Date Of Inclusion Research Articles

NSAID exposure delays time-to-pregnancy in patients with spondyloarthritis: an analysis of the GR2 prospective cohort

BackgroundThe impact of disease activity and treatment on fertility outcomes in patients with spondyloarthritis (SpA) has been little explored. This study aimed to describe median time to pregnancy (TTP) in...

Crustal thickening, exhumation and metamorphic cooling of Neoproterozoic eclogites in NE Brazil: Timescale for the assembly of West Gondwana

The high-pressure followed by high-temperature metamorphism related to the evolution of collisional orogens is the expected Pressure-Temperature-time (P-T-t) path for modern-style plate tectonics. However, these P-T-t paths are rarely preserved even in Phanerozoic orogens. In this matter, the Campo Grande migmatite-gneiss area presents an exhumed Archean crust with heterogeneous retrograde eclogites overprinted by amphibolite-facies in NE Brazil. Retrogressed eclogites in the area core are formed by Mn-rich garnet + clinopyroxene porphyroblasts layer with a minor amphibole + quartz + titanite assemblage, whereas the margins display dismembered lenses of Mg-rich garnet porphyroblasts with plagioclase + amphibole coronae and clinopyroxene + plagioclase + ortopyroxene sympleticte mainly within shear zones. Phase equilibria modelling reveals that these distinct retro-eclogites record similar eclogite conditions (up to 18 kbar and 660 ± 20 °C). Mn-rich eclogites display widespread magmatic zoned zircon grains from Mesoarchean to Paleoproterozoic and recrystallized metamorphic grains of 607.7 ± 5.4 Ma. Zircon from Mg-rich eclogites crystallized at 2.67 Ga and overgrowth rims formed at 2.0 Ga and 590.1 ± 1.8 Ma. REE in zircon lack Eu anomaly, displaying flat HREE patterns in 590.1 ± 1.8 Ma Neoproterozoic grains indicate recrystallization under eclogite-facies conditions. In situ U-Pb titanite dating yielded two younger age sets at 574.7 ± 0.5 and 562.8 ± 2.1 Ma. Lastly, in situ U-Pb dating of rutile inclusions in garnet cores present ages of 606.1 ± 4.0 Ma, whereas rutile included in retrograde coronae and sympleticte yielded concordant ages from 559.0 ± 2.3 to 523.2 ± 1.9 Ma. Thus, combined phase equilibria modelling and U-Pb ages reveal a progressive change in metamorphic conditions from eclogite conditions (at least 607.7 ± 5.4 to 590 ± 1.8 Ma; zircon dating and rutile ages included in eclogite garnet) to nearly isothermal decompression (574.7 ± 0.5 Ma; titanite age) of ancient Archean deep crust, which was followed by suggested final exhumation and metamorphic cooling at shallower crustal levels between 559.0 ± 2.3 and 523.2 ± 1.9 Ma (rutile age in retrogressed assemblage). Therefore, the high-pressure conditions followed by decompression and metamorphic cooling during sin- to post-collisional settings were associated with the final assembly of West Gondwana.

Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Breast Cancer: A Multicenter Cohort Study

Background and AimsBreast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of IBD patients with a history of breast cancer according to the subsequent IBD treatment provided. MethodsA multicenter retrospective study included consecutive IBD patients with prior breast cancer. The inclusion date corresponded to the diagnosis of index malignancy. Follow-up lasted from cancer diagnosis until the occurrence of incident cancer. ResultsAmong 207 patients included (median disease duration: 13 years [IQR 6 - 21]), first line treatment (median interval of 28 months [IQR 7 - 64]) was a conventional immunosuppressant in 19.3 % of patients, anti-TNF in 19.8 %, vedolizumab in 7.2 % and ustekinumab in 1.9 %.After a median follow-up of 71 months [IQR, 34 - 148], 42 (20%) incident cancers were observed (34 breast cancer recurrences). Adjusted incidence rates per 1000 person-years were 10.2 (95%CI 6.0- 16.4) for the untreated arm and 28.9 (95%CI 11.6-59.6) for exposed patients (p= 0.0519). There was no significant difference between treated patients and controls regarding incident-cancer free survival rates (p=0.4796). In multivariable analysis, factors associated with incident cancer were stage T4d (p=0.036), triple negative tumor (p=0.016) and follow-up of less than 71 months (p=0.005). ConclusionWe did not find a statistically significant increase in incident breast cancer related to IBD treatment beyond the already known poor prognostic factors of breast cancer.

Causes and predictors of long-term mortality in patients referred to a cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) programs have proven to reduce short-term mortality in patients with ischemic heart disease (IHD) and hospitalization rates in patients with heart failure (HF) (1-3). However, there is insufficient evidence about long-term mortality (>24-36 months) for patients receiving treatments based on recent clinical practice recommendations. Purpose To assess the long-term prognosis and predictors of mortality in a heterogenous group of patients referred to cardiac rehabilitation, and to obtain a detailed overview of death causes. Methods An inferential analysis of consecutive patients referred for exercise-based CR at a single site between January 2016 and January 2021 was performed. Included subjects were classified attending to four indications for referral: IHD, HF, valvular heart disease (VHD) and cancer therapy-related cardiovascular toxicity (CTR-CVT). Patients who did not initiate the CR program or were referred for other indications were excluded. The primary endpoint was all cause death. The secondary endpoint was cardiovascular (CV) death. A survival analysis was performed using Kaplan Meier estimates for each referral indication and a Cox proportional hazards model was fitted to investigate mortality predictors. The initiation of the exercise program was considered the inclusion date, and patients were followed until they met the primary endpoint or censored by January 2024. Results A total of 1180 patients were included in the analysis (81% male, mean age 61 ± 11 years), with a median follow-up of 5.3 years. Most of the patients had been referred due to IHD (87%), while the proportion for HF, VHD, and CTR-CVT was 9.9%, 1.8% and 1.4%, respectively. Seventy-eight patients (6.6%) died during follow-up, with a Kaplan-Meier estimated survival of 94.5% at 5 years (95% CI 93.2%-95.9%). Nineteen patients (24.4%) died due to a cardiovascular event, mostly sudden cardiac death (47%). The predominant non-CV causes of death were infectious disease (36%) and cancer (34%). A multivariate Cox model analysis (Table 1) showed an increased risk of all cause death for patients referred due to HF (HR 2.95, 95% CI 1.33 - 6.55), VHD (HR 5.55, 95% CI 1.19 - 25.9) and CTR-CVT (22.47, 95% IC 7.32 - 68.95) when compared to IHD (Figure 1). Other significant predictors of mortality were LVEF <40%, male sex, age, diabetes, peripheral vascular disease, and multivessel coronary disease. Only LVEF <40%, VHD, CTR-CVT and peripheral vascular disease were independent predictors of CV death. Conclusion Patients who initiated an exercise-based CR program had a low risk of all cause death at 5 years. Indications for CR other than IHD were associated with higher mortality rates after adjusting for confounder variables, likely due to a selection bias of patients in advanced stages of the disease.Table 1.Cox models for all-cause deathFigure 1.KM plot for all-cause death

Exploring Burden of Disease Metrics in EU legislation: A Systematic Analysis

Abstract Background The burden of disease (BoD) methodology is a valuable tool for evidence-based policymaking. However, there is currently no systematic analysis available regarding its use in the European Union (EU) legislation framework. This study aims to describe the implementation of BoD methodology in EU legislation. Methods A search was conducted on EUR-Lex, the official and most comprehensive platform to access EU legal documents. The main inclusion criteria in the analyses were date of publication (between 2004 and 2023, accounting for EU-25) and inclusion of BoD metrics (years of life lost - YLL, years lived with disability - YLD or disability-adjusted life years - DALY). Descriptive and network analysis were conducted to analyse the legislation content. Results Out of 2592 documents, 191 met the set criteria. Ten were legally binding, and 69% were published after 2018. The European Commission (n = 152) was the most regular issuing institution. BoD was mainly used as an argument (n = 93) and for impact assessment (n = 50). The metrics were commonly presented in the main text (n = 122) and in the annex (n = 48). EuroVoc domains like environment and social questions prevailed. The most frequent EuroVoc terms were climate change policy (n = 45), EU environmental policy (n = 32) and pollution control measures (n = 32). Discussion Despite the growing recognition of BoD metrics in supporting policymaking, only 191 documents published over the past 20 years within the EU legislation make reference to this methodology. Greater efforts in knowledge dissemination and directing research towards specific policy uptake may increase the application of BoD studies in EU policies. By advocating for increased awareness, promoting collaboration between researchers and policymakers, and targeting research efforts towards specific policy needs, a more comprehensive integration of BoD methodologies into EU legislation can be achieved, contributing for evidence-informed policies. Key messages • There were only 191 documents of the EU legislative documents published in the past 20 years mention burden of disease metrics, mainly addressing environmental and social issues. • There is a need to increase EU policy uptake from BoD studies, by conducting policy-oriented research, and building capacity among researchers and policymakers on BoD methodology.

Metamorphic and chronological records of early Permian continental collision in Beni Bousera granulites (Internal Rif belt): implications for the tectonic evolution of northern Morocco during Pangea construction

This work presents petrological data obtained from shielded mineral inclusions within large garnets from the Beni Bousera metamorphic unit (internal Rif belt, northern Morocco) combined with in situ U‒Th‒Pb dating of monazite inclusions. In the considered Beni Bousera metapelites, the occurrence of mineral inclusions of kyanite + rutile + plagioclase + K-feldspar + quartz ± graphite trapped in garnet cores is diagnostic of high-pressure granulite-facies metamorphism. Geothermobarometry combined with thermodynamic modelling yields minimal P ‒ T conditions of approximately 1.37–1.5 GPa and 780–795°C, consistent with the development of palaeogradients during crustal thickening in collision belts. A concordant U/Pb age of 281 ± 3 Ma is obtained from associated monazite inclusions in the same garnet cores. These new petrochronological data attest to the early Permian continental collision in northern Morocco. The obtained dataset is constrained with petrological and geochronological parameters available on other neighbouring segments of the Variscan belt. Within the framework of recently unified full plate reconstruction models, the presented tectonic scenario suggests that all these orogenic segments were built during the late Carboniferous–early Permian crustal thickening at the northwestern Gondwana margin in response to the convergence of Laurentia and Gondwana during the late stages of Pangaea construction.

Reduced Intensity transplantation vs chemotherapy in CR1. A prospective, pseudorandomized study in 50–70 year old AML patients

The aim of this prospective, international multicenter, pseudorandomized study comparing RICT HCT to standard-of-care chemotherapy in intermediate- or high-risk AML patients 50–70 years using the donor versus no-donor concept. Part 1 included only patients with potential family donors (RD) at the date of HLA-typing of the first potential sibling or CR-date, if later. Part 2 allowed the inclusion of patients without a possible sibling donor using the start of an unrelated donor (URD) search as inclusion date. 360 patients were registered and 309 analyzed. The median follow-up was 47 months (1–168). There was no difference in overall survival (OS) between the RD (n = 124) and the Control (n = 77) groups (p = 0.50, 3-year OS RD: 0.41(95% CI; 0.32–0.50); Controls: 0.49 (95% CI; 0.37–0.59)). The main cause of death was relapse (67% RD; 88% Controls). In Part 2, the 3-year OS was 0.60 (95% CI 0.50–0.70) for URD-HCT (n = 86) and 0.37 (95% CI 0.13–0.62) for Controls (n = 20), respectively (p = 0.10). When analyzing transplanted patients (Part 2), the OS at 3-years was higher for URD-HCT than RD-HCT (0.67 (0.55–0.76) vs. 0.42 (0.26–0.57; p = 0.005). This study doesn’t support elderly HLA-identical siblings as donors for older AML patients undergoing a RICT allogeneic HCT in first CR.

Human leukocyte antigen HLA-B*57:01 status in HIV-1 patients developing hypersensitivity reactions in Benin: a pilot study

BackgroundAntiretroviral drugs in people living with HIV-1 (PLHIV-1) often trigger side effects which may lead to discontinuation or failure of treatment. Human Leukocyte Antigen B*57:01 (HLA-B*57:01) allele is known to predict hypersensitivity reactions to Abacavir. Very few data are available on the prevalence of HLA-B*57:01 allele in PLHIV-1 in African countries. This study aimed to screen for HLA-B*57:01 allele in PLHIV-1 in Benin.MethodsThis pilot study was carried out on one hundred ten PLHIV-1 enrolled in two health facilities in Benin. Socio-demographic and clinical data were collected. Biological data were determined and HLA-B*57:01 allele was genotyped, using Single Specific Primer-Polymerase Chain Reaction in blood samples.Results70% of participants were female. PLHIV-1 were under TDF + 3TC + DTG (47.2%) or TDF + 3TC + EFV (57.3%). Their median age was 41 [36-48.75] years and the average CD4 + T cell count was 249 [130-381.25] cells/µl. The average viral load in treatment failure PLHIV-1 was 4.7 [3.9–5.2] Log10. At the inclusion date, twenty-nine (26.4%) PLHIV-1 under TDF + 3TC + EFV have developed hypersensitivity reactions. None of 110 patients had shown HLA-B*5701 allele.ConclusionOur study revealed that HLA-B*57:01 allele was very rare in PLHIV-1 in Benin, suggesting that its screening before starting the Abacavir regimen did not seem necessary.

Origin of the Dongga Au deposit in the giant Xiongcun porphyry Cu–Au district, Tibet, China: Constraints from multiple isotopes (Re, Os, He, Ar, H, O, S, Pb) and fluid inclusions

The Dongga Au deposit (9.55 t Au; average grade = 6.9 g/t [up to 61.6 g/t]) is located in the Xiongcun giant porphyry Cu–Au district of the Gangdese porphyry Cu belt, Tibet. Its mineralization age, ore-forming processes, and relationship to adjacent porphyry mineralization remain unclear. To address this, we conducted a geological, pyrite Re–Os dating, He–Ar–H–O–S–Pb isotopic, and fluid inclusion study of the Dongga deposit. Pyrite samples from ore-bearing chlorite–sulfide veins yielded a weighted-mean Re–Os age of 178.4 ± 2.6 Ma (MSWD=0.01), implying the deposit formed during the Early Jurassic. Fluid inclusion analyses yielded homogenization temperatures of 237–360 °C for quartz–sulfide veins and 125–201 °C for late quartz veins, with corresponding salinities of 2.7–43.8 and 0.9–9.9 wt% NaCleq, respectively. Fluid inclusion analyses of pyrite samples yielded 3He/4He and 40Ar/36Ar values of 0.50–1.08 Ra and 325.1–559.4, respectively, and δD and δ18Ofluid values of –86.2 ‰ to –72.1 ‰ and –5.6 ‰ to 3.9 ‰, respectively. The He–Ar–H–O isotopic data suggest the mineralizing fluids were derived mainly from a crustal source with a small mantle contribution, and also contained a mixture of magmatic and meteoric waters. The S (δ34S = –1.57 ‰ to –0.55 ‰) and Pb (206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb are 18.17–18.41 ‰, 15.55–15.63 ‰ and 38.15–38.37 ‰, respectively) isotopic compositions of pyrite suggest the ore-forming metals were derived from a magma source in the mantle containing minor amounts of subducted sediment. Based on the geology, and isotopic and fluid inclusion data, we infer that mixing between magmatic and meteoric waters was the main trigger of Au precipitation. In addition, based on the geochronological, spatial, and genetic relationships with the adjacent No.2 deposit in the Xiongcun ore district, we propose that the Dongga Au deposit is a sub-epithermal deposit, which represents the transition between porphyry and epithermal deposits. The two deposits constitute a porphyry system and record the continuous evolution of hydrothermal fluids transported outwards in a porphyry system.

Primary outcome analysis of the ORCHESTRA trial: A randomized phase III trial of additional tumor debulking to first-line palliative systemic therapy for patients with multiorgan metastatic colorectal cancer.

LBA3502 Background: The phase-3, investigator-initiated, ORCHESTRA trial (NCT01792934) was conducted to prospectively evaluate overall survival (OS) benefit from tumor debulking in addition to standard palliative systemic therapy in patients with multiorgan metastatic colorectal cancer (mCRC). Local therapy of metastases is increasingly discussed as part of the treatment plan for patients with multiorgan mCRC in analogy to selected patients with oligometastatic disease for whom this is standard of care. Treatment decisions are made on a daily base in multidisciplinary teams (MDT) worldwide, but evidence of superiority for additional local therapy over systemic therapy alone based on a head-to-head comparison is lacking. Methods: Between May 2013 and May 2023, 454 patients were enrolled in 28 hospitals. Patients with multiorgan mCRC as described in Table, were eligible if at least 80% tumor debulking was deemed feasible by resection, radiotherapy and/or thermal ablative therapy at the start of first-line palliative systemic therapy according to the MDT. Upon clinical benefit after 3 or 4 cycles of respectively capecitabine or 5-fluorouracil/leucovorin and oxaliplatin ± bevacizumab, 382 patients were randomized 1:1 to continuation with systemic therapy alone in the standard arm or to tumor debulking followed by restart of the systemic therapy in the experimental arm. The primary endpoint was OS, from the date of inclusion to the date of death. Secondary endpoints included progression free survival (PFS) and treatment related adverse events. OS and PFS were analyzed by means of multivariable Cox proportional hazards regression analysis where the variables used in the randomization process were included as covariates. Results: 382 patients were randomized to either receive standard palliative systemic therapy in the standard arm (N=192) or to receive additional tumor debulking to palliative systemic therapy in the experimental arm (N=190). Baseline characteristics of patients were in standard arm versus (vs) experimental arm: median age 64 vs 64 years, male 69% vs 67%, >2 organs involved 38% vs 40%, baseline LDH >250 U/L 17% vs 16%, baseline CEA >200 ng/ml 5% vs 8%. At data cut-off on April 4th, 2024, a total of 153 OS events were observed in the standard arm and 155 OS events in the experimental arm. Median follow up was 32.3 months. Median OS in the standard arm was 27.5 months versus 30.0 months in the experimental arm (adjusted HR 0.88 [95% CI 0.70-1.10] p=0.225). Median PFS in the standard arm was 10.4 months versus 10.5 months in the experimental arm (adjusted HR 0.83 [95% CI 0.67-1.02], p=0.076). Details on local treatment modalities being applied, including rate of successful radical debulking and related adverse events, will be presented at the meeting. Conclusions: Additional tumor debulking to standard first-line palliative systemic therapy failed to improve overall survival for patients with multiorgan metastatic colorectal cancer. The increasing use of local therapies for patients with mCRC needs further consideration. Clinical trial information: NCT01792934 . [Table: see text]

Real-world first-line treatment patterns and outcomes in patients with locally advanced or metastatic urothelial carcinoma in the United States.

e23287 Background: Historically, cisplatin-containing chemotherapy has been the recommended first-line (1L) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC). For those ineligible for cisplatin due to poor performance status, impaired renal function, or comorbidities, alternative choices include carboplatin-based chemotherapy and PD-1/L1 inhibitors. This study aimed to describe real-world treatment patterns and overall survival (OS) among US Medicare patients with la/mUC receiving 1L therapy. Methods: This retrospective study used Medicare fee-for-service claims data from 2015 through 2022 to identify patients diagnosed with la/mUC who received systemic treatment. Initiation of 1L therapy was the index date for study inclusion; treatment patterns and OS were assessed until end of data availability, discontinuation of health plan enrollment, or death. OS was estimated using the Kaplan–Meier approach, and a log-rank test was used to compare OS across the following 1L treatment groups: platinum-based chemotherapy (PBC; cisplatin- and carboplatin-based), non-PBC monotherapy, and PD-1/L1 inhibitor monotherapy. Hazard ratios (HRs) were estimated across groups using Cox proportional hazards models adjusting for baseline characteristics. Results: Of 13,104 patients included in this analysis, 77.5% were male, and mean (SD) age was 76.2 (7.5) years. The most commonly observed 1L treatment categories were PBC (cisplatin-based, 19.7%; carboplatin-based, 28.4%), PD-1/L1 inhibitors (34.8%), non-PBC (13.7%), and other combination therapies (2.9%). Common comorbidities included renal disease (39.9%), chronic obstructive pulmonary disease (36.1%), and diabetes (32.2%). Compared with patients in the cisplatin cohort, patients in other cohorts had higher NCI Comorbidity Index scores. Median duration of 1L treatment was 3.5 months for PD-1/L1 inhibitors, 3.2 months for carboplatin, 3.0 months for cisplatin, and 2.0 months for non-PBC. Median OS was longest with cisplatin (17.0 months; IQR: 7.8–51.9), followed by non-PBC (14.7; 5.5–39.7), carboplatin (10.5; 4.9–25.1), and PD-1/L1 inhibitors (9.4; 2.8–27.9). In the adjusted Cox model, all treatment groups had statistically significantly higher hazards of death compared with cisplatin, with an HR (95% CI) of 1.50 (1.41, 1.59; P< 0.001) for PD-1/L1 inhibitors, 1.38 (1.30, 1.46; P< 0.001) for carboplatin, and 1.11 (1.03, 1.19; P= 0.007) for non-PBC. Conclusions: In this large retrospective study of US Medicare patients from 2015–2022 with la/mUC, PBC was the most common 1L treatment, followed by PD-1/L1 inhibitors and non-PBC. While cisplatin-treated patients had longer OS than patients in other groups, treatment durations were short, and OS was generally poor across regimens. These findings highlight an unmet need for more effective 1L therapies in la/mUC.

#581 Therapeutic management of patients with GPA and MPA: a nationwide observational study in France

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. Treatment per rituximab was approved in 2013, and recent guidelines recommend corticosteroids sparing. A real-life pharmacoepidemiologic retrospective study was set up to describe the demographic characteristics of hospitalized GPA and MPA patients and compare the treatments of patients included before rituximab approval (over 2010–2012, Group 1) and after rituximab approval in France (over 2014–2017, Group 2). Method All adult patients hospitalized for GPA or MPA between January 1, 2010 and December 31, 2017 were included from the French National Health Insurance database (SNDS) which covers >97.5% of French population. Patients were separated in 2 groups according to their date of inclusion: (i) Over 2010-2012 for group 1 and (ii) over 2014-2017 for group 2. Descriptive analyses were performed. Kaplan-Meier method was used to model the duration of treatment induction and maintenance. Fine and Gray tests were used to compare treatment phases durations. Results The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Group 1 consisted of 694 and 283 GPA and MPA patients respectively; group 2 included 668 and 463 GPA and MPA patients respectively. Mean age and the sex ratio were stable over time. During the first year after inclusion, the proportion of patients with first-time hospitalized infections, diabetes or renal failure increased between 2010–2012 and 2014–2017. Between the two inclusion periods, the proportions of patients treated with rituximab increased both in the induction and maintenance phases whereas treatment with azathioprine declined (Table 1). As for methotrexate, cyclophosphamide and glucocorticoids, the proportions remained stable. Conclusion According to real-life, pharmacoepidemiologic data in GPA and MPA patients, the introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids, although corticosteroids sparing should become a standard of care with the emerging treatment regimens. No reductions in adverse events were observed with the increased use of rituximab.

Gender affirming treatment and employment rate in 3,812 Danish transgender persons and 38,120 controls.

Gender affirming care could be associated with higher employment rate. We assessed employment rates in transgender persons compared to controls and demographic, health and treatment-related factors associated with employment in transgender persons. National register-based cohort study in Danish persons with diagnosis code of gender dysphoria during year 2000-2021. Five age-matched controls of the same sex at birth and five age-matched controls of the other sex at birth were included. The date of study inclusion was the first date of transgender diagnosis. Employment was the primary study outcome. The cohort included 3,812 transgender persons and 38,120 cisgender controls. The median age (interquartile range) was 19 (15; 24) years for transgender men, n = 1,993 and 23 (19; 33) years for transgender women, n = 1,819. In transgender men compared to control cisgender women, the odds ratio (95% confidence interval) for employment was 0.33 (0.29; 0.38) before study inclusion and 0.24 (0.20; 0.29) in the fifth calendar year after index; in transgender women compared to control cisgender men, corresponding ORs were 0.30 (0.70; 0.34) and 0.21 (0.18; 0.25). Similar findings were found between transgender persons and cisgender controls of other sex. Use of gender affirming hormone in transgender men increased probability of employment at all time points with odds ratio after 5 years: 1.61 (1.08; 2.42), p = 0.02 (95% confidence interval). In transgender women, use of hormone treatment was not associated with changed employment rates, 5 years odds ratio 1.31 (0.94; 1.82), p = 0.11. Masculinizing hormone treatment was associated with higher probability of employment.

The role of traditional Chinese medicine on fracture surgery, hospitalization, and total mortality risks in diabetic patients with osteoporosis.

Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.

A Late Jurassic Epithermal Pb-Zn Deposit: Insights from Rb-Sr Dating of Quartz-Hosted Fluid Inclusions and Sphalerite Chemical Composition

The Kangjiawan Pb-Zn deposit, situated within the Shuikoushan polymetallic ore field in Changning, Hunan Province, China, is a large-scale Pb-Zn deposit unearthed in 1976. Based on detailed geological field investigations, this study presents the results of the Rb-Sr isotopic dating, electron probe microanalyses (EPMAs), and LA-ICP-MS analyses of the Kangjiawan Pb-Zn deposit in order to determine the ore-forming age and the occurrence of trace elements in sphalerite and thereby constrain the genesis of the deposit. The Rb-Sr dating of quartz-hosted fluid inclusions yielded an Rb-Sr isochron age of 150 ± 4 Ma, with an initial 87Sr/86Sr ratio of 0.71101 ± 0.00008 (MSWD = 1.1), suggesting that the Pb-Zn mineralization of the Kangjiawan deposit took place during the Late Jurassic, coeval with the magmatic activities within the ore field. EPMA and LA-ICP-MS analyses showed that Fe, Mn, and Cd were primarily incorporated into the sphalerite lattice through isomorphous substitution. Specifically, Fe and Mn substituted for Zn, whereas Cd replaced both Fe and Zn. Other elements such as Cu, Sb, and Sn occurred within the sphalerite lattice through mineral micro-inclusions or isomorphic substitution. EPMAs and LA-ICP-MS results showed that the FeS contents in sphalerite were less than 14.33%, with corresponding ore-forming temperatures below 259 °C. The LA-ICP-MS results showed that sphalerites from the Kangjiawan Pb-Zn deposit had relatively high Ga/In ratios ranging from 0.01 to 144, providing further support for medium-to-low-temperature mineralization. The trace element compositions of sphalerites from the Kangjiawan Pb-Zn deposit exhibit skarn-type characteristics, suggesting a potential association with contemporary magmatic activities within the Shuikoushan ore field. During the Late Jurassic, extensive granitic magmatic activities occurred in the study area. At the late stage of magma crystallization, hydrothermal fluid containing Pb and Zn precipitated at medium-to-low temperatures and generated the Kangjiawan Pb-Zn deposit.

Comparative Evaluation of the Effectiveness of Adductor Canal Block versus Conservative Treatment for the Management of Anteromedial Knee Pain in Knee Osteoarthritis: A Prospective Study

Abstract Context: Knee osteoarthritis (KOA) is the most common type of lower extremity osteoarthritis (OA), with pain being the predominant symptom, leading to significant morbidity and impaired quality of life. Objectives: This study was designed to ascertain the effectiveness of ultrasound-guided adductor canal block (ACB), ensuing functional improvement and change in the quality of life in KOA patients with anteromedial knee pain and compare it with conservative treatment. Materials and Methods: A total of 196 patients were recruited for this trial and initially treated conservatively with oral analgesics and exercise. At the end of 2 and 4 weeks from the inclusion date, they were offered a crossover to the intervention with ACB for the saphenous nerve. The outcome measures, such as Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Timed Up and Go test, number of analgesics ingested per day and World Health Organization Quality of Life-BREF (WHOQoL-BREF) scores, were recorded at pre-decided time points. Results: After multiple structured follow-ups, 76 and 86 patients were analysed in the intervention and conservative groups, respectively. The two groups had no significant differences in the demographic and clinical patterns. The intervention group showed improvements in VAS (at week 2) (P &lt; 0.05), WOMAC and the number of analgesics ingested per day (weeks 2 and 4) (P &lt; 0.05). At ‘week 8’ follow-up, most patient outcomes including physical health and psychological domains of WHOQoL-BREF scores were better for conservative group (P &lt; 0.05). The rest of the outcome measures were comparable for both groups at all time points. No adverse events were reported. Conclusion: This study suggests that ACB is effective only for a short duration and does not offer any significant advantage over conservative management in the long run.

Associations between diabetes and cancer: A 10-year national population-based retrospective cohort study

AimsTo investigate the risk of cancer in people with diabetes compared to the population without diabetes and to gain insight into the timely association between diabetes and cancer at national level. MethodsA retrospective cohort study was conducted to analyse the role of diabetes in the development of cancer, based on service utilisation and antidiabetic dispensing data of the population between 2010 and 2021. Univariate and multivariate Cox regression were used to examine how diabetes status, in relationship with age and sex are related to the time to cancer diagnosis. ResultsExamining a population of 3 681 774 individuals, people with diabetes have a consistently higher risk for cancer diagnosis for each cancer site studied. Diabetes adds the highest risk for pancreatic cancer (HR = 2.294, 99 % CI: 2.099; 2.507) and for liver cancer (HR = 1.830, 99 % CI: 1.631; 2.054); it adds the lowest – but still significant – risk for breast cancer (HR = 1.137, 99 % CI: 1.055; 1.227) and prostate cancer (HR = 1.171, 99 % CI: 1.071; 1.280).The difference in cancer rate is driven by the younger age group (40–54 years: for patients with diabetes 5.4 % vs. controls 4.4 %; 70–89 years: for patients with diabetes 12.7 % vs. controls 12.4 %). There are no consistent results whether the presence of diabetes increases the risk of cancer diagnosis differently in males and females. The cancer incidence starts to increase before the diagnosis of diabetes and peaks in the year after. By the year after the start of the inclusion date, the incidence is 114/10,000 population in the control group, vs 195/10,000 population in the group with diabetes. Following this, the incidence drops close to the control group. ConclusionsScreening activities should be revised and the guidelines on diabetes should be complemented with recommendations on cancer prevention also considering that the cancer incidence is highest around the time of the diagnosis of diabetes. For prostate cancer, our results contradict many previous studies, and further research is recommended to clarify this.

Cardiac Rehabilitation Increases Plasma Klotho Levels.

Background: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV events, although its potential relationship with changes in MM is unknown. Methods: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups. Results: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. -49 pg/mL; p < 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. -17.3 RU/dL; p < 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% [+44 to +205]; p = 0.003). Conclusions: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR.

Success in Heart Failure? An Investigation of Heart Failure Readmission Rates and Medication Regimen Optimization.

In May 2022, the American College of Cardiology updated their guideline-directed medical therapy for congestive heart failure (CHF) to include four pillars of therapy. These pillars aim to better control patients with heart failure (HF) and reduce the incidence of hospitalization by including an evidence-based beta-blocker, an angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker/angiotensin receptor/ neprilysin inhibitor, a mineralocorticoid receptor antagonist, and newly recommended sodium glucose cotransporter 2-inhibitors. This study at University of Florida Health Central Florida Hospitals reviewed patients who were diagnosed with CHF and recorded if they were readmitted with a HF exacerbation within 30 days of an initial index admission. Patients had data obtained retrospectively using electronic medical records from patient hospital encounters within the study inclusion dates; 7/1/2022-9/30/2022. Hospital readmission rates for patients with CHF, and information on each patient's medication regimen was collected to see if they met medication optimization criteria. A total of 252 patients were evaluated, with 157 meeting the inclusion criteria. Of the patients included, 23 (14.6%) experienced a hospital readmission within 30 days because of acute HF exacerbation or worsening HF. After reviewing medication regimens, 60 patients (38.2%) were receiving treatment with one pillar of therapy, 72 (45.8%) with two pillars of therapy, 12 (7.6%) with three pillars of therapy, and one patient was treated with all four pillars of therapy. In conclusion, this study showed that the recommended pillars of therapy are not being implemented and patients with CHF may benefit from medication optimization.

Prevalence of chronic kidney disease in Tunisian diabetics: the TUN-CKDD survey.

In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR). This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages. The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m² within 13.3% of subjects wit h CKD. 18.9% had both criteria. In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices.