bluuebunny/crossref_metadata_2025 huggingface dataset:
TREK-1 and TREK-2 Knockout Mice Are Not Resistant to Halothane or Isoflurane
Authors: Spencer Kira A. , Woods Christian B. , Worstman Hailey M. , Johnson Simon C. , Ramirez Jan-Marino , Morgan Philip G. , Sedensky Margaret M.
Published: April 2023

Background

A variety of molecular targets for volatile anesthetics have been suggested, including the anesthetic-sensitive potassium leak channel, TREK-1. Knockout of TREK-1 is reported to render mice resistant to volatile anesthetics, making TREK-1 channels compelling targets for anesthetic action. Spinal cord slices from mice, either wild type or an anesthetic- hypersensitive mutant, Ndufs4, display an isoflurane-induced outward potassium leak that correlates with their minimum alveolar concentrations and is blocked by norfluoxetine. The hypothesis was that TREK-1 channels conveyed this current and contribute to the anesthetic hypersensitivity of Ndufs4. The results led to evaluation of a second TREK channel, TREK-2, in control of anesthetic sensitivity.

Methods

The anesthetic sensitivities of mice carrying knockout alleles of Trek-1 and Trek-2, the double knockout Trek-1;Trek-2, and Ndufs4;Trek-1 were measured. Neurons from spinal cord slices from each mutant were patch clamped to characterize isoflurane-sensitive currents. Norfluoxetine was used to identify TREK-dependent currents.

Results

The mean values for minimum alveolar concentrations (± SD) between wild type and two Trek-1 knockout alleles in mice (P values, Trek-1 compared to wild type) were compared. For wild type, minimum alveolar concentration of halothane was 1.30% (0.10), and minimum alveolar concentration of isoflurane was 1.40% (0.11); for Trek-1tm1Lex
, minimum alveolar concentration of halothane was 1.27% (0.11; P = 0.387), and minimum alveolar concentration of isoflurane was 1.38% (0.09; P = 0.268); and for Trek-1tm1Lzd
, minimum alveolar concentration of halothane was 1.27% (0.11; P = 0.482), and minimum alveolar concentration of isoflurane was 1.41% (0.12; P = 0.188). Neither allele was resistant for loss of righting reflex. The EC50 values of Ndufs4;Trek-1tm1Lex
did not differ from Ndufs4 (for Ndufs4, EC50 of halothane, 0.65% [0.05]; EC50 of isoflurane, 0.63% [0.05]; and for Ndufs4;Trek-1tm1Lex
, EC50 of halothane, 0.58% [0.07; P = 0.004]; and EC50 of isoflurane, 0.61% [0.06; P = 0.442]). Loss of TREK-2 did not alter anesthetic sensitivity in a wild-type or Trek-1 genetic background. Loss of TREK-1, TREK-2, or both did not alter the isoflurane-induced currents in wild-type cells but did cause them to be norfluoxetine insensitive.

Conclusions

Loss of TREK channels did not alter anesthetic sensitivity in mice, nor did it eliminate isoflurane-induced transmembrane currents. However, the isoflurane-induced currents are norfluoxetine-resistant in Trek mutants, indicating that other channels may function in this role when TREK channels are deleted.

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A Dose-finding Study of Sugammadex for Reversal of Rocuronium in Cardiac Surgery Patients and Postoperative Monitoring for Recurrent Paralysis
Authors: Bowdle T. Andrew , Haththotuwegama Kishanee J. , Jelacic Srdjan , Nguyen Sharon T. , Togashi Kei , Michaelsen Kelly E.
Published: April 2023

Background

The dose of sugammadex recommended by the manufacturer for reversal of rocuronium is 2 mg/kg when the train-of-four count is 2 or more and 4 mg/kg when it is less than 2 but there is a posttetanic count of at least 1. The purpose of this dose-finding study was to titrate sugammadex to produce a train-of-four ratio 0.9 or greater at the conclusion of cardiac surgery, and to continue monitoring neuromuscular blockade in the intensive care unit to identify recurrent paralysis. The hypothesis was that many patients would require less than the recommended dose of sugammadex, but that some would require more, and that recurrent paralysis would not occur.

Methods

Neuromuscular blockade was monitored using electromyography during cardiac surgery. Administration of rocuronium was at the discretion of the anesthesia care team. During sternal closure, sugammadex was titrated in 50-mg increments every 5 min until a train-of-four ratio 0.9 or greater was obtained. Neuromuscular blockade was monitored with electromyography in the intensive care unit until sedation was discontinued before extubation or for a maximum of 7 h.

Results

Ninety-seven patients were evaluated. The dose of sugammadex required to achieve a train-of-four ratio of 0.9 or greater varied from 0.43 to 5.6 mg/kg. There was a statistically significant relationship between the depth of neuromuscular blockade and the sugammadex dose required for reversal, but there was a large variation in dose required at any depth of neuromuscular blockade. Eighty-four of 97 patients (87%) required less than the recommended dose, and 13 (13%) required more. Two patients required additional sugammadex administration for recurrent paralysis.

Conclusions

When sugammadex was titrated to effect, the dose was usually less than the recommended dose, but it was more in some patients. Therefore, quantitative twitch monitoring is essential for ascertaining that adequate reversal has taken place after sugammadex administration. Recurrent paralysis was observed in two patients.

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State Variation in Severe Maternal Morbidity Among Individuals With Medicaid Insurance
Authors: Admon Lindsay K. , Auty Samantha G. , Daw Jamie R. , Kozhimannil Katy B. , Declercq Eugene R. , Wang Na , Gordon Sarah H.
Published: April 2023

OBJECTIVE:

To measure variation in delivery-related severe maternal morbidity (SMM) among individuals with Medicaid insurance by state and by race and ethnicity across and within states.

METHODS:

We conducted a pooled, cross-sectional analysis of the 2016–2018 TAF (Transformed Medicaid Statistical Information System Analytic Files). We measured overall and state-level rates of SMM without blood transfusion for all individuals with Medicaid insurance with live births in 49 states and Washington, DC. We also examined SMM rates among non-Hispanic Black and non-Hispanic White individuals with Medicaid insurance in a subgroup of 27 states (and Washington, DC). We generated unadjusted rates of composite SMM and the individual indicators of SMM that comprised the composite. Rate differences and rate ratios were calculated to compare SMM rates for non-Hispanic Black and non-Hispanic White individuals with Medicaid insurance.

RESULTS:

The overall rate of SMM without blood transfusion was 146.2 (95% CI 145.1–147.3) per 10,000 deliveries (N=4,807,143). Rates of SMM ranged nearly threefold, from 80.3 (95% CI 71.4–89.2) per 10,000 deliveries in Utah to 210.4 (95% CI 184.6–236.1) per 10,000 deliveries in Washington, DC. Non-Hispanic Black individuals with Medicaid insurance (n=629,774) experienced a higher overall rate of SMM (212.3, 95% CI 208.7–215.9) compared with non-Hispanic White individuals with Medicaid insurance (n=1,051,459); (125.3, 95% CI 123.2–127.4) per 10,000 deliveries (rate difference 87.0 [95% CI 82.8–91.2]/10,000 deliveries; rate ratio 1.7 [95% CI 1.7–1.7]). The leading individual indicator of SMM among all individuals with Medicaid insurance was eclampsia, although the leading indicators varied across states and by race and ethnicity. Many states were concordant in leading indicators among the overall, non-Hispanic Black, and non-Hispanic White populations (ie, in Oklahoma sepsis was the leading indicator for all three). Most states, however, were discordant in leading indicators across the three groups (ie, in Texas eclampsia was the leading indicator overall, pulmonary edema or acute heart failure was the leading indicator among the non-Hispanic Black population, and sepsis was the leading indicator among the non-Hispanic White population).

CONCLUSION:

Interventions aimed at reducing SMM and, ultimately, mortality among individuals with Medicaid insurance may benefit from the data generated from this study, which highlights states that have the greatest burden of SMM, the differences in rates among non-Hispanic Black populations compared with non-Hispanic White populations, and the leading indicators of SMM overall, by state, and by race and ethnicity.
Identification of Factors Associated With 30-day Readmissions After Posterior Lumbar Fusion Using Machine Learning and Traditional Models
Authors: Rezaii Paymon G. , Herrick Daniel , Ratliff John K. , Rusu Mirabela , Scheinker David , Desai Atman M.
Published: April 2023

Study Design.

A retrospective cohort study.

Objective.

To identify the factors associated with readmissions after PLF using machine learning and logistic regression (LR) models.

Summary of Background Data.

Readmissions after posterior lumbar fusion (PLF) place significant health and financial burden on the patient and overall health care system.

Materials and Methods.

The Optum Clinformatics Data Mart database was used to identify patients who underwent posterior lumbar laminectomy, fusion, and instrumentation between 2004 and 2017. Four machine learning models and a multivariable LR model were used to assess factors most closely associated with 30-day readmission. These models were also evaluated in terms of ability to predict unplanned 30-day readmissions. The top-performing model (Gradient Boosting Machine; GBM) was then compared with the validated LACE index in terms of potential cost savings associated with the implementation of the model.

Results.

A total of 18,981 patients were included, of which 3080 (16.2%) were readmitted within 30 days of initial admission. Discharge status, prior admission, and geographic division were most influential for the LR model, whereas discharge status, length of stay, and prior admissions had the greatest relevance for the GBM model. GBM outperformed LR in predicting unplanned 30-day readmission (mean area under the receiver operating characteristic curve 0.865 vs. 0.850, P<0.0001). The use of GBM also achieved a projected 80% decrease in readmission-associated costs relative to those achieved by the LACE index model.

Conclusions.

The factors associated with readmission vary in terms of predictive influence based on standard LR and machine learning models used, highlighting the complementary roles these models have in identifying relevant factors for the prediction of 30-day readmissions. For PLF procedures, GBM yielded the greatest predictive ability and associated cost savings for readmission.

Level of Evidence.

3
Laminectomy With Fusion is Associated With Greater Functional Improvement Compared With Laminectomy Alone for the Treatment of Degenerative Lumbar Spondylolisthesis
Authors: Shukla Geet G. , Chilakapati Sai S. , Matur Abhijith V. , Palmisciano Paolo , Conteh Fatu , Onyewadume Louisa , Duah Henry , Griffith Azante , Tao Xu , Vorster Phillip , Gupta Sahil , Cheng Joseph , Motley Benjamin , Adogwa Owoicho
Published: April 2023

Study Design.

Systematic review and Meta-analysis.

Objective.

To compare outcomes and complications profile of laminectomy alone versus laminectomy and fusion for the treatment of degenerative lumbar spondylolisthesis (DLS).

Summary of Background Data.

Degenerative lumbar spondylolisthesis is a common cause of back pain and functional impairment. DLS is associated with high monetary (up to $100 billion annually in the US) and nonmonetary societal and personal costs. While nonoperative management remains the first-line treatment for DLS, decompressive laminectomy with or without fusion is indicated for the treatment-resistant disease.

Methods.

We systematically searched PubMed and EMBASE for RCTs and cohort studies from inception through April 14, 2022. Data were pooled using random-effects meta-analysis. The risk of bias was assessed using the Joanna Briggs Institute risk of bias tool. We generated odds ratio and standard mean difference estimates for select parameters.

Results.

A total of 23 manuscripts were included (n=90,996 patients). Complication rates were higher in patients undergoing laminectomy and fusion compared with laminectomy alone (OR: 1.55, P<0.001). Rates of reoperation were similar between both groups (OR: 0.67, P=0.10). Laminectomy with fusion was associated with a longer duration of surgery (Standard Mean Difference: 2.60, P=0.04) and a longer hospital stay (2.16, P=0.01). Compared with laminectomy alone, the extent of functional improvement in pain and disability was superior in the laminectomy and fusion cohort. Laminectomy with fusion had a greater mean change in ODI (−0.38, P<0.01) compared with laminectomy alone. Laminectomy with fusion was associated with a greater mean change in NRS leg score (−0.11, P=0.04) and NRS back score (−0.45, P<0.01).

Conclusion.

Compared with laminectomy alone, laminectomy with fusion is associated with greater postoperative improvement in pain and disability, albeit with a longer duration of surgery and hospital stay.
Risk of ICU Admission and Related Mortality in Patients With Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors: A Territory-Wide Retrospective Cohort Study
Authors: Ng Pauline Yeung , Ng Andrew Kei-Yan , Ip April , Wu Mei-Zhen , Guo Ran , Yiu Kai-Hang
Published: April 2023

OBJECTIVES:

The benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the occurrence rate of adverse cardiac and renal outcomes in patients with type 2 diabetes has been well described in randomized trials. Whether this benefit extends to patients at the most severe end of the disease spectrum requiring admission to the ICU remains to be examined.

DESIGN:

Retrospective observational study.

SETTING:

Data were obtained from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System).

PATIENTS:

All adult patients (age ≥ 18 yr) with type 2 diabetes and newly prescribed SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors between January 1, 2015, and December 31, 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

After 1:2 propensity score matching, a total of 27,972 patients (10,308 SGLT2 inhibitors vs 17,664 DPP-4 inhibitors) were included in the final analysis. The mean age was 59 ± 11 years, and 17,416 (62.3%) were male. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with decreased ICU admission (286 [2.8%] vs 645 [3.7%]; hazard ratio [HR], 0.79; 95% CI, 0.69–0.91; p = 0.001) and lower risks of all-cause mortality (315 [3.1%] vs 1,327 [7.5%]; HR, 0.44; 95% CI, 0.38–0.49; p < 0.001), compared with DPP-4 inhibitors. The severity of illness upon ICU admission by Acute Physiology and Chronic Health Evaluation IV-predicted risk of death was also lower in SGLT2 inhibitors users. Admissions and mortality due to sepsis were lower in SGLT2 inhibitor users compared with DPP-4 inhibitor users (admissions for sepsis: 45 [0.4%] vs 134 [0.8%]; p = 0.001 and mortality: 59 [0.6%] vs 414 [2.3%]; p < 0.001, respectively).

CONCLUSIONS:

In patients with type 2 diabetes, SGLT2 inhibitors were independently associated with lower rates of ICU admission and all-cause mortality across various disease categories.
IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial*
Authors: Angriman Federico , Muttalib Fiona , Lamontagne François , Adhikari Neill K. J. ,   LOVIT Investigators
Published: April 2023

OBJECTIVES:

The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis.

DESIGN:

Bayesian reanalysis of a randomized placebo-controlled trial.

SETTING:

Thirty-five ICUs.

PATIENTS:

Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission.

INTERVENTIONS:

Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04–1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00–1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97–1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98–1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94–1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92–1.19; probability of harm, 76%) priors.

CONCLUSIONS:

The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.
A robust microsatellite instability detection model for unpaired colorectal cancer tissue samples
Authors: Zhang Zili , Wan Hua , Xu Bing , He Hongyang , Shan Guangyu , Zhang Jingbo , Wu Qixi , Li Tong
Published: April 2023

Background:

Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples.

Methods:

From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR.

Results:

We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes (MLH1, MSH2, MSH6, and PMS2).

Conclusion:

MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.
Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States
Authors: Zheng Rongshou , Zhao Hong , An Lan , Zhang Siwei , Chen Ru , Wang Shaoming , Sun Kexin , Zeng Hongmei , Wei Wenqiang , He Jie
Published: April 2023

Background:

Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period.

Methods:

Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States.

Results:

The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas.

Conclusions:

The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries
Low diastolic blood pressure and adverse outcomes in inpatients with acute exacerbation of chronic obstructive pulmonary disease: A multicenter cohort study
Authors: Zhou Chen , Yi Qun , Luo Yuanming , Wei Hailong , Ge Huiqing , Liu Huiguo , Li Xianhua , Zhang Jianchu , Pan Pinhua , Yi Mengqiu , Cheng Lina , Liu Liang , Zhang Jiarui , Peng Lige , Aili Adila , Liu Yu , Pu Jiaqi , Zhou Haixia
Published: April 2023

Background:

Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients.

Methods:

Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes.

Results:

Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53–3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32–2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24–1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality.

Conclusion:

Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients.

Clinical Trial Registration:

Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Lifetime Prevalence of Psychiatric Disorders in Adolescents with Unexplained Weight Loss, Underweight, or Poor Appetite
Authors: Witte Micaela A. , Harbeck Weber Cynthia , Lebow Jocelyn , LeMahieu Allison , Geske Jennifer , Witte Nathaniel , Whiteside Stephen , Loth Katie , Sim Leslie
Published: April 2023

Background:

When adolescents present with symptoms of unexplained weight loss, underweight, or poor appetite, eating disorders (EDs) are commonly on the list of differential diagnoses. However, the relationship of these symptoms to other psychiatric disorders is often less clear.

Methods:

Using the Rochester Epidemiology Project database, a retrospective cohort study of adolescents (13–18 years) with billing diagnoses of weight loss, underweight, or loss of appetite was conducted between January 2005 and December 2017. Patients who presented with conditions commonly associated with weight loss, underweight, or poor appetite (e.g., cancer) were excluded. This study sought to examine the proportion of patients who received ED and psychiatric diagnoses within 5 years of the index visit and patient characteristics associated with these diagnoses.

Results:

Of 884 patients diagnosed with symptoms of unexplained weight loss, underweight, or poor appetite, 662 patients (M age = 15.8; SD = 1.6; 66.0% female) met study criteria. Within 5 years of the index visit, the lifetime prevalence of all psychiatric disorders was 70% (n = 461) and of EDs was 21% (n = 141). For both psychiatric disorders and EDs, sex and race were significantly associated with receiving a diagnosis within 5 years. Decrease in body mass index (BMI) percentile was associated with receiving an ED diagnosis, whereas the highest historical BMI percentile was associated with receiving a psychiatric diagnosis.

Conclusion:

Patients presenting with symptoms of unexplained weight loss, underweight, or poor appetite are at risk not only for EDs but also for other psychiatric disorders that may require further assessment and follow-up.
Prenatal Ambient Air Pollutant Mixture Exposure and Early School-age Lung Function
Authors: Hsu Hsiao-Hsien Leon , Wilson Ander , Schwartz Joel , Kloog Itai , Wright Robert O. , Coull Brent A. , Wright Rosalind J.
Published: April 2023

Introduction:

Research linking prenatal ambient air pollution with childhood lung function has largely considered one pollutant at a time. Real-life exposure is to mixtures of pollutants and their chemical components; not considering joint effects/effect modification by co-exposures contributes to misleading results.

Methods:

Analyses included 198 mother-child dyads recruited from two hospitals and affiliated community health centers in Boston, Massachusetts, USA. Daily prenatal pollutant exposures were estimated using satellite-based hybrid chemical-transport models, including nitrogen dioxide(NO2), ozone(O3), and fine particle constituents (elemental carbon [EC], organic carbon [OC], nitrate [NO3
–], sulfate [SO4
2–], and ammonium [NH4
+]). Spirometry was performed at age 6.99 ± 0.89 years; forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75) z-scores accounted for age, sex, height, and race/ethnicity. We examined associations between weekly-averaged prenatal pollution mixture levels and outcomes using Bayesian Kernel Machine Regression-Distributed Lag Models (BKMR-DLMs) to identify susceptibility windows for each component and estimate a potentially complex mixture exposure-response relationship including nonlinear effects and interactions among exposures. We also performed linear regression models using time-weighted-mixture component levels derived by BKMR-DLMs adjusting for maternal age, education, perinatal smoking, and temperature.

Results:

Most mothers were Hispanic (63%) or Black (21%) with ≤12 years of education (67%). BKMR-DLMs identified a significant effect for O3 exposure at 18–22 weeks gestation predicting lower FEV1/FVC. Linear regression identified significant associations for O3, NH4
+, and OC with decreased FEV1/FVC, FEV1, and FEF25-75, respectively. There was no evidence of interactions among pollutants.

Conclusions:

In this multi-pollutant model, prenatal O3, OC, and NH4
+ were most strongly associated with reduced early childhood lung function.
A multistrain probiotic increases the serum glutamine/glutamate ratio in patients with cirrhosis: a metabolomic analysis
Authors: Laghi Luca , Román Eva , Lan Qiuyu , Nieto Juan Camilo , Canalda-Baltrons Aleix , Poca Maria , Sánchez-Rodríguez Maria B. , Clària Joan , Alvarado Edilmar , Cuyàs Berta , Sánchez Elisabet , Vidal Sílvia , Guarner Carlos , Escorsell Àngels , Manichanh Chaysavanh , Soriano German
Published: April 2023

To explore the potential mechanisms underlying the effects of a probiotic in cirrhotic patients, we analyzed the blood metabolome using proton nuclear magnetic resonance (1H-NMR) spectroscopy in 32 patients with cirrhosis and cognitive dysfunction or falls. Patients were randomized to receive a multistrain probiotic or placebo for 12 weeks. Among the 54 metabolites identified, the only significant changes in the probiotic group were an increase in glutamine, a decrease in glutamate, and an increase in the glutamine/glutamate ratio. In the placebo group, glutamate increased and the glutamine/glutamate ratio decreased. Our results suggest the multistrain probiotic could influence glutamine/glutamate metabolism, increasing the capacity of ammonia detoxification.
Identifying chronic low back pain phenotypic domains and characteristics accounting for individual variation: a systematic review
Authors: Hassan Samah , Nesovic Karlo , Babineau Jessica , Furlan Andrea D. , Kumbhare Dinesh , Carlesso Lisa C.
Published: April 2023

Interpatient variability is frequently observed among individuals with chronic low back pain (cLBP). This review aimed at identifying phenotypic domains and characteristics that account for interpatient variability in cLBP. We searched MEDLINE ALL (through Ovid), Embase Classic and EMBASE (through Ovid), Scopus, and CINAHL Complete (through EBSCOhost) databases. Studies that aimed to identify or predict cLBP different phenotypes were included. We excluded studies that focused on specific treatments. The methodological quality was assessed using an adaptation of the Downs and Black tool. Forty-three studies were included. Although the patient and pain-related characteristics used to identify phenotypes varied considerably across studies, the following were among the most identified phenotypic domains and characteristics that account for interpatient variability in cLBP: pain-related characteristics (including location, severity, qualities, and duration) and pain impact (including disability, sleep, and fatigue), psychological domains (including anxiety and depression), behavioral domains (including coping, somatization, fear avoidance, and catastrophizing), social domains (including employment and social support), and sensory profiling (including pain sensitivity and sensitization). Despite these findings, our review showed that the evidence on pain phenotyping still requires further investigation. The assessment of the methodological quality revealed several limitations. We recommend adopting a standard methodology to enhance the generalizability of the results and the implementation of a comprehensive and feasible assessment framework to facilitate personalized treatments in clinical settings.
Childhood Cholestatic Liver Diseases that Persist Into Adulthood
Authors: Chan Alvin P. , Venick Robert S.
Published: April 2023

Children with cholestatic liver diseases are increasingly living into adulthood, thanks to innovations in medical and surgical therapies. The excellent outcomes observed in pediatric liver transplantation for diseases, such as biliary atresia, have transformed the life trajectory of children born with once-fatal liver diseases. The evolution of molecular genetic testing, has helped expedite the diagnosis of other cholestatic disorders, improving the clinical management, disease prognosis, and family planning for inherited disorders, such as progressive familial intrahepatic cholestasis and bile acid synthesis disorders. The expanding list of therapeutics, including bile acids and the newer ileal bile acid transport inhibitors, has also helped slow the progression of disease and improve the quality of life for certain diseases, like Alagille syndrome. More and more children with cholestatic disorders are expected to require care from adult providers familiar with the natural history and potential complications of these childhood diseases. The aim of this review is to bridge the gap between pediatric and adult care in children with cholestatic disorders. The present review addresses the epidemiology, clinical features, diagnostic testing, treatment, prognosis, and transplant outcomes of 4 hallmark childhood cholestatic liver diseases: biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, and bile acid synthesis disorders.
Effect of miR-145 on intracardiac thrombosis in patients with rheumatic heart disease complicated with atrial fibrillation: A retrospective analysis
Authors: Zhang Xiong , Deng Kai , Ren Xu-Ai , Su Xiao-Ming
Published: April 2023

Patients with rheumatic heart disease (RHD) and atrial fibrillation (AF) often have a risk of intracardiac thrombosis. Exfoliated thrombus is easy to cause embolic diseases. This study revealed the risk of intracardiac thrombosis in patients with RHD with AF by exploring the expression of plasma microRNA miR-145. The expression of plasma miR-145 in 58 patients with RHD complicated with AF was detected by real-time quantitative polymerase chain reaction [28 cases in thrombus (TH) group and 30 cases in non-thrombus (NTH) group]. At the same time, a healthy control group (33 cases) was established. The correlation between miR-145 and thrombosis in RHD was analyzed. The expression of plasma miR-145 in TH group and NTH group decreased significantly, especially in TH group (P < .01). In TH group and NTH group, the expression of miR-145 was negatively correlated with D-Dimer level, Factor XI concentration and tissue factor level as well as left atrial diameter (all P < .01, respectively). The receiver operating curve analysis showed that the expression of miR-145 had diagnostic significance for RHD and its intracardiac thrombosis. In this study, we suggest that the change of plasma miR-145 expression in patients with RHD is related to coagulation activity and fibrinolysis, which can predict the risk of intracardiac thrombosis.
Metagenomic next-generation sequencing performed on blood samples for the early recognition of severe Pneumocystis pneumonia in critical hematological patients
Authors: Shen Xiang-Dong , Pan Xu-Dong , Shi Sen-Sen , Xu Ting , Xue Sheng-Li , Wang Jun , Wan Chao-Ling , Yao Yu-Ting , Lei Wei , Tao Tao
Published: April 2023

Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.
Gastrointestinal Talaromyces marneffei infection in a man with AIDS: A case report
Authors: Peng Renping , Peng Zhipeng , Mou Minhong , Wang Qiudong , Huang Man , Zou Jun
Published: April 2023

Rationale:

Reports of intestinal Talaromyces marneffei infection have increased year by year, but those of gastric infection remain rare. Here, we report disseminated talaromycosis with gastric and intestinal ulcers in an AIDS patient who was treated by antifungal agents and a proton pump inhibitor and achieved a satisfactory outcome.

Patient concerns:

A 49-year-old man developed a gastrointestinal illness with main abdominal distension, poor appetite and a positive HIV infection to our AIDS clinical treatment center.

Diagnoses:

Electronic gastrointestinal endoscopy showed that the patient had multiple ulcers in the gastric angle, gastric antrum and large intestine. Gastric Helicobacter pylori infection was ruled out by paraulcerative histopathological analysis and a C14 urea breath test. The diagnosis was confirmed by gastroenteroscopic biopsy and metagenomic next-generation sequencing of gastric ulcer tissue.

Interventions:

Symptomatic and supportive treatments [a proton pump inhibitor and gastrointestinal motility promotion] were initiated. The patient was prescribed sequential antifungal therapy with amphotericin B (0.5 mg/kg·d, 2 weeks) and itraconazole (200 mg, q12h, 10 weeks), and then followed with itraconazole for long-term secondary prevention (200 mg, qd).

Outcomes:

The combined use of antifungal agents and a proton pump inhibitor improved the patient’s condition, and he was discharged home 20 days later. He had no gastrointestinal symptom during 1 year of telephone-based follow-up.

Lessons:

In endemic areas, clinicians should be alert to the possibility of Talaromyces marneffei infection presenting with gastric ulcers in patients with AIDS, after excluding Helicobacter pylori infection.
Whether induction of labor ahead in low-risk women improves pregnancy outcomes?: A retrospective cohort, observational study
Authors: Ren Huiyan , Zuo Qing , Pan Yi , Zhu Xinxin , Yin Tingting , Zhang Min , Yin Yin , Ge Zhiping , Jiang Ziyan , Lu Hongmei
Published: April 2023

The appropriate timing of delivery for pregnancies has always been a concern for medical staff, and the timing of elective labor induction at 41 weeks in low-risk pregnant women has always been controversial. We compared maternal and fetal outcomes between gestational age at 40 0/7 to 40 6/7 and 41 0/7 to 41 6/7 weeks. This retrospective cohort study was conducted at the obstetrics department of Jiangsu Province Hospital from January 1st to December 31st in 2020. Maternal medical records and neonatal delivery data were collected. One-way analysis of variance, Mann–Whitney U test, χ2 test, Fisher exact test and logistig regression analysis were performed. The study included 1569 pregnancies, with 1107 (70.6%) delivered at 40 0/7 to 40 6/7 weeks and 462 (29.4%) delivered at 41 0/7 to 41 6/7 weeks. Intrapartum cesarean section (8% vs 16%, P < .001), meconium-stained amniotic fluid (13% vs 19%, P = .004), episiotomy (41% vs 49%, P = .011), and macrosomia (13% vs 18%, P = .026) were significantly lower at 40 0/7 to 40 6/7 weeks. The premature rupture of membranes rate (22% vs 12%, P < .001), vaginal delivery rate of artificial rupture of membrane induction (83% vs 71%, P = .006) and balloon catheter combined with oxytocin induction (88% vs 79%, P = .049) were significantly higher at 40 0/7 to 40 6/7 weeks. Low-risk women who delivered at 40 0/7 to 40 6/7 weeks showed better outcomes in terms of the mother’s and baby’s health, such as decreased rates of intrapartum cesarean section, meconium-stained amniotic fluid, episiotomy, and macrosomia, compared with those who delivered at 41 0/7 to 41 6/7 weeks.
Expression profile analysis of lncRNA and mRNA in uterosacral ligaments of women with pelvic organ prolapse by RNA-seq
Authors: Zhao Xinrui , Li Ping , Wang Lu , Zhang Ping , Liu Peishu
Published: April 2023

Pelvic organ prolapse (POP) is a conventional gynecological condition and the mechanism is not entirely clear. Although an increasing number of studies revealed that long non-coding RNAs (lncRNAs) have essential functions in many diseases, little knowledge has been acquired in POP. The current study aimed to investigate the regulatory mechanism of lncRNA in POP. In this report, we investigated the expression profile of lncRNAs and mRNAs between POP and the control groups in human uterosacral ligament (hUSL) tissues through RNA-seq. Cytoscape was used to construct a POP-specific lncRNA-mRNA network and select key molecules. This RNA-Seq analysis uncovered a total of 289 lncRNAs, and 41 lncRNAs and 808 mRNAs were differentially expressed between the POP and non-POP groups. Four lncRNAs were identified and validated by real-time PCR. The result of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) indicated that differentially expressed lncRNAs were abundant in the biological processes and signaling pathways concerned in POP. The differentially expressed lncRNAs were mainly enriched in protein binding, the single-organism cellular process, and cytoplasmic part. The network was constructed based on the correlation analyses of the abnormally expressed lncRNAs and their target proteins to imitate their interactions. Taken together, this study was the first to demonstrate the differential expression profiles of lncRNA in POP and normal tissues by sequencing technology. Our study indicated that lncRNAs could correlate with the development of POP and may be as significant genes in the diagnosis and treatment of POP.
Usability and understandability of a web-based medical communication aid for patients with ankylosing spondylitis in South Korea: A mixed-methods study
Authors: Lee Sang-Hoon , Park YoungJu , Choi Chan-Bum , Kim Yong-Gil , Kim Jung-Ae , Cha Hoon-Suk
Published: April 2023

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis which causes potentially debilitating pain and loss of mobility. Biologics represent a highly effective treatment option in AS. Nonetheless, the choice of biologics often involves complex decision-making. A web-based medical communication aid (MCA) was designed to support information exchange and shared decision-making process between physicians and biologics naïve AS patients. This study aimed to assess the usability of the MCA prototype and the understandability of the MCA contents among rheumatologists and AS patients in South Korea. This was a cross-sectional study using a mixed-methods approach. Treating rheumatologists from major hospitals and their AS patients were recruited in this study. Participants navigated through the MCA and provided feedbacks, guided by interviewers using the think-aloud (TA) method. Participants were then asked to complete a set of surveys. The qualitative and quantitative data were analyzed to determine the usability of the MCA prototype and the understandability of the MCA contents. The MCA prototype received above average rating for usability and high rating for the understandability of its contents. Additionally, participants rated that the quality of information presented in the MCA as high. Analysis of the qualitative data highlighted three key aspects of the MCA; the usefulness of the MCA, the need to present concise and relevant content; and the importance of an intuitively designed tool. Overall, participants found the MCA to be potentially valuable in supporting the current unmet needs in clinical care and had expressed a willingness to use the MCA. The MCA had great potential in supporting shared decision-making by improving patients’ knowledge on disease and treatment options, as well as clarifying patients’ personal preferences and values in the management of AS.
Intractable hyponatremia secondary to syndrome of inappropriate antidiuresis complicated with empty sella: A case report
Authors: Zheng Wenli , Fan Shiqin , Chen Jie , Ma Jing
Published: April 2023

Rationale:

Hyponatremia is a common electrolyte disorder in elderly critically ill patients, and it may be associated with poor outcomes, higher morbidity, and mortality. Syndrome of inappropriate antidiuresis (SIAD) is one of the main causes of hyponatremia, with an insidious onset that is highly misdiagnosed. Primary empty sella lesions are specific, mostly asymptomatic, and easily overlooked. SIAD combined with empty sella is much rarer in clinic, this article focuses on the diagnosis and management of an elderly patient with intractable hyponatremia secondary to syndrome of inappropriate antidiuresis complicated with empty sella.

Patient concerns:

An 85-year-old male patient with severe pneumonia presented with progressive and intractable hyponatremia.

Diagnoses:

The patient had clinical signs of persistent hyponatremia, low plasma osmolality, elevated urinary sodium excretion, and hyponatremia that worsened with increased intravenous rehydration and was effective with appropriate fluid restriction. The diagnosis of SIAD combined with empty sella was made in combination with the findings of the pituitary and its target gland function.

Interventions:

Numerous screenings were performed to clarify the cause of hyponatremia. His overall condition was poor due to recurrent episodes of hospital-acquired pneumonia. We treated with ventilation support, circulatory support, nutritional support, anti-infection, and continuous correction of electrolyte imbalance.

Outcomes:

His hyponatremia gradually improved through aggressive infection control, appropriate fluid restriction (intake controlled at 1500–2000mL/d), continuous electrolyte correction, supplementation with hypertonic salt solution, and potassium replacement therapy.

Lessons:

Electrolyte disorders, especially hyponatremia, are very common in critically ill patients, but the etiology of hyponatremia is challenging to diagnose and treat, and timely attention and proper diagnosis of SIAD and individualized treatment are the significance of this article.