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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]

Proximally, the arrector pili muscle (APM) attaches to the follicular stem cell niche in the bulge, but its distal properties are comparatively unclear. In this work, a novel method employing an F-actin probe, phalloidin, was employed to visualize the APM anatomy. Phalloidin staining of the APM was validated by comparison with conventional antibodies/stains and by generating three-dimensional reconstructions. The proximal attachment of the APM to the bulge in 8 patients with androgenic alopecia was studied using Masson's trichrome stain. Phalloidin visualized extensive branching of the APM. The distal end of the human APM exhibits a unique 'C'-shaped structure connecting to the dermal-epidermal junction. The proximal APM attachment was observed to be lost or extremely miniaturized in androgenic alopecia. The unique shape, location, and attachment sites of the APM suggest a significant role for this muscle in maintaining follicular integrity. Proximally, the APM encircles the follicular unit and only attaches to the primary hair follicle in the bulge; this attachment is lost in irreversible hair loss. The APM exhibits an arborized morphology as it ascends toward the epidermis, and anchors to the basement membrane. [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]

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]

Mesangial metrics reflect glomerular filtration surface area in diabetes. The point-sampled intercept (PSI) method is the conventional method to calculate these parameters. However, this is time consuming and subject to underestimation. We introduce a novel three-dimensional (3D) reconstruction method applicable to light microscopy to measure mesangial metrics. Transmission electron microscopy (TEM), PSI and our new 3D imaging methods were used to quantify mesangial metrics from 22 patients with type 2 diabetes, normo-, micro- and macroalbuminuria and an estimated glomerular filtration rate of <60 mL/min/1.73 m2. Repeated-measures ANOVA test was used to test the equality of the measurement means from the three methods and the degree of inter method variability. Repeated-measures and post-estimation ANOVA tests together with correlation coefficient measurements were used to compare the methods with TEM as reference. There was a statistically significant difference in mesangial volume measurements (F(2, 16) = 15.53, p = 0.0002). The PSI method underestimated measurements compared to TEM and 3D methods by 30% (p = 0.001) and 15%, respectively (p < 0.001). 3D and TEM measurements did not differ significantly. 3D reconstruction is a reliable and time efficient method for calculating mesangial metrics. It may prove to be a useful tool in clinical and experimental diabetic kidney disease. [ABSTRACT FROM AUTHOR]

The article presents a case of a 45-year-old female whose disseminated superficial actinic porokeratosis (DSAP) lesions worsened following her application of spray tan. Her new lesions showed increased keratosis and hyperpigmentation. Also discussed is the main ingredient of spray tans called dihydroxyacetone (DHA), also called glycerone.

A letter to the editor is presented which discusses the case of a 35-year-old, 6-week pregnant woman with a 7-day history of a red and itchy rash on her left breast and is indicative of iododerma in pregnancy.