Climate Change and Obesity.

Global warming and the rising prevalence of obesity are well described challenges of current mankind. Most recently, the COVID-19 pandemic arose as a new challenge. We here attempt to delineate their relationship with each other from our perspective. Global greenhouse gas emissions from the burning of fossil fuels have exponentially increased since 1950. The main contributors to such greenhouse gas emissions are manufacturing and construction, transport, residential, commercial, agriculture, and land use change and forestry, combined with an increasing global population growth from 1 billion in 1800 to 7.8 billion in 2020 along with rising obesity rates since the 1980s. The current Covid-19 pandemic has caused some decline in greenhouse gas emissions by limiting mobility globally via repetitive lockdowns. Following multiple lockdowns, there was further increase in obesity in wealthier populations, malnutrition from hunger in poor populations and death from severe infection with Covid-19 and its virus variants. There is a bidirectional relationship between adiposity and global warming. With rising atmospheric air temperatures, people typically will have less adaptive thermogenesis and become less physically active, while they are producing a higher carbon footprint. To reduce obesity rates, one should be willing to learn more about the environmental impact, how to minimize consumption of energy generating carbon dioxide and other greenhouse gas emissions, and to reduce food waste. Diets lower in meat such as a Mediterranean diet, have been estimated to reduce greenhouse gas emissions by 72%, land use by 58%, and energy consumption by 52%.

Severe Hypocalcemia and Transient Hypoparathyroidism After Hyperthermic Intraperitoneal Chemotherapy.

Dear Editors,Hypocalcemia is not unusual in patients hospitalized for critical illness and has also been described after general surgery in addition to head and neck surgical procedures 1 2 3. Hypocalcemic events commonly occur in the setting of massive blood transfusion, albumin deficiency, vitamin D deficiency, and/or hypomagnesemia. In the absence of these factors, only slight decreases in calcium levels within the normal range have been reported during surgical procedures 1. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) causing asymptomatic hypocalcemia has only been reported in two previous studies 4 5. The etiology is unclear. We here report a patient who developed severe symptomatic hypocalcemia likely as a result of a profound inflammatory reaction with transient hypoparathyroidism after HIPEC.

Performance of the Afirma genomic sequencing classifier versus gene expression classifier: An institutional experience.

BACKGROUND: The use of fine-needle aspiration (FNA) to triage thyroid nodules has resulted in a significant reduction in thyroid surgery. However, approximately one-third of FNA specimens fall into the "indeterminate" category. The Afirma gene expression classifier (GEC) has been used to identify benign nodules with a high sensitivity and negative predictive value. However, the specificity and positive predictive value of the "suspicious" category are low. The updated Afirma genomic sequencing classifier (GSC) has been reported to demonstrate increased specificity while maintaining a high sensitivity and negative predictive value. METHODS: The authors retrospectively investigated 272 indeterminate thyroid FNA specimens (Bethesda categories III and IV) from nodules measuring >1 cm using the Afirma GEC or GSC tests (July 2012-January 2019). RESULTS: Of the 194 nodules tested using the Afirma GEC, a benign result was obtained in 88 cases (45.4%). In comparison, 52 of 78 FNA samples (66.7%) tested using GSC yielded a benign result (P = .002). In the GEC group, there were 31 cases with oncocytic cytology, 5 of which (16.1%) were benign on Afirma and 26 of which (83.9%) were suspicious on Afirma. In contrast, in the GSC group, there were 10 cases with oncocytic cytology, 8 of which (80%) were benign on Afirma and only 2 of which (20%) were found to be suspicious on Afirma (P < .001). The positive predictive value of the GSC group (57.1%) was higher than that of the GEC group (36.7%); however, there was no statistical significance noted (P = .15). CONCLUSIONS: A larger percentage of indeterminate thyroid FNA specimens were classified as benign using the Afirma GSC compared with the Afirma GEC, especially among samples with oncocytic features. The Afirma GSC appears to have a higher benign call rate compared with the Afirma GEC.

Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer.

BACKGROUND: Advances in cancer immunotherapy have generated encouraging results in multiple malignancies refractory to standard chemotherapies. As the use of immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side effects associated with these agents, termed immune related adverse events (irAE), is expected to increase. The frequency of significant irAE in ICI treated patients is about 10-20% and early recognition is critical to prevent serious morbidity and even mortality. New onset autoimmune diabetes mellitus (DM) associated with immune checkpoint inhibitor treatment is extremely rare, occurring in less than 1% of patients. Autoimmune DM often presents as diabetic ketoacidosis, a medical emergency requiring immediate treatment. We describe the first reported case of a patient with lung cancer who developed autoimmune diabetes after nivolumab treatment and was found to have three diabetes related (islet) autoantibodies present before ICI treatment and seroconversion of another after ICI treatment and onset of autoimmune DM. CASE PRESENTATION: A 34 year old African American woman with metastatic non-small cell lung cancer (NSCLC) was treated with nivolumab in the second line setting after disease progression following standard chemoradiation therapy. After receiving two doses of nivolumab, the patient developed abrupt onset of hyperglycemia and diabetic ketoacidosis. Autoimmune diabetes was diagnosed on the basis of undetectable C-peptide levels, seropositivity of three diabetes related (islet) autoantibodies and absolute insulin dependence. The patient eventually required use of continuous subcutaneous insulin infusion (insulin pump) due to erratic glycemic excursions and multiple readmissions for DKA. Human leucocyte antigen (HLA) genoyping revealed none of the high risk haplotypes associated with the development of type 1 diabetes. Interestingly, a frozen blood sample obtained prior to treatment with nivolumab tested positive for three of the four diabetes related (islet) autoantibodies despite no prior history of diabetes and no family history of diabetes. Notably, at the time of manuscript preparation, the patient is without evidence of NSCLC recurrence with no further treatment since the nivolumab therapy. CONCLUSION: New onset autoimmune diabetes mellitus associated with nivolumab has been described only in case reports and occurs at rates of < 1% in the large clinical trials which garnered FDA approval in the second line setting for NSCLC. As ICI use continues to expand across a wide variety of malignancies, clinicians must maintain a high index of suspicion for irAE, including autoimmune DM and other endocrinopathies. A multidisciplinary team and thorough education of the patient are recommended to optimize management of new onset adult autoimmune DM. Our patient may have been at greater risk for the development of ICI related autoimmune diabetes due to the presence of three diabetes related autoantibodies prior to therapy; however, about half of the reported cases of autoimmune DM after anti-PD-1 therapy occurred in patients with no detectable diabetes related autoantibodies. Further studies are needed to delineate genetic and immunologic biomarkers that may be useful in identifying patients at risk of developing ICI related autoimmune DM.

Prostate Cancer Patients With Unmanaged Diabetes or Receiving Insulin Experience Inferior Outcomes and Toxicities After Treatment With Radiation Therapy.

BACKGROUND: The purpose of the study was to determine the effect of type 2 diabetes mellitus (T2DM) on outcomes and toxicities among men with localized prostate cancer receiving definitive radiation therapy. PATIENTS AND METHODS: We performed a retrospective review of 3217 patients, from 1998 to 2013, subdivided into 5 subgroups: (I) no T2DM; (II) T2DM receiving oral antihyperglycemic agent that contains metformin, no insulin; (III) T2DM receiving nonmetformin oral agent alone, no insulin; (IV) T2DM receiving any insulin; and (V) T2DM not receiving medication. Outcome measures were overall survival, freedom from biochemical failure (BF), freedom from distant metastasis, cancer-specific survival, and toxicities. Kaplan-Meier analysis, log rank tests, Fine and Gray competing risk regression (to adjust for patient and lifestyle factors), Cox models, and subdistribution hazard ratios (sHRs) were used. RESULTS: Of the 3217 patients, 1295 (40%) were low-risk, 1192 (37%) were intermediate-risk, and 652 (20%) were high risk. The group I to V distribution was 81%, 8%, 5%, 3%, and 4%. The median dose was 78 Gy, and the median follow-up time was 50 (range, 1-190) months. Group V had increased mortality (sHR, 2.1; 95% confidence interval [CI], 0.66-1.54), BF (sHR, 2.14; 0.88-1.83), and cause-specific mortality (sHR, 3.87; 95% CI, 1.31-11). Acute toxicities were higher in group IV versus group I (genitourinary: 38% vs. 26%; P = .01; gastrointestinal: 21% vs. 5%; P = 001). Late toxicities were higher in groups IV and V versus group I (12%-14% vs. 2%-6%; P < .01). CONCLUSION: Men with T2DM not receiving medication and men with T2DM receiving insulin had worse outcomes and toxicities compared to other patients.