Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

BACKGROUND & AIMS: Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. METHODS: Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. RESULTS: A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). CONCLUSIONS: FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Injection Site Reaction to Various Insulins as Type III Allergy With Urticarial Vasculitis in a Patient With Type I Diabetes Mellitus.

ABSTRACT: Injection site reactions are defined as skin reactions at the injection site to drugs administered subcutaneously. Pathophysiologically, these reactions are based on different immunological mechanisms. We report the case of a 49-year-old patient with type 1 diabetes mellitus (first diagnosis in 1994 at the age of 23 years). Continuous subcutaneous insulin infusion using an insulin pump has been used for many years. The patient presented to the department of dermatology with progressive symptoms in the area of the insulin injection sites on the lower abdomen, accompanied by pain, burning, erythema, tenderness, and the formation of subcutaneous nodules. Previous attempts to use different insulins and to change the injection sites did not improve his symptoms. Furthermore, the symptoms appeared within hours after the insulin pump was attached, so that the injection site has to be changed as soon as every 48 hours. No anaphylactic shock was reported at any time. Multiple histological specimens were obtained from an older lesion on the abdomen as well as from test sites after standard allergological tests (prick and intradermal tests) of various insulins. Histologically, these biopsies showed the image of an extensive deep-reaching small vessel vasculitis with the aspect of an urticarial vasculitis and confirmed the diagnosis of an injection-site reaction that can be characterized as a type III hypersensitivity reaction.

[Diabetes mellitus in Anaesthesia - Optimal Blood Sugar Control in the Perioperative Phase]. / Diabetes mellitus in der Anästhesie ­ optimale perioperative Blutzuckerkontrolle.

Uncontrolled high blood sugar can be dangerous for diabetics throughout the perioperative period - in particular, when blood glucose levels exceed a threshold of 250 mg/dl or HbA1c levels are higher than 8.5 - 9%. In such cases, all elective surgery should be withheld to minimize the risk of severe complications. Due to their cardiovascular comorbidities, diabetics are commonly overrepresented in hospitals, tend to require inpatient care for an extended period of time, and suffer from higher mortality rates. In order to reduce negative outcomes, blood glucose levels should be targeted to 140 - 180 mg/dl on intensive care units or during surgery. Current literature suggests that non-critically ill diabetics should be treated with rapid-acting insulin analogues subcutaneously in operating theatres, whereas critically ill patients should receive continuous intravenous insulin infusions using a standardized protocol. In summary, this review can give a hand in dealing with diabetics during the perioperative period and offers guidance in controlling blood sugar levels with the help of oral antidiabetic drugs and insulin.

Hepatic steatosis in patients with acromegaly.

OBJECTIVE: Comorbid NAFLD is increasingly being diagnosed in patients with diabetes and nondiabetic endocrinopathies. The aim of this study was to assess hepatic steatosis noninvasively by transient elastography in patients with acromegaly. DESIGN: A cross-sectional study including 22 patients with acromegaly. METHODS: Hepatic steatosis was quantified using controlled attenuation parameter (CAP) during elastography. Anthropometric measurements were obtained, serum liver function tests and lipid and hormone profiles were measured, and prosteatogenic gene variants were genotyped using standard assays. RESULTS: In total, 41% of patients were women (mean age 60 ± 14.7 years, mean BMI 31.2 ± 4.6 kg/m2). Hepatic steatosis, as defined by CAP > 248 dB/m, was present in 66% of patients. Five (45%) of the patients with hepatic steatosis also had fibrosis, and one presented with cirrhosis. Nine patients were carriers of the PNPLA3 p.I148M prosteatogenic [M] risk allele, eight of whom were heterozygotes. CAP values were significantly (P = .045) higher in these patients and corresponded to advanced steatosis, as compared to patients with the wild-type genotype, who demonstrated CAP values consistent with mild steatosis (311 ± 33 dB/m. vs 254 ± 62 dB/m). CAP values did not differ significantly in carriers of distinct TM6SF2 and MBOAT7 genotypes; however, carriers of the risk alleles displayed higher CAP as compared to wild-type patients. CONCLUSIONS: This study shows that in patients with acromegaly, carriers of the PNPLA3 susceptibility allele are at risk of developing hepatic steatosis, as assessed by CAP. Comorbid NAFLD might compound prognosis in such patients; thus, further research into the pathomechanisms and treatment of NAFLD in acromegaly is warranted.

Patient radiation dose in percutaneous biliary interventions: recommendations for DRLs on the basis of a multicentre study.

OBJECTIVE: Percutaneous biliary interventions (PBIs) can be associated with a high patient radiation dose, which can be reduced when national diagnostic reference levels (DRLs) are kept in mind. The aim of this multicentre study was to investigate patient radiation exposure in different percutaneous biliary interventions, in order to recommend national DRLs. METHODS: A questionnaire asking for the dose area product (DAP) and the fluoroscopy time (FT) in different PBIs with ultrasound- or fluoroscopy-guided bile duct punctures was sent to 200 advanced care hospitals. Recommended national DRLs are set at the 75th percentile of all DAPs. RESULTS: Twenty-three facilities (9 interventional radiology depts. and 14 gastroenterology depts.) returned the questionnaire (12%). Five hundred sixty-five PBIs with 19 different interventions were included in the analysis. DAPs (range 4-21,510 cGy·cm2) and FTs (range 0.07-180.33 min) varied substantially depending on the centre and type of PBI. The DAPs of initial PBIs were significantly (p < 0.0001) higher (median 2162 cGy·cm2) than those of follow-up PBIs (median 464 cGy·cm2). There was no significant difference between initial PBIs with ultrasound-guided bile duct puncture (2162 cGy·cm2) and initial PBIs with fluoroscopy-guided bile duct puncture (2132 cGy·cm2) (p = 0.85). FT varied substantially (0.07-180.33 min). CONCLUSIONS: DAPs and FTs in percutaneous biliary interventions showed substantial variations depending on the centre and the type of PBI. PBI with US-guided bile duct puncture did not reduce DAP, when compared to PBI with fluoroscopy-guided bile duct puncture. National DRLs of 4300 cGy·cm2 for initial PBIs and 1400 cGy·cm2 for follow-up PBIs are recommended. KEY POINTS: • DAPs and FTs in percutaneous biliary interventions showed substantial variations depending on the centre and the type of PBI. • PBI with US-guided bile duct puncture did not reduce DAP when compared to PBI with fluoroscopy-guided bile duct puncture. • DRLs of 4300 cGy·cm2for initial PBIs (establishing a transhepatic tract) and 1400 cGy·cm2for follow-up PBIs (transhepatic tract already established) are recommended.

Selective association of nonaspirin NSAIDs with risk of diverticulitis.

PURPOSE: The purpose of this study is to investigate the association of intake of nonsteroidal anti-inflammatory drugs (NSAIDs) and in particular nonaspirin NSAIDs and compare it with other risk factors for the progression of diverticulosis to diverticulitis in patients who underwent colonoscopy. METHODS: A total of 194 patients who underwent complete colonoscopy in our center between 2012 and 2016 were recruited: 144 with diverticulosis without prior diverticulitis (median age 71 years, 59.7% men) and 50 with diverticulitis (median age 64 years, 54.0% men). Data concerning current and previous medication as well as concomitant diseases were collected using a structured questionnaire and by revision of patients medical charts. RESULTS: Patients with diverticulitis were significantly (p < 0.001) younger as compared to individuals with plain diverticulosis (median age 64 versus 71 years, respectively). The intake of NSAIDs significantly (p = 0.002) increased the risk of prior diverticulitis (OR 3.2, 95% CI 1.5-6.9). In the multivariate model, both age (p < 0.001) and NSAIDs (p = 0.03) proved to be independent determinants of diverticulitis. When analyzing aspirin intake, it was not associated with diverticulitis. CONCLUSIONS: Our study demonstrates, in line with previous reports, that intake of NSAIDs is associated with diverticulitis. We show in particular that nonaspirin NSAIDs might be selectively associated with diverticulitis. These results point to divergent role of aspirin and nonaspirin NSAIDs in the development of diverticulitis.

Preservation of hormonal function by identifying pituitary gland at endoscopic surgery.

OBJECTIVE: The endonasal endoscopic approach has been established for perisellar tumor surgery with a higher resection rate and reduced complications. We analyzed the potential to identify the pituitary gland under endoscopic view, at surgery and see its relation to postoperative hormonal insufficiency in endonasal endoscopic procedures. METHODS: Between January 2011 and January 2014, 70 cases of pituitary adenomas with preoperative intact pituitary function underwent endoscopic endonasal transsphenoidal procedures for intrasellar pathologies. Endocrinologists and neurosurgeons followed these patients prospectively. Special attention was paid to intraoperative identification of gland tissue, surgical complications, degree of resection and postoperative hormonal insufficiency. RESULTS: The pituitary gland was identified in 57 out of 70 procedures (81.4%). Eleven percent (8 of 70 patients) had persistent pituitary insufficiency. Two of these 8 patients belonged to the group with pituitary gland identification (2 out of 57); thus, when the pituitary gland was identified during the procedure postoperative hormonal insufficiency was seen in 3.5% of cases. Failure of pituitary gland identification presented with hormonal insufficiency of 46.2%. In analysis with Fisher's exact test, there was a high significant correlation between the identification of the pituitary gland intraoperatively and normal pituitary function postoperatively (p<0.005). On follow up radical tumor resection was seen in 88% (62 of 70 patients). CONCLUSIONS: This study indicates that identification and preservation of pituitary gland tissue and function is possible in endoscopic transsphenoidal surgery. This preservation of gland tissue is a positive predictor of postoperative normal pituitary function.

Sneaky side effects and ineffectiveness of an immunotherapy with ipilimumab in a case of metastatic melanoma.

Ipilimumab is an anti-CTLA-4 antibody that is approved for the treatment of metastatic malignant melanoma. Side-effects are mostly immune-mediated and in many cases the lack of specific symptoms leads to delayed diagnosis and treatment of adverse events. We present the case of a female patient who experienced an uncommon combination of adverse reactions while undergoing therapy with ipilimumab and where the absence of specificity of the symptoms led to late diagnosis and treatment of side effects. Autoimmune disease was neither associated with tumor response nor with prolonged survival.

Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes.

Contradictory results for concentrations of vitamin B12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) have been reported. We tested the hypothesis that the extracellular vitamin B12 markers are not reflecting the intracellular vitamin B12-dependent biochemical reactions in individuals with type 2 diabetes. The study included 92 patients with diabetes and 72 controls with similar age and sex distribution. We measured vitamin B12 markers [MMA, total serum vitamin B12, holoTC, total homocysteine (tHcy)], red blood cell (RBC)-B12, and the plasma concentrations of the methylation markers [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)]. In comparison to controls, diabetic patients showed significantly higher concentrations of plasma SAH (median 15.1 vs. 11.8 nmol/L; p < 0.001) and lower SAM/SAH ratio (9.1 vs. 8.2; p = 0.006). Concentrations of total vitamin B12 and holoTC did not differ significantly between the groups, but plasma MMA concentrations were significantly higher in diabetics (250 vs. 206 nmol/L). However, RBC-B12 was lower in diabetics compared to controls (median 230 vs. 260 pmol/L; p = 0.001). The inverse correlation between MMA and RBC-B12 was stronger in the controls compared to that in the patients (correlation coefficient in controls R = -0.446, p = 0.001; in patients R = -0.289, p = 0.022). Metformin treatment was associated with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index. In conclusion, patients with type 2 diabetes showed normal extracellular vitamin B12, but disturbed intracellular B12-dependent biochemical reactions. Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12.