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Introduction: Given the unique natural history of GBA -related Parkinson's disease ( GBA -PD) and the potential for novel treatments in this population, genetic testing prioritization for the identification of GBA -PD patients is crucial for prognostication, individualizing treatment, and stratification for clinical trials. Assessing the predictive value of certain clinical traits for the GBA -variant carrier status will help target genetic testing in clinical settings where cost and access limit its availability., Methods: In-depth clinical characterization through standardized rating scales for motor and non-motor symptoms and self-reported binomial information of a cohort of subjects with PD (n = 100) from our center and from the larger cohort of the Parkinson's Progression Marker Initiative (PPMI) was utilized to evaluate the predictive values of clinical traits for GBA variant carrier status. The model was cross-validated across the two cohorts., Results: Leveraging non-motor symptoms of PD, we established successful discrimination of GBA variants in the PPMI cohort and study cohort (AUC 0.897 and 0.738, respectively). The PPMI cohort model successfully generalized to the study cohort data using both MDS-UPDRS scores and binomial data (AUC 0.740 and 0.734, respectively) while the study cohort model did not., Conclusions: We assessed the predictive value of non-motor symptoms of PD for identifying GBA carrier status in the general PD population. These data can be used to determine a simple, clinically oriented model using either the MDS-UPDRS or subjective symptom reporting from patients. Our results can inform patient counseling about the expected carrier risk and test prioritization for the expected identification of GBA variants., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giulietta Maria Riboldi reports financial support was provided by Prevail Therapeutics. G.R. is supported by grants from Michael J Fox Foundation, Parkinson’s Foundation, Department of Defense (PD210038), NIH (R01NS116006, R01NS133742), and received a previous research grant from Prevail Therapeutics. A.F. is supported by grants from the NIH (R01NS109367, R01DC018805, R01NS115929) and NSF (CRCNS 1912286). J.G., K.A., and S.F. report no specific funding related to this work. Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: The first year of dialysis is critical given the significant risk for complications following dialysis initiation. We analysed complications during the first year among incident peritoneal dialysis (PD) patients., Methods: This retrospective cohort study comprised adult kidney failure patients starting PD in Baxter Renal Care Services in Colombia, receiving their first PD catheter between 1 January 2017 and 31 December 2020 and were followed up for up to 1 year. We analysed incidence, causes and factors associated with complications using logistic regression and transfer to haemodialysis (HD) using the Fine-Gray regression model., Results: Among 4743 patients receiving their first PD catheter: 4628 (97.6%) of catheter implantations were successful; 377 (7.9%) patients experienced early complications. The incidence rate of complications during the year was 0.51 events per patient-year (95% CI: 0.48-0.54). Age, obesity and urgent start were associated with higher probability of complications after catheter implantation. The cumulative incidence of transfer to HD within 1 year of PD initiation was 10.1% [95% CI: 9.2-11.1%]. The hazard function for transfer to HD showed an accelerating pattern during the first month followed by progressive decrease during the first year., Conclusions: In this large population of incident PD patients, there is a high primary catheter placement success rate. Urgent start, age ≥65 years, obesity, centre size ≥150 PD patients and diabetes were risk factors associated with early complications. The follow-up of the cohort from day 1 of PD treatment showed that the risk for transfer to HD was higher during the first month., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ASR is full-time employee of Baxter Healthcare Corporation, Deerfield, IL, USA; JIV and LEN are full-time employee of Baxter Renal Care Services Bucaramanga, Colombia; SP is an employee of Department of Statistics, Science Faculty, National University of Colombia, Bogota DC, Colombia, and he has received honorarium for consultancy and statistical analysis from Baxter Renal Care Services-Colombia; KA, AA, YA and JCC are full-time employee of Baxter Renal Care Services, Bogota DC, Colombia; BL is an employee of Division of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; MS is full-time employee of Baxter Renal Care Services-Latin America, Bogota DC, Colombia and PR is an employee of Baxter Healthcare Corporation, Zürich, Switzerland.

Background: Salivary gland ultrasound (SGU) provides information about structural gland abnormalities that can be graded and used for primary Sjögren's syndrome (pSS) diagnosis. Its potential role as a prognostic marker for detecting patients at high risk of lymphoma and extra-glandular manifestations is still under evaluation. We aim to assess the usefulness of SGU for SS diagnosis in routine clinical practice and its relationship with extra-glandular involvement and lymphoma risk in pSS patients., Methods: We designed a retrospective observational single-center study. Data was collected using the electronic health records of patients referred to an ultrasound outpatient clinic for evaluation over a 4-year period. Data extraction included demographics, comorbidities, clinical data, laboratory tests, SGU results, salivary gland (SG) biopsy, and scintigraphy results. Comparisons were made between patients with and without pathological SGU. The external criterion for comparison was the fulfillment of the 2016 ACR/EULAR pSS criteria., Results: A total of 179 SGU assessments were included from this 4-year period. Twenty-four cases (13.4%) were pathological. The most frequently diagnosed conditions prior to SGU-detected pathologies were pSS (9.7%), rheumatoid arthritis (RA) (13.1%), and systemic lupus (4.6%). One hundred and two patients (57%) had no previous diagnosis (sicca syndrome work-up); of these, 47 patients (46.1%) were ANA positive and 25 (24.5%) anti-SSA positive. In this study, the sensitivity and specificity of SGU for SS diagnosis were 48% and 98% respectively, with a positive predictive value of 95%. There were statistically significant relationships between a pathological SGU and the presence of recurrent parotitis (p=.0083), positive anti-SSB antibodies (p=.0083), and a positive sialography (p=.0351)., Conclusions: SGU shows high global specificity but low sensitivity for pSS diagnosis in routine care. Pathological SGU findings are associated with positive autoantibodies (ANA and anti-SSB) and recurrent parotitis., (Copyright © 2022 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background: Genetic mutations in beta-glucocerebrosidase (GBA) represent the major genetic risk factor for Parkinson's disease (PD). GBA participates in both the endo-lysosomal pathway and the immune response, two important mechanisms involved in the pathogenesis of PD. However, modifiers of GBA penetrance have not yet been fully elucidated., Methods: We characterized the transcriptomic profiles of circulating monocytes in a population of patients with PD and healthy controls (CTRL) with and without GBA variants (n = 23 PD/GBA, 13 CTRL/GBA, 56 PD, 66 CTRL) and whole blood (n = 616 PD, 362 CTRL, 127 PD/GBA, 165 CTRL/GBA). Differential expression analysis, pathway enrichment analysis, and outlier detection were performed. Ultrastructural characterization of isolated CD14+ monocytes in the four groups was also performed through electron microscopy., Results: We observed hundreds of differentially expressed genes and dysregulated pathways when comparing manifesting and non-manifesting GBA mutation carriers. Specifically, when compared to idiopathic PD, PD/GBA showed dysregulation in genes involved in alpha-synuclein degradation, aging and amyloid processing. Gene-based outlier analysis confirmed the involvement of lysosomal, membrane trafficking, and mitochondrial processing in manifesting compared to non-manifesting GBA-carriers, as also observed at the ultrastructural levels. Transcriptomic results were only partially replicated in an independent cohort of whole blood samples, suggesting cell-type specific changes., Conclusions: Overall, our transcriptomic analysis of primary monocytes identified gene targets and biological processes that can help in understanding the pathogenic mechanisms associated with GBA mutations in the context of PD., (© 2022. The Author(s).)

Ramírez-Vélez, R, Castro-Astudillo, K, Correa-Bautista, JE, González-Ruíz, K, Izquierdo, M, García-Hermoso, A, Álvarez, C, Ramírez-Campillo, R, and Correa-Rodríguez, M. The effect of 12 weeks of different exercise training modalities or nutritional guidance on cardiometabolic risk factors, vascular parameters and physical fitness in overweight adults: cardiometabolic high-intensity interval training-resistance training randomized controlled study. J Strength Cond Res 34(8): 2178-2188, 2020-Evidence suggests that exercise training improves cardiometabolic risk factors. The aim of this study was to investigate whether 12 weeks of high-intensity interval training (HIIT), resistance training (RT), concurrent training (CT = HIIT + RT), or nutritional guidance (NG) induced improvements in cardiometabolic risk factors, vascular parameters, and physical fitness in overweight adults, and to compare the responses between the 4 intervention groups. This is a twelve-weeks factorial randomized design examining the effects of different exercise regimes and/or NG on anthropometric and body composition (fat and lean mass at whole body, trunk fat, fat mass index, appendicular muscle mass, and waist circumference); cardiometabolic risk factors and vascular parameters (blood lipids, fasting glucose, blood pressure, flow-mediated dilation [FMD%], aortic pulse wave velocity (PWV), and augmentation index); and physical fitness (cardiorespiratory fitness and handgrip strength). Adjusted mixed linear models revealed a significant improvement in cardiorespiratory fitness (mL·kg·min): HIIT +8.3, RT +4.1, and CT +6.3 (all p < 0.001). The improvement difference between the groups was statistically significant between the HIIT and NG group (p = 0.014), (time × group interaction F(23.564); p < 0.001; η partial = 0.365). In addition, the RT and CT groups have a significant positive impact on PWV (m·s) (d = 0.391 and 0.229 respectively; p < 0.001, (time × group interaction F(5.457); p = 0.003; η partial = 0.280). Hereafter, the RT group has a significant positive impact on the FMD (%) in comparison to HIIT, CT, or NG group (time × group interaction F(2.942); p = 0.044; η partial = 0.174). The main findings of this study are that 12 weeks of HIIT leads to significant improvements in cardiorespiratory fitness, whereas RT resulted in improvements in the vascular profile, supporting the positive effect of both training programs for cardiometabolic risk factors in sedentary and overweight adults.

The objectives of this secondary analysis are (1) to investigate the differential effects of exercise training modalities-high-intensity interval training (HIIT), resistance training (RT), combined training (CT = HIIT + RT), and/or nutritional guidance (NG) alone-on local fat/lean mass indexes in adults with excess of adiposity; (2) to identify the individual patterns of response based on either a clinical criterion of weight loss (≥5%) and/or technical error (TE) of measurement of local fat/lean mass indexes; and (3) to assess the individual change for body composition parameters assigned either to HIIT, RT, CT, and/or NG groups utilizing a TE. A 12-week trial was conducted in 55 participants randomized to one of the four interventions. The primary outcome was clinical change in body weight (i.e., weight loss of ≥5%). Secondary outcomes included change in ratio of android and gynoid fat mass, as well as local fat and lean mass indexes (arms, trunk, and legs), before and after intervention. The main findings from the current analysis revealed that (i) after 12 weeks of follow-up, significant decreases in several body composition indexes were found including body weight, arm, trunk, and legs fat mass, and android and gynecoid fat mass were observed in HIIT, RT, and CT groups ( p < 0.05); (ii) a significant proportion of individuals showed a positive response following 12 weeks of training, led by the HIIT group with 44% and followed by RT with 39% in 9 indexes; (iii) the HIIT group showed lowest rates of adverse responders with (6%); and (iv) the individual patterns of response utilizing clinically meaningful weight loss were not necessarily associated with the corresponding individual training-induced changes in body composition indexes in adults with excess of adiposity. Overall, the study suggests that HIIT has an important ability to reduce the prevalence of non-response to improve body composition indexes.

♦ BACKGROUND: Peritonitis is the most important complication of peritoneal dialysis (PD), and early peritonitis rate is predictive of the subsequent course on PD. Our aim was to calculate the early peritonitis rate and to identify characteristics and predisposing factors in a large nationwide PD provider network in Colombia. ♦ METHODS: This was a historical observational cohort study of all adult patients starting PD between January 1, 2012, and December 31, 2013, in 49 renal facilities in the Renal Therapy Services in Colombia. We studied the peritonitis rate in the first 90 days of treatment, its causative micro-organisms, its predictors and its variation with time on PD and between individual facilities. ♦ RESULTS: A total of 3,525 patients initiated PD, with 176 episodes of peritonitis during 752 patient-years of follow-up for a rate of 0.23 episodes per patient year equivalent to 1 every 52 months. In 41 of 49 units, the rate was better than 1 per 33 months, and in 45, it was better than 1 per 24 months. Peritonitis rates did not differ with age, ethnicity, socioeconomic status, or PD modality. We identified high incidence risk periods at 2 to 5 weeks after initiation of PD and again at 10 to 12 weeks. ♦ CONCLUSION: An excellent peritonitis rate was achieved across a large nationwide network. This occurred in the context of high nationwide PD utilization and despite high rates of socioeconomic deprivation. We propose that a key factor in achieving this was a standardized approach to management of patients., (Copyright © 2017 International Society for Peritoneal Dialysis.)

Background and Objective: Colombia is a country of diverse geographic regions, some with mountainous terrain that can make access to urban areas difficult for individuals who live in remote areas. In 2005, a program was initiated to establish remote peritoneal dialysis (PD) centers in Colombia to improve access to PD for patients with end-stage renal disease who face geographic or financial access barriers., Patients and Methods: The present study was a multi-center cohort observational study of prevalent home PD patients who were at least 18 years of age and were being managed by one of nine established remote PD centers in Colombia over a 2-year period. Data were collected from clinical records, databases, and patient interviews. Patient survival, incidence of peritonitis, and rate of withdrawal from PD therapy were assessed., Results: A total of 345 patients were eligible for the study. The majority (87.8%) of patients lived on one to two times a minimum monthly salary (equivalent to US$243 - US$486). On average, patients traveled 1.2 hours and 4.3 hours from their home to their remote PD center or an urban reference renal clinic, respectively. The incidence rate of peritonitis was 2.54 episodes per 100 patient-months of therapy. A bivariate analysis showed a significantly higher risk of peritonitis in patients who were living on less than one times a monthly minimum salary (p < 0.05) or who had a dirt, cement, or unfinished wood floor (p < 0.05). The 1-year and 2-year patient survival rates were 92.44% and 81.55%, respectively. The 1-year and 2-year technique survival rates were 97.27% and 89.78%, respectively., Conclusions: With the support of remote PD centers that mitigate geographic and financial barriers to healthcare, home PD therapy is a safe and appropriate treatment option for patients who live in remote areas in Colombia., (Copyright © 2015 International Society for Peritoneal Dialysis.)