bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Predictive Scoring System for Bone Union Rate After Conservative Management of Lumbar Spondylolysis
Authors: Gamada Hisanori , Tatsumura Masaki , Asada Tomoyuki , Okuwaki Shun , Nagashima Katsuya , Yosuke Takeuchi , Funayama Toru , Yamazaki Masashi
Published: July 2024

Study Design.

A single-center retrospective cohort study.

Objectives.

To develop a predictive scoring system for bone union after conservative treatment of lumbar spondylolysis and assess its internal validity.

Summary of Background Data.

Lumbar spondylolysis, a common stress fracture in young athletes, is typically treated conservatively. Predicting bone union rates remains a challenge.

Methods.

This study included patients aged ≤18 years with lumbar spondylolysis undergoing conservative treatment. A multivariable logistic regression analysis was used to develop a scoring system containing six factors: sex, age, lesion level, main side stage of the lesion, contralateral side stage of the lesion, and spina bifida occulta. The predictive scoring system was internally validated from the receiver operating characteristic (ROC) curve using bootstrap methods.

Results.

The final analysis included 301 patients with 416 lesions, with an overall bone union rate of 80%. On multivariable analysis, the main and contralateral stages were identified as factors associated with bone union. The predictive scoring system was developed from the main side stage score (prelysis, early=0, progressive stage=1) and the contralateral side stage score (none=0, prelysis, early, progressive stage=1, terminal stage=3). The area under the curve was 0.855 (95% confidence interval: 0.811–0.896) for the ROC curve, showing good internal validity. The predicted bone union rates were generally consistent with the actual rates.

Conclusions.

A simple predictive scoring system was developed for bone union after conservative treatment of lumbar spondylolysis, based on the stage of the lesion on the main and contralateral sides. The predicted bone union rate was approximately 90% for a total score of 0–1 and ≤30% for a score of 3–4. This system demonstrated good internal validity, suggesting its potential as a useful tool in clinical decision making for the management of spondylolysis.
Provision of Inpatient Rehabilitation to Individuals with Lower-Limb Amputation in Canada: An Epidemiological Analysis
Authors: Imam Bita , Miller William C. , Tregobov Noah
Published: July 2024

Objective

The aim of this study was to determine the proportion of individuals with major lower-limb amputation (LLA) who received inpatient rehabilitation in Canadian provinces, their rehabilitation length, and their functional independence level at admission and discharge.

Methods

Major LLA records from April 1, 2006, to March 31, 2012, were obtained from the Canadian Institute for Health Information and linked to National Rehabilitation Reporting System data (Quebec data were unavailable). The proportions of individuals who received inpatient rehabilitation, mean length of stay, and Functional Independence Measure (FIM) scores (admission and discharge) were calculated.

Results

A total of 16,114 new individuals had major LLAs in nine Canadian provinces over the study period; 18% received inpatient rehabilitation. The mean (SD) length of stay was 37.3 (25.2) days. Nova Scotia and Ontario had the highest provision of inpatient rehabilitation (n = 235, 28.6% and n = 1779, 23.4%, respectively). Newfoundland and Labrador had the longest mean (SD) inpatient rehabilitation stay, 62.6 (36.6) days. Prince Edward Island had the highest FIM scores at admission and discharge (mean = 105.3, SD = 12.8; mean = 111.3, SD = 12.9 days, respectively).

Conclusions

We found that 18% of individuals with major LLA received inpatient rehabilitation across nine Canadian provinces. Costs and resource demands may prevent inpatient rehabilitation provision. Novel, cost-effective strategies may facilitate the provision of rehabilitation services.

Clinical Relevance

Despite the benefits of rehabilitation for individuals with major LLA, especially those whose amputations resulted from a traumatic incident, only 18% of patients with major LLA received inpatient rehabilitation across nine provinces between 2006 and 2012. Provinces with longer durations of inpatient rehabilitation reported higher levels of functional independence when patients with LLA were discharged.
Crystalloid volume versus catecholamines for management of hemorrhagic shock during esophagectomy: assessment of microcirculatory tissue oxygenation of the gastric conduit in a porcine model using hyperspectral imaging – an experimental study
Authors: Studier-Fischer Alexander , Özdemir Berkin , Rees Maike , Ayala Leonardo , Seidlitz Silvia , Sellner Jan , Kowalewski Karl-Friedrich , Haney Caelan Max , Odenthal Jan , Knödler Samuel , Dietrich Maximilian , Gruneberg Daniel , Brenner Thorsten , Schmidt Karsten , Schmitt Felix C. F. , Weigand Markus Alexander , Salg Gabriel Alexander , Dupree Anna , Nienhüser Henrik , Mehrabi Arianeb , Hackert Thilo , Müller Beat Peter , Maier-Hein Lena , Nickel Felix
Published: July 2024

Introduction:

Oncologic esophagectomy is a two-cavity procedure with considerable morbidity and mortality. Complex anatomy and the proximity to major vessels constitute a risk for massive intraoperative hemorrhage. Currently, there is no conclusive consensus on the ideal anesthesiologic countermeasure in case of such immense blood loss. The objective of this work was to identify the most promising anesthesiologic management in case of intraoperative hemorrhage with regards to tissue perfusion of the gastric conduit during esophagectomy using hyperspectral imaging.

Material and methods:

An established live porcine model (n=32) for esophagectomy was used with gastric conduit formation and simulation of a linear stapled side-to-side esophagogastrostomy. After a standardized procedure of controlled blood loss of about 1 l per pig, the four experimental groups (n=8 each) differed in anesthesiologic intervention, that is, (I) permissive hypotension, (II) catecholamine therapy using noradrenaline, (III) crystalloid volume supplementation, and (IV) combined crystalloid volume supplementation with noradrenaline therapy. Hyperspectral imaging tissue oxygenation (StO2) of the gastric conduit was evaluated and correlated with systemic perfusion parameters. Measurements were conducted before (T0) and after (T1) laparotomy, after hemorrhage (T2), and 60 min (T3) and 120 min (T4) after anesthesiologic intervention.

Results:

StO2 values of the gastric conduit showed significantly different results between the four experimental groups, with 63.3% (±7.6%) after permissive hypotension (I), 45.9% (±6.4%) after catecholamine therapy (II), 70.5% (±6.1%) after crystalloid volume supplementation (III), and 69.0% (±3.7%) after combined therapy (IV). StO2 values correlated strongly with systemic lactate values (r=−0.67; CI −0.77 to −0.54), which is an established prognostic factor.

Conclusion:

Crystalloid volume supplementation (III) yields the highest StO2 values and lowest systemic lactate values and therefore appears to be the superior primary treatment strategy after hemorrhage during esophagectomy with regards to microcirculatory tissue oxygenation of the gastric conduit.
Exploring potential plasma drug targets for cholelithiasis through multiancestry Mendelian randomization
Authors: Liu Xiaoduo , Shi Lubo , Zhang Shutian , Zhou Anni
Published: July 2024

Background:

Cholelithiasis poses significant health and economic burdens, necessitating novel pharmacological targets to enhance treatment efficacy.

Method:

Based on genome-wide association analysis studies, the authors performed a two-sample Mendelian randomization (MR) analysis based on plasma proteomics to explore potential drug targets in European (nCase=40 191 and nControl=361 641) and Asian (nCase=9305 and nControl=168 253) populations. The authors confirmed the directionality and robust correlation of the drug targets with the results through reverse MR analysis, Steiger filtering, Bayesian colocalization, phenotype scanning, and replication in multiple databases. Further exploration of the safety and possible mechanisms of action of phenome-wide MR analysis and protein–protein interactions (PPIs) as individual drug targets was performed.

Results:

Our proteomics-based MR analyses suggested that FUT3 (OR=0.87; 95% CI: 0.84–0.89; P=4.70×10−32), NOE1 (OR=0.58; 95% CI: 0.52–0.66; P=4.21×10−23), UGT1A6 (OR=0.68; 95% CI: 0.64–0.73; P=9.58×10−30), and FKBP52 (OR=1.75; 95% CI: 1.37–2.24; P=8.61×10−6) were potential drug targets in Europeans, whereas KLB (OR=1.11; 95% CI: 1.07–1.16; P=7.59×10−7) and FGFR4 (OR=0.94; 95% CI: 0.91–0.96; P=4.07×10−6) were valid targets in East Asians. There was no reverse causality for these drug targets. Evidence from Bayesian colocalization analyses supported that exposure and outcome shared consistent genetic variables. Phenome-wide MR analysis suggested the potential deleterious effects of NOE1 and FGFR4. PPI analysis confirmed the pathways associated with the potential targets involved in bile acid metabolism.

Conclusions:

Genetically predicted levels of the plasma proteins FUT3, NOE1, UGT1A6, and FKBP52 have the potential as prospective targets in Europeans. Moreover, the plasma levels of KLB and FGFR4 may serve as potential targets for the treatment of cholelithiasis in East Asians.
Perioperative intravenous lidocaine infusion improves postoperative analgesia after hysterectomy: a systematic review and meta-analysis of randomized controlled trials
Authors: Tang Peng , Sun Qingxia , Li Zhihao , Tong Xiangyi , Chen Fengshou
Published: July 2024

Background:

The effectiveness of intravenous lidocaine in reducing acute pain after hysterectomy remains uncertain. The authors conducted a meta-analysis of randomized controlled trials (RCTs) to investigate the impact of intravenous lidocaine on posthysterectomy recovery.

Methods:

This study was completed based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. A systematic search was conducted in PubMed/MEDLINE, the Cochrane Controlled Trials Register (CENTRAL), and Embase up to 27 July 2023. The authors identified RCTs involving hysterectomy patients comparing lidocaine to a placebo. Outcome measures included postoperative pain scores at rest and during movement, opioid consumption, postoperative nausea and vomiting (PONV), improvements in functional gastrointestinal recovery, and Quality of Recovery scores.

Results:

Nine RCTs were included in the meta-analysis, comprising 352 patients who received intravenous lidocaine and 354 controls. The analysis revealed that intravenous lidocaine significantly reduced postoperative pain scores at rest at 2, 6, 8, and 24 h following hysterectomy, as well as postoperative opioid consumption within 24 h and PONV rates. Furthermore, no observed benefit was noted in shortening the time to first flatus with intravenous lidocaine administration posthysterectomy.

Conclusion:

Intravenous lidocaine administration effectively reduces acute postoperative pain, opioid consumption, and PONV rates following hysterectomy. Lidocaine serves as an opioid-sparing agent, reducing the morphine equivalent dose while maintaining a similar degree of postoperative pain.
Results From the Big Ten COVID-19 Cardiac Registry: Impact of SARS-COV-2 on Myocardial Involvement
Authors: Albrecht Jennifer S. , Greenshields Joel T. , Smart Suzanne , Law Ian H. , Rink Larry R. , Daniels Curt J. , Rajpal Saurabh , Chung Eugene H. , Jeudy Jean , Kovacs Richard , Womack Jason , Esopenko Carrie , Bosha Philip , Terrin Michael , Rosenthal Geoffrey L. , Peterson Andrew R.
Published: July 2024

Objective:

COVID-19 has been associated with myocardial involvement in collegiate athletes. The first report from the Big Ten COVID-19 Cardiac Registry (Registry) was an ecological study that reported myocarditis in 37 of 1597 athletes (2.3%) based on local clinical diagnosis. Our objective was to assess the relationship between athlete and clinical characteristics and myocardial involvement.

Design:

Cross-sectional study.

Setting:

We analyzed data from 1218 COVID-19 positive Big Ten collegiate athletes who provided informed consent to participate in the Registry.

Participants:

1218 athletes with a COVID-19–positive PCR test before June 1, 2021.

Assessment of Independent Variables:

Demographic and clinical characteristics of athletes were obtained from the medical record.

Main Outcome Measures:

Myocardial involvement was diagnosed based on local clinical, cardiac magnetic resonance (CMR), electrocardiography, troponin assay, and echocardiography. We assessed the association of clinical factors with myocardial involvement using logistic regression and estimated the area under the receiver operating characteristic (ROC) curve.

Results:

25 of 1218 (2.0%) athletes met criteria for myocardial involvement. The logistic regression model used to predict myocardial involvement contained indicator variables for chest pain, new exercise intolerance, abnormal echocardiogram (echo), and abnormal troponin. The area under the ROC curve for these indicators was 0.714. The presence of any of these 4 factors in a collegiate athlete who tested positive for COVID-19 would capture 55.6% of cases. Among noncases without missing data, 86.9% would not be flagged for possible myocardial involvement.

Conclusion:

Myocardial involvement was infrequent. We predicted case status with good specificity but deficient sensitivity. A diagnostic approach for myocardial involvement based exclusively on symptoms would be less sensitive than one based on symptoms, echo, and troponin level evaluations. Abnormality of any of these evaluations would be an indication for CMR.
COVID-19 Infection in Ultramarathon Runners: Findings of the Ultrarunners Longitudinal TRAcking Study
Authors: Jastifer James R. , Jastifer Ethan J. , Hoffman Martin D.
Published: July 2024

Objective:

Ultramarathon runners are a unique patient population who have been shown to have a lower rate of severe chronic medical conditions. This study aimed to determine the effect that COVID-19 infection has had on this population and their running behavior.

Design:

The Ultrarunners Longitudinal TRAcking (ULTRA) Study is a large longitudinal study of ultramarathon runners. Questions on health status, running behavior, and COVID-19 infection were included in the most recent survey.

Setting:

Community survey.

Participants:

Seven hundred thirty-four ultramarathon runners participated in the study.

Interventions:

None.

Main Outcome Measures:

Personal, exercise, and COVID-19 infection history.

Results:

52.7% of study participants reported having been symptomatic from a COVID-19 infection, with 6.7% testing positive multiple times. Participants required a total of 4 days of hospitalization. The most common symptoms included fever (73.6%), fatigue (68.5%), sore throat (68.2%), runny nose (67.7%), and cough (67.4%). Cardiovascular symptoms, which are of particular interest in the running population, included shortness of breath (46.3%), tachycardia (44.7%), chest pain (36.2%), and wheezing (33.3%). A total of 50 subjects (6.8%) reported long COVID (symptoms lasting more than 12 weeks).

Conclusions:

Severe COVID-19 infection has been rare in this population of ultramarathon runners, although symptomatic infection that affects running is common. To support the well-being of this group of highly active athletes, clinicians should appreciate that cardiovascular symptoms are common and the long-term significance of these symptoms in runners is unknown.

Level of Evidence:

Level 2 prospective study.
Is Access to Optimal Concussion Care for Pediatric Athletes Limited by Geography?
Authors: Powers Ryan , Trevino Robert , Erpenbach Holly , Thomas Danny
Published: July 2024

Objective:

To evaluate access to optimal concussion care based on a pediatric patients' geography; the hypothesis is that differential access across the Unites States exists.

Design:

Employed a novel strategy using internet searches to find local care, mimicking what families might do in different parts of the country.

Setting:

Virtual internet searches.

Participants:

Not applicable.

Independent Variable:

Various metropolitan and rural geographic regions within each state in the United States.

Main Outcome Measures:

Evaluate access (defined as distance to clinic and ability to see pediatric patients) and optimal care (defined as self-referral process and presence of multidisciplinary care).

Results:

Search strategy yielded 490 results. Overall ∼60% were within 50 miles of searched locations with significant differences in access based on rural versus metropolitan areas (P < 0.0001); in rural areas, only ∼22% of results were within 50 miles. Only about one-third of the results (n = 157) saw pediatric patient with no differences between regions. There was significant regional and geographic variation for optimal care regarding both self-referral processes and access to multidisciplinary care. A diverse group of specialists was represented in search results for concussion care.

Conclusions:

Nationwide, there is an overall lack of access to multidisciplinary concussion care for pediatric patients. Additionally, those in rural communities face more limitations related to access to facilities with increased distances from closest clinic sites.
Vedolizumab versus ustekinumab in Crohn’s disease with prior anti-tumor necrosis factor failure: an updated meta-analysis
Authors: Milioli Natália Junkes , Fernandes Matheus Vanzin , Correa Tulio L. , Antunes Vanio , Martins Otávio Cosendey , Florêncio de Mesquita Cynthia , Baraldo Stefano , Furfaro Federica
Published: July 2024

Ustekinumab and vedolizumab are key treatment options for Crohn’s disease patients who fail anti-tumor necrosis factor (TNF) therapy. This updated meta-analysis aims to compare the efficacy and safety of these two drugs. We performed a systematic review in PubMed, Embase, and Cochrane databases searching for randomized and nonrandomized studies comparing vedolizumab versus ustekinumab in patients with Crohn’s disease with previous anti-TNF failure or intolerance. The primary outcome was steroid-free clinical remission (SFR) at the pos-induction (12–16 weeks) and maintenance period (48–52 weeks). The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I
2 statistics. This meta-analysis included 11 studies and 2724 patients. There was a significant difference favoring ustekinumab in SFR at pos-induction (OR, 1.44; 95% CI, 1.11–1.88; P = 0.006; I
2 = 27%) and maintenance periods (OR, 1.86; 95% CI, 1.23–2.82; P = 0.003; I
2 = 80%), in clinical remission at pos-induction period (OR, 2.04; 95% CI, 1.58–2.63; P < 0.001; I
2 = 3%), and in treatment discontinuation due to adverse events (OR, 0.31; 95% CI, 0.16–0.60; P < 0.001; I
2 = 0%). In patients with Crohn’s disease with prior anti-TNF failure, ustekinumab showed higher SFR during both the pos-induction and maintenance period and a lower rate of treatment discontinuation due to adverse events.
Incidence of Adverse Events Using Flumazenil in Patients With Iatrogenic Benzodiazepine Delirium: A Retrospective Study
Authors: Hieger Michelle A. , Moore Philip W. , Maskell Kevin F.
Published: July 2024

Background:

Flumazenil is a competitive benzodiazepine (BZD) antagonist most used for treating delirium in BZD overdoses. Since its introduction, many have expressed concerns about its safety secondary to the risk of inducing BZD withdrawal and refractory seizures.

Study Question:

What is the incidence of adverse drug events after the administration of flumazenil in patients with suspected iatrogenic BZD delirium?

Study Design:

This is a retrospective cross-sectional study of patients from a single center from 2010 to 2013. Patients experiencing delirium after receiving BZDs in the hospital were included if they had a bedside toxicology consult and were administered flumazenil. Patients were excluded if they were given BZDs for ethanol withdrawal or if they did not have mental status documentation before and after flumazenil administration. Descriptive statistics were calculated.

Measures and Outcomes:

The primary outcome was the incidence of adverse drug events after flumazenil administration. The secondary outcome was the efficacy of flumazenil determined by the patient's mental status.

Results:

A total of 501 patient records were reviewed, and 206 patients were included in the final analysis. Of those patients, 172 (83.5%) experienced an objective improvement in their mental status within 1 hour after flumazenil administration. A total of 5 patients experienced adverse events (2.4%), 95% confidence interval (0.78, 5.54). Of these, 3 patients experienced minor agitation or restlessness without pharmacologic intervention. Two patients experienced moderate agitation or restlessness that resolved with haloperidol or physostigmine administration. No patients had a reported seizure, 95% confidence interval (0.0, 1.77).

Conclusions:

Flumazenil seems to be a safe and effective intervention for the reversal of delirium secondary to iatrogenic BZD administration.
Frontloading Home Physical Therapy Visits for Patients With Heart Failure
Authors: Dias Konrad J. , Child Jeffrey , Blackinton Mary T. , Wilson Stanley , Brown Dustin R. , Collins Sean M.
Published: July 2024

Frontloading home care visits has been found to be effective in the nursing profession but has not been investigated in physical therapy (PT) practice. This study aimed to examine the impact of frontloading home PT visits on function in persons with heart failure (HF). This was a prospective multi-center randomized controlled trial with blinded raters. A total of 82 ambulatory patients with a primary diagnosis of HF discharged from an acute care facility to home care participated in the study. Subjects were randomly allocated to an experimental frontloaded group (FLG) or control group (CG) for 4 weeks. FLG visit frequencies were five sessions per week for 2 weeks, and three sessions per week for 2 weeks. The CG received two sessions per week for 4 weeks. Functional measures including the 2-minute step test (2MST), 2-minute walk test (2MWT), gait speed (GS), Timed Up and Go (TUG), and 30-second chair rise test (30-CRT) were collected at the onset of care, at the end of 2 weeks and 4 weeks. The groups were statistically similar at baseline for all measures. All subjects significantly improved scores in all functional measures over time, within-subject main effect (p < .01). Significant between-subject effects were noted for 30-CRT (p = .04). Interaction effects were noted for GS (p = .03) and TUG test (p = .02). This is the first study to report meaningful improvements in function in individuals with HF. Significant treatment effect differences between the FLG and CG were found for GS, TUG, and 30-CRT. Future studies should examine the use of a standardized intervention to validate the effectiveness of frontloading home visits on quality of life and readmission rates.
Standardizing Fetal Movement Monitoring using Count the Kicks
Authors: Burgess Adriane , Aucutt Megan , Coleman Sarah L.
Published: July 2024

Stillbirth affects 1 in 175 pregnancies in the United States. There are significant racial and ethnic disparities in rates of stillbirth. Rates of stillbirth are highest among non-Hispanic Native Hawaiian or Other Pacific Islander and non-Hispanic Black women, more than twice the rate of non-Hispanic White women. Stillbirth is a public health crisis that warrants attention as it has significant physical, psychosocial, and economic effects on women and their family. Many stillbirths occur due to placental insufficiency, causing a lack of oxygenation of the fetus, which can result in decreased movement. Pregnant patients who experience stillbirth often observe decreased fetal movement days before birth. Daily fetal movement monitoring has the potential to identify pregnancies at risk so providers can intervene. Count the Kicks is a fetal movement monitoring program that provides standardized education and resources for expectant parents. Increased awareness of providers and childbearing families about the importance of fetal movement monitoring, standardized provision of education on fetal movement counting, and what to do if a baby's normal movement patterns change can be helpful in promoting healthy pregnancy outcomes.
Emotional Awareness Is Correlated With Ambulatory Heart Rate Variability: A Replication and Extension
Authors: Spangler Derek P. , Reis Harry T. , Hsu Chiu-Hsieh , Zareba Wojciech , Lane Richard D.
Published: July 2024

Objective

In healthy volunteers, a positive association has previously been observed between emotional awareness (EA), the ability to identify and describe emotional experiences in oneself and others, and resting heart rate variability (HRV), which is dominated by vagus nerve activity. The current study aimed to investigate the EA-HRV association across multiple assessments in a “real-world” ambulatory context in patients with long QT syndrome (LQTS) who are at genetic risk for sudden cardiac death.

Methods

Participants (157 LQTS patients; MeanAge = 35.1, SDAge = 10.4; 115 women) completed the levels of emotional awareness scale (LEAS) on one occasion, which served as our measure of EA. In an ecological momentary assessment study involving 10 assessments per day over 3 days, multiple 5-minute ECG assessments (mean = 24.6, SD = 5.1) were obtained in each patient using a Holter monitor, from which high-frequency HRV (HF-HRV) was computed on each occasion.

Results

There was a significant positive association between LEAS scores and HF-HRV controlling for biobehavioral covariates. We also detected a similar inverse relation between EA and mean heart rate.

Conclusion

These findings suggest that, in patients with a well-defined genetic risk for ventricular arrhythmia and sudden death, the ability to experience emotions in a complex and differentiated way covaries with greater parasympathetic influences on the heart. These findings are consistent with the overlapping neural substrates of EA and HRV and their common contribution to adaptive emotional responding, consistent with the Neurovisceral Integration Model.
Pediatric Anatomy of the Sternocleidomastoid Muscle on Magnetic Resonance Imaging Views
Authors: Beger Burhan , Yalinkiliç Abdulaziz , Erdem Mehmet Zeki , Mengi Sevinç , Beger Orhan
Published: July 2024

Objective:

This study aimed to investigate morphologic features of the sternocleidomastoid muscle (SCM) in children for pediatric head-neck surgeries.

Methods:

Magnetic resonance imaging images of 84 (46 males/38 females) pediatric patients aged ages 1 to 18 years (mean age: 9.38 ± 4.46 y) constituted the study universe. The size of SCM (including its height, width, and angulation) was measured, and the origin types of SCM were noted.

Results:

All patients had SCM bilaterally. The origin variation of SCM was observed in 22 sides (13.10%). The authors observed type 1 in 146 sides (86.90%), type 2a in 15 sides (8.90%), type 3 in 2 sides (1.20%), type 4 in 1 side (0.60%), and type 5 in 4 sides (2.40%). The absence and presence of SCM variation were not affected by sex (P = 0.370) and side (P = 0.360). All measured parameters were similar in right and left sides, and also in males and females, except from the angle between the junction of the sternal and clavicular heads of SCM. The angle was greater in males than females (P = 0.004). All measured parameters increased with advancing age (between 1 and 18 y; P < 0.05).

Conclusion:

The authors’ SCM-related data may be useful for clinicians to estimate the size origin variations of SCM in children.
Association of Hospital System Affiliation with Spending and Postoperative Outcomes
Authors: Diaz Adrian , Nuliyalu Usha , Ryan Andrew M , Dimick Justin B , Ibrahim Andrew M , Nathan Hari
Published: July 2024

Objective:

To determine whether hospital system affiliation was associated with changes in surgical episode spending or postoperative outcomes.

Background:

Over 70% of US hospitals are now part of a hospital system. The presumed benefits of hospital consolidation include concentrating volume and expertise, care integration, and investment in quality improvement. However, there is conflicting evidence as to whether expanding hospital systems are actually reducing health spending or improving quality. These observations call into question whether systems are leveraging their collective volume and experience to standardize care and maximize efficiencies.

Methods:

The American Hospital Association Annual Survey was used to identify whether a hospital was part of a system and in which year a hospital joined the respective system. Using 100% Medicare claims data, we identified fee-for-service Medicare patients undergoing elective inpatient coronary artery bypass graft colon resection, lung resection, hip replacement, or knee replacement from 2010 to 2018. We used a difference-in-differences framework to evaluate hospital spending and outcomes before and after joining a system. The primary outcome was Medicare 30-day episode spending, with specific attention to the total episode payment, index hospitalization, and post-acute care components. Secondary outcomes included serious complications, 30-day mortality, and 30-day readmission.

Results:

The cohort included 3,395,565 Medicare beneficiaries who underwent surgery between 2010 and 2018. Patients were treated at 3961 hospitals, of which 1097 (27.7%) were never in a system, 2262 (57.1%) were always in a system, and 602 (15.2%) joined a system during the study period. By 1 year after system affiliation, 30-day episode spending had decreased by $303 (95% CI: 63, 454, P=0.01), and after 5 years, 30-day episode spending decreased by $429 (95% CI: 5, 853, P=0.04). One year after system association, index hospitalization spending was not statistically different from before system affiliation ($−30, 95% CI: −160, 100, P=0.65). Conversely, 1 year after system association, postacute care spending decreased by $268 (95% CI: 107, 429, P<0.01) and remained lower for ≥5 years. There was no significant change in hospitals serious complications (−0.14, 95% CI: −0.40, 0.11, P=0.27), 30-day readmission (−0.14, 95% CI:−0.52, 0.25, P=0.48), or 30-day mortality (−0.08, 95% CI: −0.18, 0.03, P=0.17), 1 year after joining a system; similar patterns were observed at three and ≥5 years.

Conclusions:

system affiliation was associated with a small decrease in 30-day episode spending, driven by decreased spending in postacute care services. Notably, there was no difference in postoperative outcomes after system affiliation.
Codon-Optimized and de novo–Synthesized E-Selectin/AAV2 Dose–Response Study for Vascular Regeneration Gene Therapy
Authors: Voza Francesca A. , Byrne Barry J. , Ortiz Yulexi Y. , Li Yan , Le Nga , Osafo Lucy , Ribieras Antoine C. , Shao Hongwei , Huerta Carlos Theodore , Wei Yuntao , Falero-Diaz Gustavo , Franco-Bravo Andres , Lassance-Soares Roberta M. , Vazquez-Padron Roberto I. , Liu Zhao-Jun , Velazquez Omaida C.
Published: July 2024

Objective:

This study focuses on dose–response investigation using a codon-optimized and de novo–synthesized E-Selectin/AAV2 (E-Sel/AAV2) vector in preparation for Investigational New Drug enabling of subsequent clinical studies.

Background:

Gene therapy is a potential solution for patients suffering from chronic limb-threatening ischemia. Understanding the dose for effective gene delivery is crucial for future Investigational New Drug–enabling studies.

Methods:

Expression of the codon-optimized E-Selectin gene was assessed by flow cytometry following in vitro cell transfection assay and RT-qPCR for murine limbs injected in vivo with AAV-m-E-Selectin (E-Sel/AAV2). Dose–response studies involved 3 cohorts of FVB/NJ mice (n=6/group) with escalating log doses of E-Selectin/AAV2 injected intramuscularly in divided aliquots, ranging from 2 × 109 VG to 2 × 1011 VG, into ischemic limbs created by left femoral artery/vein ligation/excision and administration of nitric oxide synthase inhibitor, L-NAME. Limb perfusion, extent of gangrene free limb, functional limb recovery, and therapeutic angiogenesis were assessed.

Results:

Codon-optimized E-Sel/AAV2 gene therapy exhibits a superior expression level than WT E-Sel/AAV2 gene therapy both in vitro and in vivo. Mice treated with a high dose (2 × 1011 VG) of E-Sel/AAV2 showed significantly improved perfusion indices, lower Faber scores, increased running stamina, and neovascularization compared with lower doses tested with control groups, indicating a distinct dose-dependent response. No toxicity was detected in any of the animal groups studied.

Conclusions:

E-Sel/AAV2 Vascular Regeneration Gene Therapy holds promise for enhancing the recovery of ischemic hindlimb perfusion and function, with the effective dose identified in this study as 2 × 1011 VG aliquots injected intramuscularly.
Treadmill training improves neural function recovery in rats with spinal cord injury via JAK2/STAT3 signaling pathway and attenuating apoptosis
Authors: Li Meng , Mo Jinfeng , Wu Deguang , He Haibo , Hu Panyong
Published: July 2024

To investigate the role of JAK2/STAT3 signaling pathway in neural function recovery in rats with spinal cord injury (SCI) after treadmill training. Sprague–Dawley rats were randomly divided into four groups: (a) sham group; (b) SCI group; (c) SCI+treadmill training group (SCI/TT); and (d) SCI/TT+AG490 group (a JAK2 inhibitor) (n = 12). The 12 Sprague–Dawley rats in each group were randomly assigned into 1st, 3rd, 7th, and 14th day subgroups. The Basso–Beattie–Bresnahan (BBB) locomotor rating scale was used to assess the spinal cord function, and JAK2, STAT3, and IL-6 protein expressions in the rat spinal cord were evaluated by western blot. The level of cell apoptosis and expressions of apoptotic proteins were evaluated by TUNEL assay and immunohistochemistry, respectively. Rats in the SCI+TT group showed a significantly higher BBB score after SCI compared with the SCI group and the SCI/TT+AG490 group. Mechanistically, the JAK2/STAT3 signal pathway was immediately activated after SCI compared with sham group, and JAK2 and STAT3 were obviously upregulated when treadmill training was performed (P < 0.05). Results of TUNEL assay showed that the apoptotic rate in SCI/TT was significantly lower than that in the SCI group and SCI/TT+AG490 group (P < 0.05). Besides, the IL-6 expression in the SCI/TT group was significantly attenuated compared with the SCI group (P < 0.05). Our results showed that physical treadmill training can enhance activation of JAK2/STAT3 signal pathway and attenuate apoptosis in the injured spinal cord, resulting in better functional recovery. These results underline the importance of synergistic treatment strategies for SCI.
Clusterin attenuates blood–brain barrier damage and cognitive impairment by inhibiting astrocyte aging in mice with sepsis-associated encephalopathy
Authors: Xiao Ping , Wen Yin , Du Guoqiang , Luo Ensi , Su ZhiWei , Liao Zhong , Ding Hongguang , Li Weifeng
Published: July 2024

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis, however, its exact mechanism remains unknown. This study aimed to evaluate whether clusterin is essential to the development of SAE during the aging process of astrocytes. In the study, septic mice were established with cecal ligation and puncture (CLP) and lipopolysaccharides were applied to astrocytes in vitro. Evan’s blue dye was used in vivo to show blood–brain barrier (BBB) permeability. A morris water maze test was conducted to assess cognitive functions of the mice. Clusterin-knockout mice were used to examine the effect of clusterin on sepsis. The astrocytes were transfected with lentivirus expressing clusterin cDNA for clusterin overexpression or pYr-LV-clusterin small hairpin RNA for clusterin knockdown in vitro. The expression of clusterin, p-p53, p21, GDNF, and iNOS was detected. he CLP mice exhibited a higher clusterin expression in hippocampus tissue, aging astrocytes, lower GDNF expression and higher iNOS expression, accompanied with BBB damage and cognitive deficiency. Following clusterin knockout, this pathological process was further enhanced. In vitro, following lipopolysaccharides treatment, astrocytes exhibited increased clusterin, p-p53, p21, iNOS and decreased GDNF. Following clusterin knockdown, the cells exhibited a further increase in p-p53, p21, and iNOS and decrease in GDNF. Clusterin overexpression, however, helped inhibit astrocytes aging and neuroinflammation evidenced by decreased p-p53, p21, iNOS and increased GDNF. The present study has revealed that clusterin may exert its neuroprotective effect by preventing aging in astrocytes, suppressing the secretion of iNOS and promoting GNDF release.
Preliminary Guidelines for Resuming Electroconvulsive Therapy After a Complication of Status Epilepticus
Authors: Hazimeh Maya , Arnoudse Nicholas , Wilson Saydra , Walczak Thaddeus , Nahas Ziad
Published: July 2024

Electroconvulsive therapy (ECT) is an effective and safe treatment for severe major depressive disorder. However, status epilepticus is a rare yet serious complication that can occur following treatment. We present a case of a patient with severe major depression who experienced convulsive status epilepticus during the first treatment of her fourth ECT course. Electroconvulsive therapy treatment was then discontinued, and the patient underwent unsuccessful medication trials. Due to deterioration of depressive symptoms, ECT resumption was considered 3 months later after the patient had been maintained on an antiepileptic drug and no further seizures had occurred. Electroconvulsive therapy was resumed with a detailed safety protocol that included electroencephalographic monitoring before and after ECT treatment, remaining on an antiepileptic drug during the course of treatment, performing ECT in the operating room, and preparing seizure-terminating drugs before each treatment. The patient completed her ECT course with no tardive seizures or other neurological complications. We present the safety measures taken for resumption of ECT in our patient, and we offer preliminary clinical guidelines for resuming ECT after a complication of status epilepticus.
Assessment of clinical outcomes in patients with inflammatory arthritis: analysis from the UK Medical Cannabis Registry
Authors: Francis Ann , Erridge Simon , Holvey Carl , Coomber Ross , Guru Rahul , Darweish Medniuk Alia , Sajad Mohammed , Searle Robert , Usmani Azfer , Varma Sanjay , Rucker James , Platt Michael , Holden Wendy , Sodergren Mikael H.
Published: July 2024

The aim of this study was to assess changes in validated patient-reported outcome measures after initiation of cannabis-based medicinal products (CBMPs) and the safety of CBMPs in patients with inflammatory arthritis. A prospective case series from the UK Medical Cannabis Registry was analyzed. The primary outcomes changes were in Brief Pain Inventory, McGill Pain Questionnaire, EuroQol 5-dimension 5-level (EQ-5D-5L), Generalised Anxiety Disorder-7 questionnaire, and Single-Item Sleep Quality Scale at 1, 3, 6, and 12 months of follow-up compared with baseline. Adverse events were analyzed in accordance with Common Terminology Criteria for Adverse Events, v.4.0. Statistical significance was defined as a P-value less than 0.050. Eighty-two patients met the inclusion criteria. Initiation of CBMP treatment was associated with improvements in Brief Pain Inventory, McGill Pain Questionnaire, EQ-5D-5L, Generalised Anxiety Disorder-7 questionnaire, and Single-Item Sleep Quality Scale at 1, 3, 6, and 12 months compared with baseline (P < 0.050). There were 102 (44.35%) mild adverse events, 97 (42.17%) moderate adverse events, and 31 (13.48%) severe adverse events recorded by 21 (25.61%) participants. This study suggests that CBMP treatment is associated with pain improvement and increased health-related quality of life for inflammatory arthritis patients. While causality cannot be inferred in this observational study, the results support the development of randomized control trials for inflammatory arthritis pain management with CBMPs.
DETECTION AND ANTIBIOTIC RESISTANCE OF SALMONELLA ISOLATES FROM SELECTED POULTRY FARMS IN DAR ES SALAAM, TANZANIA.
Authors: Mwambene Saxon Joseph , Mtenga Adelard B. , Chengula Augustino A. , Hoza Abubakar S.
Published: July 2024

Introduction

Salmonella, one of the most frequent foodborne bacteria, is linked to 155,000 annual mortality and 93.8 million foodborne illnesses. Rampant use of antibiotic agents to combat Salmonellosis in poultry has contributed to the emergence of resistance against commonly used antibiotics.

Methodology

A cross-section study was conducted between January and June 2023. Purposive sampling was used to select farms, poultry faecal droppings were collected to determine the occurrence of multidrug-resistant (MDR) Salmonella spp. Samples were examined for the presence of Salmonella by standard microbiological techniques. Conventional biochemical tests and molecular methods such as PCR and partial DNA sequencing were used for the identification of Salmonella isolates. Antimicrobial susceptibility testing was performed to identify Salmonella isolates resistant to seven commonly used classes of antibiotics.

Results

The overall Salmonella spp isolated from faecal droppings from the selected farms was 6.04% (n=48). Of the PCR-confirmed isolates, 64.3% (n=18) were resistant to more than two classes of antibiotics and hence considered MDR. The highest resistance was observed with ampicillin (92.9%), followed by tetracycline (69%), ciprofloxacin (42.9%), sulfonamide (42.9%), gentamicin (35.7%), and azithromycin (28.9%). All the isolates were susceptible to chloramphenicol (100%). Twenty-eight (28) isolates were sequenced and only sixteen (16) sequences met the criteria for phylogenetic analysis. All the sixteen (16) Sequences clustered together with Salmonella enterica sub spp. enterica with accession number EU348369 which was isolated from chickens, pigs, and foods.

Conclusion

The observed high level of antibiotic resistance found in this study could be attributed to the unwarranted use of antibiotics. To limit the use of antibiotics in poultry farming at the farm level, immediate action is needed including advocating for prudent use of antibiotics in poultry production systems by strengthening extension services to poultry farmers and use of farm biosecurity.
Hormonal dynamics reveal a stimulatory role for secretoneurin in zebrafish ovulation
Authors: Peng Di , Lu Chunyu , Spadacini Victoria , Mitchell Kimberly , Tan Yongjun , Zhang Dapeng , Levavi-Sivan Berta , Hu Wei , Trudeau Vance L.
Published: July 2024

Surge release of luteinizing hormone (Lh) from the pituitary is essential for fertility as it triggers ovulation. While secretoneurin (SN) is a phylogenetically conserved secretogranin-2 derived peptide that stimulates Lh, its role in ovulation has not been established. To directly compare periovulatory changes in the classical hormones to the emerging reproductive neuropeptides SNa and SNb, simultaneous mass spectrometry measurement of 9 peptides and 5 steroids was conducted in female zebrafish. Regression analysis indicated that levels of SNa1-34 in the brain peaked when type 3 gonadotropin-releasing hormone (Gnrh3) increased (R2=0.71) at the time of the Lh surge, 3.5 h before ovulation. In contrast, levels of the naturally occurring derivative SNa1-14 were highest at ovulation, while SNb1-31 was invariable. The bioactivities of SNa1-34 and SNa1-14 were investigated. After injection of SNa1-34 in females that had been isolated from males, 61% (11/18) ovulated within 6 h, which was like the effects of the Lh analog human chorionic gonadotropin (hCG) (72%; 13/18 females). SNa1-34 could induce ovulation by stimulating time-dependent expression ofgnrh3in the brain,chorionic gonadotropin alpha (cga), luteinizing hormone b (lhb)subunit in pituitary, and thenuclear progesterone receptor (npr)in ovaries. In contrast, SNa1-14 exhibited far fewer effects on gene expression and did not induce ovulation. Our results support the proposal that SN is a reproductive hormone.

Significance statement

Secretogranin-2 is a secretory granule protein that is enzymatically processed to the bioactive neuropeptide secretoneurin. It is produced in hypothalamic neurons and anterior pituitary cells, and we providein vivoevidence that secretoneurin plays an important role to induce ovulation. Secretoneurin levels in the brain increase concomitantly with gonadotropin-releasing hormone prior to ovulation in normal zebrafish. Injection of a synthetic secretoneurin peptide increased expression of reproduction-related genes at all levels of the hypothalamic-pituitary-ovarian axis. Secretoneurin stimulates ovulation in otherwise anovulatory females. Together these data place the evolutionarily conserved secretoneurin amongst other critical neuroendocrine regulators. Secretoneurin or synthetic agonists could be used to improve breeding in fish species, or to potentially help with infertility treatments
Drugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention
Authors: Bogin Bryan A. , Levine Zachary A.
Published: July 2024

Drugging intrinsically disordered proteins (IDPs) has historically been a major challenge due to their lack of stable binding sites, conformational heterogeneity, and rapid ability to self-associate or bind non-specific neighbors. Furthermore, it is unclear whether binders of disordered proteins i) induce entirely new conformations or ii) target transient pre-structured conformations via stabilizing existing states. To distinguish between these two mechanisms, we utilize molecular dynamics simulations to induce structured conformations in islet amyloid polypeptide (IAPP), a disordered endocrine peptide implicated in Type II Diabetes. Using umbrella sampling, we measureconformation-specificaffinities of molecules previously shown to bind IAPP to determine if they can discriminate between two distinct IAPP conformations (fixed in either ⍺-helix or β-sheet). We show our two-state model of IAPP faithfully predicts the experimentally observed selectivity of two classes of IAPP binders while revealing differences in their molecular mechanisms of binding. Specifically, the binding preferences of foldamers designed for human IAPP was not fully accounted for by conformational selection, unlike β-breaking peptides designed to mimic IAPP self-assembly sequences. Furthermore, the binding of these foldamers, but not β-breaking peptides, was disrupted by changes in the rat IAPP sequence. Taken together, our data quantifies the sequence and conformational specificity for IAPP binders and reveals conformational selection sometimes overrides sequence-level specificity. This work highlights the important role of conformational selection in stabilizing IDPs, and it reveals how fixed conformations can provide a tractable target for developing disordered protein binders.
PEPCy: Photostable fluoromodules for live cell, super-resolution microscopy of surface proteins
Authors: Sasazawa Moeka , Chimthanawala Afroze , Zeng Rui , Kim Danah , Buchan Katherine , Zhang Ming , Saurabh Saumya
Published: July 2024

We report the evolution and application of two genetically encoded tags that bind the cyanine dyes Cy3 or Cy5 with high specificity and selectivity, in addition to enhancing their photostability. These tags, which we call PEPCy, can be used to target membrane proteins such as G-protein coupled receptors. Due to their orthogonality and high binding-affinity for cognate cyanine dyes, the PEPCy tags can be used for wash-free labeling of cell surface receptors to observe their dynamics at a single molecule level. Together with self-labeling tags, these photostability enhancing proteins against cyanine dyes present a novel, complementary and powerful approach to explore protein dynamics with high spatiotemporal resolution.