bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital Network Centralization of Primary Total Joint Arthroplasty Is Associated With Reduced Early Complication Rates But Not Reduced Readmission or Reoperation Rates: A Retrospective Database Study
Authors: Ricciardi Benjamin F. , Ramirez Gabriel , Schloemann Derek T. , Myers Thomas G. , Thirukumaran Caroline P. 
Published: October 2024

Background: Hospital networks centralize primary total joint arthroplasty (TJA) within their existing systems to develop specialized service lines with higher surgical volumes to reduce adverse events. It is not known what role hospital network centralization has had on primary TJA outcomes. Purpose: We sought to determine whether the degree of hospital network centralization for primary TJA is associated with (1) 90-day postoperative complication rates, (2) 90-day hospital readmission rates, or (3) 1-year revision rates. Methods: We conducted a retrospective database study of Medicare Part A beneficiaries who underwent inpatient primary TJA for osteoarthritis in 2016 and 2017 ( n = 523,142 patients); individual hospital-level characteristics and hospital networks were also identified ( n = 360 unique networks, n = 3339 hospitals). Patients having surgery at a hospital that was not a member of a health care network were excluded ( n = 163,998 patients) because we wanted to examine only the role of network structures on outcomes; this resulted in a cohort of 359,144 patients. Hospital network centralization, which was defined as the percentage of total network cases performed at the highest volume hospital and categorized into quartiles (eg, lowest 25% of networks by concentration, 26%–50% of networks by concentration, etc). Primary outcomes included postoperative 90-day complications, 90-day readmissions, and 1-year revisions. Multivariable logistic and linear regressions evaluated associations of hospital network centralization with outcomes and controlled for relevant patient-level and hospital-level covariates, including hospital network volumes. Results: Odds of 90-day complications were lower in the most centralized hospital networks than in least centralized networks (odds ratio [OR] = 0.85; 95% confidence interval [CI]: 0.75, 0.95). Degree of centralization was not associated with readmissions or 1-year revision rates. Non-modifiable patient and individual hospital characteristics appeared to have a greater association with complications, readmissions, and early revision rates than hospital network centralization or volume. Conclusion: This retrospective database study found that increased centralization of primary TJA within a hospital network was associated with lower 90-day complication rates but not with 90-day readmission or 1-year revision rates. This suggests that structural changes within hospital networks may be beneficial to reduce early complications in this patient population. In addition, our findings suggest that risk adjustment in assessing non-modifiable patient and hospital risk factors may be important when assessing TJA outcomes.
Does endoscopic carpal tunnel release during distal radial fracture fixation improve outcomes? A randomized controlled trial
Authors: Monteerarat Yuwarat , Sirasittikarn Sawitt , Pimpan Niya , Wejjakul Witchuree , Limthongthang Roongsak , Laohaprasitiporn Panai 
Published: October 2024

This study investigated the functional outcome of prophylactic carpal tunnel release during distal radial fracture fixation. A total of 60 patients undergoing anterior locking plate fixation for a distal radial fracture were randomized into two groups: one having prophylactic endoscopic carpal tunnel release and the other serving as a control. Functional outcomes were assessed using the Patient-Reported Wrist Evaluation, Quick Disabilities of the Arm, Shoulder, and Hand, EuroQol 5-Dimension 5-Level questionnaire, Boston Carpal Tunnel Questionnaire, Pain Numerical Rating Scale, grip strength and finger-to-palm distance over a 12-month period. The study found no significant differences in overall functional outcomes or complications between the groups. Level of evidence: I
Baseline patient demographics for TETRIS: a prospective, noninterventional study to characterize the use of triple therapy for COPD in Germany
Authors: Vogelmeier Claus F. , Beeh Kai-Michael , Kardos Peter , Paulsson Thomas , Rohde Gernot , Watz Henrik , Compton Chris , Mohan Tharishini , Claussen Jing 
Published: October 2024

Background: Evidence on how decisions regarding escalation to triple therapy and de- or re-escalation are taken and the rationale on which these decisions are based is currently limited in Germany. Objectives: The TETRIS study aims to elucidate influences on treatment decisions surrounding triple therapy in a real-world practice setting in Germany. Design: TETRIS is an ongoing, multicenter, prospective, observational cohort study recruiting patients with chronic obstructive pulmonary disease (COPD) with or without asthma who have already been treated with triple therapy for 2–48 weeks. Methods: For better representation of the treatment reality in Germany, patients are recruited from general practitioners and pulmonologists. Data are collected in two parts. Part 1 involves cross-sectional phenotyping of patients at enrollment. Part 2 involves a 2-year longitudinal follow-up period to monitor/document all visits by the patients during the 24-month observation period per routine clinical practice. Here, we report the demographic and baseline characteristics of 1213 eligible patients recruited to part 1 of the study. Results: The mean patient age was 66.4 years overall, and 29.3% (356/1213) of patients had no comorbidities. The mean CAT score was 19.4; the number of exacerbations and hospitalizations due to exacerbations in the past 3 years before starting triple therapy was 0.6 and 0.1, respectively. Dual bronchodilation with a long-acting muscarinic antagonist (LAMA) plus a long-acting β-2 agonist (LABA) was the most common therapy for COPD before initiation of triple therapy in 58.3% of patients. Conclusion: In this real-world setting in Germany, patients with COPD have a relatively low reported exacerbation rate but high symptom burden, and over 70% are multimorbid. Triple therapy is initiated in patients who are primarily highly symptomatic despite being on LAMA + LABA. Future prospective studies in patients with multimorbidity are warranted to better understand the treatment landscape across the disease spectrum. Trial registration: https://clinicaltrials.gov/study/NCT04657211
Cost-Effectiveness Analysis of Molecular Testing for Indeterminate Thyroid Nodules in Nova Scotia
Authors: MacKay Colin , Turner Brooke , Clarke Scott , Wallace Timothy , Rigby Matthew H. 
Published: October 2024

Background The objective of the following retrospective review was to perform a cost-effectiveness analysis of the use of molecular testing of indeterminate thyroid nodules compared to current management practices in Nova Scotia, Canada. Methods All cases of cytologically indeterminate thyroid nodules from January 1st, 2014 to December 31st, 2018 were reviewed. All interventions related to an indeterminate thyroid nodule were recorded. Patients were excluded if less than 18 years old if no further information regarding medical management was electronically available beyond the diagnosis of an indeterminate thyroid nodule, history of radiation, or previous thyroid surgery prior to diagnosis of an indeterminate thyroid nodule in the remaining lobe. Microcosting was performed to determine the cost of all relevant interventions including repeat fine needle aspiration biopsy, ultrasound, thyroid surgery(s), and molecular testing. Institution-specific transition state probabilities were calculated and used to build a cost-effectiveness analysis model. Model output was an incremental cost-effectiveness ratio, defined as the ratio of cost difference to effectiveness difference between routine molecular testing and the current management strategy, yielding cost per surgery avoided. Results The mean effectiveness of the current management of indeterminate thyroid nodules in Nova Scotia based on the American Thyroid Association guidelines is 64% at a mean cost of $6431, while the simulated mean effectiveness of routine molecular testing is 89% at a mean cost of $8414. Differences in management strategies generated an incremental cost-effectiveness ratio of $7876 per surgery avoided. Conclusion Routine molecular testing is the more effective strategy for the appropriate management of indeterminate thyroid nodules; however, it comes at a higher mean cost compared to the current management strategy. As the cost of molecular testing continues to decrease, and the cost of OR resources continues to rise, molecular testing is likely to become the optimal strategy in Nova Scotia.
Observational study of the Amaze™ asthma disease management platform
Authors: Alladina Jehan , Moschovis Peter P , Gandhi Hitesh N , Carstens Donna , Bacci Elizabeth D , Cutts Katelyn , Coyne Karin S , Goldsborough Karen , Jiang Dawei , O’Brien Conor , Bernard Kinane T 
Published: October 2024

Objective Asthma is often inadequately controlled, which can result in exacerbations that lead to unplanned healthcare visits. Mobile application (app) use could help manage asthma exacerbations. We implemented the Amaze™ asthma disease management platform in clinical practice and assessed user satisfaction, usage, and usability. Methods Adults with asthma and healthcare professionals (HCPs) were enrolled from a community allergy practice ( ClinicalTrials.gov Identifier: NCT04901260) and a large academic hospital ( ClinicalTrials.gov Identifier: NCT04868500). Primary and exploratory outcomes included assessment of platform design, patient app usage, patient-reported daily asthma status, emergency room/urgent care visits, and ease of implementation by HCPs. The system usability scale and a post-clinic visit survey were also administered. HCPs/staff monitored the Amaze dashboard to assess patient needs and completed a post-study survey. Results Overall, 159 patients and five HCPs participated in the study. Patients’ mean (SD) age was 38.7 (16.4) years; most were female (78%) and White (78%). Mean patient app usage began at 3.6 days/week but declined to 1.0 day/week by the end of the study. Throughout the study, most daily entries (>69%) reported patient asthma status as “good.” Most patients were satisfied/very satisfied with the app (66%) and reported it helped them during discussions with their HCP (44%). Most patients rated the usability of Amaze as “excellent” (49%) or “good” (30%). Most HCPs (71%) reported that Amaze was “very easy” to implement. Conclusions Most patients and HCPs were satisfied with Amaze. The Amaze platform may help patients and HCPs monitor asthma status, which could improve asthma control.
The Effects of Heat Therapy During Immobilization and Rehabilitation on Muscle Atrophy and Strength Loss at Return to Sports in Healthy Humans
Authors: Labidi Mariem , Alhammoud Marine , Mtibaa Khouloud , Ihsan Mohammed , Elhusseiny Rabi , Deldicque Louise , Nader Nelda , Nasir Nada , Papakostas Emmanouil , Olory Bruno , Cruz Flavio , Farooq Mohammed , Sanchez Anthony M.J. , d’Hooghe Pieter , Tourny Claire , Racinais Sebastien 
Published: October 2024

Background: Animal research suggests that repeated heat exposures may stimulate skeletal muscle protein synthesis and downregulate protein degradation. Hypothesis: Repeated heat exposures during ankle immobilization and rehabilitation would preserve human muscle strength and mass. Study Design: Controlled laboratory study. Methods: A total of 20 male participants (age, 33.6 ± 2.8 years; weight, 83.8 ± 9.2 kg; height, 182 ± 6 cm) underwent 4 weeks of supervised training, 2 weeks of single-lower leg immobilization, and 2 weeks of supervised rehabilitation before return to sports (RTS). Participants were split into 2 groups: (1) whole-body heat therapy (HEAT) and (2) sham treatment (SHAM) throughout the immobilization and rehabilitation periods. Measures of muscle strength (isometric and isokinetic), volume (magnetic resonance imaging and ultrasound), and muscle biopsies were obtained preimmobilization, postimmobilization, and at RTS. Results: Maximal isometric strength of the plantarflexors was lower at RTS compared with preimmobilization in SHAM ( P = .027) but not HEAT ( P = .301). Isokinetic strength during a fatigue test was higher at RTS compared with preimmobilization in HEAT ( P = .039) but not SHAM ( P = .245). Pennation angle and muscle thickness were lower at postimmobilization compared with preimmobilization only in SHAM ( P≤ .027). Muscle cross-sectional area decreased in soleus and both gastrocnemius medialis and lateralis (all P≤ .035) in SHAM, but only in gastrocnemius medialis in HEAT. There was a large ( d = 0.91) but not significant ( P = .054) decrease in the ratio of phosphorylated/total nuclear factor-kappa B (NFκB) from preimmobilization to postimmobilization in HEAT only. There was an increase in phosphorylated fork head box O proteins (FoxO) only in HEAT ( P = .034), suggesting a decrease in FoxO activity. Caspase 3 expression increased from preimmobilization to postimmobilization in SHAM only ( P = .004). Conclusion: These results indicate that using heat therapy throughout immobilization and rehabilitation reduces skeletal muscle atrophy and maintains plantarflexor strength in healthy humans. Moreover, heat therapy may lead to the inactivation of the FoxO and NFκB signaling pathways involved in atrophy. Clinical Relevance: Repeated heat exposures should be considered a novel therapeutic intervention to counteract muscle atrophy during immobilization.
The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice
Authors: Fisher Allison L. , Phillips Sydney , Wang Chia-Yu , Paulo Joao A. , Xiao Xia , Xu Yang , Moschetta Gillian A. , Xue Yongqiang , Mancias Joseph D. , Babitt Jodie L. 
Published: October 2024

Abstract
The liver hormone hepcidin regulates systemic iron homeostasis to provide enough iron for vital processes while limiting toxicity. Hepcidin acts by degrading its receptor ferroportin (encoded by Slc40a1) to decrease iron export to plasma. Iron controls hepcidin production in part by inducing liver endothelial cells (LECs) to produce bone morphogenetic proteins (BMPs) that activate hepcidin transcription in hepatocytes. Here, we used in vitro and in vivo models to investigate whether ferroportin contributes to LEC intracellular iron content to modulate BMP expression and, thereby, hepcidin. Quantitative proteomics of LECs from mice fed different iron diets demonstrated an inverse relationship between dietary iron and endothelial ferroportin expression. Slc40a1 knockdown primary mouse LECs and endothelial Slc40a1 knockout mice exhibited increased LEC iron and BMP ligand expression. Endothelial Slc40a1 knockout mice also exhibited altered systemic iron homeostasis with decreased serum and total liver iron but preserved erythropoiesis. Although endothelial Slc40a1 knockout mice had similar hepcidin expression to control mice, hepcidin levels were inappropriately high relative to iron levels. Moreover, when iron levels were equalized with iron treatment, hepcidin levels were higher in endothelial Slc40a1 knockout mice than in controls. Finally, LEC ferroportin levels were inversely correlated with hepcidin levels in multiple mouse models, and treatment of hepcidin-deficient mice with mini-hepcidin decreased LEC ferroportin expression. Overall, these data show that LEC ferroportin modulates LEC iron and consequently BMP expression to influence hepcidin production. Furthermore, LEC ferroportin expression is regulated by hepcidin, demonstrating a bidirectional communication between LECs and hepatocytes to orchestrate systemic iron homeostasis.
Saliva of persons with hemophilia A triggers coagulation via extrinsic tenase complexes
Authors: Thaler Johannes , Tripisciano Carla , Kraemmer Daniel , Hau Chi , Samadi Nazanin , Ruf Wolfram , Pabinger Ingrid , Knoebl Paul , Nieuwland Rienk , Ay Cihan 
Published: October 2024

Abstract
Human saliva contains extracellular vesicles (EVs). These EVs expose extrinsic tenase complexes of tissue factor (TF) and activated factor VII (FVIIa), and trigger blood coagulation. Here, we show that EVs exposing extrinsic tenase complexes are also present in saliva of persons with severe hemophilia A, that is, persons with FVIII deficiency. Addition of these salivary EVs to autologous FVIII-deficient blood results in FXa generation, thereby compensating for the lack of FXa generation via intrinsic tenase (FVIIIa/FIXa) complexes. Consistently, in our retrospective analysis of persons with severe hemophilia A who do not receive prophylactic FVIII substitution, oropharyngeal mucosal bleedings are infrequent and self-limited. Conversely, in saliva of persons with severe FVII deficiency, in whom oropharyngeal bleedings are prevalent, functional extrinsic tenase complexes are absent, because EVs lack FVII. Saliva of persons with severe FVII deficiency is unable to restore blood coagulation, which is because of the absence of FVII in both their saliva and blood. Picomolar levels of recombinant FVIIa can restore the coagulant potential of saliva of persons with FVII deficiency. Taken together, our findings may explain the paucity of oropharyngeal bleedings in persons with hemophilia A as well as the occurrence of such bleedings in persons with severe FVII deficiency.
Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical study
Authors: Antypiuk Ada , Vance S. Zebulon , Sharma Richa , Passos Sara , Asperti Michela , Navaneethabalakrishan Shobana , Dürrenberger Franz , Manolova Vania , Vinchi Francesca 
Published: October 2024

Abstract
Although iron overload is a common feature in myelodysplastic syndromes (MDS), it remains unclear how iron excess is detrimental for disease pathophysiology. Taking advantage of complementary approaches, we analyzed the impact of iron overload and restriction achieved through genetic activation of ferroportin (FPN) via the C326S mutation (FPNC326S) and pharmacologic inhibition (vamifeport) of the iron exporter FPN, respectively, in a MDS mouse model. Although FPNC326S-induced iron overload did not significantly improve the late stages of erythroid maturation, vamifeport-mediated iron restriction ameliorated anemia and red blood cell maturation in MDS mice, through the reduction of oxidative stress and apoptosis in erythroid progenitors. Iron overload aggravated, and restriction alleviated, reactive oxygen species formation, DNA damage, and cell death in hematopoietic stem and progenitor cells (HSPCs), resulting in altered cell survival and quality. Finally, myeloid bias, indicated by expanded bone marrow myeloid progenitors and circulating immature myeloid blasts, was exacerbated by iron excess and attenuated by iron restriction. Overall, vamifeport treatment resulted in improved anemia and significant survival increment in MDS mice. Interestingly, the combined therapy with vamifeport and the erythroid maturation agent luspatercept has superior effect in improving anemia and myeloid bias as compared with single treatments and offers additive beneficial effects in MDS. Our results prove, to our knowledge, for the first time in a preclinical model, that iron plays a pathologic role in transfusion-independent MDS. This is likely aggravated by transfusional iron overload, as suggested by observations in the FPNC326SMDS model. Ultimately, the beneficial effects of pharmacologic FPN inhibition uncovers the therapeutic potential of early prevention of iron toxicity in transfusion-independent MDS.
Can a single question replace patient-reported outcomes in the follow-up of elbow arthroplasty? A validation study
Authors: Macken Arno A. , Prkic Ante , Koenraadt-van Oost Iris , Buijze Geert A. , The Bertram , Eygendaal Denise 
Published: October 2024

Abstract
Background
To assess the results after elbow arthroplasty it is essential to gather patient-reported outcome measures (PROMs). However, the acquisition of PROMs poses a challenge because of potential low literacy, lengthiness and diversity of questionnaires, and questionnaire fatigue. Instead of a questionnaire, patient-reported outcomes can be collected using a single assessment numeric evaluation (SANE), the subjective elbow value (SEV). The aim of this pilot study is to assess the correlation between the SEV and conventionally used patient reported outcome measures (PROMs) after elbow arthroplasty.

Materials and methods
The SEV was added to our follow-up system in 2021, consisting of a scale from 0 to 10 in which the patients are asked to rate the overall functionality of their elbow, 0 corresponds to very poor functionality and 10 to a perfectly functional or healthy elbow. All patients who underwent elbow arthroplasty (total or radial head) and responded to the SEV question were retrospectively identified and included. The correlation between the SEV at the final follow-up and the Oxford Elbow Score (OES), and between the SEV and the Quick Disbailities of the Arm, Shoulder, and Hand (quickDASH) score was assessed using Pearson’s r.

Results
In total, 82 patients responded to the SEV question and were included in the study, with a median follow-up of 5 years [interquartile range (IQR) 3–7]. Of these patients, 17 (21%) underwent radial head arthroplasty and 65 (79%) total elbow arthroplasty. The Pearson’s r for the correlation between SEV and OES was 0.502 (p < 0.001) and between the SEV and the QuickDASH −0.537 (p < 0.001), which correspond to a moderate correlation.

Conclusions
The SEV shows a moderate correlation with conventional PROMs, demonstrating its potential in simplifying the follow-up of elbow arthroplasty, possibly decreasing time, costs, and patients’ questionnaire fatigue compared with conventional PROM questionnaires.
Evidence level: III.
CO2 delivery techniques in mini-sternotomy surgery and neurological events: a multicentric study
Authors: Weltert Luca P. , Audisio Katia , Torre Michele La , Dell’Aquila Michele , Cancelli Gianmarco , Lodo Vittoria , Caldonazo Tulio , Rossi Camilla S. , Soletti Giovanni J. , Garufi Luigi , Centofanti Paolo , De Paulis Ruggero , Rinaldi Mauro 
Published: October 2024

Abstract
Background
The impact of air bubbles into the cerebral circulation after open heart surgery has been a topic of discussion since the introduction of the heart-lung machine. The aim of the study was to evaluate whether the use of a dedicated commercial sponge diffuser is better than a custom-made narrow section cannula or the absence of CO2 in preventing neurological events after aortic valve replacement via J mini-sternotomy.

Methods
Three cohorts of J-shaped mini-sternotomy performed at three different centers were prospectively compared: CO2 supplied via sponge diffuser, CO2 supplied via cannula, and no CO2 supply. Propensity matching was used to obtain comparable groups. The primary endpoints were postoperative stroke, transitory ischemic attack, convulsions, and dizziness. Secondary endpoints were 30-day mortality, duration of mechanical ventilation, and intensive care unit length of stay.

Results
275 patients were enrolled in the study. After propensity matching, the sponge diffuser cohort had a significantly lower duration of mechanical ventilation (P < 0.001) and 30-day mortality (P = 0.05) when compared to the cannula cohort and the no-CO2 cohort, a lower incidence of all neurological events (P = 0.03) and dizziness (P = 0.05) when compare to the no-CO2 cohort, and a lower intensive care unit length of stay when compared to the cannula cohort (P = 0.001).

Conclusions
The sponge diffuser used to deliver the CO2 into the surgical field during aortic valve replacement via J mini-sternotomy has been demonstrated to guarantee better neurological outcomes compared to a custom-made narrow section cannula or the absence of CO2.