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Background and Purpose: The aim was to investigate whether neurofilament light chain (NfL) and profilin‐1 (PFN‐1) might qualify as surrogate disease and treatment‐response biomarkers by correlating their concentrations dynamic with clinical status in a cohort of 30 adult spinal muscular atrophy type 3 patients during nusinersen therapy up to 34 months. Methods: Neurofilament light chain was measured in cerebrospinal fluid at each drug administration with a commercial enzyme‐linked immunosorbent assay (ELISA); PFN‐1 concentrations were tested in serum sampled at the same time points with commercial ELISA assays. Functional motor scores were evaluated at baseline, at the end of the loading phase and at each maintenance dose and correlated to biomarker levels. The concurrent effect of age and clinical phenotype was studied. Results: Neurofilament light chain levels were included in the reference ranges at baseline; a significant increase was measured during loading phase until 1 month. PFN‐1 was higher at baseline than in controls and then decreased during therapy until reaching control levels. Age had an effect on NfL but not on PFN‐1. NfL was partially correlated to functional scores at baseline and at last time point, whilst no correlation was found for PFN‐1. Conclusion: Cerebrospinal fluid NfL levels did not qualify as an optimal surrogate treatment biomarker in adult spinal muscular atrophy patients with a long disease duration, whilst PFN‐1 might to a greater extent represent lower motor neuron pathological processes. The observed biomarker level variation during the first 2 months of nusinersen treatment might suggest a limited effect on axonal remodeling or rearrangement. [ABSTRACT FROM AUTHOR]

The importance of physico-chemical processes at the particle scale for the engineering scale behaviour of fine-grained geomaterials is undisputed. Yet, despite great advances in the discipline, experimental evidence that fully resolves the clay micromechanics i.e. linking the evolving microstructure and interparticle actions under loading, is lacking. This paper will discuss the challenges ahead in quantifying the evolving kinematics and interparticle interactions of fine-grained geomaterials. As such, the current limitations, and the potential opportunities of experimental methodologies for manipulating, monitoring and (post-mortem) analysing fine-grained materials at the particle scale will be discussed. In addition to the need of integrating multiple experimental techniques that span several length scales and modalities, the critical role of advanced data reduction and analysis is highlighted, as required for a measurement as opposed to qualitative observation. Throughout the paper, the link between experimental clay micromechanics and modelling will be discussed.

Objective: Renal Tumor biopsy (RTB) can assist clinicians in determining the most suitable approach for treatment of renal cancer. However, RTB's limitations in accurately determining histology and grading have hindered its broader adoption and data on the concordance rate between RTB results and final pathology after surgery are unavailable. Therefore, we aimed to develop a machine learning algorithm to optimize RTB technique and to investigate the degree of concordance between RTB and surgical pathology reports., Materials and Methods: Within a prospectively maintained database, patients with indeterminate renal masses who underwent RTB at a single tertiary center were identified. We recorded and analyzed the approach (US vs. CT), the number of biopsy cores (NoC), and total core tissue length (LoC) to evaluate their impact on diagnostic outcomes. The K-Nearest Neighbors (KNN), a non-parametric supervised machine learning model, predicted the probability of obtaining pathological characterization and grading. In surgical patients, final pathology reports were compared with RTB results., Results: Overall, 197 patients underwent RTB. Overall, 89.8% (n=177) and 44.7% (n=88) of biopsies were informative in terms of histology and grading, respectively. The discrepancy rate between the pathology results from renal tissue biopsy (RTB) and the final pathology report following surgery was 3.6% (n=7) for histology and 5.0% (n=10) for grading. According to the machine learning model, a minimum of 2 cores providing at least 0.8 cm of total tissue should be obtained to achieve the best accuracy in characterizing the cancer. Alternatively, in cases of RTB with more than two cores, no specific minimum tissue threshold is required., Conclusions: The discordance rates between RTB pathology and final surgical pathology are notably minimal. We defined an optimal renal biopsy strategy based on at least 2 cores and at least 0.8 cm of tissue or at least 3 cores and no minimum tissue threshold., Patients Summary: RTB is a useful test for kidney cancer, but it's not always perfect. Our study shows that it usually matches up well with what doctors find during surgery. Using machine learning can make RTB even better by helping doctors know how many samples to take. This helps doctors treat kidney cancer more accurately., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: There is inconsistent data regarding the possible inaccuracies in dynamic penile color Doppler duplex ultrasound (CDDU) measurements in men with penile curvature because of Peyronie's disease (PD). We sought to explore the relationship between the degree of penile curvature and CDDU parameters in men with PD., Materials and Methods: Comprehensive data from 154 consecutive men presenting with PD as their primary complaint at a single academic center were prospectively collected and analyzed. All men underwent CDDU. Penile curvature was measured using a goniometer at time of maximum erection during CDDU. Patients were grouped based on CDDU parameters into-normal (average peak systolic velocity [PSV] ≥ 35 cm/s and resistance index [RI] ≥ 0.85) and pathological CDDU (average PSV < 35 cm/s and/or RI < 0.85). Descriptive statistics was used to compare the two subcohorts. Linear regression models were fitted to explore the association between the degree of penile curvature and dynamic CDDU parameters., Results: Overall, the median interquartile range (IQR) age was 56 (48-63) years. The median (IQR) PSV and degree of penile curvature were 48.8 cm/s (37.9-58.5) and 40 degrees (30-60), respectively. At CDDU, the degrees of penile curvature were as follows: 10-30 degrees in 63 (40.9%) men, 30-70 degrees in 70 (45.5%) men, and 70-90 degrees in 21 (13.6%) men, respectively. Of all, 116 (75.3%) patients showed a PSV > 35 cm/s and RI ≥ 0.85. Patients with pathologic vs. normal CDDU parameters did not differ in median (IQR) curvature (32.5° [30°-58.7°] vs. 40° [30°-65°], p = 0.5) or in the distribution across curvature range groups. Linear regression analysis revealed that the degree of penile curvature did not significantly correlate with PSV at CDDU (coefficient: 0.06, p = 0.3)., Conclusions: Our study confirms the lack of a significant correlation between the severity of penile curvature and CDDU parameters in men presenting with PD. These findings emerge to be relevant in terms of a more accurate management work-up for PD patients and hold insightful medicolegal implications and in the real-life setting., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background and Objective: Metabolic syndrome (MetS) is a clinical condition associated with higher rates of overall and cardiovascular mortality. There is scarce evidence regarding the impact of MetS on surgical and functional outcomes for patients undergoing partial nephrectomy (PN) for clinically localized small renal masses (SRMs)., Methods: We analyzed data from a prospectively maintained institutional database for 690 patients with cT1a renal cancer undergoing PN between 2000 and 2023 at a tertiary referral center. MetS was defined according to international guidelines. Cumulative incidence curves were used to estimate the 5-yr risk of stage IIIB-V chronic kidney disease (CKD) stage and other-cause mortality (OCM). Multivariable regression models were used to analyze the impact of MetS on the risk of complications, acute kidney injury (AKI), stage IIIB-V CKD, and OCM., Key Findings and Limitations: Overall, 10% of the PN cohort had MetS. The MetS group was older (median age 70 yr, interquartile range [IQR] 65-74 vs 61 yr, IQR 50-69; p  < 0.001) and had worse preoperative kidney function (median estimated glomerular filtration rate 65 [IQR 62-81] vs 88 [IQR 69-98] ml/min/1.73 m 2 ; p  < 0.001) than the group without MetS. The MetS group had higher incidence of complications (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.05-3.08; p  = 0.03) and postoperative AKI (OR 3.17, 95% CI 1.54-6.41; p  = 0.001). The 5-yr risk of stage IIIB-V CKD (45% vs 7.2%; hazard ratio [HR] 2.34, 95% CI 1.27-4.30; p  = 0.006) and OCM (14% vs 3.5%; HR 3.00, 95% CI 1.06-8.55; p  = 0.039) were also higher in the MetS group. The main limitations are the extended accrual time and unmeasured confounders that could potentially affect outcomes., Conclusions and Clinical Implications: Patients with MetS had worse postoperative, functional, and survival outcomes after SRM surgery in comparison to patients without MetS. Multidisciplinary care could help in reducing the preoperative metabolic burden in these patients. Further research should explore if alternative approaches (eg, surveillance or focal therapy) could minimize postoperative comorbidities and protect long-term renal function in this population., Patient Summary: Patients with a condition called metabolic syndrome who have part of their kidney removed for small kidney tumors are at higher risk of complications and long-term kidney issues. Patient care from a multidisciplinary team could help in reducing the metabolic burden before surgery. Further research is needed to explore if less invasive treatment options could reduce these risks., (© 2024 The Author(s).)

Effective live-imaging techniques are crucial to assess neuronal morphology in order to measure neurite outgrowth in real time. The proper measurement of neurite outgrowth has been a long-standing challenge over the years in the neuroscience research field. This parameter serves as a cornerstone in numerous in vitro experimental setups, ranging from dissociated cultures and organotypic cultures to cell lines. By quantifying the neurite length, it is possible to determine if a specific treatment worked or if axonal regeneration is enhanced in different experimental groups. In this study, the aim is to demonstrate the robustness and accuracy of the Incucyte Neurotrack neurite outgrowth analysis software. This semi-automatic software is available in a time-lapse microscopy system which offers several advantages over commonly used methodologies in the quantification of the neurite length in phase contrast images. The algorithm masks and quantifies several parameters in each image and returns neuronal cell metrics, including neurite length, branch points, cell-body clusters, and cell-body cluster areas. Firstly, we validated the robustness and accuracy of the software by correlating its values with those of the manual NeuronJ, a Fiji plug-in. Secondly, we used the algorithm which is able to work both on phase contrast images as well as on immunocytochemistry images. Using specific neuronal markers, we validated the feasibility of the fluorescence-based neurite outgrowth analysis on sensory neurons in vitro cultures. Additionally, this software can measure neurite length across various seeding conditions, ranging from individual cells to complex neuronal nets. In conclusion, the software provides an innovative and time-effective platform for neurite outgrowth assays, paving the way for faster and more reliable quantifications.

Purpose: In absence of predictive models, preoperative estimation of the probability of completing partial (PN) relative to radical nephrectomy (RN) is invariably inaccurate and subjective. We aimed to develop an evidence-based model to assess objectively the probability of PN completion based on patients' characteristics, tumor's complexity, urologist expertise and surgical approach., Design, Setting and Participants: 675 patients treated with PN or RN for cT 1-2 cN 0 cM 0 renal mass by seven surgeons at one single experienced centre from 2000 to 2019., Outcomes Measurements and Statistical Analyses: The outcome of the study was PN completion. We used a multivariable logistic regression (MVA) model to investigate predictors of PN completion. We used SPARE score to assess tumor complexity. We used a bootstrap validation to compute the model's predictive accuracy. We investigated the relationship between the outcomes and specific predictors of interest such as tumor's complexity, approach and experience., Results: Of 675 patients, 360 (53%) were treated with PN vs. 315 (47%) with RN. Smaller tumors [Odds ratio (OR): 0.52, 95%CI 0.44-0.61; P < 0.001], lower SPARE score (OR: 0.67, 95%CI 0.47-0.94; P = 0.02), more experienced surgeons (OR: 1.01, 95%CI 1.00-1.02; P < 0.01), robotic (OR: 10; P < 0.001) and open (OR: 36; P < 0.001) compared to laparoscopic approach resulted associated with higher probability of PN completion. Predictive accuracy of the model was 0.94 (95% CI 0.93-0.95)., Conclusions: The probability of PN completion can be preoperatively assessed, with optimal accuracy relaying on routinely available clinical information. The proposed model might be useful in preoperative decision-making, patient consensus, or during preoperative counselling., Patient Summary: In patients with a renal mass the probability of completing a partial nephrectomy varies considerably and without a predictive model is invariably inaccurate and subjective. In this study we build-up a risk calculator based on easily available preoperative variables that can predict with optimal accuracy the probability of not removing the entire kidney., Competing Interests: Declaration of competing interest A. Necchi reports honoraria from Roche, Merck Sharp & Dohme, AstraZeneca, Janssen Pharmaceuticals and Foundation Medicine; has served as a consultant or advisor for Merck Sharp & Dohme, Bristol-Myers Squibb, Rainier Therapeutics, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen Pharmaceuticals, Incyte, Seattle Genetics, Astellas Pharma and Rainier Therapeutics; has received research funding from Incyte, Merck Sharp & Dohme (institution), and AstraZeneca (institution); and has received travel funding from Roche, Merck Sharp & Dohme, Astra Zeneca, and Janssen Pharmaceuticals outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, and only 50% of patients with T2DM achieve or maintain adequate glycemic control with pharmacological therapies. Metabolic surgery demonstrated superior efficacy compared to medical therapy but is unfeasible for most patients with T2DM. Duodenal mucosal resurfacing (DMR) by hydrothermal mucosal ablation, recellularization via electroporation therapy (ReCET), and photodynamic therapy are novel endoscopic procedures that use thermal, electrical, and photochemical energy, respectively, to ablate and reset dysfunctional duodenal mucosa. We assessed the data on the effects of these techniques on glycemic control and nonalcoholic fatty liver disease (NAFLD)., Methods: We systematically searched independently and in duplicate English and non-English language publications through January 31st, 2024. Outcomes assessed were an improvement in different metabolic health parameters and the safety of duodenal mucosal ablation (DMA) procedures. Outcomes were presented descriptively., Findings: We selected 12 reports reporting results from 3 randomized and 6 uncontrolled trials (seven evaluating DMR, two evaluating ReCET, all with a low risk of bias) for a total of 317 patients enrolled. DMA reduced HbA1c, fasting plasma glucose, and liver fat. When combined with newer antidiabetic drugs, it allowed insulin discontinuation in up to 86% patients. No major safety signal emerged., Conclusions: All DMA techniques improve glucose homeostasis; DMR and ReCET appear to be safe in patients with T2DM. If confirmed by future randomized trials and by trials with histological endpoints in NAFLD, then DMA appears to be a promising alternative or complement option to medications for T2DM and NAFLD treatment., Funding: This study received no funding., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Duodenal mucosa ablation (DMA) is a novel approach to treat diabetes, consisting of endoscopic ablation of dysfunctional diabetic duodenal mucosa, which, following the healing response, is replaced by normally functioning mucosa. Two techniques, duodenal mucosal resurfacing (DMR) and recellularization via electroporation therapy (ReCET), recently showed promise in type 2 diabetes mellitus (T2DM) patients., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC)., Methods: cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM + . Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals., Results: 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55 months [32.8-107.2] vs. 20 months [9.0-45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1-4] vs. 1[1-1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20 mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70-0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97-1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01-1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06-1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07-1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07-1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04-1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01-1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM + . Furthermore, number (OR:1.08; 95% CI 1.04-1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09-1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM + . Survival analysis showed a median second PFS of 10.9 years (95% CI 3.3-not reached) for LC and a 3.8 years (95% CI 3.2-8.4) for RCCM + . The median OS time was 6.5 years (95% CI 4.4-not reached) for LC and 6 years (95% CI 4.3-11.6) for RCCM + ., Conclusions: Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: NASH confers an increased liver-related and kidney morbidity. Phospholipid curcumin (Meriva) is a phospholipid formulation with ameliorated systemic curcumin absorption and delivery. We assessed the safety and efficacy of Meriva in NASH., Approach and Results: In this double-blind trial, 52 patients with biopsy-proven NASH (71% with stage ≥F2 fibrosis, 58% with stage A2-G2/A2-G3a chronic kidney disease) were randomized 1:1 to receive Meriva 2 g/d or placebo for 72 weeks. The primary endpoint was NASH resolution with no worsening of fibrosis. The secondary endpoints included a ≥1 stage liver fibrosis improvement with no NASH worsening; regression of significant (ie, stage ≥F2) fibrosis and CKD; and improvement in renal, glucose, lipid, and inflammatory parameters. We also explored the treatment effect on hepatic activation of NF-kB, a key proinflammatory transcription factor and a major target of curcumin. Fifty-one patients (26 on Meriva and 25 on placebo) completed the trial. Sixteen (62%) patients on Meriva versus 3 (12%) patients on placebo had NASH resolution (RR = 5.33 [95% CI = 1.76-12.13]; p = 0.003). Thirteen (50%) patients on Meriva versus 2 (8%) patients on placebo had ≥1 stage fibrosis improvement (RR = 6.50 [1.63-21.20]; p = 0.008). Eleven (42%) patients on Meriva versus 0 (0%) on placebo had regression of significant liver fibrosis (RR = 18.01 [1.43-36.07]; p = 0.02). Hepatic NF-kB inhibition predicted NASH resolution (AUC = 0.90, 95% CI = 0.84-0.95) and fibrosis improvement (AUC = 0.89, 95% CI = 0.82-0.96). Thirteen (50%) patients on Meriva versus 0 (0%) on placebo had chronic kidney disease regression (RR = 10.71 [1.94-17.99)]; p = 0.004). Compared with placebo, Meriva improved eGFR (difference in adjusted eGFR change: +3.59 [2.96-4.11] mL/min/1.73 m 2 /y, p = 0.009), fasting glucose(-17 mg/dL; 95% CI = -22, -12), HbA1c (-0.62%; 95% CI = -0.87%, -0.37%), LDL-C (-39 mg/dL; 95% CI = -45, -33), triglycerides (-36 mg/dL, 95% CI = -46, -26), HDL-C (+10 mg/dL; 95% CI = +8, +11), and inflammatory markers. Adverse events were rare, mild, and evenly distributed., Conclusions: In patients with NASH, Meriva administration for 72 weeks was safe, well-tolerated, and improved liver histology, possibly through NF-kB inhibition, kidney disease, and metabolic profile., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort., Methods: Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM)., Results: Patients with TT showed lower BMI (24 vs. 26 kg/m 2 ) and preoperative Hb (11 vs. 14 g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5 cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03)., Conclusions: The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver., Design: Cohort study including patients with PaO 2 /FiO 2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO 2 /FiO 2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%-50% increase 4) increase >50%., Setting: 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina., Patients: 273 patients., Interventions: None., Main Variables of Interest: Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified., Results: Baseline PaO 2 /FiO 2 was 116 [97-135]mmHg (115 [94-136] in survivors vs. 117 [98-134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO 2 /FiO 2 values; 46(16%) increased PaO 2 /FiO 2 ≤25%; 55 (21%) increased it 25%-50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO 2 /FiO 2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO 2 /FiO 2 after 24h being in prone, and number of prone cycles., Conclusions: Older patients unable to improve PaO 2 /FiO 2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO 2 /FiO 2 increase over baseline, beyond the initial value, was independently associated with higher mortality., (Copyright © 2023 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Background: Epidemiological data on patients with COVID-19 referred to specialized weaning centers (SWCs) are sparse, particularly in low- and middle-income countries. Our aim was to describe clinical features, epidemiology, and outcomes of subjects admitted to SWCs in Argentina., Methods: We conducted a prospective, multi-center, observational study between July 2020-December 2021 in 12 SWCs. We collected demographic characteristics, laboratory results, pulmonary function, and dependence on mechanical ventilation at admission, decannulation, weaning from mechanical ventilation, and status at discharge. A multiple logistic model was built to predict home discharge., Results: We enrolled 568 tracheostomized adult subjects after the acute COVID-19 phase who were transferred to SWCs. Age was 62 [52-71], males 70%, Charlson comorbidity index was 2 [0-3], and length of stay in ICU was 42 [32-56] d. Of the 315 ventilator-dependent subjects, 72.4% were weaned, 427 (75.2%) were decannulated, and 366 subjects (64.5%) were discharged home. The mortality rate was 6.0%. In multivariate analysis, age (odds ratio 0.30 [95% CI 0.16-0.56], P < .001), Charlson comorbidity index (odds ratio 0.43 [95% CI 0.22-0.84], P < .01), mechanical ventilation duration in ICU (odds ratio 0.80 [95% CI 0.72-0.89], P < .001), renal failure (odds ratio 0.40 [95% CI 0.22-0.73], P = .003), and expiratory muscle weakness (odds ratio 0.35 [95% CI 0.19-0.62], P < .001) were independently associated with home discharge., Conclusions: Most subjects with COVID-19 transferred to SWCs were weaned, achieved decannulation, and were discharged to home. Age, high-comorbidity burden, prolonged mechanical ventilation in ICU, renal failure at admission, and expiratory muscle weakness were inversely associated with home discharge., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Serum biomarkers that might detect clinical progression are currently lacking for Spinal and bulbar muscular atrophy (SBMA), thus limiting the effectiveness of possible future pharmacological trials. Elevation of cardiac troponin T (cTnT) unrelated to myocardial damage in a motor neuron (MN) disease as amyotrophic lateral sclerosis (ALS) was associated to disease severity. We enrolled 47 SBMA patients and 5 Spinal muscular atrophy (SMA) type 3 adult patients as control group; each SBMA patient was evaluated at baseline and at one-year follow-up visit. Demographic and clinical data including functional scores (SBMAFRS) were collected; serum was collected as standard of care and tested for cardiac troponins. Levels of cTnT but not cTnI were increased in SBMA with respect to reference values; unlike other neuromuscular diseases, SMA patients had overall normal cTnT values. Median cTnT concentrations did not change after one year and values were correlated to motor function, particularly with lower limb subdomain, at baseline only. Variations of cTnT and of SBMAFRS were unrelated. The cautiously promising results of cTnT as potential biomarker should undergo a more extensive clinical validation, including studies with longer follow-up period. When evaluating SBMA patients for a potential cardiac damage cTnI testing should be coupled or preferred to cTnT., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Multiple system atrophy (MSA) is considered a primarily sporadic neurodegenerative disease, but the role of genetic is poorly understood., Case: We present a female patient of Moroccan origin who developed a rapidly progressive non-levodopa responsive parkinsonism, gait and balance problems, and dysautonomia including severe bulbar symptoms. She was diagnosed with MSA Parkinsonian-type (MSA-P) and suddenly died at night at 58 years of age. Reduced striatal DAT-SPECT, putaminal hyperintensity on T2-MRI, and hypometabolism with FDG-PET were present. Genetic testing documented a G2019S mutation in the LRRK2 gene. A skin biopsy was obtained and used to perform alpha-synuclein RT-QuIC, which was negative, and immunohistochemical analysis, which demonstrated abnormal alpha-synuclein deposits in cutaneous nerves. Elevated blood neurofilament light chain levels were also documented., Conclusions: LRRK2 mutations are the most common cause of monogenic Parkinson's disease (PD) and G2019S is the most frequent variant. Our patient presented with biological, clinical, and radiological features of MSA, but genetic testing revealed a G2019S LRRK2 mutation, which has been previously reported only in one other case of pathologically proven MSA but with mild progression. In our patient, post-mortem confirmation could not be performed, but RT-QuIC and immunohistochemical findings on skin biopsy support the diagnosis of MSA. G2019S LRRK2 may be linked to an increased risk of MSA. Cases of atypical parkinsonism with rapid disease course should be screened for PD-related genes especially in populations with a high prevalence of mutations in known genes., (© 2023. Fondazione Società Italiana di Neurologia.)