Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies—Acting Now before It Is Too Late—A Joint Call for Action

Contains fulltext : 225815.pdf (publisher's version ) (Open Access)The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics [...].4 p

Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines

Oertelt-Prigione S, Parol R, Krohn S, Preißner R, Regitz-Zagrosek V. Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines. BMC Medicine. 2010;8(1): 70.© 2010 Oertelt-Prigione et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women

Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension.</p> <p>Case presentation</p> <p>We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy.</p> <p>Conclusion</p> <p>We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.</p

Sex differences in the morphological failure patterns following hip resurfacing arthroplasty

<p>Abstract</p> <p>Background</p> <p>Metal-on-metal hybrid hip resurfacing arthroplasty (with a cementless acetabular component and a cemented femoral component) is offered as an alternative to traditional total hip arthroplasty for the young and active adult with advanced osteoarthritis. Although it has been suggested that women are less appropriate candidates for metal-on-metal arthroplasty, the mechanisms of prosthesis failure has not been fully explained. While specific failure patterns, particularly osteonecrosis and delayed type hypersensitivity reactions have been suggested to be specifically linked to the sex of the patient, we wished to examine the potential influence of sex, clinical diagnosis, age of the patient and the size of the femoral component on morphological failure patterns in a large cohort of retrieved specimens following aseptic failure of hip resurfacing arthroplasty.</p> <p>Methods</p> <p>Femoral remnants retrieved from 173 hips with known patient's sex were morphologically analyzed for the cause of failure. The results were compared with the control group of the remaining 31 failures from patients of unknown sex. The odds ratios (OR) and 95% confidence intervals (CI) of the following morphologically defined variables were calculated using logistic regression analysis: periprosthetic fractures (n = 133), osteonecrosis (n = 151), the presence of excessive intraosseous lymphocyte infiltration (n = 11), and interface hyperosteoidosis (n = 30). Logistic regression analysis was performed both unadjusted and after adjustment for sex, age, the size of the femoral component, and preoperative clinical diagnosis.</p> <p>Results</p> <p>Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, <it>P </it>for difference = 0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, <it>P </it>for difference = 0.01). However, women had a higher OR for both the presence of excessive intraosseous lymphocyte infiltration (adjusted OR: 10.22, 95% CI 0.79, 132.57, <it>P </it>for difference = 0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, <it>P </it>for difference = 0.03).</p> <p>Conclusions</p> <p>Within the limitations of this study, we demonstrated substantial sex differences in distinct failure patterns of metal-on-metal hip resurfacing. Recognition of pathogenically distinct failure modes will enable further stratification of risk factors for certain failure mechanisms and thus affect future therapeutic options for selected patient groups.</p

Sex impacts Th1 cells, Tregs, and DCs in both intestinal and systemic immunity in a mouse strain and location-dependent manner

Background: Males and females have a different predisposition for the development of intestinal disorders, like inflammatory bowel disease (IBD). We hypothesized that sex specific differences in intestinal immune responses may underlie this bias. To test this hypothesis, we studied sex differences in immune cell populations in the Peyer's patches (PP). For comparison with systemic immunity, we studied spleen cells. Methods: Two mouse strains with different susceptibility for developing colitis (BALB/c and C57Bl/6) were used. Using flow cytometry, we measured the percentage of T cells, Th1, Th17, and Treg cells in the PP and spleen. In addition, we measured the percentages of NK cells, macrophages, myeloid, and lymphoid dendritic cells (DCs) and their expression of CD80 and CD103. Moreover, we measured percentages of monocyte subsets in the peripheral circulation. Results were tested using two-way ANOVA, p <0.05. Results: Males had a lower percentage of T cells in both PP and spleen (PP BALB/c 22.1 %, B6 13.6 %; spleen BALB/c 4.7 %, B6 19.9 %) but a higher percentage of Th1 cell in both tissues (PP BALB/c 350 %, B6 109.5 %; spleen BALB/c 48.7 %, B6 41.9 %) than females. They also had a higher percentage of Tregs in the spleen than females (BALB/c 20.5 %, B6 4.5 %). Furthermore, males had a higher percentage of CD80(+) DCs in both the PP and spleen (lymphoid DCs in PP BALB/c 104.7 %, B6 29.6 %; spleen BALB/c 72.2 %, B6 44.2 %; myeloid DCs in PP BALB/c 80.5 %, B6 93.3 %; spleen BALB/c 88.5 %, B6 50.8 %) and a higher percentage of lymphoid CD103(+) DCs in the spleen than females (BALB/c 41.5 %, B6 28.3 %). The percentage of NK cells was decreased in the spleen (BALB/c 12.5 %, B6 25.1 %) but increased in the PP (BALB/c 75.7 %, B6 78.6 %) of males as compared with females. Strain differences were also found in the PP; BALB/c mice had a higher percentage of T cells (males 58.1 %, females 75.5 %), a higher Th/Tc ratio (males 81.0 %, females 134.2 %), less FoxP3(+)CD25(-) T cells (males 14.6 %, females 30.0 %), more DCs (males 14.8 %, females 15.7 %) and macrophages (males 67.9 %, females 141.2 %), and more NK cells (males 160 %, females 164.3 %) than BALB/c mice. Conclusions: In this study, we show sex differences in intestinal and peripheral immune populations. These differences may underlie sex differences in intestinal disorders like IBD, and this information may be an important knowledge for the treatment of intestinal-related diseases

Prevalence of primary biliary cirrhosis in adults referring hospital for annual health check-up in Southern China

<p>Abstract</p> <p>Background</p> <p>Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitocondrial autoantibodies (AMA) which has an essential role also for diagnosis. In addition, also some anti-nuclear antibodies (ANA) have been shown to be highly specific PBC. The purpose of this study was to assess the prevalence of PBC among the adults referring hospital for annual health check-up in Southern China by screening sera for PBC-specific autoantibodies.</p> <p>Methods</p> <p>AMA and ANA were screened in 8,126 adults (mean age 44 ± 15 years, 48% females) by indirect immunofluorenscence (IIF). Positive sera were tested by ELISA/immunoblotting for AMA-M2, anti-sp100 and anti-gp210. A diagnosis of PBC was re-assessed six months after the initial testing.</p> <p>Results</p> <p>Out of 8,126 individuals 35 were positive for AMA and 79 positive for ANA. Nineteen, 4, and 3 of the subjects positive for AMA and/or ANA showed reactivity for AMA-M2, anti-sp100 or gp210, respectively, further tested with ELISA/immunoblotting. Fourteen in the 39 individuals positive for AMA at IIF, AMA-M2, anti-gp210, or anti-sp100 had abnormal cholestatic liver functional indices. One definite and 3 probable PBC diagnosis could be made in 4 cases including 3 females and 1 male after half a year.</p> <p>Conclusions</p> <p>We found a point prevalence rate of PBC among Southern Chinese adults attending for yearly health check-up of 492 cases per million (95% CI, 128 to 1,093) and 1,558 cases per million (95% CI, 294 to 3,815) for women over 40, a finding similar to prevalence reported in other geographical areas.</p