015 using codes from the International Classification of Diseases, tenth revision (ICD‐10). Main outcome measures The risk of CVD after PPH. Results Among 150 381 women who gave birth during the study period, 9107 were diagnosed with PPH and 899 were treated with transfusion. The risk of CVD in women with PPH was no different than in women without PPH, after adjustment (HR 1.03, 95% CI 0.93–1.13). The risk of CVD in women with PPH requiring transfusion was significantly increased compared with women without PPH, after adjustment (HR 1.60, 95% CI 1.25–2.06). The risk of CVD in women with PPH without transfusion was not significantly different compared with women without PPH (HR 0.96, 95% CI 0.86–1.07). Conclusions Postpartum haemorrhage (PPH) requiring transfusion is associated with an increased risk of CVD. Guidelines for management should be established, and further studies on the mechanisms involved should be conducted. Tweetable abstract PPH requiring transfusion is associated with an increased risk of CVD.