bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRPA1 rare variants in chronic neuropathic and nociplastic pain patients
Authors: Marchi Margherita , Salvi Erika , Andelic Mirna , Mehmeti Elkadia , D'Amato Ilaria , Cazzato Daniele , Chiappori Federica , Lombardi Raffaella , Cartelli Daniele , Devigili Grazia , Dalla Bella Eleonora , Gerrits Monique , Almomani Rowida , Malik Rayaz A. , Ślęczkowska Milena , Mazzeo Anna , Gentile Luca , Dib-Hajj Sulayman , Waxman Stephen G. , Faber Catharina G. , Vecchio Eleonora , de Tommaso Marina , Lauria Giuseppe 
Published: April 2023

Abstract
Missing aspects of the heritability of chronic neuropathic pain, as a complex adult-onset trait, may be hidden within rare variants with low effect on disease risk, unlikely to be resolved by a single-variant approach. To identify new risk genes, we performed a next-generation sequencing of 107 pain genes and collapsed the rare variants through gene-wise aggregation analysis. The optimal unified sequence kernel association test was applied to 169 patients with painful neuropathy, 223 patients with nociplastic pain (82 diagnosed with chronic widespread pain and 141 with fibromyalgia), and 216 healthy controls. Frequency and features of variants in TRPA1, which was the most significant gene, were further validated in 2 independent cohorts of 140 patients with chronic pain (90 with painful neuropathy and 50 with chronic widespread pain) and 34 with painless neuropathy. The effect of aminoacidic changes were modeled in silico according to physicochemical characteristics. TRPA1 was significantly enriched of rare variants which significantly discriminated chronic pain patients from healthy controls after Bonferroni correction (P = 6.7 × 10−4, ρ = 1), giving a risk of 4.8-fold higher based on the simple burden test (P = 0.0015, OR = 4.8). Among the 32 patients harboring TRPA1 variants, 24 (75%) were diagnosed with nociplastic pain, either fibromyalgia (12; 37.5%) or chronic widespread pain (12; 37.5%), whereas 8 (25%) with painful neuropathy. Irrespective of the clinical diagnosis, 12 patients (38%) complained of itch and 10 (31.3%) of cold-induced or cold-accentuated pain, mostly episodic. Our study widens the spectrum of channelopathy-related chronic pain disorders and contributes to bridging the gap between phenotype and targeted therapies based on patients' molecular profile.
Effects of Adalimumab Entering National Reimbursement on Medical Costs for Patients With Psoriasis: A 4-Year Single-Center Retrospective Study in China
Authors: Li Yu , Zhu Bo-Kun , Min Qing-Sheng , Ju Mei , Li Min 
Published: April 2023

Objective:
Adalimumab (ADA) is expensive and rarely used among patients. However, its cost for moderate to severe chronic plaque psoriasis can now be reimbursed since its addition to the National Reimbursement Drug List (NRDL) in January 2020. Therefore, we conducted this study to estimate the medical cost of ADA and its influencing factors in patients with psoriasis using ADA and thus gain a better understanding of the effect of the NRDL adjustment in China.

Methods:
This retrospective study evaluated the medical cost of ADA before and after the addition of ADA to the NRDL (2018—2022) among 320 patients in a large professional dermatology specialty hospital. Descriptive analysis, Welch’s analysis of variance, and multiple regression analysis were used to evaluate the medical cost and influencing factors.

Results:
Before ADA was added to the NRDL, patients’ mean total cost and ADA cost were ¥24,243.56 ± 16,346.53 and ¥20,391.11 ± 14,440.69, respectively. After ADA became covered by the NRDL, the above 2 expenses decreased to ¥10,461.19 ± 7,554.66 and ¥8,775.27 ± 7,092.16, respectively. This significant decrease in the cost of ADA resulted in a significant 110.5-times increase in ADA use. Statistically significant differences were found in the total cost, patient type (outpatient/inpatient), insurance status (yes/no), reimbursement status (before/after), and age. Medical insurance reimbursement (P < 0.001, β = -0.468, before reimbursement = 1, after reimbursement = 2) was the most significant influencing factor, followed by patient type (P = 0.018, β = -0.215, outpatient = 1, inpatient = 2) and age (P = 0.0046, β = -0.174).

Conclusion:
Medical insurance reimbursement is the most important factor affecting patients’ total cost of ADA by reducing the economic burden, enhancing the availability of ADA, and stimulating the need for treatment.
Brain imaging after cardiac arrest
Authors: Beekman Rachel , Hirsch Karen G. 
Published: April 2023

Purpose of review
Many patients who survive a cardiac arrest have a disorder of consciousness in the period after resuscitation, and prediction of long-term neurologic outcome requires multimodal assessments. Brain imaging with computed tomography (CT) and MRI is a key component. We aim to provide an overview of the types of neuroimaging available and their uses and limitations.

Recent findings
Recent studies have evaluated qualitative and quantitative techniques to analyze and interpret CT and MRI to predict both good and poor outcomes. Qualitative interpretation of CT and MRI is widely available but is limited by low inter-rater reliability and lack of specificity around which findings have the highest correlation with outcome. Quantitative analysis of CT (gray–white ratio) and MRI (amount of brain tissue with an apparent diffusion coefficient below certain thresholds) hold promise, though additional research is needed to standardize the approach.

Summary
Brain imaging is important for evaluating the extent of neurologic injury after cardiac arrest. Future work should focus on addressing previous methodological limitations and standardizing approaches to qualitative and quantitative imaging analysis. Novel imaging techniques are being developed and new analytical methods are being applied to advance the field.
Airway management during cardiac arrest
Authors: Penketh James , Nolan Jerry P. 
Published: April 2023

Purpose of review
Despite improvements over time, cardiac arrest continues to be associated with high rates of mortality and morbidity. Several methods can be used to achieve airway patency during cardiac arrest, and the optimal strategy continues to be debated. This review will explore and summarize the latest published evidence for airway management during cardiac arrest.

Recent findings
A large meta-analysis of out-of-hospital cardiac arrest (OHCA) patients found no difference in survival between those receiving tracheal intubation and those treated with a supraglottic airway (SGA). Observational studies of registry data have reported higher survival to hospital discharge in patients receiving tracheal intubation or an SGA but another showed no difference. Rates of intubation during in-hospital cardiac arrest have decreased in the United States, and different airway strategies appear to be used in different centres.

Summary
Observational studies continue to dominate the evidence base relating to cardiac arrest airway management. Cardiac arrest registries enable these observational studies to include many patients; however, the design of such studies introduces considerable bias. Further randomized clinical trials are underway. The current evidence does not indicate a substantial improvement in outcome from any single airway strategy.
Perspectives on peripheral perfusion assessment
Authors: Kattan Eduardo , Ibarra-Estrada Miguel , Ospina-Tascón Gustavo , Hernández Glenn 
Published: April 2023

Purpose of review
The ANDROMEDA-SHOCK trial positioned capillary refill time (CRT) assessment as a novel resuscitation target for septic shock.
The purpose of this article is to summarize pathophysiological determinants of CRT, review new technical developments on peripheral perfusion assessment, and explore recent evidence on the role of CRT monitoring in septic shock and other critical conditions.

Recent findings
A growing body of evidence supports the role of peripheral perfusion assessment as a warning and prognostic signal in a variety of clinical conditions among severely ill patients. Recent physiological studies demonstrated a rapid improvement of CRT after a single fluid bolus or a passive leg raising maneuver, a fact which may have diagnostic and therapeutic implications. Moreover, a couple of posthoc analyses of ANDROMEDA-SHOCK trial, reinforce that a normal CRT at the start of septic shock resuscitation, or its rapid normalization, thereafter may be associated with significant better outcomes.

Summary
Recent data confirm the relevance of peripheral perfusion assessment in septic shock and other conditions in critically ill patients. Future studies should confirm these findings, and test the potential contribution of technological devices to assess peripheral perfusion.
The pulmonary artery catheter
Authors: Arias-Ortiz Julian , Vincent Jean-Louis 
Published: April 2023

Purpose of review
To review recently published data on pulmonary artery catheter (PAC) use in critically ill patients and consider optimal use of the PAC in personalized clinical practice.

Recent findings
Although PAC use has decreased considerably since the mid-1990s, PAC-derived variables can still have an important role in elucidating hemodynamic status and directing management in complex patients. Recent studies have suggested benefit, notably in patients having cardiac surgery.

Summary
Only a small number of acutely ill patients require a PAC and insertion should be individualized based on clinical context, availability of trained staff, and the possibility that measured variables will be able to help guide therapy.
How to assess tissue oxygenation?
Authors: De Backer Daniel , Ospina-Tascón Gustavo A. 
Published: April 2023

Purpose of review
To discuss the different techniques used to assess tissue oxygenation in critically ill patients.

Recent findings
While historically the analysis of oxygen consumption (VO2)/oxygen delivery (DO2) relationships has provided important information, methodological limitations prevent its use at bedside. PO2 measurements, while attractive, are unfortunately of limited value in the presence of microvascular blood flow heterogeneity which is observed in many critically ill conditions including sepsis. Surrogates of tissue oxygenation are hence used. Elevated lactate levels may suggest inadequate tissue oxygenation, but other sources than tissue hypoxia can also contribute to hyperlactatemia so that lactate measurements should be used in combination with other measurements of tissue oxygenation. Venous O2 saturation can be used to evaluate the adequacy of DO2 in respect to VO2, but it can be misleading normal or even high in sepsis. Measurements of Pv-aCO2 and computation of Pv-aCO2/CavO2 are very promising as physiologically sound, easy to measure, rapidly respond to therapy, and are associated with outcome. An elevated Pv-aCO2 reflects an impaired tissue perfusion while an increased Pv-aCO2/CavO2 ratio reflects tissue dysoxia.

Summary
Recent studies have highlighted the interest of surrogate measurements of tissue oxygenation and in particular PCO2 gradients.
The Natural History of Pancreatic Cystic Lesions in Liver Transplant Recipients
Authors: Canakis Andrew , Vittal Anusha , Deliwala Smit , Twery Benjamin , Canakis Justin , Patel Preet , Chahal Prabhleen 
Published: April 2023

Objectives
The management of incidentally discovered pancreatic cystic lesions (PCLs) with surveillance or resection often requires shared decision-making. Patients with cirrhosis are more likely to have PCLs discovered due to increased imaging, and those undergoing liver transplantations (LTs) may be at increased risk of carcinogenesis due to immunosuppressive medications. Our study aimed to characterize the outcomes and risk of malignant progression of PCLs in post-LT patients.

Methods
Multiple databases were searched for studies looking at PCLs in post-LT patients from inception until February 2022. Primary outcomes were the incidence of PCLs in LT recipients and progression to malignancy. Secondary outcomes included development of worrisome features, outcomes of surgical resection for progression, and change in size.

Results
A total of 12 studies with 17,862 patients with 1411 PCLs were included. The pooled proportion of new PCL development in post-LT patients was 68% (95% confidence interval [CI], 42–86; I
2 = 94%) over the follow-up of 3.7 (standard deviation, 1.5) years. The pooled progression of malignancy and worrisome features was 1% (95% CI, 0–2; I
2 = 0%) and 4% (95% CI, 1–11; I
2 = 89%), respectively.

Conclusions
Compared with nontransplant patients, incidental PCLs do not carry a higher risk of malignancy.
Predictors of Delayed Diagnosis of Pediatric CNS Tumors in the Emergency Department
Authors: Young Ann L. , Monuteaux Michael C. , Cooney Tabitha M. , Michelson Kenneth A. 
Published: April 2023

Objective
Central nervous system (CNS) tumor diagnoses are frequently delayed in children, which may lead to adverse outcomes and undue burdens on families. Examination of factors associated with delayed emergency department (ED) diagnosis could identify approaches to reduce delays.

Study Design
We performed a case-control study using data from 2014 to 2017 for 6 states. We included children aged 6 months to 17 years with a first diagnosis of CNS tumor in the ED. Cases had a delayed diagnosis, defined as 1 or more ED visits in the 140 days preceding tumor diagnosis (the mean prediagnostic symptomatic interval for pediatric CNS tumors in the United States). Controls had no such preceding visit.

Results
We included 2828 children (2139 controls, 76%; 689 cases, 24%). Among cases, 68% had 1 preceding ED visit, 21% had 2, and 11% had 3 or more. Significant predictors of delayed diagnosis included presence of a complex chronic condition (adjusted odds ratio [aOR], 9.73; 95% confidence interval [CI], 6.67–14.20), rural hospital location (aOR, 6.37; 95% CI, 1.80–22.54), nonteaching hospital status (aOR, 3.05, compared with teaching hospitals; 95% CI, 1.94–4.80), age younger than 5 years (aOR, 1.57; 95% CI, 1.16–2.12), public insurance (aOR, 1.49, compared with private; 95% CI, 1.16–1.92), and Black race (aOR, 1.42, compared with White; 95% CI, 1.01–1.98).

Conclusions
Delayed ED diagnosis of pediatric CNS tumors is common and frequently requires multiple ED encounters. Prevention of delays should focus on careful evaluation of young or chronically ill children, mitigating disparities for Black and publicly insured children, and improving pediatric readiness in rural and nonteaching EDs.
Evaluation of the Renal Angina Index to Predict the Development of Acute Kidney Injury in Children With Sepsis Who Live in Middle-Income Countries
Authors: Suárez María Del Pilar , Fernández-Sarmiento Jaime , González Luz Esthella , Rico Mayerly Prada , Barajas Juan Sebastián , Amaya Ricardo Gastelbondo 
Published: April 2023

Objective
The renal angina index (RAI) provides a clinically feasible and applicable tool to identify critically ill children at risk of severe acute kidney injury (AKI) in high-income countries. Our objective was to evaluate the performance of the RAI as a predictor of the development of AKI in children with sepsis in a middle-income country and its association with unfavorable outcomes.

Methods
This is a retrospective cohort study in children with sepsis hospitalized in the pediatric intensive care unit (PICU) between January 2016 and January 2020. The RAI was calculated 12 hours after admission to predict the development of AKI and at 72 hours to explore its association with mortality, the need for renal support therapy, and PICU stay.

Results
We included 209 PICU patients with sepsis with a median age of 23 months (interquartile range, 7–60). We found that 41.1% of the cases (86/209) developed de novo AKI on the third day of admission (KDIGO 1, 24.9%; KDIGO 2, 12.9%; and KDIGO 3, 3.3%).
Overall mortality was 8.1% (17/209), higher in patients with AKI (7.7% vs 0.5%, P < 0.01). The RAI on admission was able to predict the presence of AKI on day 3 (area under the curve (AUC), 0.87; sensitivity, 94.2%; specificity, 100%; P < 0.01), with a negative predictive value greater than 95%. An RAI greater than 8 at 72 hours was associated with a greater risk of mortality (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 2.0–3.2; P < 0.01), a need for renal support therapy (aOR, 2.9; 95% CI, 2.3–3.6; P < 0.01), and a PICU stay of more than 10 days (aOR, 1.54; 95% CI, 1.1–2.1; P < 0.01).

Conclusions
The RAI on the day of admission is a reliable and accurate tool for predicting the risk of developing AKI on day 3, in critically ill children with sepsis in a limited resource context. A score greater than eight 72 hours after admission is associated with a higher risk of death, the need for renal support therapy, and PICU stay.
The Fidelity of a Pharmacy-Based Oral HIV Pre-Exposure Prophylaxis Delivery Model in Kenya
Authors: Omollo Victor , Asewe Magdaline , Mogere Peter , Maina Gakuo , Kuo Alexandra P. , Odoyo Josephine , Oware Kevin , Baeten Jared M. , Kohler Pamela , Owens Tamara , Bukusi Elizabeth A. , Ngure Kenneth , Ortblad Katrina F. 
Published: April 2023

Background:
HIV pre-exposure prophylaxis (PrEP) delivery at private pharmacies is a promising new differentiated service delivery model that may address barriers to PrEP delivery at public health care facilities. We measured the fidelity of this model (ie, delivery as intended) in a pilot study in Kenya.

Setting:
Five private, retail pharmacies in Kisumu and Thika Counties.

Methods:
Trained pharmacy providers delivered PrEP services, including identifying eligible clients, counseling on HIV risk, assessing PrEP safety, testing for HIV, and dispensing PrEP. Pharmacy clients completed surveys that assessed the fidelity of the services received after each visit. Standardized client actors (ie, mystery shoppers) were trained on 4 different case scripts, then made unannounced pharmacy visits, and then completed a 40-item checklist that assessed the fidelity and quality of service delivery components.

Results:
From November 2020 to December 2021, 287 clients initiated and 159 (55%) refilled PrEP. At initiation, most clients were counseled on PrEP adherence (99%, 284 of 287) and potential side effects (97%, 279 of 287) and all received provider-assisted HIV self-testing before PrEP dispensing (findings consistent across refill visits). Nine standardized client actors completed 15 pharmacy visits. At each visit, most actors were asked about their behaviors associated with HIV risk (80%, 12/15) and all were counseled on PrEP safety and side effects. All actors reported that pharmacy providers treated them with respect.

Conclusions:
In this first pilot study of pharmacy-delivered PrEP services in Africa, the fidelity of service delivery was high, suggesting that trained providers at private pharmacies can deliver quality PrEP services.
Diagnosing viral encephalitis and emerging concepts
Authors: Yong Heather Y.F. , Pastula Daniel M. , Kapadia Ronak K. 
Published: April 2023

Purpose of reviewThis review offers a contemporary clinical approach to the diagnosis of viral encephalitis and discusses recent advances in the field. The neurologic effects of coronaviruses, including COVID-19, as well as management of encephalitis are not covered in this review.Recent findingsThe diagnostic tools for evaluating patients with viral encephalitis are evolving quickly. Multiplex PCR panels are now in widespread use and allow for rapid pathogen detection and potentially reduce empiric antimicrobial exposure in certain patients, while metagenomic next-generation sequencing holds great promise in diagnosing challenging and rarer causes of viral encephalitis. We also review topical and emerging infections pertinent to neuroinfectious disease practice, including emerging arboviruses, monkeypox virus (mpox), and measles.SummaryAlthough etiological diagnosis remains challenging in viral encephalitis, recent advances may soon provide the clinician with additional tools. Environmental changes, host factors (such as ubiquitous use of immunosuppression), and societal trends (re-emergence of vaccine preventable diseases) are likely to change the landscape of neurologic infections that are considered and treated in clinical practice.
Epidemiological and genomic investigation of chikungunya virus in Rio de Janeiro state, Brazil, between 2015 and 2018
Authors: Moreira Filipe Romero Rebello , de Menezes Mariane Talon , Salgado-Benvindo Clarisse , Whittaker Charles , Cox Victoria , Chandradeva Nilani , de Paula Hury Hellen Souza , Martins André Frederico , das Chagas Raphael Rangel , Brasil Rodrigo Decembrino Vargas , Cândido Darlan da Silva , Herlinger Alice Laschuk , Ribeiro Marisa de Oliveira , Arruda Monica Barcellos , Alvarez Patricia , Tôrres Marcelo Calado de Paula , Dorigatti Ilaria , Brady Oliver , Voloch Carolina Moreira , Tanuri Amilcar , Iani Felipe , de Souza William Marciel , Cardozo Sergian Vianna , Faria Nuno Rodrigues , de Aguiar Renato Santana 
Published: April 2023

AbstractSince 2014, Brazil has experienced an unprecedented epidemic caused by chikungunya virus (CHIKV), with several waves of East-Central-South-African (ECSA) lineage transmission reported across the country. In 2018, Rio de Janeiro state, the third most populous state in Brazil, reported 41% of all chikungunya cases in the country. Here we use evolutionary and epidemiological analysis to estimate the timescale of CHIKV-ECSA-American lineage and its epidemiological patterns in Rio de Janeiro. We show that the CHIKV-ECSA outbreak in Rio de Janeiro derived from two distinct clades introduced from the Northeast region in mid-2015 (clade RJ1,n= 63/67 genomes from Rio de Janeiro) and mid-2017 (clade RJ2,n= 4/67). We detected evidence for positive selection in non-structural proteins linked with viral replication in the RJ1 clade (clade-defining: nsP4-A481D) and the RJ2 clade (nsP1-D351G). Finally, we estimate the CHIKV-ECSA’s basic reproduction number (R0) to be between 1.2 to 1.6 and show that its instantaneous reproduction number (Rt) displays a strong seasonal pattern with peaks in transmission coinciding with periods of highAedes aegyptitransmission potential. Our results highlight the need for continued genomic and epidemiological surveillance of CHIKV in Brazil, particularly during periods of high ecological suitability, and show that selective pressures underline the emergence and evolution of the large urban CHIKV-ECSA outbreak in Rio de Janeiro.
Long-Term Clinical Outcomes in Critically Ill Patients with Sepsis and Pre-existing Sarcopenia: A Retrospective Cohort Study
Authors: Darden Nola , Sharma Sonakshi , Wu Xue , Mancini Benjamin , Karamchandani Kunal , Bonavia Anthony S 
Published: April 2023

ABSTRACTPurposeCritically ill patients with sepsis account for significant disease morbidity and healthcare costs. Sarcopenia has been proposed as an independent risk factor for poor short-term outcomes, although its effect on long-term outcomes remains unclear.MethodsRetrospective cohort analysis of patients treated at a tertiary care medical center over 6 years (09/2014 - 12/2020). Critically ill patients meeting Sepsis-3 criteria were included, with sarcopenia defined by skeletal muscle index at the L3 lumbar area on abdominal Computed-Tomography scan. The prevalence of sarcopenia and its association with clinical outcomes was analyzed.ResultsSarcopenia was present in 34 (23%) of 150 patients, with median skeletal muscle indices of 28.1 cm2/m2and 37.3 cm2/m2in sarcopenic females and males, respectively. In-hospital mortality was not associated with sarcopenia when adjusted for age and illness severity. One year mortality was increased in sarcopenic patients, after adjustment for illness severity (HR 1.9, p = 0.02) and age (HR 2.4, p = 0.001). However, it was not associated with increased likelihood for discharge to long-term rehabilitation or hospice care in adjusted analyses.ConclusionSarcopenia independently predicts one year mortality but is not associated with unfavorable hospital discharge disposition in critically ill patients with sepsis.