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Background: Recent research suggested that hospital infections are a predictive marker for physical non-recovery one year after cardiothoracic surgery. The purpose of this study was to explore whether this risk factor is etiologic. Additional, the influence of a potential effect modifying factor, diabetes mellitus, was investigated. Methods: In this multicenter study, patients underwent elective or urgent cardiothoracic surgery between 01-01-2015 and 31-12-2019, and completed pre- and one year post-operative Short Form Health Survey 36/12 quality of life questionnaires. A binary logistic regression model, in which the inverse of the propensity score for infection risk was included as a weight variable, was used. Second, this analysis was stratified for diabetes mellitus status. Results: 8577 patients were included. After weighing for the propensity score, the standardized mean differences of all variables decreased and indicated sufficient balance between the infection and non-infection groups. Hospital infections were found to be a risk factor for non-recovery after cardiothoracic surgery in the original and imputed dataset before weighting. However, after propensity score weighing, hospital infections did not remain significantly associated with recovery (OR for recovery = 0.79; 95% CI [0.60–1.03]; p = 0.077). No significant interaction between diabetes mellitus and hospital infections on recovery was found (p = 0.845). Conclusions: This study could not convincingly establish hospital infections as an etiologic risk factor for non-improvement of physical recovery in patients who underwent cardiothoracic surgery. In addition, there was no differential effect of hospital infections on non-improvement of physical recovery for patients with and without diabetes mellitus. Trial registration International Clinical Trials Registry Platform ID NL9818; date of registration, 22-10-2021 (https://trialsearch.who.int/). [ABSTRACT FROM AUTHOR]

Background: Long-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD., Methods: This retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported., Results: Patients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients' total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment., Conclusions: The significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations., (© 2024. The Author(s).)

Chronic pain impacts more than one in five adults in the United States (US) and the costs associated with the condition amount to hundreds of billions of dollars annually. Despite the tremendous impact of chronic pain in the US and worldwide, the standard of care for diagnosis depends on subjective self-reporting of pain state, with no effective objective assessment procedure available. This study investigated the application of signal processing and machine learning to electroencephalography (EEG) data for the development of classification algorithms capable of differentiating subjects in pain from pain free subjects. In this study, nineteen (19) channels of EEG data were obtained from subjects in an eyes closed resting state, and ultimately data from 186 participants were used for algorithm development, including 35 healthy controls and 151 chronic pain patients. Signal processing was applied to identify noise free segments of EEG data and 6375 quantitative EEG (qEEG) measures were calculated for each subject. Various machine learning methodologies were applied to the data, with Elastic Net chosen as the optimal methodology. The final classifier developed using Elastic Net contained 34 qEEG features with non-zero weights. The classifier was able to differentiate pain versus no pain subjects with an accuracy of 79.6%, sensitivity of 82.2%, and specificity of 66.7%. The features used in the classifier were evaluated and found to align well with contemporary literature regarding changes in neurological characteristics associated with chronic pain.

Introduction: Osteoarthritis (OA) and calcium pyrophosphate deposition (CPPD) often co-exist, this resulting in a clinical condition characterized by amplified inflammation and more severe and faster cartilage degeneration compared to OA alone. Our study aims to explore the efficacy of a therapeutic approach that addresses both conditions, using a combination of a high molecular weight hyaluronic acid (HMWHA) and collagen tripeptide (CTP). Additionally, safety profile and baseline characteristic predictive value were evaluated., Methods: We conducted a retrospective study on patients diagnosed with symptomatic knee OA (KOA) and CPPD treated by ultrasound (US) guided intraarticular injections of HMWHA-CT in the outpatient clinics of the Interdisciplinary Pain Medicine Unit at Santa Maria Maddalena Hospital, Occhiobello, Italy and in the Rheumatology Unit of the Emergency County Hospital Craiova, Romania (ECH Craiova). All the patients underwent clinical and US evaluation at baseline, 1, 3, and 6 months. From clinical point of view, Numeric Rating Scale (NRS) pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were recorded. US data included detection of synovitis, cartilage damage, osteophytes, and CPPD deposits. Clinical efficacy was defined with NRS and WOMAC variations in respect to baseline and using the minimal clinically important difference values: an improvement of 2 point for NRS pain and 10 for the total score for WOMAC., Results: Twenty-nine patients (34 knees) were injected and evaluated. Overall pain levels, as measured by NRS, demonstrated a consistent decrease in patients across all follow-up intervals, with the most substantial improvement at the 6-month compared to baseline measurements. A significative proportion of patients achieved the minimum clinically detectable improvement, specifically 79% for NRS and 83% for WOMAC (19 and 20 patients, respectively)., Conclusion: Our data showed a significant efficacy of ultrasound guided HMWHA-CT, in patients with KOA and CPPD, thus making it reasonable to consider that the combination of HMWHA and CTP can provide a strong anti-inflammatory effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Porta, Filippucci, Cipolletta, La Grua, Barni, Sirotti and Vreju.)

Background: Uncertainty and inconsistency in terminology regarding the risk factors (RFs) for in-hospital falls are present in the literature., Objective: (1) To perform a literature review to identify the fall RFs among hospitalized adults; (2) to link the found RFs to the corresponding categories of international health classifications to reduce the heterogeneity of their definitions; (3) to perform a meta-analysis on the risk categories to identify the significant RFs; (4) to refine the final list of significant categories to avoid redundancies., Methods: Four databases were investigated. We included observational studies assessing patients who had experienced in-hospital falls. Two independent reviewers performed the inclusion and extrapolation process and evaluated the methodological quality of the included studies. RFs were grouped into categories according to three health classifications (ICF, ICD-10, and ATC). Meta-analyses were performed to obtain an overall pooled odds ratio for each RF. Finally, protective RFs or redundant RFs across different classifications were excluded., Results: Thirty-six articles were included in the meta-analysis. One thousand one hundred and eleven RFs were identified; 616 were linked to ICF classification, 450 to ICD-10, and 260 to ATC. The meta-analyses and subsequent refinement of the categories yielded 53 significant RFs. Overall, the initial number of RFs was reduced by about 21 times., Conclusion: We identified 53 significant RF categories for in-hospital falls. These results provide proof of concept of the feasibility and validity of the proposed methodology. The list of significant RFs can be used as a template to build more accurate measurement instruments to predict in-hospital falls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 La Porta, Valpiani, Lullini, Negro, Pellicciari, Bassi, Caselli, Pecoraro and Govoni.)

Objective: The objective of this study was to perform a meta-analysis of the minimal clinically important difference (MCID) of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and its shortened version (ie, the QuickDASH)., Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, Cochrane Library, and Scopus were searched up to July 2022. Studies on people with upper limb musculoskeletal disorders that calculated the MCID by anchor-based methods were included. Descriptive and quantitative synthesis was used for the MCID and the minimal detectable change with 90% confidence (MDC90). Fixed-effects models and random-effect models were used for the meta-analysis. I2 statistics was computed to assess heterogeneity. The methodological quality of studies was assessed with the Consensus-Based Standards for the Selection of Health Measurement Instruments checklist for measurement error and an adaptation of the checklist for the studies on MCID proposed by Bohannon and Glenney., Results: Twelve studies (1677 patients) were included, producing 17 MCID estimates ranging from 8.3 to 18.0 DASH points and 8.0 to 18.1 QuickDASH points. The pooled MCIDs were 11.00 DASH points (95% CI = 8.59-13.41; I2 = 0%) and 11.97 QuickDASH points (95% CI = 9.60-14.33; I2 = 0%). The pooled MDC90s were 9.04 DASH points (95% CI = 6.46-11.62; I2 = 0%) and 9.03 QuickDASH points (95% CI = 6.36-11.71; I2 = 18%). Great methodological heterogeneity in the calculation of the MCID was identified among the primary studies., Conclusion: Reasonable MCID ranges of 12 to 14 DASH points and 12 to 15 QuickDASH points were established. The lower boundaries represent the first available measure above the pooled MDC90, and the upper limits represent the upper 95% CI of the pooled MCID., Impact: Reasonable ranges for the MCID of 12 to 14 DASH points and 12 to 15 QuickDASH points were proposed. The lower boundaries represent the first available measure above the pooled MDC90, and the upper limits represent the upper 95% CI of the pooled MCID. Information regarding the interpretability of the 2 questionnaires was derived from very different methodologies, making it difficult to identify reliable thresholds. Now clinicians and researchers can rely on more credible data. The proposed MCIDs should be used to assess people with musculoskeletal disorders. Heterogeneity was found related particularly to the anchor levels used in the primary studies. To promote comparability of MCID values, shared rules defining the most appropriate types of anchoring will be needed in the near future., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite aggressive multimodal treatment, the outcomes of pediatric patients with high-risk (HR) neuroblastoma (NB) remain poor. The rationale for allogeneic hematopoietic stem cell transplantation (allo-HCT) to treat NB was based on the possible graft-versus-tumor effect; however, toxicity limits its efficacy. We sought to prospectively assess the feasibility and efficacy of allo-HCT using a reduced-intensity conditioning regimen in pediatric patients with HR NB in a multicenter phase II trial. Primary endpoints were the rate of neutrophil and platelet engraftment, 5-year transplantation-related mortality (TRM), and disease-free survival (DFS). Secondary endpoint measures included the incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD. Fifty-one patients were enrolled in the study. The 5-year cumulative incidence (CuI) of TRM was 29.4 ± 6.4%, and that of DFS was 11.8 ± 4.5%. Patients undergoing allo-HCT within 1 year of diagnosis or with bone marrow as their stem cell source had a higher DFS probability. The CuI of neutrophil engraftment, platelet engraftment, and grade II-IV aGVHD was 97.9 ± 2.1%, 93.8 ± 3.5%, and 47.1 ± 7.0%, respectively. The development of new therapeutic strategies could further improve disease control., (Copyright © 2024. Published by Elsevier Inc.)

Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism., (© 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Introduction: AADCd is an ultrarare, underdiagnosed neurometabolic disorder for which a screening test (3-OMD dosing on dried blood spot (DBS)) and targeted gene therapy (authorized in the EU and the UK) are available. Therefore, it is mandatory to raise awareness of presenting symptoms and signs among practitioners. Delivering scientifically sound information to promote screening of patients with the correct cluster of symptoms and signs would be critical., Materials and Methods: In light of the lack of sound evidence on this issue, expert opinion level of evidence was elicited with the Delphi method. Fourteen steering committee members invited a panel of 29 Italian experts to express their opinions on a series of crucial but controversial topics related to using 3-OMD DBS as a screening method in AADCd. Clusters of symptoms and signs were divided into typical or atypical, depending on age groups. Inclusion in newborn screening programs and the usefulness of a clinical score were investigated. A five-point Likert scale was used to rate the level of priority attributed to each statement., Results: The following statements reached the highest priority: testing pediatric patients with hypotonia, developmental delay, movement disorders, and oculogyric crises; inclusion of 3-OMD dosing on DBS in neonatal screening programs; development of a clinical score to support patients' selection for 3-OMD screening; among atypical phenotypes based on clinical characteristics of Italian patients: testing patients with intellectual disability and parkinsonism-dystonia. Discussion . Clusters of symptoms and signs can be used to prioritize testing with 3-OMD DBS. A clinical score was rated as highly relevant for the patient's selection. The inclusion of 3-OMD dosing in newborn screening programs was advocated with high clinical priority., Competing Interests: The authors report no conflicts of interest relevant to the publication of this research., (Copyright © 2024 Carlotta Spagnoli et al.)

Objectives: Over the last years ultrasound has shown to be an important tool for evaluating lung involvement, including interstitial lung disease (ILD) a potentially severe systemic involvement in many rheumatic and musculoskeletal diseases (RMD). Despite the potential sensitivity of the technique the actual use is hampered by the lack of consensual definitions of elementary lesions to be assessed and of the scanning protocol to apply. Within the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group we aimed at developing consensus-based definitions for ultrasound detected ILD findings in RMDs and assessing their reliability in dynamic images., Methods: Based on the results from a systematic literature review, several findings were identified for defining the presence of ILD by ultrasound (i.e., Am-lines, B-lines, pleural cysts and pleural line irregularity). Therefore, a Delphi survey was conducted among 23 experts in sonography to agree on which findings should be included and on their definitions. Subsequently, a web-reliability exercise was performed to test the reliability of the agreed definitions on video-clips, by using kappa statistics., Results: After three rounds of Delphi an agreement >75 % was obtained to include and define B-lines and pleural line irregularity as elementary lesions to assess. The reliability in the web-based exercise, consisting of 80 video-clips (30 for pleural line irregularity, 50 for B-lines), showed moderate inter-reader reliability for both B-lines (kappa = 0.51) and pleural line irregularity (kappa = 0.58), while intra-reader reliability was good for both B-lines (kappa = 0.72) and pleural line irregularity (kappa = 0.75)., Conclusion: Consensus-based ultrasound definitions for B-lines and pleural line irregularity were obtained, with moderate to good reliability to detect these lesions using video-clips. The next step will be testing the reliability in patients with ILD linked to RMDs and to propose a consensual and standardized protocol to scan such patients., 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. Published by Elsevier Inc.)

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34 + cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34 + cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34 + cells infused and younger age at GT affected positively the plateau of CD3 + transduced cells, lymphocytes and CD4 + CD45RA + naive T cells, whereas the cell dose positively influenced the final plateau of CD15 + transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT03478670 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Aim: This study aimed to determine safety and risk factors for adverse events (AEs) of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with long-term indwell of lumen-apposing metal stents (LAMS)., Methods: This study is a multicenter prospective observational study on consecutive high surgical-risk patients requiring gallbladder drainage who underwent EUS-GBD with LAMS over 12 months. Centralized telephone follow-up interviews were conducted every 3 months for 1 year. Patients were censored at LAMS removal, cholecystectomy, or death. AE-free survival was determined using log-rank tests. Cumulative risks were estimated using life-table analysis., Results: Eighty-two patients were included (53.7% male, median [interquartile range] age of 84.6 [76.5-89.8] years, and 85.4% with acute cholecystitis). Technical success was achieved in 79 (96.3%), and clinical success in 73 (89%). No patient was lost to follow-up; 45 patients (54.9%) completed 1-year follow-up with in situ LAMS. Median (interquartile range) LAMS indwell time was 364 (47-367) days. Overall, 12 (14.6%) patients presented 14 AEs, including 5 (6.1%) recurrent biliary events (3 acute cholangitis, 1 mild acute pancreatitis, and 1 acute cholecystitis). Patients with pancreatobiliary malignancy had an increased risk of recurrent biliary events (33% vs 1.5%, P = 0.001). The overall 1-year cumulative risk of recurrent biliary events was 9.7% (4.1-21.8%). The 1-year risk of AEs and of severe AEs was 18.8% (11-31.2%) and 7.9% (3.3-18.2%), respectively. Pancreatobiliary malignancy was the single risk factor for recurrent biliary events; LAMS misdeployment was the strongest risk factor for AEs., Conclusions: Long-term LAMS indwell does not increase the risk of delayed AEs following EUS-GBD., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: To assess the internal construct validity, including local independence, unidimensionality, monotonicity, and invariance, reliability, and targeting of the Forgotten Joint Score within the Rasch Measurement Theory framework., Design: Cross-sectional study., Patients: A total of 111 patients with total hip arthroplasty at least 3 months after surgery., Methods: The Forgotten Joint Score was submitted to each subject during their rehabilitative treatment in an Italian centre and then to Rasch analysis., Results: The base Rasch analysis showed a satisfactory fit to the model with strict unidimensionality and no differential item functioning. However, monotonicity (11 out of 12 items showed disordered thresholds) and local independence were  violated. After rescoring 10 items and creating 5 subtests to account for local dependence, the scale satisfied all the other Rasch model requirements (i.e. invariance, local independence, monotonicity, unidimensionality, and multi-group invariance), with reliability indexes (> 0.850) for measurement at the individual level and proper targeting. A raw-score-to-measure conversion table was provided., Conclusion: After structural (i.e. collapsing items categories) and non-structural (i.e. creating subtests) strategies, the Forgotten Joint Score satisfied the measurement requirements of the Rasch model, and it can be used in patients with total hip arthroplasty in clinical and research settings.