The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression. Aim: The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort. Methods: Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI. Results: Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1-133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: -19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups. Conclusion: Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

Clinical risk factors predicting genital fungal infections with sodium-glucose cotransporter 2 inhibitor treatment: The ABCD nationwide dapagliflozin audit.

INTRODUCTION: Treatment of type 2 diabetes with sodium-glucose cotransporter 2 (SGLT2) inhibitors may result in genital fungal infections. We investigated possible risk factors for developing such infections among patients treated with the SGLT2 inhibitor dapagliflozin. METHODS: The Association of British Clinical Diabetologists (ABCD) collected data on patients treated with dapagliflozin in routine clinical practice from 59 diabetes centres. We assessed possible associations of patient's age, diabetes duration, body mass index, glycated haemoglobin, renal function, patient sex, ethnicity and prior genital fungal infection, urinary tract infection, urinary incontinence or nocturia, with the occurrence of ≥1 genital fungal infection within 26 weeks of treatment. RESULTS: 1049 out of 1116 patients (476 women, 573 men) were analysed. Baseline characteristics were, mean±SD, age 56.7±10.2years, BMI 35.5±6.9kg/m2 and HbA1c 9.4±1.5%. Only patient sex (13.2% women vs 3.3% men) and prior history of genital fungal infection (21.6% vs 7.3%) were found to be associated with occurrence of genital fungal infections after dapagliflozin treatment, adjusted OR 4.22 [95%CI 2.48,7.19], P<0.001 and adjusted OR 2.41 [95% CI 1.04,5.57], P=0.039, respectively. CONCLUSION: Women and patients with previous genital fungal infections had higher risks of developing genital fungal infections with dapagliflozin treatment.

Type 2 diabetes mellitus and microvascular complications 1 year after Roux-en-Y gastric bypass: a case-control study.

AIMS/HYPOTHESIS: We aimed to examine the effects of bariatric surgery on microvascular complications in patients with type 2 diabetes using objective measures. METHODS: Prospective case-control study of 70 obese surgical patients with type 2 diabetes undergoing gastric bypass surgery matched for age, sex and duration of diabetes to 25 medical patients treated using international guidelines. Microvascular complications were assessed before and 12-18 months after intervention using urine albumin creatinine ratio (ACR) measurements, two-field digital retinal images and peripheral nerve conduction studies (in the surgical group only). RESULTS: Urine ACR decreased significantly in the surgical group but increased in the medical group. There were no significant differences between the surgical and medical groups in the changes in retinopathy. There were no changes in the nerve conduction variables in the surgical group. CONCLUSIONS/INTERPRETATION: In the short term, bariatric surgery may be superior to medical care in the treatment of diabetic nephropathy, but not retinopathy or neuropathy.

Body mass index and diabetes status do not affect postoperative infection rates after bariatric surgery.

BACKGROUND: Obesity predisposes general surgical patients to infections such as surgical site infection and respiratory tract infection. The infection rates vary by surgical approach and the type of surgery undertaken. Bariatric surgery is increasingly used to treat obesity and obesity related co-morbidities. However, little is known about the relationship between postoperative infections and patient characteristics, such as body mass index (BMI) or diabetes status, in bariatric cohorts. The objective of this study was to examine the rates of all postoperative infection in patients after bariatric surgery in relation to known risk factors. RESULTS: A total of 815 patients were included in the final analysis. During the first month after surgery, 5.2% of patients experienced an infection-related event, and surgery-related infections were most prevalent. Between the second and twelfth month postoperatively, a further 4.7% of patients experienced an infection-related event, and nonsurgical related infections were most prevalent. Infection was associated with increased length of stay in Roux-en-Y gastric bypass (RYGB) (P<.001) and sleeve gastrectomy (SG) (P = .011) but not in laparoscopic adjustable gastric banding (LAGB) (P = .41). Diabetes status and BMI were not associated with increased infection rates during the first month after surgery. CONCLUSION: Infection rates after bariatric surgery are relatively low and are associated with a prolonged length of hospital stay. Reassuringly, neither diabetic status nor BMI appear to increase the risk of postoperative infection after bariatric surgery.

Beyond weight loss: evaluating the multiple benefits of bariatric surgery after Roux-en-Y gastric bypass and adjustable gastric band.

BACKGROUND: Despite the evidence for benefits beyond weight loss following bariatric surgery, assessments of surgical outcomes are often limited to changes in weight and remission of type 2 diabetes mellitus. To address this shortfall in assessment, the King's Obesity Staging System was developed. This system evaluates the individual in severity stages of physical, psychological, socio-economic and functional disease. These are categorised into disease domains arranged so as to allow an alphabetic mnemonic as Airways, Body Mass Index (BMI), Cardiovascular, Diabetes, Economic, Functional, Gonadal, Health Status (perceived) and (body) Image. METHODS: In this cohort study, patients were assessed before and 12 months after surgery using the modified King's Obesity Staging Score. We studied 217 consecutive patients undergoing Roux-en-Y gastric bypass (RYGB; N = 148) and laparoscopic adjustable gastric band (LAGB; N = 69) using the modified King's Obesity Staging System to determine health benefits after bariatric surgery. RESULTS: Preoperatively, the groups had similar BMI, but the RYGB group had worse Airways, Cardiovascular, and Diabetes scores (p < 0.05). After surgery, RYGB and LAGB produced improvements in all scores. In a subgroup paired analysis matched for preoperative Airways, BMI, Cardiovascular, and Diabetes scores, both procedures showed similar improvements in all scores, except for BMI where RYGB had a greater reduction than LAGB (p < 0.05). CONCLUSIONS: Both RYGB and LAGB deliver multiple benefits to patients as evaluated by the modified King's Obesity Staging System beyond BMI and glycaemic markers. A validated staging score such as the modified King's Obesity Staging System can be used to quantify these benefits.