Nivolumab-induced diabetes mellitus-a case report with literature review of the treatment options.

Background: Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient's immune system. Here, we report a rare case of a new onset of diabetes mellitus (DM), caused by nivolumab, and we discuss the feasible treatment options with a focus on TNF antagonism. Case presentation: A 50-year-old man was diagnosed with metastatic renal cell carcinoma. Due to systemic progression, a combined immunotherapy with ipilimumab and nivolumab was initiated, according to the current study protocol (SAKK 07/17). The administration of ipilimumab was stopped after 10 months, due to partial response as seen in the computer tomography (CT), and nivolumab was continued as monotherapy. Fourteen months after the start of the treatment, the patient was admitted to the emergency department with lethargy, vomiting, blurred vision, polydipsia, and polyuria. The diagnosis of DM with diabetic ketoacidosis was established, although autoantibodies to ß-cells were not detectable. Intravenous fluids and insulin infusion treatment were immediately initiated with switching to a subcutaneous administration after 1 day. In addition, the patient received an infusion of the TNF inhibitor infliximab 4 days and 2 weeks after the initial diagnosis of DM. However, the C-peptide values remained low, indicating a sustained insulin deficiency, and the patient remained on basal bolus insulin treatment. Two months later, nivolumab treatment was restarted without destabilization of the diabetic situation. Conclusions: In contrast to the treatment of other irAEs, the administration of corticosteroids is not recommended in ICI-induced DM. The options for further treatment are mainly based on the low numbers of case series and case reports. In our case, the administration of infliximab-in an attempt to salvage the function of ß-cells-was not successful, and this is in contrast to some previous reports. This apparent discrepancy may be explained by the absence of insulin resistance in our case. There is so far no evidence for immunosuppressive treatment in this situation. Prompt recognition and immediate start of insulin treatment are most important in its management.

Sex-Specific Differences in Outcomes Following Thyroidectomy: A Population-Based Cohort Study.

INTRODUCTION: Numbers of thyroidectomies and awareness of postoperative quality measures have both increased. Potential sex-specific variations in clinical outcomes of patients undergoing thyroidectomy are controversial. OBJECTIVE: The aim of this study was to investigate sex-specific differences in outcomes following thyroidectomy. METHODS: This is a population-based cohort study of all adult patients undergoing either hemi- or total thyroidectomy in Switzerland from 2011 to 2015. The primary outcome was all-cause 30-day readmission rate. The main secondary outcomes were intensive care unit (ICU) admission, surgical re-intervention, in-hospital mortality, length of hospital stay (LOS), postoperative calcium disorder, vocal cord paresis, and hematoma. RESULTS: Of 16,776 patients undergoing thyroidectomy, the majority of patients undergoing thyroidectomy were female (79%), with a median age of 52 (IQR 42-64) years. Within 30 days after the surgery, male patients had significantly higher rates of hospital readmission (adjusted risk ratio [RR] 1.38; 95% confidence interval [95% CI] 1.11-1.72, p = 0.008) and higher risks for postoperative ICU admission (RR 1.25; 95% CI, 1.09-1.44, p = 0.003) than female patients. There were no significant differences among sexes in the LOS, rates of surgical re-interventions, or in-hospital mortality. While postoperative calcium disorders due to hypoparathyroidism were less prevalent among male patients (RR 0.63; 95% CI, 0.54-0.72, p < 0.001), a 2-fold higher incidence rate of postoperative hematoma was observed (RR 1.93, 95% CI, 1.51-2.46, p < 0.001). CONCLUSIONS: Male patients undergoing thyroidectomy have higher 30-day hospital readmission and ICU admission rates. Following surgery, male patients revealed higher rates of neck hematoma, while hypocalcemia was more frequent among female patients.

Association of weekend admission and clinical outcomes in hospitalized patients with sepsis: An observational study.

Sepsis is associated with impaired clinical outcomes. It requires timely diagnosis and urgent therapeutic management. Because staffing during after-hours is limited, we explored whether after-hour admissions are associated with worse clinical outcomes in patients with sepsis.In this retrospective cohort study, we analyzed nationwide acute care admissions for a main diagnosis of sepsis in Switzerland between 2006 and 2016 using prospective administrative data. The primary outcome was in-hospital mortality using multivariable logistic regression models. Secondary outcomes were intensive care unit (ICU) admission, intubation, and 30-day readmission.We included 86,597 hospitalizations for sepsis, 60.1% admitted during routine-hours, 16.8% on weekends and 23.1% during night shift. Compared to routine-hours, we found a higher odds ratio (OR) for in-hospital mortality in patients admitted on weekends (Adjusted OR 1.05, 95% confidence interval [95% CI] 1.01, 1.10, P = .041). Also, the OR for ICU admission (OR 1.14, 95% CI 1.10, 1.19, P < .001) and intubation (OR 1.18, 95% CI 1.12, 1.25 P < .001) was higher for weekends compared to routine-hours. Regarding 30-day readmission, evidence for an association could not be observed. Night shift admission, compared to routine-hours, was associated with a higher OR for ICU admission and intubation (ICU admission: OR 1.28 (1.23, 1.32), P < .001; intubation: OR 1.31, 95% CI 1.25, 1.37, P < .001) but with a lower OR for in-hospital mortality (OR 0.93, 19% CI 0.89, 0.97, P = .001).Among hospitalizations with a main diagnosis of sepsis, weekend admissions were associated with higher OR for in-hospital mortality, ICU admission, and intubation. Whether these findings can be explained by staffing-level differences needs to be addressed.

Association of comorbidities with clinical outcomes in patients after acute myocardial infarction.

BACKGROUND: Multimorbidity becomes more prevalent in patients admitted for acute myocardial infarction (AMI). We investigated the association of an increasing number of comorbidities with the excess risk of in-hospital mortality and other clinically outcomes in hospitalized AMI patients. METHODS: In this population-based cohort study, we analyzed 104'906 admissions for AMI between 2012 and 2018 in Switzerland. We stratified patients based on four different age categories and investigated the association of the number of five common comorbidities (diabetes, chronic kidney-, chronic obstructive pulmonary-, cerebrovascular-, and peripheral artery disease) and risk of in-hospital mortality and other outcomes. RESULTS: A total of 5'029 admitted AMI patients (4.8%) died during the hospital stay. We found a stepwise increase in mortality risk with each additional comorbidity. Compared to AMI patients with no comorbidity, comorbid patients had a 26% increased risk for mortality (adjusted odds ratio [OR] 1.26, 95% confidence interval [CI] 1.20 to 1.33) with a pronounced association in younger patients. The overall risk for ICU admission, prolonged length of hospital stay (LOS), and 30-day readmission was higher in comorbid patients as compared to those without a comorbidity of interest (ICU: OR 1.19, 95% CI 1.16 to 1.22; LOS: OR 1.84, 95% CI 1.79 to 1.89; Readmission: OR 1.23, 95% CI 1.19 to 1.28), respectively. Again, the association of the numbers of prevalent comorbidities with adverse outcomes was strongest in the youngest patient population. CONCLUSIONS: In patients with AMI, the burden of comorbidities has a strong association with in-hospital mortality and other adverse outcomes - especially in younger patients.

Association of the Swiss Diagnosis-Related Group Reimbursement System With Length of Stay, Mortality, and Readmission Rates in Hospitalized Adult Patients.

Importance: In 2012, hospital reimbursement in Switzerland changed from a fee-for-service per diem system to a diagnosis-related group (SwissDRG) system. Whether this change in reimbursement is associated with harmful implications for quality of care and patient outcomes remains unclear. Objective: To examine the association of the SwissDRG implementation with length of hospital stay (LOS), in-hospital mortality, and 30-day readmission rates in the overall adult inpatient population and stratified by 5 individual diagnoses. Design, Setting, and Participants: This cohort study used administrative data from the Swiss Federal Statistical Office to investigate medical hospitalizations in Switzerland from January 1, 2009, through December 31, 2015. All hospitalizations for adult medical inpatients were included in the main analysis. Patients who presented with 1 of the 5 common medical diagnoses were included in the subanalyses: community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, acute myocardial infarction, acute heart failure, and pulmonary embolism. An interrupted time series model was used to determine changes in time trends for risk-adjusted LOS, in-hospital mortality, and 30-day readmission after the implementation of SwissDRG in 2012. Analyses were performed from March 1, 2018, to June 30, 2018, and from November 1, 2018, to December 18, 2018. Main Outcomes and Measures: Monthly patient-level data for LOS, in-hospital mortality, and 30-day readmission rates. Results: The sample included a total of 2 426 722 hospitalized adult patients. Of this total, 1 018 404 patients (41.9%; 531 226 [52.2%] male, median [interquartile range (IQR)] age of 69 [55-80] years) composed the before-SwissDRG period; 1 408 318 patients (58.0%; 730 228 [51.9%] male, median [IQR] age of 70 [56-81] years) composed the after-SwissDRG period. The overall LOS gradually decreased from unadjusted mean (SD) 8.0 (12.7) days in 2009 to 7.2 (17.3) days in 2015. This reduction in LOS, however, was not substantially greater with the implementation of SwissDRG in 2012 (risk-adjusted slope, -0.0166 days; 95% CI, -0.0223 to -0.0110 days), with an adjusted difference in slopes of 0.0000 days (95% CI, -0.0072 to 0.0072 days). Risk-adjusted all-cause in-hospital mortality declined from 4.9% in 2009 to 4.6% in 2015, with a substantially greater decline after implementation of SwissDRG (difference between monthly slopes before and after implementation, -0.0115%; 95% CI, -0.0190% to -0.0039%). In the same period, risk-adjusted 30-day readmission rates increased from 14.4% in 2009 to 15.0% in 2015, with a greater increase after SwissDRG implementation (change in monthly slope, 0.0339%; 95% CI, 0.0254%-0.0423%). Patients with acute myocardial infarction were found to have a substantially greater increase after SwissDRG implementation in 30-day readmission rates (adjusted difference in slopes, 0.1144%; 95% CI, 0.0617%-0.1671%). Conclusions and Relevance: Among medical hospitalizations in Switzerland, SwissDRG implementation appeared to be associated with an increase in readmission rates and a decrease in in-hospital mortality but not with the gradual decrease in LOS observed in the historical control period.

Cerebral venous thrombosis requiring invasive treatment for elevated intracranial pressure in women with combined hormonal contraceptive intake: risk factors, anatomical distribution, and clinical presentation.

OBJECTIVE Women taking combined hormonal contraceptives (CHCs) are generally considered to be at low risk for cerebral venous thrombosis (CVT). When it does occur, however, intensive care and neurosurgical management may, in rare cases, be needed for the control of elevated intracranial pressure (ICP). The use of nonsurgical strategies such as barbiturate coma and induced hypothermia has never been reported in this context. The objective of this study is to determine predictive factors for invasive or surgical ICP treatment and the potential complications of nonsurgical strategies in this population. METHODS The authors conducted a 2-center, retrospective chart review of 168 cases of CVT in women between 2000 and 2012. Eligible patients were classified as having had a mild or a severe clinical course, the latter category including all patients who underwent invasive or surgical ICP treatment and all who had an unfavorable outcome (modified Rankin Scale score ≥ 3 or Glasgow Outcome Scale score ≤ 3). The Mann-Whitney U-test was used for continuous parameters and Fisher's exact test for categorical parameters, and odds ratios were calculated with statistical significance set at p ≤ 0.05. RESULTS Of the 168 patients, 57 (age range 16-49 years) were determined to be eligible for the study. Six patients (10.5%) required invasive or surgical ICP treatment. Three patients (5.3%) developed refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%) were treated with barbiturate coma and induced hypothermia, with documented infectious, thromboembolic, and hemorrhagic complications. Coma on admission, thrombosis of the deep venous system with consecutive hydrocephalus, intraventricular hemorrhage, and hemorrhagic venous infarction were associated with a higher frequency of surgical intervention. Coma, quadriparesis on admission, and hydrocephalus were more commonly seen among women with unfavorable outcomes. Thrombosis of the transverse sinus was less common in patients with an unfavorable outcome, with similar distribution in patients needing invasive or surgical ICP treatment. CONCLUSIONS The need for invasive or surgical ICP treatment in women taking CHCs who have CVT is partly predictable on the basis of the clinical and radiological findings on admission. The use of nonsurgical treatments for refractory ICP, such as barbiturate coma and induced hypothermia, is associated with systemic infectious and hematological complications and may worsen morbidity in this patient population. The significance of these factors should be studied in larger multicenter cohorts.