bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prospective Cohort Study of Radiation Exposure to a Spine Surgeon’s Exposed Body Parts During Utilization of Intraoperative Radiation-based Imaging
Authors: Chauhan Daksh , Ahmad Hasan S. , Singh Shikha , Albayar Ahmed , Patel Arjun , Welch William C. , Yoon Jang W.
Published: February 2023

Study Design:

Prospective cohort study.

Summary of Background Data:

C-arm fluoroscopy and O-arm navigation are vital tools in modern spine surgeries, but their repeated usage can endanger spine surgeons. Although a surgeon’s chest and abdomen are protected by lead aprons, the eyes and extremities generally receive less protection.

Objective:

In this study, we compare differences in intraoperative radiation exposure across the protected and unprotected regions of a surgeon’s body.

Methods:

Sixty-five consecutive spine surgeries were performed by a single spine-focused neurosurgeon over 9 months. Radiation exposure to the primary surgeon was measured through dosimeters worn over the lead apron, under the lead apron, on surgical loupes, and as a ring on the dominant hand. Differences were assessed with rigorous statistical testing and radiation exposure per surgical case was extrapolated.

Results:

During the study, the measured radiation exposure over the apron, 176 mrem, was significantly greater than that under the apron, 8 mrem (P = 0.0020), demonstrating a shielding protective effect. The surgeon’s dominant hand was exposed to 329 mrem whereas the eyes were exposed to 152.5 mrem of radiation. Compared with the surgeon’s protected abdominal area, the hands (P = 0.0002) and eyes (P = 0.0002) received significantly greater exposure. Calculated exposure per case was 2.8 mrem for the eyes and 5.1 mrem for the hands. It was determined that a spine-focused neurosurgeon operating 400 cases annually will incur a radiation exposure of 60,750 mrem to the hands and 33,900 mrem to the eyes over a 30-year career.

Conclusions:

Our study found that spine surgeons encounter significantly more radiation exposure to the eyes and the extremities compared with protected body regions. Lifetime exposure exceeds the annual limits set by the International Commission on Radiologic Protection for the extremities (50,000 mrem/y) and the eyes (15,000 mrem/y), calling for increased awareness about the dangerous levels of radiation exposure that a spine surgeon incurs over one’s career.
Sarcopenia as a Risk Factor for Complications Following Pedicle Subtraction Osteotomy
Authors: Babu Jacob M. , Wang Kevin Y. , Jami Meghana , Durand Wesley M. , Neuman Brian J. , Kebaish Khaled M.
Published: February 2023

Study Design:

Retrospective cohort.

Objective:

The objective was to determine if sarcopenia is an independent risk factor for complications in adult spinal deformity (ASD) patients undergoing pedicle subtraction osteotomy (PSO) and define categories of complication risk by sarcopenia severity.

Summary of Background Data:

Sarcopenia is linked to morbidity and mortality in several orthopedic procedures. Data concerning sarcopenia in ASD surgery is limited, particularly with respect to complex techniques performed such as PSO. With the high surgical burden of PSOs, appropriate patient selection is critical for minimizing complications.

Methods:

We identified 73 ASD patients with lumbar CT/MRI scans who underwent PSO with spinal fusion ≥5 levels at a tertiary care center from 2005 to 2014. Sarcopenia was assessed by the psoas-lumbar vertebral index (PLVI). Using stratum-specific likelihood ratio analysis, patients were separated into 3 sarcopenia groups by complication risk. The primary outcome measure was any 2-year complication. Secondary outcome measures included intraoperative blood loss and length of stay.

Results:

The mean PLVI was 0.84±0.28, with 47% of patients having complications. Patients with a complication had a 27% lower PLVI on average than those without complications (0.76 vs. 0.91, P=0.021). Stratum-specific likelihood ratio analysis produced 3 complication categories: 32% complication rate for PLVI ≥ 0.81; 61% for PLVI 0.60–0.80; and 69% for PLVI < 0.60. Relative to patients with PLVI ≥ 0.81, those with PLVI 0.60–0.80 and PLVI < 0.60 had 3.2× and 4.3× greater odds of developing a complication (P<0.05). For individual complications, patients with PLVI < 1.0 had a significantly higher risk of proximal junctional kyphosis (34% vs. 0%, P=0.022), while patients with PLVI < 0.8 had a significantly higher risk of wound infection (12% vs. 0%, P=0.028) and dural tear (14% vs. 0%, P=0.019). There were no significant associations between sarcopenia, intraoperative blood loss, and length of stay.

Conclusions:

The increasing severity of sarcopenia is associated with a significantly and incrementally increased risk of complications following ASD surgery that require PSO.

Level of Evidence:

Level III.
Synergistic effects of combined therapy with cerebrolysin and enriched environment on anxiety-like behavior and spatial cognitive deficits in posttraumatic stress disorder-like mouse model
Authors: Hosseini Leila , Sadigh-Eteghad Saeed , Farajdokht Fereshteh , Salehi-Pourmehr Hanieh , Pasokh Amir , Ziaee Mojtaba , Sandoghchian Shotorbani Siamak , Hosseini Mir-Jamal , Mahmoudi Javad
Published: February 2023

Posttraumatic stress disorder (PTSD) is a serious neuropsychiatric disorder that occurs after exposure to stressful, fearful, or troubling events. Cerebrolysin (CBL), consists of low molecular weights neurotrophic factors and amino acids obtained from purified porcine brain proteins. This study aimed to evaluate the possible therapeutic effects of enriched environment (EE) and CBL alone or combined for reducing anxiety and cognitive deficits in PTSD-like mouse models. For this purpose, inescapable electric foot shocks were delivered to Balb/c mice for two consecutive days. Then mice were treated with CBL (2.5 mL/kg) and/or were kept in EE (2 h per day) or received their combination for 14 consecutive days. The hole-board test and Lashley III paradigm were used to assess anxiety and spatial learning and memory, respectively. Changes in the serum corticosterone level and expression of synaptic elements, including; growth-associated protein 43, post-synaptic density 95, and synaptophysin were assessed in the hippocampus. This model caused anxiety and spatial memory impairment associated with increased serum corticosterone levels and decreased synaptic elements. Nevertheless, CBL and/or combination treatment could reverse behavioral and molecular alterations. Our findings indicated that CBL, separately or in combination with EE, is effective in reducing anxiety and spatial memory impairment in PTSD-like mice.
The CKS1/CKS2 Proteostasis Axis Is Crucial to Maintain Hematopoietic Stem Cell Function
Authors: Grey William , Atkinson Samantha , Rix Beatrice , Casado Pedro , Ariza-McNaughton Linda , Hawley Cathy , Sopoena Miriam L. , Bridge Katherine S. , Kent David , Cutillas Pedro R. , Bonnet Dominique
Published: February 2023

Long-term hematopoietic stem cells are rare, highly quiescent stem cells of the hematopoietic system with life-long self-renewal potential and the ability to transplant and reconstitute the entire hematopoietic system of conditioned recipients. Most of our understanding of these rare cells has relied on cell surface identification, epigenetic, and transcriptomic analyses. Our knowledge of protein synthesis, folding, modification, and degradation—broadly termed protein homeostasis or “proteostasis”—in these cells is still in its infancy, with very little known about how the functional state of the proteome is maintained in hematopoietic stem cells. We investigated the requirement of the small phospho-binding adaptor proteins, the cyclin-dependent kinase subunits (CKS1 and CKS2), for maintaining ordered hematopoiesis and long-term hematopoietic stem cell reconstitution. CKS1 and CKS2 are best known for their roles in p27 degradation and cell cycle regulation, and by studying the transcriptome and proteome of Cks1

−/−
and Cks2

−/−
mice, we demonstrate regulation of key signaling pathways that govern hematopoietic stem cell biology including AKT, FOXO1, and NFκB, together balancing protein homeostasis and restraining reactive oxygen species to ensure healthy hematopoietic stem cell function.
Return to the Emergency Department Within 3 Months Following Pediatric Acute Concussion
Authors: Engel Jake , van Ierssel Jacqueline Josee , Osmond Martin H. , Tsampalieros Anne , Webster Richard , Zemek Roger
Published: February 2023

Objective:

To determine the proportion of concussed children returning to the emergency department (ED) for a concussion-related reason within 3 months of initial presentation and to determine which clinical composite score (5P or Post-Concussion Symptom Inventory) best predicts a return visit.

Setting, Design, and Participants:

We combined a secondary analysis of data from the prospectively collected 5P study with a retrospective medical record review of children aged 5 to 18 years who returned to the Children's Hospital of Eastern Ontario (CHEO) ED for a concussion-related reason within 3 months of an acutely diagnosed concussion. Among 770 eligible participants, 632 children (median age: 11.8 [interquartile range (IQR), 9.0-14.5] years; 58.9% male) were included in the study.

Main Measures:

The primary outcome was the number of patients who returned to CHEO ED for a concussion-related reason within 3 months of an acute concussion diagnosed at CHEO ED. The secondary outcome was number of patients who returned within 14 days.

Results:

Forty-seven children (7.4%; 95% confidence interval [CI]: 5.6-9.7) had a concussion-related return to the ED within 3 months, the majority of which occurred in the first 14 days (29/47; 61.7%; 95% CI: 47.4-74.2). History of migraines (21.3% vs 9.7%; P = .03) were more common in those with a return visit. Headache was the most frequently reported symptom (87.2%) on revisit. Females aged 13 to 18 years had the highest return rate (survival rate: 85.8% [95% CI: 79.8-92.3]) compared with males and younger age groups. In multivariable Cox hazards regression modeling, inclusion of risk scores improved prognostication (pseudo R
2 = 8%). The difference in pseudo R
2 between 5P and Post-Concussion Symptom Inventory is small.

Conclusion:

Most children and adolescents do not return to the ED following an acute concussion. Female youth with medium to high 5P scores at the index concussion visit may benefit from early referral to interdisciplinary specialty concussion care to guide treatment in anticipation of prolonged symptoms. By identifying these risk factors at the initial ED visit, healthcare and patient burden may be reduced.
Considerations for Implementing the Post-Concussion Collegiate Return-to-Learn Protocol in the National Collegiate Athletic Association Power 5 Conferences
Authors: Memmini Allyssa K. , Kinnett-Hopkins Dominique L. , Hasson Rebecca E. , Rifat Sami F. , Broglio Steven P.
Published: February 2023

Objective:

Although concussions affect millions of young adults annually, researchers have yet to assess factors that may affect future implementation of post-concussion academic supports within higher education. Therefore, we sought to evaluate preimplementation outcomes of the acceptability, feasibility, appropriateness, and readiness for change of the Post-Concussion Collegiate Return-to-Learn (RTL) Protocol among university stakeholders.

Setting:

An online survey.

Participants:

A convenience sample (N = 49; 63.3% female) of athletic trainers (ATs; n = 25, age = 30.1 ± 7.6 years) and university faculty/staff (n = 24, age = 38.3 ± 9.9 years) across the National Collegiate Athletic Association (NCAA) Power 5 Conferences from January to February 2022.

Design:

A cross-sectional study.

Main Measures:

To compare preimplementation outcome measures using the Acceptability of Intervention Measure (AIM), Feasibility of Intervention Measure (FIM), Intervention Appropriateness Measure (IAM), and Organizational Readiness for Implementing Change (ORIC) regarding the RTL protocol between ATs and university faculty/staff. Additional outcomes included internal and external barriers to implementing at their respective institutions. Statistical analyses were conducted using Mann-Whitney U tests, with effect sizes estimated using eta-squared coefficient (η2).

Results:

Quantitative analyses yielded no statistically significant group differences (Ps > .05) across the AIM, FIM, and IAM outcomes, indicating both groups perceived the protocol to be acceptable, feasible, and appropriate. Moreover, ATs reported higher agreement regarding motivation, desire, willingness to do “whatever it takes,” commitment, and determination to implement the novel protocol than faculty/staff. Further, ATs reported higher agreement regarding their institution's confidence to keep track of its progress, support adjustment, maintain momentum, manage institutional politics, coordinate tasks, encourage investment, and handle the challenges of future implementation of the RTL protocol.

Conclusions:

Preliminary findings suggest ATs and university faculty/staff across the NCAA Power 5 Conferences may perceive the RTL protocol to be acceptable, feasible, and appropriate for future use; however, noteworthy internal and external barriers may influence its uptake. Future research should utilize implementation frameworks to support the protocol's adoption and reach.
Trends and Surgeon Variations in Early Regrafts After Endothelial Keratoplasty: Analysis of the National Medicare Data Set
Authors: Huh Dana D. , Dun Chen , Fliotsos Michael J. , Jeng Bennie H. , Stoeger Christopher G. , Makary Martin , Woreta Fasika A. , Wolle Meraf , Srikumaran Divya
Published: February 2023

Purpose:

The aims of this study were to determine national-level trends in early regraft rates and examine patient-level and surgeon-level characteristics associated with early regrafts.

Methods:

This was a retrospective, cohort study. We identified beneficiaries aged 65 years or older in the 2011 to 2020 Medicare carrier claims data set who underwent Endothelial keratoplasty (EK) and subsequently underwent an early regraft. The incidence of early regraft for each year was calculated and patient-level and surgeon-level characteristics associated with regrafts were examined using a multivariable regression model.

Results:

Of 114,383 EK procedures, 4119 (3.60%) were followed by an early regraft, with no significant variations in the rates between years (P = 0.59). Factors associated with higher odds of early regraft were Black compared with White race (OR 1.151; 95% confidence interval (CI) 1.018–1.302) and the highest quartile of income versus the lowest quartile (OR 1.120; 95% CI 1.002–1.252). Factors associated with lower odds were female sex (OR 0.889; 95% CI 0.840–0.942), receiving surgery in a hospital-based outpatient department versus an ambulatory center (OR 0.813; 95% CI 0.740–0.894), and having a surgeon with the highest quartile of annual EK volume versus the lowest (OR 0.726; 95% CI 0.545–0.967). Early regraft rates among surgeons ranged from 0% to 58.8% with a median [interquartile range] of 3.13 [0–6.15].

Conclusions:

We found no significant increases in the early regraft rates over the past decade in the United States. Patient male sex and Black race, ambulatory surgery center-based location of the surgery, and low surgeon EK volume were associated with early regrafts. Substantial surgeon variability in regraft rates may indicate opportunities for improvement through development of best practices on perioperative management and patient counseling.
Association of Area Deprivation Index With Severity of COVID-19 in Pediatric Patients: A Multisite Study of Racially and Ethnically Diverse Children
Authors: Acosta Sebastian , Suresh Srinivasan , Ettinger Anna K. , Savorgnan Fabio , Annapragada Ananth , Kannikeswaran Nirupama , Sethuraman Usha
Published: February 2023

Area deprivation index (ADI) is associated with the risk of severe COVID-19 in adults. However, this association has not been established in children. Information on ADI, demographics, clinical features, disease severity, and outcomes was analyzed for 3434 children with COVID-19. A multivariate logistic regression revealed that non-Hispanic Asians, extremes of weight, and higher ADI were associated with severe disease.
Recurrence Following Globe Sparing Excision for Basal Cell Carcinoma with Anterior Orbital Invasion
Authors: Tong Jessica Y. , Martin Peter A. , Tumuluri Krishna , Selva Dinesh
Published: February 2023

Purpose:

Globe-sparing excision for periocular basal cell carcinoma (BCC) with orbital invasion has evident benefits, but the ensuing morbidity and characteristics of recurrence are not well elucidated. This study aims to describe the extent of visual morbidity following globe-sparing excision, and the clinicoradiological characteristics of tumor recurrence.

Methods:

Multicentre retrospective case series.

Results:

Eight patients were identified for inclusion in this series. Time to recurrence following globe-sparing excision ranged from 3 to 12 years. Seven patients (87.5%) presented with recurrent disease originating from the medial canthus. Clinical features at presentation included contracture (n=4, 50.0%), upper lid ptosis (n=3, 37.5%), a palpable mass (n=2, 25.0%), and hypoesthesia (n=2, 25.0%). Radiologically, tumor recurrence was predominantly characterized by isointense signals on T1 and T2-weighted sequences (n=5, 62.5%) with moderate contrast enhancement. The most common histologic subtype in recurrent tumors was a mixed nodular and infiltrative growth pattern (n=5, 62.5%). Perineural invasion was a feature in four (50%) cases. Salvage therapy in the form of exenteration was performed in seven cases. Vismodegib and adjuvant radiotherapy were provided for one case with surgically unresectable tumor recurrence.

Conclusions:

Globe-sparing excision for invasive periocular BCC can be complicated by late recurrence that develops rapidly despite silent neuroimaging for years. Early clinical signs are subtle. High-risk features predictive of recurrence include medial canthus location, mixed histological subtypes, and perineural invasion. Patients with such characteristics require lifelong clinical and imaging surveillance following globe-sparing excision.
Superior Visual Field Testing Using Virtual Reality With and Without Eye Tracking for Functional Upper Eyelid Surgery Evaluation: A Pilot Study
Authors: Patel Annika J. , Lee Wendy W. , Ziff Matteo , Munshi Hounsh , Chang Ta C. , Grajewski Alana L. , Wester Sara T. , Tse David T. , Tse Brian C.
Published: February 2023

Purpose:

To assess the sensitivity and specificity of superior visual field tests administered in virtual reality (VR) with eye tracking (VR-ET) and without eye tracking (VR0) for the fulfillment of insurance coverage criteria for functional upper eyelid surgery as compared with standard automated perimetry (SAP).

Methods:

This prospective cross-sectional study included 78 eyes from 41 patients with ptosis, brow ptosis, and dermatochalasis undergoing functional upper eyelid surgery evaluation. Participants underwent serial superior visual field tests using SAP and VR0 or VR-ET in randomized order. Fulfillment of insurance coverage criteria for blepharoplasty was defined as a 30% increase in the grid seen from the untaped to the taped state. The main outcome measure was the sensitivity and specificity of VR0, VR-ET, and overall VR in meeting insurance coverage criteria as compared with SAP.

Results:

VR had a sensitivity of 84.1% and specificity of 67.6%, with no significant difference between VR0 and VR-ET. SAP agreed on insurance coverage criteria fulfillment with VR0 in 28 (71.8%) eyes and with VR-ET in 32 (82.1%) eyes. Insurance coverage criteria fulfillment rates varied significantly by diagnosis on SAP (p = 0.012) but not VR (p = 0.059).

Conclusions:

VR may be an alternative to SAP for functional upper eyelid surgery evaluation. Future studies are needed to determine differences in patient satisfaction, testing and waiting time, and test-retest reliability between VR and SAP.
Plasma Cell-Free DNA After Embolization
Authors: Sun Yi , Cai Ren , Wang Zhenfeng , Wang Deming , Zhao Xiong , Yue Xiaojie , Gu Hao , Shi Hao , Liu Yun , Fan Xindong , Su Lixin
Published: February 2023

Objectives:

To identify genetic variants in venous malformations for noninvasive diagnosis using peripheral plasma Cell-free DNA (cfDNA) after ethanol embolization.

Method:

In this prospective, multicenter and cross-sectional study with a total of 121 patients with venous malformation, next-generation sequencing with a targeted panel of 40 specific genes was conducted to detect variants. We collected peripheral blood samples, cfDNA samples isolated from peripheral plasma before and 1 hour after ethanol embolization in 24 patients in a pilot study, and paired lesion plasma samples in 7 of those patients. Then variant profiles of peripheral postembolization plasma cfDNA were prospectively collected and analyzed from 97 patients in an independent validation group.

Results:

Variants were detected in cfDNA samples, but none was detected in paired peripheral blood. The prevalence of TEK/PIK3CA variant in peripheral pre-embolization, postembolization, and lesion plasma cfDNA were 12.5%, 87.5%, and 71.4% (P < .0001), respectively, which areas under the ROC curve of 0.5625 (P = .4579), 0.9375 (P < .0001), and 0.8571 (P = .0253), respectively. In a prospective independent validation group with postembolization cfDNA analysis in 97 patients, 119 variants were identified in 90.7% (88/97) of patients with areas under the ROC curve of 0.9545 (P < .0001).

Conclusion:

cfDNA from peripheral postembolization plasma bears safe, sensitive, and reliable diagnostic potential for venous malformations.
Can Referees Assess Head Contact Penalties Correctly in Canadian Youth Ice Hockey? A Video Analysis Study
Authors: Williamson Rylen A. , Kolstad Ash T. , Eliason Paul H. , Hagel Brent E. , Emery Carolyn A.
Published: February 2023

Objective:

To help address the high concussion burden in Canadian youth ice hockey, our primary objective was to examine the concurrent validity of youth ice hockey referees' ability to assess head contacts (HCs) and associated penalties using video analysis methods after implementation of the “zero tolerance for HC” policy by Hockey Canada.

Study Design:

Cross-sectional study.

Participants:

Certified Level II-III referees in Alberta, Canada.

Intervention:

A secured online survey with 60 videos (10 to 15 seconds) containing a player-to-player physical contact with or without a HC from elite U15 (ages 13 to 14) youth ice hockey games.

Outcome Measures:

Survey questions were completed by all referees for each video, including (1). ‘Did you see a player-to-player contact?’, (2). ‘Should a penalty be assessed?’, and if yes, (3). ‘Which player, penalty type, and penalty intensity?’ Referee assessments were compared with a consensus agreement from 2 national and member (top level) gold standard referees for concurrent validity through percent agreement and sensitivity/specificity measures.

Results:

Complete-case analysis of 100 referees (131 recruited) showed an overall median agreement of 83.5% (sensitivity = 0.74; specificity = 0.69) with the gold standard. Agreement with the gold standard was highest for HC infractions [85.1% (sensitivity = 0.80; specificity = 0.69)], followed by HC penalty type (81.5%) and penalty intensity (53.7%).

Conclusions:

Concurrent validity through percent agreement was high (>80%) compared with the gold standard for identifying both HC and other infractions; however, it was moderate for penalty intensity. Although knowledge of identifying HCs and penalties in this survey was acceptable, this study suggests in-game factors (eg, game management and positioning) may be a primary limitation for HC enforcement.
King-Devick Test in Wheelchair Sports: Identifying Normative Values and Effects of Exertion on Outcomes
Authors: Barfield Jean-Paul , Linens Shelley , Mickle Angela
Published: February 2023

Objective:

To establish normative baseline values on the King-Devick (KD) Test for contact wheelchair sport participants. The secondary purpose was to examine the effect of physical exertion on test score.

Design:

Quasiexperimental.

Setting:

Competitive disability sport venues before practices or games.

Participants:

One-hundred 43 wheelchair rugby or wheelchair basketball (WBB) players completed the study. Participants were predominantly men (87.5%) and played WBB (84%).

Intervention:

30-m wheelchair sprint test to fatigue.

Main Outcome Measure:

King-Devick Baseline Score.

Results:

Mean KD baseline score was 59.16 ± 15.56 seconds with significant differences (P< 0.05) identified by sport and impairment type, but not sex. Athletes with spina bifida and cerebral palsy had significantly higher mean baseline KD times than athletes with spinal cord injury. KD scores improved by 3.5% in athletes who reported “light” to “somewhat hard” exertion (RPE = 13). In a subset of athletes who performed sprints until an RPE of 18 was reached, 8 of 12 players (66.7%) demonstrated an improvement in KD score; however, large increases by a few participants caused the noticeable change.

Conclusions:

Normative values for wheelchair contact sport athletes are meaningfully slower than able-bodied sports participants. KD score improved with exertion with the greater improvement after moderate-intensity compared with vigorous-intensity exercise. These findings can be applied clinically to monitor athlete safety.
Effect of Temperature on Thrombogenicity Testing of Biomaterials in an In Vitro Dynamic Flow Loop System
Authors: Patel Mehulkumar , Jamiolkowski Megan A. , Vejendla Anjali , Bentley Viviana , Malinauskas Richard A. , Lu Qijin
Published: February 2023

To develop and standardize a reliable in vitro dynamic thrombogenicity test protocol, the key test parameters that could impact thrombus formation need to be investigated and understood. In this study, we evaluated the effect of temperature on the thrombogenic responses (thrombus surface coverage, thrombus weight, and platelet count reduction) of various materials using an in vitro blood flow loop test system. Whole blood from live sheep and cow donors was used to assess four materials with varying thrombogenic potentials: negative-control polytetrafluoroethylene (PTFE), positive-control latex, silicone, and high-density polyethylene (HDPE). Blood, heparinized to a donor-specific concentration, was recirculated through a polyvinyl chloride tubing loop containing the test material at room temperature (22–24°C) for 1 hour, or at 37°C for 1 or 2 hours. The flow loop system could effectively differentiate a thrombogenic material (latex) from the other materials for both test temperatures and blood species (p < 0.05). However, compared with 37°C, testing at room temperature appeared to have slightly better sensitivity in differentiating silicone (intermediate thrombogenic potential) from the relatively thromboresistant materials (PTFE and HDPE, p < 0.05). These data suggest that testing at room temperature may be a viable option for dynamic thrombogenicity assessment of biomaterials and medical devices.
Less Invasive Left Ventricular Unloading With Impella May Improve the Clinical Outcomes of Fulminant Myocarditis
Authors: Kawamura Takuji , Toda Koichi , Yoshioka Daisuke , Kawamura Masashi , Saito Tetsuya , Kawamura Ai , Nakamoto Kei , Sakata Yasushi , Miyagawa Shigeru
Published: February 2023

Fulminant myocarditis (FM) requiring temporary mechanical circulatory support (t-MCS) has a high mortality rate. Peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pump (IABP) are sometimes insufficient to induce cardiac recovery. For patients with FM refractory to VA-ECMO with IABP, we have applied a biventricular assist device (BIVAD) or Impella to unload the left ventricle and to fully support the systemic circulation. In the last 10 years, 37 refractory FM patients histologically diagnosed with myocarditis and who did not recover with VA-ECMO were treated with BIVAD (n = 19) or Impella (n = 18). No significant difference was found between the Impella and BIVAD groups in preoperative findings other than serum creatinine level. Seventeen of 18 patients in the Impella group were successfully weaned from t-MCS in 9 (6–12) days. Conversely, the temporary BIVAD was removed in 21 (11–38) days in 10 of 19 patients. Six patients died while on temporary BIVAD because of multiple organ failure and cerebral bleeding, and three patients required conversion to implantable VAD. Compared with BIVAD, left ventricular unloading with Impella could be less invasive and could promote cardiac recovery in refractory FM patients. The Impella has the potential to provide effective temporary MCS for FM patients.
Does low-density lipoprotein fully explain atherosclerotic risk in familial hypercholesterolemia?
Authors: Clarke Shoa L.
Published: February 2023

Purpose of review

Familial hypercholesterolemia (FH) is a monogenic disorder of elevated low-density lipoprotein cholesterol (LDL-C) from birth leading to increased risk for atherosclerotic cardiovascular disease. However, not all carriers of FH variants display an FH phenotype. Despite this fact, FH variants confer increased risk for atherosclerotic disease in population cohorts. An important question to consider is whether measurements of LDL-C can fully account for this risk.

Recent findings

The atherosclerotic risk associated with FH variants is independent of observed adult LDL-C levels. Modeling adult longitudinal LDL-C accounts for more of this risk compared to using a single measurement. Still, even when adjusting for observed longitudinal LDL-C in adult cohorts, FH variant carriers are at increased risk for coronary artery disease. Genetic analyses, observational studies, and clinical trials all suggest that cumulative LDL-C is a critical driver of cardiovascular risk that may not be fully appreciated by routine LDL-C measurements in adulthood. As such, FH variants confer risk independent of adult LDL-C because these variants increase cumulative LDL-C exposure starting from birth.

Both research and clinical practice focus on LDL-C measurements in adults, but measurements during adulthood do not reflect lifelong cumulative exposure to LDL-C. Genetic assessments may compliment clinical assessments by better identifying patients who have experienced greater longitudinal LDL-C exposure.
Nonalcoholic fatty liver disease: an update
Authors: Bedogni Giorgio , Palmese Francesco , Foschi Francesco Giuseppe
Published: February 2023

Purpose of review

We discuss two recent controversial issues in the research field of fatty liver: the proposal to replace nonalcoholic fatty liver disease (NAFLD) with metabolically associated fatty liver disease (MAFLD) and the suggestion to extend to primary care the noninvasive testing for liver fibrosis that was developed for secondary care.

Recent findings

There is preliminary evidence that MAFLD-only patients are at greater risk of fibrosis than NAFLD-only patients. There are a large number of false positives associated with the downshift of noninvasive testing for liver fibrosis from secondary to primary care.

More studies are needed to compare the MAFLD and NAFLD operational definitions. Noninvasive testing of liver fibrosis also needs further evaluation before it can be used in primary care or in the general population.
Factors Associated With the Occurrence of Adverse Effects Resulting From Hypodermoclysis in Older Adults in Palliative Care: A Cohort Study
Authors: de Souza Raquel Eustaquia , Quispe Mendoza Isabel Yovana , Reis Adriano Max Moreira , Tavares João Paulo de Almeida , Guimarães Gilberto de Lima , Simino Giovana de Paula Rezende , Moura Ravena Rieelly Araújo , da Silva Silmar Maria
Published: February 2023

This study aimed to analyze the factors associated with local adverse effects resulting from hypodermoclysis in older adult patients in palliative care. The study involved 127 older adults undergoing palliative care at a hospital in southeastern Brazil. Data collection was performed from August to November 2019. Patients aged 60 years or older, with a prescription for hypodermoclysis at the time of admission and who were not receiving hypodermoclysis at the time of admission, were included. Data collected included sociodemographic, clinical, pharmacotherapeutic, and adverse effects of hypodermoclysis administration. Most participants were women (59.0%), with a mean age of 78.5 years. Frailty was the most prevalent diagnosis (26.8%), and 80.2% of patients were in the end-of-life stage. There was an incidence of 24.0% of adverse events, with catheter obstruction and swelling in the surrounding area of the hypodermoclysis site being the most frequent at 11.3% and 8.5%, respectively. Ondansetron administration by hypodermoclysis was 3 times more likely to have an adverse effect compared to not using this drug. In contrast, a protective factor was evident with the administration of 0.9% sodium chloride, which contributed to the reduction of complications. The occurrence of adverse effects from hypodermoclysis in the study population of older adults in palliative care was low.
Distinguishing Autoimmune Hepatitis From Steatohepatitis in Adolescents With Obesity and Positive Screening Alanine Aminotransferase
Authors: Hildreth Amber , Shapiro Warren L. , Lowenthal Brett M. , Goyal Anurag , Schwimmer Jeffrey B.
Published: February 2023

Screening children with obesity for nonalcoholic fatty liver disease leads to identification of elevated alanine aminotransferase (ALT) and is a common cause for referral to pediatric gastroenterology. Guidelines recommend that children with positive screening ALT be evaluated for causes of ALT elevation beyond nonalcoholic fatty liver disease. One clinical challenge is that autoantibodies can be present in patients with obesity and thus may or may not represent autoimmune hepatitis. This case series highlights the importance of a comprehensive evaluation to reach an accurate diagnosis.
Is Reflex Parotitis a Forgotten or an Unknown Pathology?
Authors: Fernández-Olarte Humberto , Ratinoff Marcos , López Juan Pablo , Castel-Belmonte Isabel
Published: February 2023

Reflex parotitis is a recurrent parotid inflammation caused by an imbalance in the parasympathetic innervation of the salivary gland. However, due to a poor understanding of its pathophysiology, it can go unnoticed. Causes of ignored norms can trigger these repetitive episodes of glandular disease with a difficult diagnosis and inadequate treatment.
THE EFFECTS OF DNASE I AND LOW-MOLECULAR-WEIGHT HEPARIN IN A MURINE MODEL OF POLYMICROBIAL ABDOMINAL SEPSIS
Authors: Medeiros Sarah K. , Sharma Neha , Dwivedi Dhruva , Cani Erblin , Zhou Ji , Dwivedi Naviya , Sohrabipour Sahar , Liaw Patricia C.
Published: February 2023

Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in the form of nucleosomes. In vitro, DNA activates coagulation and inhibits fibrinolysis, whereas histones activate platelets and are cytotoxic to endothelial cells. Previous studies have targeted CFDNA or histones in animal models of sepsis using DNase I or heparins, respectively, which has reduced inflammatory and thrombosis markers, thereby improving survival. In this study, we explored the possibility that the combination of DNase I and a low-molecular weight heparin (LMWH) may be a better therapeutic approach than monotherapy in a murine model of abdominal sepsis. Methods: C57Bl/6 mice (8–12 weeks old, both sexes) were subjected to either cecal ligation and puncture or sham surgery. Mice were given antibiotics, fluids, and either saline, DNase I (intraperitoneally, 20 mg/kg/8 h), LMWH (dalteparin, subcutaneously 500 IU/kg/12 h), or a combination of both (n = 12–31). Mice were monitored over 72 h for survival. Organs and blood were harvested for analysis. Levels of LMWH, CFDNA, IL-6, citrullinated histone-H3, thrombin-antithrombin complexes, and protein C were measured in plasma. Results: Administration of either DNase I (81.8%) or LMWH (83.3%, prophylactic range of 0.12 ± 0.07 IU/mL achieved) improved the survival of septic mice compared with saline- (38.7%) and combination-treated mice (48.8%, P < 0.05). Combination-treated mice also showed a small but insignificant improvement in survival compared with saline-treated cecal ligation and puncture mice. Monotherapies may be improving survival by reducing blood bacterial loads, citrullinated histone-H3, and thrombin-antithrombin complexes, and improving protein C levels. Conclusions: Compared with saline- and combination-treated mice, administration of monotherapies to septic mice improved survival. These findings suggest that there may be a negative drug-drug interaction between DNase I and LMWH when DNase I is administered intraperitoneally in a murine model of polymicrobial abdominal sepsis.
LOW DOSE OF ESMOLOL ATTENUATES SEPSIS-INDUCED IMMUNOSUPPRESSION VIA MODULATING T-LYMPHOCYTE APOPTOSIS AND DIFFERENTIATION
Authors: Ma Ying , Cheng Zhenshun , Zheng Yong , Wang Wei , He Shaojun , Zhou Xiaolian , Yang Jiong , Wei Chaojie
Published: February 2023

Background: Immunosuppression caused by immune cell apoptosis and an imbalance of T helper 2 cells (TH2) and T helper 1 cells (TH1), is associated with poor outcomes in septic patients. Esmolol was reported to improve survival by modulating immune responses in septic shock. Whether esmolol could alleviate sepsis-induced immunosuppression and the optimal dose are unclear. Methods: Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (esmolol: 5 mg·kg−1·h−1) and CLP + E-18 (esmolol: 18 mg·kg−1·h−1) groups. Eight rats were underwent sham operation. Eighteen hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and T-lymphocyte subsets counts were determined by flow cytometry, and the expression of p-Akt, Bcl-2, cleaved Caspase-3, and p-Erk1/2 in splenic CD4+ T-lymphocytes was determined by western blot and immunohistochemistry. β1-Adrenoreceptor expressions were evaluated using real-time polymerase chain reaction and immunohistochemistry. Results: Cecal ligation and puncture induced tachycardia, hypotension, hyperlactatemia, and multiple organ injury. Heart rate was unchanged in the CLP + E-5 group but decreased in the CLP + E-18 group. Hypotension, lactatemia, and multiple organ injuries were improved only in the CLP + E-5 group. T-lymphocyte apoptosis and TH2/TH1 ratio was decreased in CLP + E-5 but not in CLP + E-18. p-Akt and Bcl-2 expressions were increased, while cleaved Caspase-3 and p-Erk1/2 expressions were decreased in CLP + E-5. β1-Adrenoreceptor expressions were unchanged in both CLP + E-5 and CLP + E-18 groups. Conclusions: Low dose of esmolol reduced T-lymphocyte apoptosis and restored TH2/TH1 ratio in septic shock. Esmolol might modulate Akt/Bcl-2/Caspase-3 pathway to relieve T-lymphocyte apoptosis and inhibit Erk1/2 activity to decrease TH0 differentiation to TH2. Esmolol may be a potential immunoregulator of septic shock.
EFFECTS OF MESENCHYMAL STEM CELLS ON POSTRESUSCITATION RENAL AND INTESTINAL INJURIES IN A PORCINE CARDIAC ARREST MODEL
Authors: Chen Chuang , Ma Shuangshuang , Liao Lyuzhao , Xiao Yu , Dai Haiwen
Published: February 2023

Objectives: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes postresuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in a porcine CA model. Methods: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. Mesenchymal stem cells were differentiated from human embryonic stem cells and then intravenously administered at a dose of 2.5 × 106/kg at 1.5 and 3 d before the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid–binding protein, and diamine oxidase at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues. Results: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid–binding protein, and diamine oxidase were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSC administration significantly decreased the levels of renal and intestinal injury biomarkers compared with those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group. Conclusions: MSC administration was effective in alleviating postresuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.
Population structure and antimicrobial resistance patterns ofSalmonellaTyphi and Paratyphi A amid a phased municipal vaccination campaign in Navi Mumbai, India
Authors: Da Silva Kesia Esther , Date Kashmira , Hirani Nilma , LeBoa Christopher , Jayaprasad Niniya , Borhade Priyanka , Warren Joshua , Shimpi Rahul , Hoffman Seth Ari Sim-Son , Mikoleit Matthew , Bhatnagar Pankaj , Cao Yanjia , Dutta Shanta , Luby Stephen P , Andrews Jason R.
Published: February 2023

We performed whole genome sequencing of 174SalmonellaTyphi and 54SalmonellaParatyphi A isolates collected through prospective and retrospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patters of emergence and spread of antimicrobial resistance. Additionally, we evaluated the relationship between the spatial distance between households and genetic clustering of isolates using hierarchical Bayesian models. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 mutations in the quinolone resistance determining region, conferring high-level resistance. Two H58 isolates carried an IncX3 resistance plasmid containingblaSHV-12, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistantS. Typhi isolates from India have evolved independently on multiple occasions. AmongS. Typhi isolates, we identified two main clades circulating in Navi Mumbai (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (OR 0.72 per km; 95% CrI: 0.66-0.79). This effect was seen for distances up to 5 km (OR 0.65 per km; 95% CrI: 0.59-0.73) but was not seen for distances beyond 5 km (OR 1.02 per km; 95% CrI: 0.83-1.26). Our findings indicate thatS. Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial-genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission.
Neurocognitive Dysfunction in Children and Adolescents with Mental Illness
Authors: Nesamoney Sean , Hilton Rachel A. , Tozzi Leonardo , Williams Leanne M.
Published: February 2023

Introduction

Robust evidence from adult samples indicates that neurocognitive dysfunction is a hallmark of many mental illnesses, contributing to the loss of daily function and quality of life that these illnesses cause. However, it is still unclear whether neurocognitive deficits associated with mental illnesses begin to manifest well before adulthood. The current study addresses this gap by evaluating neurocognitive function in four groups of children and adolescents with different mental illnesses compared to their matched healthy peers.

Methods

We evaluated the neurocognitive performance of four samples of youth diagnosed with ADHD (N=343), Anorexia (N=40), First-onset psychosis (N=25), and Conversion Disorder (N=56) with age-matched healthy controls. Performance was assessed using an objective assessment battery designed for use across diagnoses and settings and validated for its correlations with underlying brain structure and function. The resulting analyses assessed accuracy and reaction time performance for neurocognitive domains well established in the adult literature, such as cognitive flexibility, executive function, response inhibition, verbal fluency, verbal memory, visual memory, sustained attention, and working memory. Clinical and healthy group performance was compared using non-parametric testing.

Results

Distinct profiles of neurocognitive dysfunction were detected for each diagnosis. Particularly, children and adolescents with ADHD diffusely performed worse than their healthy counterparts, with exceptional impairment in working memory. Children and adolescents with anorexia displayed more specific impairments limited to response inhibition and verbal memory. While youth with ADHD had the most cognitive domains affected, youth with first-onset psychosis displayed the most severe impairments compared to healthy controls. Finally, deficits in conversion disorder were limited to cognitive flexibility, executive function, decision making, response inhibition, and working memory. These findings suggest that neurocognitive impairment in mental illness is transdiagnostic and can be detected as early as childhood or adolescence with standardized computerized testing.
Heart disease mortality in cancer survivors: A population-based study in Japan
Authors: Gon Yasufumi , Zha Ling , Sasaki Tsutomu , Morishima Toshitaka , Ohno Yuko , Mochizuki Hideki , Sobue Tomotaka , Miyashiro Isao
Published: February 2023

Background

The association between cancer survivors and heart disease mortality remains unclear. This study analyzed the risk of fatal heart disease in cancer survivors.

Methods

Data from the Osaka Cancer Registry collected between 1985 and 2013 and data from the vital statistics in Japan were retrospectively analyzed. Causes of death were investigated.

Standardized mortality ratios (SMRs) were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Poisson regression models were used to estimate the risk of fatal heart disease in patients with cancer and other cancer subgroups.

Results

In total, 688,473 cancer patients were included in the analysis, and 337,117 patients died during the study period. Among them, 10,781 patients died of heart disease, with 5,020 of these patients having ischemic heart disease; 3,602 patients, heart failure; 441 patients, hypertensive disease; and 1,718 patients, other heart diseases. The SMR (95% confidence interval [CI]) for heart disease was 2.85 (2.80–2.91). The SMRs (95% CIs) for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (3.17–3.35); 2.69 (2.60–2.78), and 4.47 (4.07–4.90), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. The multivariable Poisson regression model showed that males were more likely to die of heart disease than females (relative risk, 1.39; 95% CI, 1.34–1.45). Notably, the risk of fatal heart disease among cancer survivors has decreased in recent years.

Conclusions

Cancer survivors have a higher risk of fatal heart disease than the general population.