Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

Cytotoxic T‐lymphocyte‐associated protein 4 expressed by melanoma cells does not affect melanoma‐specific cytotoxic T lymphocytes in the effector phase

Cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the important molecules that regulate the anti‐melanoma T‐cell response. Currently, there are some reports showing that CTLA‐4 is expressed not only by T cells but also by various kinds of tumor cells, including melanoma cells. However, there is no report that shows the role of CTLA‐4 expressed by melanoma cells in melanoma‐specific cytotoxic T‐lymphocyte (CTL) response. In this report, we confirmed substantial CTLA‐4 expression and the localization of CTLA‐4 in melanoma cell lines and tissues. Also, we examined its impact on melanoma‐specific CTL in vitro, and found that CTLA‐4 expressed by melanoma cells does not affect melanoma‐specific CTL in the effector phase. Our findings suggest the importance of elucidating the role of CTLA‐4 expressed by melanoma cells, particularly in anti‐CTLA‐4 antibody therapy.     

Circulating CCL20: A potential biomarker for active vitiligo together with the number of Th1/17 cells

Background

Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.

Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion

Background

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.

Rates of reoperation and nonoperative intervention within 30 days of bariatric surgery

BackgroundComplications arising from laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are not insignificant and can necessitate additional invasive interventions or reoperations.ObjectivesIn this study, we identify early complications that result in nonoperative and operative interventions after LSG and LRYGB, the timeframe within which to expect them, and factors that influence the likelihood of their occurrence.SettingMulti-institutional database from across North America.MethodsData for this study were obtained from Metabolic and Bariatric Accreditation and Quality Improvement Program participant use files for 2015 and 2016. Statistical analysis was performed using STATA 15. Univariate analysis using Χ² for categoric data and independent t test for continuous data was performed to determine between group differences. Multivariable logistic regression analysis was used to identify predictors of operative and nonoperative reinterventions.ResultsIn 2015 and 2016, 243,747 underwent LRYGB or LSG, of which 3013 (1.24%) required a second operative procedure and 1536 (0.63%) required an invasive but nonoperative intervention. Complications occurred in 5.48% of LRYGB patients and 2.28% of LSG patients, the most common of which was bleeding. LSG was associated with far fewer nonoperative and operative interventions (.85% versus 2.2%, respectively) than LRYGB (.67% versus 2.5%). Renal insufficiency, including dialysis dependency, was an important predictor of reoperations among bariatric surgery patients. This was also true of nonoperative interventions; however, history of pulmonary embolism, and use of therapeutic anticoagulation were marginally stronger predictors.ConclusionsIn a representative, multinational sample, operative and nonoperative interventions were half as likely among LSG patients compared with LRYGB; however, overall rates still remained low. These findings, in conjunction with new efficacy data demonstrating comparable long-term weight loss between LRYGB and LSG, provide further support for the safety, effectiveness, and cost efficiency of LSG.     

“Diabetes care at doorsteps”: A customised mobile van for the prevention,screening, detection and management of diabetes in the urban underprivileged populations of Delhi

Diabetes is on the rise in India and recently shown to be increasing in the urban underprivileged. Lack of awareness of the disease, its complications, combined with lack of financial resources among the underprivileged, often results in late detection and more complications in them. To combat this, healthcare delivered at the doorstep through the use of a customised mobile medical van is a potentially attractive option.We used a customized mobile van (included trained personnel, glucose meters, fundus evaluation camera, apparatus for detection of neuropathy and foot circulation and net enabled Skype calling for remote consultation) for educating general population regarding healthy lifestyle and screening, management and intervention in patients with diabetes.The project covered 10 underprivileged areas (n, 2,31,000 people) in Delhi. Total of 24,072 individuals (10.9% of total population) attended 352 awareness sessions. A total 3,12,347 visits (included repeat visits) were carried out for screening, education and management for obesity and diabetes. During screening (n, 16,834), 2933 subjects (18.7%) had high random blood glucose levels (>200 mg/dL) and had a blood pressure averaging 127.1 ± 23.6/81.3 ± 16.6 mm of mercury (n, 16,339). A pre-post intensive lifestyle counselling for 6 months in a subset of 352 diabetic patients (of which 77.8% i.e. n, 274 were overweight/obese) showed a significant lowering in weight (p < 0.001). In addition, 292 frontline workers and 256 paramedical workers were given training regarding lifestyle and diabetes, over 20 sessions.Based on achievements of this project of spreading awareness, screening, and management of diabetes and obesity in the large number of individuals in urban underprivileged colony, we believe this project could be extended to other cities and rural areas of India, and to other developing countries as well.