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Diabetic kidney disease (DKD) is a highly prevalent complication of diabetes and the leading cause of end‐stage kidney disease. Inflammation is recognized as an important driver of progression of DKD. Activation of the immune response promotes a pro‐inflammatory milieu and subsequently renal fibrosis, and a progressive loss of renal function. Although the role of the innate immune system in diabetic renal disease has been well characterized, the potential contribution of the adaptive immune system remains poorly defined. Emerging evidence in experimental models of DKD indicates an increase in the number of T cells in the circulation and in the kidney cortex, that in turn triggers secretion of inflammatory mediators such as interferon‐γ and tumor necrosis factor‐α, and activation of cells in innate immune response. In human studies, the number of T cells residing in the interstitial region of the kidney correlates with the degree of albuminuria in people with type 2 diabetes. Here, we review the role of the adaptive immune system, and associated cytokines, in the development of DKD. Furthermore, the potential therapeutic benefits of targeting the adaptive immune system as a means of preventing the progression of DKD are discussed. [ABSTRACT FROM AUTHOR]

Aims: To evaluate diagnostic performance of glomerular filtration rate (GFR) estimated by modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), full age spectrum (FAS), and revised Lund-Malmö (r-LM) equations in adults with diabetes.Methods: Individuals were included in this cross-sectional study if they had at least 1 measurement of technetium-99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) GFR (mGFR) and serum creatinine (1487 patients with 2703 measures). GFR calculated by estimation equations was compared with mGFR. Diagnostic performance was assessed using concordance correlation coefficient (CCC), bias, precision, accuracy, reduced major axis regression (RMAR), and Bland-Altman plot. Analysis was repeated in subgroups based on sex, diabetes type, Hemoglobin A1C, and GFR level.Results: Of all patients, 1189 (86%) had type 2 diabetes. Mean mGFR, MDRD, CKD-EPI, FAS, and revised Lund-Malmö eGFR were 66, 72, 74, 71, and 67 mL/min/1.73m2, respectively. Overall, the r-LM had the highest CCC (0.83), lowest bias (-1.4 mL/min/1.73 m2), highest precision (16.2 mL/min/1.73 m2), and highest accuracy (P10 = 39%). The RMAR (slope, intercept) in r-LM, FAS, MDRD, and CKD-EPI was 1.18, -13.35; 0.97, -2.9; 1, -6.4, and 1.04, -11.3, respectively. The Bland-Altman plot showed that r-LM had the lowest mean difference and the narrowest 95% limit of agreement (-1.0, 54.1 mL/min/1.73 m2), while mean difference was more than 5-fold higher in FAS, MDRD, and CKD-EPI (-5.2, -6.3, and -8.2, respectively).Conclusions: In adults with diabetes the revised Lund-Malmö performs better than MDRD, CKD-EPI, and FAS in calculating point estimates of GFR. [ABSTRACT FROM AUTHOR]

Objectives: Denosumab is often used in men with advanced prostate cancer to prevent skeletal‐related events, but can be associated with severe hypocalcaemia. Our objective was to review the pathophysiology, identify risk factors and provide recommendations for prevention and management of denosumab‐associated hypocalcaemia. Design: We reviewed the literature regarding denosumab‐associated severe hypocalcaemia, defined as necessitating hospitalization for intravenous calcium treatment, in the context of prostate cancer. Patients: Men with prostate cancer with severe denosumab‐associated hypocalcemia. Results: We identified 20 men with prostate cancer with severe denosumab‐associated hypocalcemia, including the present case. Median age (range) was 70 years (45‐86). All had skeletal metastases and presented with symptomatic hypocalcemia 16 days (4‐35) after the initial (n = 18) or second (n = 2) denosumab treatment, with a serum total calcium of 1.36 mmol/L (1.13‐1.91). The key risk factor was presence of active osteoblastic metastases, evidenced by elevated serum alkaline phosphatase, 838 U/L (58‐2620) and supportive imaging. Other risk factors reported in some men included vitamin D deficiency (<50 nmol/L), 25‐OH vitamin D 44 nmol/L (22‐81), renal impairment, serum creatinine 103 μmol/L (62‐1131) and hypomagnesaemia, 0.82 mmol/L (0.29‐1.20). Men received intravenous calcium infusions for 16 days (1‐90), and median total intravenous elemental calcium requirements were 3.17 g (0.47‐26.65). Conclusions: Denosumab treatment in men with metastatic prostate cancer can be associated with life‐threatening hypocalcaemia requiring prolonged hospitalization for intravenous calcium treatment. Modifiable risk factors should be corrected before denosumab administration. In men with active osteoblastic metastases, consideration should be given to delay denosumab treatment until underlying disease activity is controlled, and/or be administered with close monitoring and proactive treatment with calcium and calcitriol. [ABSTRACT FROM AUTHOR]

Objective: Limited studies have examined the association between diabetes and HbA1c with postoperative outcomes. We investigated the association of diabetes, defined categorically, and the association of HbA1c as a continuous measure, with postoperative outcomes.Research Design and Methods: In this prospective, observational study, we measured the HbA1c of surgical inpatients age ≥54 years at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed with diabetes if they had preexisting diabetes or an HbA1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA1c between 5.7 and 6.4% (39 and 48 mmol/mol). Patients with an HbA1c <5.7% (39 mmol/mol) were categorized as having normoglycemia. Baseline demographic and clinical data were obtained from hospital records, and patients were followed for 6 months. Random-effects logistic and negative binomial regression models were used for analysis, treating surgical units as random effects. We undertook classification and regression tree (CART) analysis to design a 6-month mortality risk model.Results: Of 7,565 inpatients, 30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson comorbidity index (excluding diabetes and age), estimated glomerular filtration rate, and length of surgery, diabetes was associated with increased 6-month mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05-1.58]; P = 0.014), major complications (1.32 [1.14-1.52]; P < 0.001), intensive care unit (ICU) admission (1.50 [1.28-1.75]; P < 0.001), mechanical ventilation (1.67 [1.32-2.10]; P < 0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR] 1.08 [95% CI 1.04-1.12]; P < 0.001). Each percentage increase in HbA1c was associated with increased major complications (aOR 1.07 [1.01-1.14]; P = 0.030), ICU admission (aOR 1.14 [1.07-1.21]; P < 0.001), and hospital LOS (aIRR 1.05 [1.03-1.06]; P < 0.001). CART analysis confirmed a higher risk of 6-month mortality with diabetes in conjunction with other risk factors.Conclusions: Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA1c were independently associated with a higher risk of adverse outcomes after surgery. [ABSTRACT FROM AUTHOR]

It is unknown if high prolactin levels during pregnancy contribute to the development of gestational diabetes. We hypothesized that higher prolactin levels are associated with reduced glucose tolerance, as determined by higher 2-h glucose level from an oral glucose tolerance test in pregnancy. The 75-g oral glucose tolerance test was carried out at 28 weeks of gestation in 69 participants. A multiple regression analysis was used to determine the relationship between serum prolactin and 2-h glucose levels. Multivariable regression analysis showed an independent and significant relationship between third trimester prolactin and 2-h glucose levels post oral glucose tolerance test. Higher prolactin levels were associated with higher glucose levels independent of age, body mass index, gravidity and parity. Higher prolactin levels associated with reduced glucose tolerance in the third trimester of pregnancy suggests the possible independent role of prolactin in the pathogenesis of gestational diabetes. [ABSTRACT FROM AUTHOR]

The arrector pili muscle (APM) consists of a small band of smooth muscle that connects the hair follicle to the connective tissue of the basement membrane. The APM mediates thermoregulation by contracting to increase air-trapping, but was thought to be vestigial in humans. The APM attaches proximally to the hair follicle at the bulge, a known stem cell niche. Recent studies have been directed toward this muscle's possible role in maintaining the follicular integrity and stability. This review summarizes APM anatomy and physiology and then discusses the relationship between the follicular unit and the APM. The potential role of the APM in hair loss disorders is also described, and a model explaining APM changes in hair loss is proposed. [ABSTRACT FROM AUTHOR]

Ichthyosiform dermatosis is a term referred to a group of disorders that have as their basis a disorder of keratinization (1). These conditions which are present at birth result in a generalized dry, scaly skin without any inflammation. There are several types of ichthyosis based on their clinical presentation and mode of inheritance. The most common types are: ichthyosis vulgaris, X-linked recessive ich - thyosis, epidermolytic hyperkeratosis (bullous), lamellar ichthyosis and non-bullous ichthyosiform erythroderma. Lamellar ichthyosis, which is inherited in an autosomal recessive pattern, shows genetic heterogeneity with the most severe type being due to mutations in the transglutaminase- 1 gene. This condition presents with skin changes at birth and cases are referred to as collodion babies. Initially, the stratum corneum is smooth and appears as though it is covered with cellophane. This layer is discarded a few days after birth, leaving a generalized inflamed and scaly appearance. The skin is tight at this stage and may cause ectropion, and difficulties in feeding and temperature regulation. Lamellar ichthyosis is characterized by plate-like scales that last for life and can significantly impact the patient's quality of life (2). We report here a case of multiple extraspinal hyperostoses concomitant with marked osteoporosis and vitamin D deficiency in a patient taking acitretin for 20 years due to severe congenital lamellar ichthyosis. [ABSTRACT FROM AUTHOR]

Background: Specialist care may improve outcomes for inpatients with diabetes. However, research specific to type 1 diabetes (T1D) is lacking. We aimed to investigate whether automatic alerts from the Electronic Medical Record (EMR) enable prompt review of inpatients with T1D by a specialist diabetes team. Methods: The type 1 diabetes identification ("T1DI") initiative was established to improve identification and review of inpatients with T1D by a specialist diabetes team. A specific T1DI code was entered into the EMR of patients with T1D. On subsequent admission, the specialist diabetes team received an automatic message and generated a list of inpatients requiring review. "T1DI" admissions of more than 1-day were analysed over a 1-year period (1 January-31 December 2018). The control group was T1D admissions as coded by health information services following discharge. Analysis was performed for patients admitted to units other than endocrinology to investigate review outcomes. Data was analysed using Chi2 (categorical), Wilcoxon rank sum (continuous) and random effects logistic or negative binomial regression models. Results: There were 136 admissions of adults with T1D over the study period (T1DI n=67, control n=69). The median age was 49 (IQR 33-64) years; 53% were females. Specialist diabetes team review was more common in the T1DI cohort compared to the control group (endocrinology review AOR 10.27, CI 2.26-46.55, P=0.003; diabetes education review AOR 7.22, CI 2.73-19.10, P<0.001). Prompt endocrinology review (no later than day 2 of admission) was more likely in T1DI inpatients (AOR 2.77, CI 1.15-6.65, P=0.023). Conclusion: The T1DI initiative was associated with improvements in occurrence and timing of specialist diabetes team review for inpatients with T1D. This initiative could be implemented in other hospitals with EMR systems, enabling more effective identification and management of T1D in the inpatient setting. Disclosure: R. Loveridge: None. N. Torkamani: None. S.L. Patterson: None. L. Churilov: None. E.I. Ekinci: None. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a highly prevalent complication of diabetes and is the leading cause of ESKD. The role of T lymphocytes in DKD remains unclear. We aimed to determine the distribution of T lymphocytes in renal biopsies in people with T2DM with varying degrees of kidney function and albuminuria. Fresh renal biopsy samples were provided by the Victorian Cancer Biobank at the time of surgery from individuals undergoing partial/complete nephrectomy or from people with diabetes who had a renal biopsy for clinical indications at Austin Health. Participants were divided into the following groups: Diabetic kidney disease group (DKD was diagnosed by clinical and histologic characteristics), nondiabetic and intact renal function (Control) (eGFR > 60ml/min/m2, no albuminuria) and nondiabetic kidney disease (NDKD) (eGFR < 60ml/min/m2, no history of diabetes). DKD group was further stratified into normo-, micro-, or macroalbuminuria groups. Sections were immunostained with CD3 antibody. Results showed higher level of creatinine, systolic blood pressure, and reduced level of eGFR, poor glycemic control in people with DKD and macroalbuminuria as compared with people without diabetes. T lymphocytes numbers were significantly increased in the interstitial compartment of people with T2DM and macroalbuminuria compared to those without diabetes, suggesting the immunopathologic role of T lymphocytes in the development of DKD. Disclosure: L. Kong: None. S. Andrikopoulos: None. R. MacIsaac: None. N. Torkamani: None. M. Coughlan: None. D. Power: None. E.C. Marin: None. L.K. Mackay: None. E.I. Ekinci: None. [ABSTRACT FROM AUTHOR]

Context: The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests., Objective: To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women., Design: Cross-sectional case-control study., Setting: General community., Participants: Transgender women, cisgender male and cisgender female controls., Main Outcome Measures: Citrated blood samples were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram); and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented., Results: Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum amplitude + 6.94 mm (3.55, 10.33); P < 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91); P = 0.009; peak thrombin + 38.10 nM (2.27, 73.94); P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25); P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters., Conclusion: Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Timely detection leading to the implementation of reno-protective measures reduces the progression of diabetic kidney disease. Estimated glomerular filtration rate (eGFR) is a major surrogate of kidney function. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation is a tool to estimate GFR. This protocol outlines a systematic-review, assessing the diagnostic accuracy of the CKD-EPI equation in adults with diabetes., Methods and Analysis: MEDLINE, Embase, Cochrane Central Register of Controlled Trials and grey literature will be searched for publications in English, Farsi, Dutch and Chinese from 2009 (when CKD-EPI was first introduced) to January 2019. Bridging searches will be conducted to capture literature published from January 2019 until final review publication. The inclusion criteria will be (1) study participants with diabetes; (2) age ≥18 years; (3) creatinine-based CKD-EPI eGFR as index test; (4) measured GFR using the clearance/plasma disappearance of inulin, iohexol, iothalamate, diethylenetriamine-pentaacetic acid (DTPA) or chromium labelled ethylenediaminetetraacetic acid (Cr-EDTA) as reference test; (5) report of the diagnostic accuracy of the index test. Exclusion criteria will be participants with renal transplant, chronic use of corticosteroids, chronic inflammatory diseases, pregnancy, non-diabetes related kidney disease, thalassaemia, heart failure, pregnancy and potential kidney donors as well as critically ill patients. Screening, eligibility check, risk of bias assessment and data extraction will be carried out by two independent reviewers. Any discrepancies will be discussed, and third-party opinion will be sought. The risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A quantitative synthesis of the aggregated-data will be used if the included studies are homogenous., Ethics and Dissemination: No ethics approval is required. The outcome will be published in a peer-reviewed journal. The results will help researchers and clinicians evaluate the diagnostic accuracy of the creatinine-based CKD-EPI eGFR in adults with diabetes., Prospero Registration Number: CRD42018108776., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Limited studies have examined the association between diabetes and HbA 1c with postoperative outcomes. We investigated the association of diabetes, defined categorically, and the association of HbA 1c as a continuous measure, with postoperative outcomes., Research Design and Methods: In this prospective, observational study, we measured the HbA 1c of surgical inpatients age ≥54 years at a tertiary hospital between May 2013 and January 2016. Patients were diagnosed with diabetes if they had preexisting diabetes or an HbA 1c ≥6.5% (48 mmol/mol) or with prediabetes if they had an HbA 1c between 5.7 and 6.4% (39 and 48 mmol/mol). Patients with an HbA 1c <5.7% (39 mmol/mol) were categorized as having normoglycemia. Baseline demographic and clinical data were obtained from hospital records, and patients were followed for 6 months. Random-effects logistic and negative binomial regression models were used for analysis, treating surgical units as random effects. We undertook classification and regression tree (CART) analysis to design a 6-month mortality risk model., Results: Of 7,565 inpatients, 30% had diabetes, and 37% had prediabetes. After adjusting for age, Charlson comorbidity index (excluding diabetes and age), estimated glomerular filtration rate, and length of surgery, diabetes was associated with increased 6-month mortality (adjusted odds ratio [aOR] 1.29 [95% CI 1.05-1.58]; P = 0.014), major complications (1.32 [1.14-1.52]; P < 0.001), intensive care unit (ICU) admission (1.50 [1.28-1.75]; P < 0.001), mechanical ventilation (1.67 [1.32-2.10]; P < 0.001), and hospital length of stay (LOS) (adjusted incidence rate ratio [aIRR] 1.08 [95% CI 1.04-1.12]; P < 0.001). Each percentage increase in HbA 1c was associated with increased major complications (aOR 1.07 [1.01-1.14]; P = 0.030), ICU admission (aOR 1.14 [1.07-1.21]; P < 0.001), and hospital LOS (aIRR 1.05 [1.03-1.06]; P < 0.001). CART analysis confirmed a higher risk of 6-month mortality with diabetes in conjunction with other risk factors., Conclusions: Almost one-third of surgical inpatients age ≥54 years had diabetes. Diabetes and higher HbA 1c were independently associated with a higher risk of adverse outcomes after surgery., (© 2018 by the American Diabetes Association.)

The hair follicle is a complete mini-organ that lends itself as a model for investigation of a variety of complex biological phenomena, including stem cell biology, organ regeneration and cloning.  The arrector pili muscle inserts into the hair follicle at the level of the bulge- the epithelial stem cell niche.  The arrector pili muscle has been previously thought to be merely a bystander and not to have an active role in hair disease. Computer generated 3D reconstructions of the arrector pili muscle have helped explain why women with androgenetic alopecia (AGA) experience diffuse hair loss rather than the patterned baldness seen in men.  Loss of attachment between the bulge stem cell population and the arrector pili muscle also explains why miniaturization is irreversible in AGA but not alopecia areata. A new model for the progression of AGA is presented.