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A retrospective multicenter cohort study of patients with sarcoidosis and renal involvement
No full textAbstract Background Sarcoidosis is a multisystem granulomatous disease that can involve the kidneys. Renal involvement is often asymptomatic and underdiagnosed, yet timely recognition and treatment are crucial to prevent irreversible kidney damage. Despite its importance, there is a lack of established treatment guidelines for renal sarcoidosis. Methods We conducted a retrospective multicenter study across six Dutch hospitals, including patients with biopsy-proven renal sarcoidosis diagnosed between 2010 and 2024. Clinical, laboratory, histopathological, treatment, and outcome data were collected from electronic medical records. Descriptive statistics were used to summarize findings. Results Twenty-nine patients with biopsy-proven renal sarcoidosis were included (median age 56 years; 66% male). Lung involvement was present in 48%, and hypercalcemia in 45% of patients. At diagnosis, median serum creatinine was 242 µmol/L and median eGFR was 23 mL/min/1.73 m². Granulomatous inflammation was present in 76% of biopsies. All patients received corticosteroids as first-line therapy (median initial prednisone dose 0.66 mg/kg/day). Maximal improvement in kidney function was observed within one month of treatment; no significant predictors for early response were identified. Relapses occurred in 48% of patients (median time to first relapse: 7 months), often during or after tapering of corticosteroids. Additional immunosuppressive agents were used in 45% of patients, mainly after relapse. No baseline factors predicted relapse risk. Conclusions This study confirms the heterogeneous presentation of sarcoidosis and underscores the need for better biomarkers to guide treatment and decision making in these patients. Early corticosteroid therapy leads to rapid improvement in kidney function, but relapse is common during tapering. Steroid-sparing agents are effective for relapsing disease. Close monitoring during and after corticosteroid tapering is warranted. Our findings support a treatment protocol starting with prednisone 0.5–1 mg/kg/day, followed by gradual tapering, and the addition of steroid-sparing agents in case of relapse. Further prospective studies are needed to optimize treatment strategies and identify predictive markers for relapse and response. Clinical trial number Not applicable
Mechanism for adverse renal effects from heavy metals exposure in the CRIC study
No full textAbstract Background Chronic kidney disease (CKD) poses a major public health challenge, resulting in substantial illness, death, and financial strain. The potential role of environmental factors, such as heavy metal (HM) exposure, in the exacerbation of the disease is increasingly recognized but not well understood. This study aims to shed light on the impact of HMs on the progression of CKD. Methods In this study, we examined nail clippings and plasma samples from 20 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC), a multi-center study designed to investigate risk factors for CKD progression and cardiovascular outcomes. HM concentrations were quantified using inductively coupled plasma mass spectrometry (ICP/MS). We selected participants from two groups based on CKD progression: stable disease (n = 10) and fast-progressing disease (n = 10). We descriptively summarized variables within the groups and used Mann-Whitney and Fisher’s exact tests for between-group comparisons of continuous and categorical variables, respectively. Results Baseline demographic characteristics differed between stable and fast-progressors, with fast-progressors having higher body mass index (BMI) and higher systolic blood pressure. Distinct patterns in HM concentrations were observed. Subjects with more rapid CKD progression displayed higher median baseline metal burdens (293 µg/g) compared to those with stable disease (267 µg/g), but the differences did not reach statistical significance. Markers of ER stress, mitochondrial stress, and inflammation did not show statistically significant differences. Conclusion This study offers preliminary data regarding a potential association between HM exposure and progression of CKD. Although comparisons did not reach statistical significance, they suggest potential pathways through which HMs may influence disease progression. Future studies with larger cohorts are necessary to validate these findings, improve statistical power, and further elucidate the roles of HMs in CKD progression. This research underscores the importance of considering environmental factors in the management of chronic diseases
Ultrasound-guided sharp recanalization for valve-related stenosis in the arteriovenous fistula: a single-center retrospective cohort study
No full textAbstract Objective To compare the efficacy and safety of ultrasound-guided sharp recanalization (USR) with those of conventional percutaneous transluminal angioplasty (PTA) in the treatment of venous valve-related stenosis (VVRS) in arteriovenous fistulas (AVFs). Methods This single-center retrospective cohort study included patients treated between January 2023 and June 2024. Seventy-eight patients met the inclusion criteria; after excluding 13 patients lost to follow-up, 65 were analyzed (USR n = 33; PTA n = 32). One-to-one propensity score matching generated 32 matched pairs (USR n = 32; PTA n = 32). The primary outcome was 12-month primary patency; secondary outcomes included technical success, time to restenosis, and complications.After propensity score matching, 32 matched pairs were analyzed. Results In the matched cohort, 12-month primary patency was higher with USR than with PTA (62.5% vs. 25.0%; HR = 0.36, 95% CI 0.18–0.70; P = 0.002). Mean time to restenosis was longer in the USR group (8.25 ± 3.42 vs. 4.48 ± 2.87 months; P = 0.021). Complications were not significantly different between groups (USR 11/32 vs. PTA 5/32), and none required open surgical intervention. Conclusion USR may improve 12-month primary patency in VVRS compared with PTA without an observed increase in complications. Larger multicenter prospective studies are needed to confirm these findings
Provider perspectives on self-management of hypertension: a survey of perceptions and clinical pharmacist utilization
No full textAbstract Background Previous studies have shown pharmacist-based interventions improve blood pressure (BP) control in individuals with hypertension. Here, we evaluated provider attitudes towards the utilization of at-home self-monitoring of BP, clinical pharmacist support, and pharmacist-guided medication self-titration in the management of hypertension. Methods This was a quality improvement project at the University of Iowa Hospitals and Clinics and the Iowa City VA Health Care System. We conducted an electronic survey to determine the attitudes of providers regarding various strategies in the management of hypertension. We surveyed primary care providers, internal medicine residents, nephrologists, cardiologists, nephrology and cardiology fellows, and nurse practitioners. Continuous data were summarized with medians and interquartile ranges and compared across strata using Wilcoxon rank sum tests. Categorical variables were summarized as counts and percentages and compared using Fisher’s exact tests. Analyses were stratified by training status, specialty, and clinical setting. Open-ended comments were analyzed for overarching themes and positive, negative, or neutral sentiment. Results Of the 413 surveyed providers, 153 completed the survey, the majority of whom (78%) identified their role as clinicians. We observed high confidence in the diagnosis and treatment of hypertension among all surveyed groups. 91% of providers (N = 132) reported that at least once per week or more frequently, their decision to up-titrate BP medications was influenced by a patient’s home BP readings. Nearly half of those surveyed indicated that they had never referred their patients to a clinical pharmacist for BP medication management and a third reported doing so rarely (once or twice a month or less). Respondents, however, agreed that clinical pharmacists could support clinical decision-making for managing BP medications (68%), reduce the burden on providers (68%), and improve the safety of HTN treatment plans (72%). Conclusions Clinical pharmacists are underutilized in clinical practice although providers expressed favorable perception of clinical pharmacists’ roles in the management of hypertension. Considering the evidence that pharmacist-based management of high BP improves BP control, interventions are needed to improve pharmacist utilization in the maagement of hypertension
Distinguishing AKI from CKD: outcomes and characteristics of patients with abnormal serum creatinine and no known baseline
No full textAbstract Background Comparison of a patient’s abnormal serum creatinine result to an earlier value is fundamental to differentiating Acute Kidney Injury (AKI) from Chronic Kidney Disease (CKD), and is the first step in electronic AKI detection systems. For those patients in whom a baseline serum creatinine is unavailable, some systems generate a warning message to highlight the elevated serum creatinine but without distinguishing AKI from CKD (a “?AKI?CKD” warning). We aimed to determine demographic characteristics of this group, the proportion who had a first presentation of AKI, their clinical outcomes, and how these alert messages translate into subsequent biochemical testing and follow-up. Methods We performed a retrospective cohort analysis of adult patients with serum creatinine testing at University Hospitals of Leicester during 2019. Using the NHS England AKI detection algorithm, we identified patients with AKI Warning Test Scores (WTS) and “?AKI?CKD” warnings. The “?AKI?CKD” cohort was classified as probable AKI, probable CKD, or no follow-up result, based on subsequent serum creatinine measurements. Survival (90-day and 1-year) was analysed with Kaplan–Meier methods. Results Among 3,464 patients with “?AKI?CKD” warnings, 8.5% were probable AKI, 59.4% probable CKD, and 32.0% had no follow-up test. Probable AKI patients were younger (median age 71 versus 76 years) and more often hospitalised at warning time (56% versus 15%). One-year survival was lower in probable AKI (72%) compared to probable CKD (88%) or no follow-up (89%). Probable AKI survival was similar to AKI WTS stage 1 but better than stages 2–3. Extending baseline serum creatinine look-back to 426 days changed categorisation minimally (≤ 2%). Conclusions These findings highlight that the major feature of the “?AKI?CKD” classification is not simply misclassification between AKI and CKD, but the variability of clinical response, with one-third of patients receiving no subsequent serum creatinine test. Most patients flagged as “?AKI?CKD” likely have CKD rather than AKI, and this, coupled with comparable outcomes of the probable AKI group to early-stage AKI, suggests minimal missed population-level AKI detection. However, one-third lacked follow-up testing, highlighting missed opportunities to identify CKD. Clinical trial number Not applicable
Coexistence with Staphylococcus aureus modulates the virulence and antibiotic resistance of Pseudomonas aeruginosa
No full textAbstract Background In this study, we were aimed to investigate the impact of co-cultures of different bacterial species on bacterial antibiotic resistance and virulence. Methods The effect of co-cultures of Pseudomonas aeruginosa (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria) on antibiotic resistance, virulence and biofilm formation in P. aeruginosa was examined in vitro in 14 mixtures. These mixtures were categorized into three groups: Standard category (including standard strains), naturally co-isolated category (co-isolated from the same patient) and random co-culture category (bacterial species from different patients). Additionally, the impact of the standard category on pathogenicity was assessed in vivo using mouse model. Intergroup comparisons were conducted using multiple t-test and comparisons between treated and untreated control isolates grown under the same conditions were made. Survival experiments were analyzed using Mantel-Cox log-rank test. Results P. aeruginosa survival significantly increased in most of the co-culture mixtures when treated with meropenem (92.9%), ceftazidime (85.7%), cefepime (78.6%), gentamicin (78.6%) and ciprofloxacin (71.4%). Similarly, virulence factor production significantly increased in P. aeruginosa in most of the investigated co-cultures as follows: pyocyanin (71.4%), elastase (71.4%), protease (78.6%), hemolysin (71.4%), lecithinase (78.6%), gelatinase (63.6%) and biofilm (71.4%). At the molecular level, the relative expression of the tested virulence-encoding genes; pelA, lasB and lasA were significantly increased in at least 92.9% of the co-culture mixtures, especially in random ones, compared to their mono-culture, but with varying up-regulation degree (ranging from 1.5 to 96-fold increase). Conclusion Finally, in vitro investigations for antibiotic resistance and virulence production clearly demonstrated a synergistic interaction between P. aeruginosa and S. aureus in the co-existence mixture. Compared to P. aeruginosa mono-cultures, the co-cultured strains exhibited enhanced resistance profiles and increased expression of key virulence factors, indicating that the simultaneous presence of both species promotes mutual adaptation and potentiation of pathogenic traits. Additionally, in vivo experiments confirmed that the co-infection with S. aureus significantly enhanced the pathogenicity of P. aeruginosa, as indicated by increased mortality rates and higher bacterial counts in lung tissues. Altogether, our results shed light on the impact of the co-existence of microbial species on bacterial virulence and antibiotic resistance
Histone lactylation leads to perioperative neurocognitive disorders by promoting the expression of Ralbp1 and inducing excessive mitochondrial fission in hippocampal neurons
No full textAbstract Perioperative neurocognitive disorders (PND) is the most prevalent central nervous system (CNS) complication in older patients after surgery. Clinical and animal studies have shown that anesthesia/surgery can cause increased glycolysis and lactate production in the CNS, which is closely related to PND. However, the specific molecular mechanism by which lactate affect cognitive function remains unclear. Recent research has demonstrated that lactate can lead to neurodegenerative diseases by regulating target gene transcription through histone lactylation. The involvement of histone lactylation in PND remains to be fully elucidated. Here, we found that anesthesia/surgery induced synaptic plasticity and cognitive deficits in aged mice, accompanied by elevated hippocampal lactate and histone H3 lysine 9 lactylation (H3K9la) in neurons. Inhibiting lactate production with 2-deoxyglucose can effectively reduce synaptic and cognitive damage. To elucidate the involvement and mechanism of H3K9la in PND, we screened the target gene Ralbp1 regulated by H3K9la through CUT&Tag sequencing. The upregulation of RalBP1 can phosphorylate Drp1 Ser616 and promote mitochondrial fission, which leads to synaptic impairment of hippocampal neurons. Knockdown of Ralbp1 inhibits hippocampal neurons excessive mitochondria fission and synaptic impairment of aged mice after anesthesia/surgery, and therefore alleviates cognitive deficits. Thus, the H3K9la-RalBP1-Drp1 Ser616 pathways may provide a prospective intervention target for PND
Spatial coda Q fluctuation as a probe for heterogeneous media of Kopili fault zone, Northeast region, India
No full textAbstract In recent years, the Kopili fault reported an increase in seismic activity. Coda-wave attenuation and its frequency dependency can be used to examine the seismo-tectonics. Here, we document the regional heterogeneity in the coda attenuation. Present data in this region report Q0 (value of QC at 1 Hz) variation from 63 (for 30 s window) to 213 (for 90 s window) and n from 1.330 (for 30 s window) to 0.913 (for 90 s window). These significant fluctuations in the attenuation parameter (Q0) and frequency parameter (n), indicate a velocity inconsistency at depths of 230-270 km. This anomaly may be associated with the anisotropy originates in the asthenosphere-lithosphere transition or asthenospheric mantle at depths of 160-320 km. Accordingly, this concise work comprehensively analyzes reported implications, supported by observational evidences
Multiscale analysis and 3D inversion modelling of aeromagnetic data for mapping BIF-hosted iron deposits in the Djadom-Eta area, Southeastern Cameroon
No full textAbstract This paper deals with the lithological association and geometrical relationship between highly related magnetized bodies in the Djadom area located in the southeastern Cameroon and the North-west (NW) part of the Congo craton, which is poorly documented. To address the issue, a combined approach that involves multiscale (Residual Magnetic Intensity (RMI) and horizontal Gradient magnitude(HGM)) at different altitudes, analytic signal and three-dimensional (3D) inversion modeling were performed on aeromganetic data via Geosoft software. The application of multiscale method to the RMI and HGM at different altitudes highlights structural features and geometrical magnetic source bodies from a shallow to a depth of 6 km. Furthermore, three major WSW – ENE, WNW – ESE and W – E striking faults correspond respectively to the Djadom, Eta, and Dja faults. The analytic signal revealed high magnetization bodies along the structures. The 3D inversion model highlights high susceptibility (S > 0.02 SI) dome-like bodies that are scattered and a lower susceptibility (S < 0.02 SI) sedimentary formation associated with Djadom and Eta faults. The highest susceptibility dome-like magnetized bodies could correspond to Banded Iron Formation-hosted (BIF) formations, whose geometry was inherited from Archean tectonics ascribed to vertical tectonics that affected the study area. During mineral exploration and subsurface geophysics, these aeromagnetic maps are an important tool for geological mapping and for identifying mining targets
Assessment of current and projected runoff in the Sabarmati river basin using CMIP6 climate projections and hydrological modelling
No full textAbstract Rapid change in the regional hydrological state of a river basin under current and future climatic scenarios affects the availability of freshwater resource threatening food and water security. It is imperative to understand the present and future streamflow projections at a river basin scale for effective water resource management. In the present study, we integrate the SWAT model and CMIP6 rainfall projections to simulate present (2001–2020) and future (2021–2049) runoff in the Sabarmati River Basin (SRB). SWAT model was calibrated and validated with in-situ discharge estimates using the SUFI2 algorithm. SWAT model performed well during the calibration period (2001–2012) with NSE 0.69 and R2 0.7 indicating that the data inputs for the model can simulate the streamflow accurately. To evaluate the CMIP6 model projections, we derived historical rainfall (2001–2014) estimates from 6 CMIP6 models. It was observed that five out of the six models underestimated monthly rainfall for the Indian Summer Monsoon. Future runoff projections indicated highest runoff during October and January attributed to model uncertainty and anthropogenic influences. Changes in streamflow indicate that water management policies need to incorporate future climate scenarios and stringent research on model output dataset for simulation of future streamflow
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