bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel occupational causes of hypersensitivity pneumonitis
Authors: Walters Gareth I. , Huntley Christopher C.
Published: February 2023

Purpose of review

Hypersensitivity pneumonitis (HP) remains a challenging diagnosis, and a cause is not established in up to 50% of cases. This paper aims to update clinicians on traditional and novel occupational causes of HP, and clinical tools for identifying of causative exposures and antigens.

Recent findings

Metalworking fluid has become the most frequently cited occupational cause of HP, though geographical variations in exposures exist. Occupational HP is usually associated with work-related symptoms. Systematically derived questionnaires and compendia for HP have been developed for use in cryptogenic disease, though have previously lacked validation; these may help identify inciting antigens or relevant occupational exposures.

Clinicians should enquire about job roles and work-relatedness of symptoms when considering a diagnosis of HP. Outbreaks of metalworking fluid associated HP from around the world are well described, so clinicians should remain vigilant. The usual classification for causative antigen includes animal and plant proteins, fungi, bacteria, low-molecular weight chemicals and metals; however novel occupational exposures and work processes are frequently reported.
Association Between Preexisting Mental Health Disorders and Adverse Outcomes in Adult Intensive Care Patients: A Data Linkage Study
Authors: Pilowsky Julia K. , Elliott Rosalind , Roche Michael A.
Published: February 2023

OBJECTIVES:

Mental illness is known to adversely affect the physical health of patients in primary and acute care settings; however, its impact on critically ill patients is less well studied. This study aimed to determine the prevalence, characteristics, and outcomes of patients admitted to the ICU with a preexisting mental health disorder.

DESIGN:

A multicenter, retrospective cohort study using linked data from electronic ICU clinical progress notes and the Australia and New Zealand Intensive Care Society Adult Patient Database.

SETTING/PATIENTS:

All patients admitted to eight Australian adult ICUs in the calendar year 2019. Readmissions within the same hospitalization were excluded.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Natural language processing techniques were used to classify preexisting mental health disorders in participants based on clinician documentation in electronic ICU clinical progress notes. Sixteen thousand two hundred twenty-eight patients (58% male) were included in the study, of which 5,044 (31.1%) had a documented preexisting mental health disorder. Affective disorders were the most common subtype occurring in 2,633 patients (16.2%), followed by anxiety disorders, occurring in 1,611 patients (9.9%). Mixed-effects regression modeling found patients with a preexisting mental health disorder stayed in ICU 13% longer than other patients (β-coefficient, 0.12; 95% CI, 0.10–0.15) and were more likely to experience invasive ventilation (odds ratio, 1.42; 95% CI, 1.30–1.56). Severity of illness and ICU mortality rates were similar in both groups.

CONCLUSIONS:

Patients with preexisting mental health disorders form a significant subgroup within the ICU. The presence of a preexisting mental health disorder is associated with greater ICU length of stay and higher rates of invasive ventilation, suggesting these patients may have a different clinical trajectory to patients with no mental health history. Further research is needed to better understand the reasons for these adverse outcomes and to develop interventions to better support these patients during and after ICU admission.
Effectiveness and safety of Shexiang Baoxin Pill (MUSKARDIA) in patients with stable coronary artery disease and concomitant diabetes mellitus: a subgroup analysis of a randomized clinical trial
Authors: Zhou Jingmin , Shi Haiming , Ji Fusui , Wu Yang , Zhao Yulan , Qian Jun , Ge Junbo
Published: February 2023

Background:

Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. To evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM).

Methods:

This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty.

Results:

MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively (P = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs. 22.6% [85/376], P = 0.017). Risk of MACE (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31–1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13–0.95).

Conclusion:

As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM.

Trial Registration:

ChiCTR.org.cn, ChiCTR-TRC-12003513
Growth Trajectories in Stimulant-Treated Children Ages 6 to 12: An Electronic Medical Record Analysis
Authors: Biederman Joseph , DiSalvo Maura , Green Allison , Hutt Vater Chloe , Driscoll Haley , Faraone Stephen V.
Published: February 2023

Objective:

The aim of this study was to evaluate growth trajectories in stimulant-exposed and stimulant-unexposed children using electronic medical record data from a large health care organization attending to moderating effects of the magnitude of exposure to stimulants, sex, and race.

Methods:

Weight, height, body mass index (BMI), prescription, and sociodemographic information were extracted from the electronic medical records of a large health care organization. Included were children who were 6 to 12 years at the time they were receiving stimulants with a concurrent growth assessment (index assessment) plus 1 to 4 years of additional growth assessments thereafter. Non–attention-deficit/hyperactivity disorder (ADHD) children who were unexposed to stimulants were age and sex matched to those exposed. Stimulant exposure was examined as the total number of months with stimulant prescriptions, percentage of follow-up time exposed to stimulants, and cumulative stimulant dose.

Results:

Our sample consisted of 323 children exposed to stimulants with available growth data and 1615 unexposed children. Small but significant decreases in height trajectories were found over time in exposed children compared with those unexposed. Weight and BMI trajectories decreased in the first year of follow-up with stabilization and increased thereafter. Growth trajectory effects were largest in girls (height, weight, and BMI), White children (weight), and children with more total stimulant exposure (weight).

Conclusion:

This comprehensive analysis of an ecologically informative sample attending to key covariates of the magnitude of exposure to stimulants, sex, and race extends previous findings, showing that effects on growth trajectories are small and do not appear to pose a significant clinical concern for most children with ADHD treated with stimulants from childhood onto adolescent years.
Involvement of dopaminergic system in the dentate gyrus of the hippocampus in modulating the orofacial pain-related behaviors in the rats
Authors: Haghparast Amir , Yousefpour Mitra , Rashvand Mina , Ghahari Laya , Rohani Bita , Haghparast Abbas
Published: February 2023

Chemical stimulation of the lateral hypothalamus (LH) induces analgesia by forming neural circuitries with multiple brain regions. The involvement of hippocampal dopaminergic receptors in the LH stimulation-induced antinociception in specific pain models in animals has been documented. However, because the neural circuitries involved in the mediation of orofacial pain are not the same as those that mediate the other types of pain, the present study aims to detect the role of dopamine receptors within the dentate gyrus (DG) in the antinociceptive responses induced by LH stimulation in an animal model of orofacial pain. Male Wistar rats (220–250 g) were implanted with two separate cannulae into the LH and DG on the same side. D1- or D2-like dopamine receptor antagonist, SCH23390, or sulpiride (0.25, 1, and 4 μg) were microinjected into the DG, five minutes before intra-LH injection of carbachol (250 nM). The animals were then injected with formalin 1% (50 μL; sc) into the upper lip lateral to the nose and subjected to the orofacial formalin test. Intra-DG administration of SCH23390 or sulpiride attenuated the antinociceptive responses induced by intra-LH microinjection of carbachol during the orofacial formalin test. The findings of the current study suggest that chemical stimulation of the LH modulates orofacial pain, possibly through activation of the DG dopaminergic neurons. Due to the high incidence and prevalence of orofacial pain in the general population, understanding how such neuronal circuitry modulates nociceptive processing will advance the search for novel therapeutics.
Effects of methylphenidate on impulsive choice and delay aversion in Lewis rats
Authors: Panfil Kelsey , Small Robert , Kirkpatrick Kimberly
Published: February 2023

Attention-deficit/hyperactivity disorder (ADHD), a common behavioral disorder in children and young adults, is characterized by symptoms of impulsivity, inattention, and hyperactivity. The purpose of this study was to evaluate the Lewis rat strain as a model of ADHD by testing their impulsive choices. Lewis rats were compared to their source strain, the Wistar rat, on an impulsive choice task. Rats completed the tasks on and off methylphenidate, a commonly prescribed medication for ADHD. Off methylphenidate, Lewis rats made more impulsive choices than Wistar rats. Analyses of acquisition of choice behavior suggested that both strains were able to discriminate reward sizes, but Lewis rats still chose the smaller-sooner option more than the larger-later (LL) option when the delays to reward were the same. This may be due to an aversion to the LL lever, which was associated with the longest delays to reward. Higher doses of methylphenidate increased LL choices in Lewis rats but decreased LL choices in Wistar rats. Altogether, these results suggest Lewis rats may be a viable model for ADHD in individuals whose symptoms are characterized by impulsive choices.
Population Pharmacokinetics of Vancomycin in Patients Receiving Hemodialysis in a Malian and a French Center and Simulation of the Optimal Loading Dose
Authors: Coulibaly Balla , Maire Pascal , Guitton Jêrome , Pelletier Solenne , Tangara Moustapha , Aulagner Gilles , Goutelle Sylvain
Published: February 2023

Purpose:

Vancomycin dosing remains challenging in patients receiving intermittent hemodialysis, especially in developing countries, where access to therapeutic drug monitoring and model-based dose adjustment services is limited. The objectives of this study were to describe vancomycin population PK in patients receiving hemodialysis in a Malian and French center and examine the optimal loading dose of vancomycin in this setting.

Methods:

Population pharmacokinetic analysis was conducted using Pmetrics in 31 Malian and 27 French hemodialysis patients, having a total of 309 vancomycin plasma concentrations. Structural and covariate analyses were based on goodness-of-fit criteria. The final model was used to perform simulations of the vancomycin loading dose, targeting a daily area under the concentration–time curve (AUC) of 400–600 mg.h/L or trough concentration of 15–20 mg/L at 48 hours.

Results:

After 48 hours of therapy, 68% of Malian and 63% of French patients exhibited a daily AUC of <400. The final model was a 2-compartment model, with hemodialysis influencing vancomycin elimination and age influencing the vancomycin volume distribution. Younger Malian patients exhibited a lower distribution volume than French patients. Dosing simulation suggested that loading doses of 1500, 2000, and 2500 mg would be required to minimize underexposure in patients aged 30, 50, and 70 years, respectively.

Conclusions:

In this study, a low AUC was frequently observed in hemodialysis patients in Mali and France after a standard vancomycin loading dose. A larger dose is necessary to achieve the currently recommended AUC target. However, the proposed dosing algorithm requires further clinical evaluation.
Cultural Adaptation and Psychometric Validation of a Cardiac Knowledge Questionnaire for Chinese Immigrants
Authors: Shi Wendan , Zhang Ling , Fethney Judith , Ghisi Gabriela L.M. , Gallagher Robyn
Published: February 2023

Background

Disease-related knowledge deficits are common in Chinese immigrants living in Western countries, putting them at risk of disease progression and mortality, particularly those with a coronary heart disease (CHD) diagnosis. However, no measurement instrument is available to assess CHD-related knowledge in this population.

Objectives

The aim of this study was to culturally adapt and examine the psychometric properties of the short version of Coronary Artery Disease Education Questionnaire (CADE-Q SV) (simplified Chinese version) in Chinese immigrants with CHD.

Methods

Mandarin-speaking people recruited from medical centers and cardiology clinics across metropolitan Sydney completed the 20-item CADE-Q SV (5 domains; potential scores: 0–20). Internal consistency was assessed using Cronbach α. A subgroup (n = 40) repeated the survey 2 weeks later for test-retest reliability by intraclass correlation coefficient. Factor structure (confirmatory factor analysis) and discriminant (known-groups) validation using education and English proficiency (univariate general linear model) were also undertaken.

Results

Participants (n = 202) had a mean (SD) age of 66.08 (10.93) years, 45.1% were male, and the mean (SD) total CADE-Q SV score was 13.07 (4.57). Reliability and consistency were good (intraclass correlation coefficient > 0.70; Cronbach α coefficients > 0.70, for total and per domain, respectively). The 5-domain structure was validated by confirmatory factor analysis. The scale demonstrated discriminant validity, with low education (P < .001) and low English proficiency (P = .017) associated with lower knowledge scores.

Conclusion

The CADE-Q SV (simplified Chinese version) can be used as a valid and reliable instrument, either paper based or digital, to evaluate the CHD-related knowledge of Chinese immigrants. This scale can be adapted to other migrant populations in the future.
Organ-preserving surgery and classic surgery for pancreatic solid pseudopapillary neoplasms: a multicenter analysis from Central and Western China
Authors: Tan Chunlu , Yang Zhiqing , Li Jiang , Ji Fengming , Gou Shanmiao
Published: February 2023

Background:

Pancreatic solid pseudopapillary neoplasms (SPNs) are low-grade malignant tumors of the pancreas. Organ-preserving surgery is being increasingly performed for these tumors, although there is little evidence to support its use. This retrospective multicenter study aimed to determine the clinicopathologic characteristics of pancreatic SPNs in Central and Western China and to determine the efficacy of organ-preserving surgery.

Methods:

The clinicopathologic, treatment and follow-up data of 227 pancreatic SPN patients treated between July 2003 and December 2016 at 5 tertiary care centers were retrospectively reviewed.

Results:

Among the 227 patients (38 males, 189 females; mean age 33.30 ± 12.70 years), only 72 (31.7%) had symptoms. The mean tumor size was 55.08 ± 29.56 mm. Adjacent organ/lymphovascular invasion was present in 16 (7.1%) patients and distant metastasis in 3 (1.3%) patients; no patient had spread to distant lymph nodes. Surgery included organ-preserving surgery in 108 (47.6%) patients, classic surgery in 115 (50.7%) patients, and palliative surgery in 4 (1.8%) patients. Tumor recurrence was seen in 8 (3.6%) patients. Cox regression analysis showed positive surgical margin (P < .01) and metastasis (P = .03) to be independent predictors of recurrence. Tumor characteristics were comparable between patients receiving organ-preserving surgery and classic surgery. The risk of recurrence was also similar in both groups (P = .72).

Conclusions:

Organ-preserving surgery appears to be an effective procedure for the treatment of pancreatic SPNs. Resection surgery should aim for negative surgical margins.
Pancreatic steatosis and its correlation with clinicopathological features in patients with pancreatic neuroendocrine neoplasms
Authors: Li Yongzheng , Yang Jian , Fan Zhiyao , Dong Peng , Hu Jingjuan , Liu Shujie , Meng Yufan , Gao Changhao , Gao Xin , Pang Chaoyu , Zhan Hanxiang
Published: February 2023

Background and objective:

The incidence of pancreatic neuroendocrine neoplasms (pNENs) has been increasing year by year, and pancreatic steatosis has been paid more and more attention to by clinicians. Our study aims to reveal the correlation between pancreatic steatosis, clinicopathological parameters, and the prognosis of patients with pNENs.

Methods:

The clinicopathological data of patients with pNENs who underwent surgical resections in our institution from January 2013 to May 2022 were retrospectively analyzed. The mean computed tomography (CT) values of the pancreas and spleen were used to assess the severity of the pancreatic steatosis. Pearson Chi-square test, T test, Mann Whitney U test, Univariate Cox regression, and Multivariate Cox regression were used to explore the relationship between pancreatic steatosis and age, sex, body mass index, tumor type, tumor location, tumor stage, blood lipid, prognosis, and other factors.

Results:

A total of 122 patients were included in our study, and 19.67% have pancreatic steatosis. The incidence of pancreatic steatosis was significantly higher in patients with fatty liver than in patients without fatty liver (36.8% vs 16.5%, P = .04). In insulinoma, the incidence of pancreatic steatosis in elderly patients was significantly higher than in young and middle-aged patients (41.7% vs 9.3%, P = .025). There was no significant difference in lipid levels between the pancreatic steatosis group and the non-pancreatic steatosis group (P > .05). Kaplan-Meier curves show that the prognosis of stage III/IV patients was significantly worse than that of stage I/II patients (P < .001). However, there was no significant difference in prognosis between patients with and without pancreatic steatosis (P = .404).

Conclusion:

The incidence of pancreatic steatosis was significantly higher in those with fatty liver than those without fatty liver. There is a high incidence of pancreatic steatosis in elderly patients with insulinoma. American Joint Committee on Cancer (AJCC) stage, but not pancreatic steatosis, significantly affected the prognosis of patients with pNENs.
A Delphi Method for Development of a Barrett’s Esophagus Question Prompt List as a Communication Tool for Optimal Patient-physician Communication
Authors: Kamal Afrin N. , Wang Chih-Hung Jason , Triadafilopoulos George , Diehl David L. , DuCoin Christopher , Dunst Christy M. , Falk Gary , Iyer Prasad G. , Katzka David A. , Konda Vani J.A. , Muthusamy Raman , Otaki Fouad , Pleskow Douglas , Rubenstein Joel H. , Shaheen Nicholas J. , Sharma Prateek , Smith Michael S. , Sujka Joseph , Swanstrom Lee L. , Tatum Roger P. , Trindade Arvind J. , Ujiki Michael , Wani Sachin , Clarke John O.
Published: February 2023

Background Methods:

The question prompt list content was derived through a modified Delphi process consisting of 3 rounds. In round 1, experts provided 5 answers to the prompts “What general questions should patients ask when given a new diagnosis of Barrett’s esophagus” and “What questions do I not hear patients asking, but given my expertise, I believe they should be asking?” Questions were reviewed and categorized into themes. In round 2, experts rated questions on a 5-point Likert scale. In round 3, experts rerated questions modified or reduced after the previous rounds. Only questions rated as “essential” or “important” were included in Barrett’s esophagus question prompt list (BE-QPL). To improve usability, questions were reduced to minimize redundancy and simplified to use language at an eighth-grade level (Fig. 1).

Results:

Twenty-one esophageal medical and surgical experts participated in both rounds (91% males; median age 52 years). The expert panel comprised of 33% esophagologists, 24% foregut surgeons, and 24% advanced endoscopists, with a median of 15 years in clinical practice. Most (81%), worked in an academic tertiary referral hospital. In this 3-round Delphi technique, 220 questions were proposed in round 1, 122 (55.5%) were accepted into the BE-QPL and reduced down to 76 questions (round 2), and 67 questions (round 3). These 67 questions reached a Flesch Reading Ease of 68.8, interpreted as easily understood by 13 to 15 years olds.

Conclusions:

With multidisciplinary input, we have developed a physician-derived BE-QPL to optimize patient-physician communication. Future directions will seek patient feedback to distill the questions further to a smaller number and then assess their usability.
Up-to-Date Colonoscopy Use in Asian and Hispanic Subgroups in New York City, 2003-2016
Authors: Liang Peter S. , Dubner Rachel , Xia Yuhe , Glenn Matthew , Lin Kevin , Nagpal Neha , Ng Sandy , Trinh-Shevrin Chau , Troxel Andrea B. , Kwon Simona C.
Published: February 2023

Background:

Colorectal cancer screening uptake in the United States overall has increased, but racial/ethnic disparities persist and data on colonoscopy uptake by racial/ethnic subgroups are lacking. We sought to better characterize these trends and to identify predictors of colonoscopy uptake, particularly among Asian and Hispanic subgroups.

Study:

We used data from the New York City Community Health Survey to generate estimates of up-to-date colonoscopy use in Asian and Hispanic subgroups across 6 time periods spanning 2003-2016. For each subgroup, we calculated the percent change in colonoscopy uptake over the study period and the difference in uptake compared to non-Hispanic Whites in 2015-2016. We also used multivariable logistic regression to identify predictors of colonoscopy uptake.

Results:

All racial and ethnic subgroups with reliable estimates saw a net increase in colonoscopy uptake between 2003 and 2016. In 2015-2016, compared with non-Hispanic Whites, Puerto Ricans, Dominicans, and Central/South Americans had higher colonoscopy uptake, whereas Chinese, Asian Indians, and Mexicans had lower uptake. On multivariable analysis, age, marital status, insurance status, primary care provider, receipt of flu vaccine, frequency of exercise, and smoking status were the most consistent predictors of colonoscopy uptake (≥4 time periods).

Conclusions:

We found significant variation in colonoscopy uptake among Asian and Hispanic subgroups. We also identified numerous demographic, socioeconomic, and health-related predictors of colonoscopy uptake. These findings highlight the importance of examining health disparities through the lens of disaggregated racial/ethnic subgroups and have the potential to inform future public health interventions.
Genotype–phenotype correlation in a large cohort of pediatric patients with heterozygous and homozygous familial hypercholesterolemia
Authors: Reijman M.D. , Defesche J.C. , Wiegman A.
Published: February 2023

Background

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease (CVD). Both the heterozygous form and the very severe homozygous form can be diagnosed by genetic testing and by clinical criteria. Genetic testing can discern FH in a form caused by complete absence of the LDL-receptors, the negative variant and a form leading to reduced activity of the LDL receptors, the defective variant. The aim of this study is to provide more insight in the genotype–phenotype correlation in children and adolescents diagnosed with heterozygous FH (HeFH) and with homozygous FH (HoFH), specifically in relation to the clinical and therapeutic consequences of the negative and defective variant of FH.

Methods and Results

Data of 5904 children with a tentative diagnosis of FH referred to our center for genetic testing were collected. A lipid-profile was present in 3494 children, who became the study cohort. In this large cohort of children, which includes 2714 HeFH and 41 HoFH patients, it is shown that receptor negative variants are associated with significant higher LDL-C levels in HeFH patients than receptor defective variants (6.0 versus 4.9 mmol/L; p < 0.001). A negative/negative variant is associated with a significant higher LDL-C level jn HoFH patients than a negative/defective variant, which in itself has a higher LDL-C level than a defective/defective variant. Significantly more premature CVD is present in close relatives of children with HeFH with negative variants compared to close relatives of HeFH children with defective variants (75% vs 59%; p < 0.001).

Conclusions

Performing genetic testing and identifying the type of underlying genetic variant is of added value in order to distinguish between pediatric patients with higher risks of premature CVD and to identify those that will benefit most from new types of lipid-lowering therapies. Since in children the phenotype of FH is less affected by environmental factors, the study substantiates the genotype-phenotype correlation in this large pediatric population.
Inflammation compared to low-density lipoprotein cholesterol: two different causes of atherosclerotic cardiovascular disease
Authors: Wadström Benjamin N. , Pedersen Kasper M. , Wulff Anders B. , Nordestgaard Børge G.
Published: February 2023

Purpose of review

Inflammation is gaining attention as a target for prevention of atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to compare the evidence for inflammation with the evidence for low-density lipoprotein (LDL) cholesterol in ASCVD.

Recent findings

Evidence from human genetic studies and randomized controlled trials implicate the inflammatory pathway from the inflammasome through interleukin (IL)-1 to IL-6 as a cause of ASCVD. Higher levels of IL-6 may lead to proportionally increased risk of ASCVD, and randomized controlled trials of IL-6 inhibitors are underway. The causal evidence for LDL cholesterol in ASCVD is overwhelming and recent important findings instead revolve around development of improved LDL cholesterol lowering therapy through RNA and DNA based therapeutics. Even though some lipid-lowering therapies lower IL-6, the IL-6 inflammatory pathway and LDL cholesterol are two separate causes of ASCVD.

IL-6 mediated inflammation most likely causes ASCVD, in parallel with LDL cholesterol. However, fewer individuals in the general population are exposed to high IL-6 than high LDL cholesterol. For inflammation, future research should focus on improving efficacy and safety of anti-inflammatory therapy, and for LDL cholesterol, future research should focus on wider and more effective implementation of LDL cholesterol lowering therapy.
The road to xenotransplantation
Authors: Wolbrom Daniel H. , Kim Jacqueline I. , Griesemer Adam
Published: February 2023

Purpose of review

The aim of this study was to highlight recent progress in xenotransplantation and discuss the remaining obstacles/steps before the FDA is likely to approve a clinical trial.

Recent findings

Long-term survival of life-supporting xenografts in preclinical models has led to discussion of clinical trials of xenotransplantation. The reports of clinical cardiac xenotransplant based on compassionate use FDA approval and renal xenotransplants to brain-dead humans have led to further considerations of clinical trials. Discussions between the transplant community and the FDA have established critical next steps before a clinical trial of xenotransplants is likely to be approved. These steps include testing the clinical immunosuppression protocol and the organ from a genetically modified source animal in nonhuman primates with reproducible survival of at least 6 months. In addition, appropriate viral surveillance protocols and confirmation that the xenografts support appropriate human physiology are likely to be critical elements for FDA-approval. Finally, further studies in the human decedent model are likely to provide critical information about human immune and physiologic responses to xenografts.

This review highlights the current progress in nonhuman primate models and recent reports of human xenotransplantation. It also describes the remaining hurdles and currently understood FDA requirements that remain to be achieved before a clinical trial of xenotransplantation can be approved.
Regular Exercise is Associated with Low Fatigue Levels and Good Functional Outcomes Post-COVID-19: A Prospective Observational Study
Authors: de Avila Leyla , Price Jillian K. , Stepanova Maria , Lam Brian , Weinstein Ali A. , Pham Huong , Austin Patrick , Keo Wisna , Younossi Zaid , Afendy Mariam , Nader Samir , Terra Kathy , Cable Rebecca , Younossi Elena , Golabi Pegah , Verma Manisha , Nader Fatema , Racila Andrei , Gerber Lynn H. , Younossi Zobair M.
Published: February 2023

Objective

To identify the impact of post-acute SARS-CoV-2 infection on patient outcomes.

Design

Prospective, repeated measure, observational study of consented adults with positive SARS-CoV-2 qPCR or antigen test >28 days post-infection. Only data from the initial study visit is reported, including disease history, symptoms checklist, patient questionnaires, cognitive tests, and social/medical histories, vitals, grip strength and two-minute walk distance.

Results

218 patients were studied: 100 hospitalized (57.3 ± 15.4 yrs, 62% male, BMI: 31.3 ± 8.0) and 118 non-hospitalized (46.2 ± 14.6 yrs, 31% male, BMI: 29.7 ± 7.5). Post-COVID patients reported mean 1.76 symptoms; ≥15% reported fatigue, memory loss, and shortness of breath (SOB). Grip strength was 14% lower than norms (p < 0.0001). Fatigue (FACIT-F), mood (PHQ-9), and well-being (EQ-5D) scores were lower than the population norms (p < 0.05). Hospitalized vs non-hospitalized post-COVID patients performed worse on cognitive assessments (processing speed test - WAIS-IV Symbol Search) and reported less regular exercise (≥30 min ≥3x/week) (p < 0.05). Also, 30% had severe fatigue (by FACIT-F); those patients reported less exercise (p < 0.05). In multivariate models, lack of exercise was independently associated with multiple post-COVID-19 impairments.

Conclusions

Low levels of exercise are an independent risk factor for post-COVID sequelae. Patients who report less exercise have low grip strength, higher levels of fatigue, memory loss, SOB, depression and poorer quality of life.
New Onset Rapidly Progressive Polyarticular Tophaceous Gout Following Cerebrovascular Accident: A Case Report
Authors: Burke Lindsay A. , Niehaus William , Heronemus Marc J.
Published: February 2023

We present a novel case of new onset, polyarticular tophaceous gout which developed on the patient’s hemiparetic side several days after she was diagnosed with a middle cerebral artery stroke. This is the first case of an acute gout flare in a patient without history of gout. She was successfully treated with anakinra.
Atypical Cause for Back Pain and Sciatica in a 35-year-old Female with Fibromyalgia
Authors: Naber William J. , Netzloff Cheri L. , Bakshi Rishi R.
Published: February 2023

Spinal and extra-pelvic lesions causing sciatic symptoms are well recognized in clinical research and practice.1–5 We present a 35-yr-old woman with a history of axial back pain and fibromyalgia who presented with episodes of radicular type pain down her legs and associated bilateral tingling in her feet. Medicinal and therapeutic interventions for traditional sciatica etiologies failed to provide relief. Lumbar magnetic resonance imaging showed mild multilevel degenerative changes and partially visualized fibroids, but no other significant spinal pathology was appreciated. Subsequent pelvic magnetic resonance imaging revealed an enlarged retroverted uterus with multiple fibroid lesions. The patient elected for laparoscopic myomectomy, which improved her likelihood of fertility while drastically alleviating her axial spine and lower extremity symptomology. This case reinforces the importance of keeping a broad differential that includes intrapelvic etiologies when traditional workup and treatment for sciatic neuropathy fails. To our knowledge, this is the first reported case of sciatic neuropathy secondary to uterine fibroids treated with the intent of both fertility improvement and pain relief.
Lenacapavir and the novel HIV-1 capsid inhibitors: an emerging therapy in the management of multidrug-resistant HIV-1 virus
Authors: Lee Natalie E. , Sutherland Rebecca K.
Published: February 2023

Purpose of review

The aim of this study was to summarize current evidence regarding lenacapavir, a first in class HIV-1 capsid inhibitor, and its role as an emergent therapy for the treatment of HIV-1 infection.

Recent findings

HIV-1 capsid inhibitors (of which lenacapavir is the first in class) has been postulated to have activity against multidrug resistant HIV-1 viral isolates. Initial results from the phase 3 trial CAPELLA (combining oral and subcutaneous lenacapavir alongside failing drug therapies) suggest that there may be a role for these novel agents in a cohort of patients living with HIV-1 infection (PLWH) for whom multidrug resistance has previously been a barrier to effective therapy. Despite emergent lenacapavir resistance mutations detected in some study participants, virological suppression was still potentially attainable, offering some hope to PLWH with limited antiviral regimens available. Initial results from the CALIBRATE trial show promise for the role of lenacapavir-containing regimens in a treatment-naive cohort as well.

Lenacapavir may prove to be an adjunctive agent in the management of PLWH with significant HIV-1 drug resistance.
Application of External Nasal Skin Stretching in Asian Rhinoplasty
Authors: Tan Xiaoyan , Sun Haiyang , Yao Ping , Zitkovsky Helen , Tao Anqi , Tang Dongsheng , Yang Zhenyu , Shi Yanyan , Wang Xinyu
Published: February 2023

Asian nasal characteristics include a low dorsum, short nose, and thick skin envelope, usually requiring lengthening and elevating the nose during rhinoplasty (Facial Plast Surg Clin North Am2007;15(3):293–307, v). The increase in rhinoplasty popularity has resulted in a greater prevalence of complications. In a severely short and contracted nose, an extensively scarred or contracted soft tissue envelope results in weak laxity and extensibility of the nasal skin. For these patients, the essential component of rhinoplasty is to improve skin texture and obtain a sufficient nasal skin soft tissue envelope. Tissue expanders have previously been utilized to expand nasal skin and soft tissue (Plast Reconstr Surg2006;118(6):1447–1452;Facial Plast Surg2019;35(1):68–72). However, nasal anatomical characteristics have limited the clinical application of tissue expanders. This article introduces a simple, noninvasive, and easily adopted method of external nasal skin stretching, which was first proposed by the senior author. This approach has been accepted by rhinoplasty surgeons in China and widely used in clinic. The approach can improve skin laxity, yield extra nasal soft tissue, and create adequate soft tissue coverage of the reconstructed nasal framework to reduce the difficulty of surgery with a reliable clinical effect.
Biophotonic Effects of Low-Level Laser Therapy on Adipose-Derived Stem Cells for Soft Tissue Deficiency
Authors: Chang Cheng-Jen , Hsiao Yen-Chang , Hang Nguyen Le Thanh , Yang Tzu-Sen
Published: February 2023

Purposes

The objectives of this study are to use diode lasers for low-level laser therapy (LLLT) and to assess its applicability and effects in adipose-derived stem cell (ADSC) growth processes.

Methods

Studies were conducted on the diode laser with wavelengths of 622.7, 527.1, and 467.3 nm. The mechanism of action of LLL illumination was studied on ADSCs, isolated from human tissue, and then cultured by examining different wavelengths to determine the relevant light parameters for optimal responses. We used enzyme-linked immunosorbent assay and real-time polymerase chain to determine the percentages of fibroblast-mediated procollagen type 1 and matrix metallopeptidase 1 (MMP-1), MMP-2, and MMP-9 production at different wavelengths. The levels of lactate dehydrogenase produced by ADSCs after LLL illumination were assessed as well. Clinical results from 20 patients treated for soft tissue deficiency were collected for assessment of ADSC-assisted lipotransfer.

Results

Low-level laser (622.7 nm) illumination on cell cultures in vitro increased ADSCs proliferation, type 1 procollagen expression, collagen production, as well as MMP-1, MMP-2, and MMP-9 relative expression. Statistical analysis demonstrated a significant difference in red light (622.7 nm) versus green light (527.1 nm) and blue light (467.3 nm, P < 0.05). No significant differences were noted between the effects of green and blue lights. In clinical application, all patients attained significant improvement with treatment in the final outcome assessment after 6 months.

Conclusions

Low-level laser illumination may affect ADSCs growth processes and ADSC-assisted lipotransfer for soft tissue deformity, scar treatment, wound healing, and other reconstructive surgery.
Financial Implications of Enhanced Recovery After Surgery Protocols in Microsurgical Breast Reconstruction
Authors: Atamian Elisa K. , Suydam Rebecca , Hardy Taylor N. , Clappier Mona , Barnett Sarah , Caulfield Dana , Jelavic Matthew , Smith Mark L. , Tanna Neil
Published: February 2023

Introduction

Surgical advancements in breast reconstruction have allowed a shift toward optimizing patient-reported outcomes and efficiency measures. The enhanced recovery after surgery (ERAS) protocol has been instrumental in improving outcomes, but the effect of these protocols on health care spending has not been examined. This study aims to assess the effect of ERAS protocols on the length of hospital stay and costs associated with microsurgical breast reconstruction.

Methods

In 2018, the authors implemented an ERAS protocol for patients undergoing microsurgical breast reconstruction that included perioperative procedures involving patient education and care. Subjects included patients who underwent deep inferior epigastric perforator flap breast reconstruction at the authors' institution between 2016 and 2019. Data were gathered from the electronic medical record and the hospital system's finance department, and patients were divided into pre-ERAS and ERAS cohorts. A 2-sample t test was used for statistical analysis.

Results

The study included 269 patients with no statistically significant differences in demographic data between the cohorts. The average length of hospitalization was 3.46 days for the pre-ERAS group and 2.45 days for the ERAS group (P = 0.000). In a linear regression, the ERAS protocol predicted a 1.04-day decrease in the length of stay (P = 0.000). Overall, total direct cost decreased by 7.5% with the ERAS protocol.

Conclusion

The rising cost of health care presents a challenge for providers to reduce the cost burden placed on our health system while providing the highest-quality care. This study demonstrates that the use of standardized ERAS protocols can achieve this 2-fold goal.
Impact of Intraoperative Hypothermia on Autologous Breast Reconstruction
Authors: Chishom Taylor A. , Andersen Emily S. , Juan Hui Yu , Lele Sonia , Coots Lesley B. , Mountziaris Paschalia M.
Published: February 2023

Objective

Studies have identified perioperative hypothermia as a risk factor for impaired wound healing, increased hospital length of stay, and surgical site infection. This study examines the effect of intraoperative hypothermia on postoperative outcomes in autologous microvascular free flap breast reconstruction.

Methods

This was a retrospective review of 55 patients who experienced intraoperative hypothermia, defined as less than 35.0°C core body temperature and 99 normothermic patients who underwent autologous-based microvascular free flap breast reconstruction from 2013 to 2021. Demographics, comorbidities, smoking status, intraoperative warming devices, type of autologous reconstruction, hypothermia (and its duration), and length of surgery were collected. The outcomes assessed were infection rate, reoperation within 90 days, skin necrosis, wound healing complications, hematoma, seroma, and readmission within 90 days.

Results

In the study population of 154 consecutive patients, 8.4% had type 1 or type 2 diabetes and 3.2% were current smokers. A total of 90.3% of patients (139) underwent deep inferior epigastric perforator flap reconstruction, 7.1% (11) superficial inferior epigastric artery flap reconstruction, and 4 (2.6%) another free flap type. A total of 35.7% of the patients (55) experienced intraoperative hypothermia defined as less than 35.0°C. In the hypothermic group, a higher proportion of patients had wound healing complications (52.7% vs 29.3%, P < 0.05), hematoma (16.4% vs 5.1%, P < 0.05), and readmission for postoperative complications (34.5% vs 14.1%, P < 0.05). There was also a trend toward higher incidence of seroma (7.3% vs 5.1%), surgical site infection (12.7% vs 9.1%), skin necrosis (12.7% vs 9.1%), and unplanned reoperation within 90 days (10.9% vs 7.1%). Further analysis via Firth logistic regression demonstrated intraoperative hypothermia predicted postoperative hematoma (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.17–11.60; P < 0.05), readmission within 90 days (OR, 3.20; 95% CI, 1.45–7.08; P < 0.05), and wound healing complications (OR, 2.69; 95% CI, 1.36–5.33; P < 0.05).

Conclusions

This study demonstrates that intraoperative hypothermia is a significant risk factor for postoperative wound healing complications, hematoma, and readmission within 90 days in autologous breast reconstruction. Because of a finite amount of donor sites, it is important to find ways to minimize the risk of postoperative complications. Our results support that maintaining strict normothermia during autologous breast reconstruction can significantly improve patient outcomes and reduce morbidity.
Early versus late administration of long-acting injectable antipsychotic agents among patients with newly diagnosed schizophrenia: an analysis of a commercial claims database
Authors: Kane John M. , Chen Anna , Lim Sangtaeck , Mychaskiw Marko A. , Tian Marc , Wang Yitong , Suett Mark , Rubio Jose M.
Published: February 2023

This study was designed to assess healthcare resource utilization (HCRU) and costs in patients with newly diagnosed schizophrenia based on timing and context of long-acting injectable antipsychotic agent (LAI) initiation. Using claims data, patients (aged 18–40 years) with first schizophrenia diagnosis January 2013–September 2019 (index date), no LAI or oral antipsychotic agent claims during 12-month preindex period, and continuous benefit enrollment from 12 months before index date to 12 months after first LAI administration were identified. Patients were grouped based on timing [early (≤1 year after index date) vs. late] and circumstances [reactive (after schizophrenia-related event) vs. proactive] of LAI initiation. Of 1290 patients with at least one LAI claim, 306 met criteria for early (n = 204; reactive, n = 107; proactive, n = 97) and late (n = 102; n = 75; n = 27) initiation. HCRU and costs were numerically lower in early versus late groups, and significantly lower for proactive initiation in both groups. Comparing worst-case (late-reactive) and best-case (early-proactive) scenarios, the average annual cost difference was $7195.13 (P = 0.0233), with major drivers being emergency department ($171.28; P < 0.05) and other outpatient ($2845.73; P < 0.00001) visits. In addition to the clinical advantages previously described in the literature, the proactive use of LAIs in early-phase schizophrenia is associated with lower healthcare costs.
Shared stressful experiences affect social proximity in Merino sheep
Authors: Keshavarzi Hamideh , Lee Caroline , Dyall Tim R. , Johnson Mark , Campbell Dana L. M.
Published: February 2023

While it is well established that humans develop stronger relationship bonds when they share stressful experiences, there is little known on how shared stressful experiences may influence relationship bonding in animals. Here, we present a study looking at social proximity between individuals in small groups of Merino ewes following a shared stressful experience compared with control sheep that were not exposed to stress. Some sheep were familiar to each other. Analyses of social proximity using real-time-kinematic Global Navigation Satellite System (GNSS) on-animal devices showed sheep preferred to be closest to familiar individuals, but across the study duration they also developed a preference for the individuals they shared the stressful experience with, relative to their proximity to control individuals. These results contribute to limited research on what factors may instigate the development of bonds between unfamiliar sheep. Between-individual bonds may develop as a means of socially mediated stress buffering. Social bonding following a shared stressful experience aligns with human social relationships and increases our understanding of how animals perceive their conspecifics in relation to stressful environmental change.