bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic adaptations in metabolism and nutritional status
Authors: Haehling Stephan von , Doehner Wolfram
Published: December 2023

Metabolic imbalance in heart failure affects energy and structural metabolism. The resulting anabolic/catabolic imbalance intensifies body wasting processes, leading to sarcopenia and cachexia. Whereas sarcopenia describes the loss of functional skeletal muscle, cachexia refers to easily measurable loss of body weight without reference to a specific tissue type. Loss of appetite and malnutrition can be part of the clinical picture of body wasting, but both are not the pathophysiological foundation of the problem. Still the supply of micro- and macronutrients, as well as exercise training, can help in the treatment of wasting in heart failure. This chapter describes the definitions of, and therapeutic approaches to, wasting in patients with heart failure.
Cardiopulmonary exercise testing
Authors: Moderato Luca , Lazzeroni Davide , Adamopoulos Stamatis , Cohen-Solal Alain , Piepoli Massimo
Published: December 2023

Compared to traditional exercise tests, cardiopulmonary exercise testing (CPET) provides a complete and integrated assessment of exercise physiology involving cardiovascular, pulmonary, muscular, and cellular oxidative systems. In providing a direct measurement of oxygen consumption, CPET helps physicians to understand different causes of dyspnoea, fatigue, and exercise limitation, thereby providing unique information to differentiate between cardiac, pulmonary, or peripheral disease. CPET is also extremely helpful to optimize decision-making processes and monitoring of therapeutic effects, especially in heart failure (HF) patients. Moreover, CPET provides useful and independent prognostic markers in both the respiratory and cardiovascular systems. In HF patients, CPET allows to assess the presence of multi-organ dysfunction, including respiratory, muscular, and neurohormonal system impairment. This chapter summarizes methodological considerations, physiological implications, clinical applications, and future directions of CPET.
Heart rate reduction with ivabradine in heart failure
Authors: Böhm Michael , Komajda Michel
Published: December 2023

Ivabradine inhibits hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, and thereby the ‘funny’ channel If, leading to heart rate reduction, which is dependent on the baseline heart rate. Heart failure treatment should be optimized, in addition to guideline-directed and recommended drugs, to achieve an appropriate heart rate (i.e. 50–60 bpm) with use of ivabradine in patients with a heart rate of >70 bpm in sinus rhythm and with an ejection fraction of ≤35% (SHIFT trial). In this trial, heart rate reduction reduced cardiovascular death and heart failure hospitalization, dependent on the baseline resting heart rate. In particular, in patients with a heart rate of >75 bpm, a reduction in cardiovascular death, all-cause death, heart failure death, heart failure hospitalization, and all-cause hospitalization was observed. The optimal heart rate achieved appears to be between 50 and 60 bpm, if well tolerated, as in these patients, the lowest event rate is observed on treatment. Heart rate reduction is therefore a treatable risk factor in chronic heart failure. Observational studies support the concept that it is a risk indicator in other cardiovascular and non-cardiovascular conditions. Whether heart rate reduction is also modifying the risk in conditions other than chronic heart failure should be explored in prospective clinical trials.
Valve interventions
Authors: Orwat Stefan , Anker Stefan D , Baumgartner Helmut
Published: December 2023

Valvular heart disease (VHD) and heart failure (HF) are closely related. Untreated severe primary VHD ultimately ends up in HF being a main cause of death. Secondary VHD in HF of other causes, on the other hand, is known to aggravate morbidity and mortality. Correct distinction between primary and secondary VHD, as well as its quantification, require particular expertise and are critical as treatment strategies differ fundamentally. Whereas valve intervention is indicated early in primary VHD to avoid HF development, and definitely as soon as early symptoms of HF occur, intervention in secondary VHD is currently considered in patients who remain symptomatic despite optimal HF treatment and VHD is assumed to be a relevant driver of HF and its consequences. The evolvement of transcatheter VHD intervention has dramatically changed treatment options, particularly in secondary VHD. The multidisciplinary heart team appears essential in this context to provide appropriate management decisions.
Ancillary procedures
Authors: Coats Andrew JS , Ponikowski Piotr P , Costanzo Maria-Rosa , Abraham William T
Published: December 2023

Effective treatments for heart failure are still an urgent priority because of the large residual mortality and morbidity of this condition. Much recent innovation has been in the field of implantable devices, as well as in other procedures which offer potential benefit. Procedures that have thus far demonstrated promising results include cardiac contractility modulation, autonomic modulation, and respiratory rhythm modulation. This chapter reviews recently approved procedures and devices, and explores what might be on the horizon in this area, with already successful phase 2 trial results.
Clinical aspects of chronic kidney disease in heart failure
Authors: Martens Pieter , Rocca Hans-Peter Brunner-La
Published: December 2023

The kidney and the heart are heavily intertwined and can alter the prognosis of each other. The occurrence of heart failure (HF) in chronic kidney disease (CKD) and vice versa is very common. Adequate evaluation of kidney function encompasses both assessment of glomerular and tubular function, the latter being especially important during decongestive therapy. CKD patients are at higher risk of death from cardiovascular causes and of being admitted for an unplanned heart failure hospitalization. The importance of ensuring adequate lifesaving guideline-directed medical therapy (GDMT) is unquestioned, yet observational studies clearly indicate that patients with CKD are less likely to receive such GDMT. Small changes in eGFR after initiation of GDMT do not diminish the expected benefits from GDMT; so efforts should be made to ensure GDMT is optimized in patients with both HF and CKD. Given the reduced physiologic reserve in patients with advanced CKD, close monitoring is indicated.
Ventilatory abnormalities and sleep disordered breathing
Authors: Agostoni Piergiuseppe , Salvioni Elisabetta , Costanzo Maria Rosa , Coats Andrew JS
Published: December 2023

Abnormalities of ventilation are frequently observed in chronic heart failure patients and, at least in part, form the basis of common symptoms, such as dyspnoea, fatigue, and exercise performance limitation. They are evident during daily activities, including exercise, as well as during sleep. Abnormalities of ventilation include mechanical abnormalities of chest wall movements, and

exchange changes and ventilatory control abnormalities. They may also include specific respiratory pattern abnormalities, such as exercise-induced oscillatory breathing, sleep apnoea either obstructive or central in origin, and hypopnoea and Cheyne–Stokes respiration. All are possible targets of heart failure therapy and, most importantly, all have a strong and independent prognostic role.
Management of atrial fibrillation in heart failure
Authors: Metzner Andreas , Rottner Laura , Schleberger Ruben , Moser Fabian , Kirchhof Paulus
Published: December 2023

Heart failure and atrial fibrillation are two important epidemics in cardiovascular medicine. The two conditions often coexist. The ESC guidelines for atrial fibrillation provide a pathway to guide diagnosis and treatment of the condition. The cornerstones of atrial fibrillation treatment remain oral anticoagulation according to the CHA2DS2-VASc Score and identification and treatment of concomitant cardiovascular conditions, including heart failure. Rhythm control therapy is currently recommended to improve atrial fibrillation -related symptoms. Especially in patients with atrial fibrillation and heart failure, rhythm control therapy can have important impact on other outcomes, including heart failure progression and death. The recently published EAST-AFNET 4 trial emphasizes the necessity of early rhythm control in atrial fibrillation patients to reduce cardiovascular events. The heart failure sub-analysis and the heart failure sub-analysis of the CABANA trial both underpin that rhythm control therapy can prevent atrial fibrillation -related complications, such as cardiovascular death, stroke, and hospitalization for heart failure in patients with atrial fibrillation and heart failure across the range of left ventricular ejection fractions. Thus, rhythm control therapy emerges as the default third pillar of therapy for patients with recently diagnosed atrial fibrillation and for those with both atrial fibrillation and heart failure.
Clinical trial design and interpretation
Authors: Savarese Gianluigi , Polovina Marija , Filippatos Gerasimos
Published: December 2023

Randomized controlled trials (RCTs) represent the gold standard to test treatment benefit in medicine because randomization, unlike adjustments in observational studies, allows controlling for any known and unknown, measured and unmeasured confounder. Blinding is a further procedure used in RCTs to reduce risk of bias. Setting adequate selection criteria in RCTs is key to test the population that the intervention is intended for and to enrich the trial for the occurrence of cardiovascular endpoints and reduce the risk of competing events. However, too strict selection criteria might lead to questions bout the generalizability of RCTs findings to real-world populations. Intention-to-treat analysis is the gold standard in RCT analysis but use of per-protocol as supporting sensitivity analysis is highly recommended. Pre-specification when approaching subgroup analysis prevents the selective reporting of results and leads to more credible and valuable findings compared with post-hoc analyses. Novel and more dynamic trial design might make possible running more, more effective, and cheaper randomized controlled trials in the heart failure field.
Telemedicine and remote monitoring in heart failure
Authors: Bekfani Tarek , Koehler Friedrich , Abraham William T
Published: December 2023

Despite advances in pharmacological and device therapies for patients with heart failure (HF), morbidity and mortality, and in particular the rate of HF hospitalizations, remain very high resulting in a considerable health economic burden. Remote monitoring (RM) added to guideline-directed drug and device therapies offers an improvement in care delivery and clinical outcomes for patients regardless of left ventricular ejection fraction. Ninety per cent of HF patients exhibit volume overload when admitted to the hospital. Consequently, most RM approaches and technologies target fluid volume management as a means for improving outcomes. A great variety of innovative RM technologies, such as wearable and implantable devices, algorithms, or systems of care have been introduced and others are under investigation, to optimize volume overload management. In this chapter, we discuss unmet needs in the management of patients with HF and how some forms of RM contribute to improved patient outcomes.
Lysine acetylation regulates the AT-rich DNA possession ability of H-NS
Authors: Liu Yabo , Zhou Mengqing , Bu Yifan , Qin Liang , Zhang Yuanxing , Shao Shuai , Wang Qiyao
Published: December 2023

H-NS, the histone-like nucleoid-structuring protein in bacteria, regulates the stability of the bacterial genome by inhibiting the transcription of horizontally transferred genes, such as the type III and type VI secretion systems (T3/T6SS). While eukaryotic histone posttranslational modifications (PTMs) have been extensively studied, little is known about prokaryotic H-NS PTMs. Here, we report that the acetylation of H-NS attenuates its ability to silence horizontally transferred genes in response to amino acid nutrition and immune metabolites. Moreover, LC−MS/MS profiling showed that the acetyllysine sites of H-NS and K120 are indispensable for its DNA-binding ability. Acetylation of K120 leads to a low binding affinity for DNA and enhances T3/T6SS expression. Furthermore, acetylation of K120 impairs the AT-rich DNA recognition ability of H-NS. In addition, lysine acetylation in H-NS modulates in vivo bacterial virulence. These findings reveal the mechanism underlying H-NS PTMs and propose a novel mechanism by which bacteria counteract the xenogeneic silencing of H-NS.
Use of Rapid Antigen Triple Test Nasal Swabs (COVID-VIRO ALL-IN TRIPLEX: Severe Acute Respiratory Syndrome Coronavirus 2, Respiratory Syncytial Virus, and Influenza) in Children With Respiratory Symptoms: A Real-life Prospective Study
Authors: Cohen Robert , Haas Hervé , Romain Olivier , Béchet Stéphane , Romain Catherine , de Lays Camille de Truchis , Wollner Alain , Guiheneuf Cécile , de Pontual Loic , Levy Corinne
Published: December 2023

Background

In autumn 2022, the epidemics due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), and influenza overlapped, and these diseases can present with the same symptomatology. The use of a triple antigen test (SARS-CoV-2 + influenza A/B + RSV) seems crucial for accurate viral diagnosis in the context of implementing long-acting monoclonal antibody vaccination against RSV in the upcoming RSV season.

Methods

We assessed the usefulness of the triple test in real life in this prospective study performed from October 2022 to May 2023 and involving 116 pediatricians (2 emergency department pediatricians and 114 ambulatory pediatricians). Children <15 years old with flu-like illness (with fever), bronchiolitis (dyspnea ± wheezing), otitis, and croup were enrolled and sampled with a nasal triple test.

Results

For 8329 children with flu-like illness (65.3%), bronchiolitis (17.9%), otitis (8.8%), and croup (6.3%), the use of the triple test led to a viral diagnosis in 47.9% of cases. The highest RSV positivity occurred in children with bronchiolitis (32.9%). The highest influenza A and B positivity (24.6% and 19.6%) occurred in children with flu-like illness. A succession of 3 epidemics (RSV and influenza A and B) occurred over time with several overlap periods.

Conclusions

The triple test allowed for a viral diagnosis in half of our cases. The upcoming introduction of RSV prevention will emphasize the need for active surveillance with viral results both in ambulatory settings and hospitals.

Clinical Trials Registration. NCT0441231.
Hospitalization, disease severity and mortality rates of patients with inflammatory rheumatic diseases as compared with the normal population in the second wave of SARS-CoV-2 infections
Authors: Dallagiacoma Gloria , Weichenberger Christian X , Raffeiner Bernd , Callegher Sara Zandonella , Matzneller Peter , Hantikainen Essi , Domingues Francisco S , Karadar Lena , Kuppelwieser Iris , Masl Aaron , Mian Michael , Maier Armin , Dejaco Christian
Published: December 2023

Objective

The objective of this study was to investigate the clinical manifestations and outcome of COVID-19 in patients with inflammatory rheumatic and musculoskeletal disease (iRMD) as compared with the general population.

Methods

This is a case–control study of patients selected from the South Tyrol public health service, Italy, with and without iRMD, affected by COVID-19. We included patients ≥18 years and with a positive SARS-CoV-2 PCR test between 1 October 2020 and 1 March 2021. Cases were identified by linking the diagnosis of a rheumatic disease with PCR test positivity; these were then matched in a 1:1.8 (planned 1:2) ratio for age, sex, and date of COVID-19 diagnosis with people from the general population. The outcomes of primary interest were hospitalization, and severe course (intensive care unit, mechanical ventilation/extracorporeal membrane oxygenation, death).

Results

The study population consisted of 561 COVID-19 patients, of which 201 (mean age 60.4 years; 65.2% female) were patients with iRMD and 360 were controls from the general population (59.8 years; 64.7% female). The majority of iRMD patients (88.6%) were receiving an immunosuppressive drug at the time of COVID-19 diagnosis, and 36.3% were receiving glucocorticoids. COVID-19 related hospitalization (12.4% vs 10.6%, P = 0.49), severe course (5.0% vs 5.3%, P = 1.00), and mortality (3.5% vs 4.4%, P = 0.66) were similar between the groups. Among the hospitalized patients, mechanical ventilation was more common in iRMD patients than in controls [n = 5 (20.0%) vs n = 1 (2.6%), P = 0.035].

Conclusion

Our study indicated similar rates for admission, severe course, and mortality between patients with iRMD and controls affected by COVID-19. Among the hospitalized patients, mechanical ventilation was more frequently required in the iRMD group.
The emerging role of growth differentiation factor 15 as a potential disease biomarker in juvenile dermatomyositis
Authors: Duvvuri Bhargavi , Gonzalez-Chapa Jorge A , Pachman Lauren M , Morgan Gabrielle A , Naik Nidhi , Shenoi Susan , Lood Christian
Published: December 2023

Objective

We aimed to investigate the potential of growth differentiation factor 15 (GDF-15) as a novel biomarker for disease activity in JDM.

Methods

We recruited children with juvenile myositis including JDM (n = 77), PM (n = 6) and healthy controls (n = 22). GDF-15 levels in plasma were measured using ELISA. Statistical analyses were performed using non-parametric tests.

Results

Levels of GDF-15 were significantly elevated in JDM compared with healthy controls (P < 0.001). GDF-15 levels exhibited strong positive correlations with DASs, including the DAS total score, DAS skin score, DAS muscle score and Childhood Myositis Assessment Scale. Additionally, GDF-15 levels could differentiate between active disease and remission based on the Physician Global Assessment of muscle score. Positive correlations were observed between levels of GDF-15 and creatine kinase, neopterin and nailfold end row loops, indicating the potential involvement of GDF-15 in muscle damage, immune activation and vascular pathology. Receiver operating characteristics curve analysis showed GDF-15 to be more effective in assessing disease activity in JDM than creatine kinase [area under the curve (AUC) 0.77, P = 0.001 and AUC 0.6369, P = 0.0738, respectively].

Conclusion

GDF-15 may serve as a valuable biomarker for assessing disease activity in JDM. It exhibits better sensitivity and specificity than creatine kinase and the levels correlate with various DASs and functional measures. GDF-15 may provide valuable information for treatment decision making and monitoring disease progression in JDM.
Epidemiological survey, molecular profiling and phylogenetic analysis of cutaneous leishmaniasis in Khyber Pakhtunkhwa, Pakistan
Authors: Ullah Wasia , Khan Adil , Niaz Sadaf , Al-Garadi Maged A , Nasreen Nasreen , Swelum Ayman A , Ben Said Mourad
Published: December 2023

Background

Cutaneous leishmaniasis (CL), an emerging vector-borne ailment in Khyber Pakhtunkhwa (KPK), Pakistan, exhibits diverse spread patterns and outbreaks.

Methods

To comprehend its epidemiology and identify parasite species, we conducted an active survey on suspected CL cases (n=8845) in KPK.

Results

Microscopy and internal transcribed spacer-1 PCR–restriction fragment length polymorphism (RFLP) molecular techniques detected Leishmania spp. in blood samples. Phylogenetic analysis gauged genetic affinities with other areas. District Bannu displayed the highest CL impact (14.58%), while Swat had the lowest impact (4.33%) among cases. Annual blood examination rate, parasite incidence and slide positivity rate were 4.96 per 1000 people, 0.0233 and 0.047%, respectively. CL infections were prevalent in 1- to 20-y-olds, with males (57.17%) more vulnerable than females (42.82%). Single lesions occurred in 43.73% of patients, while 31.2% people had two lesions, 17.31% had three lesions and 7.74% had more than three lesions. Most had sand-fly exposure but lacked preventive measures like repellents and bed nets. Leishmania tropica was confirmed via RFLP analysis in amplified samples. Phylogenetic analysis unveiled genetic parallels between L. tropica of KPK and isolates from China, Iran, Afghanistan, India, Syria and Morocco.

Conclusions

Urgent comprehensive control measures are imperative. Early detection, targeted interventions and raising awareness of CL and sand-fly vectors are vital for reducing the disease's impact. International collaboration and monitoring are crucial to tackle Leishmania spp.’s genetic diversity and curtail its cross-border spread.
CE: Reducing Bias Against People with Substance Use Disorders
Authors: Ginther Jane , McNally Gretchen
Published: December 2023

Addiction is a highly misunderstood and stigmatized chronic illness frequently encountered by health care providers during routine medical care. People with substance use disorders, in particular, face extraordinary stigma and bias when interacting with health care providers, including nurses. Stigma associated with addiction contributes to health inequities and is recognized as a significant barrier to people seeking and receiving necessary health care. Since patients often spend the most time with nurses in the clinical setting, nurses are ideally positioned to address addiction stigma. However, many nurses lack knowledge about addiction, stigma, and the impact of the words they use, whether in conversation or in clinical documentation. This article reviews the consequences of addiction stigma (labeling, stereotyping, or discrimination) and the steps nurses can take to reduce biases related to substance use. A case scenario based on our experience will be used to guide a discussion of opportunities for nurses to intervene and improve care.
What U.S. Obstetricians Need to Know About Respiratory Syncytial Virus
Authors: Debessai Haben , Jones Jefferson M. , Meaney-Delman Dana , Rasmussen Sonja A.
Published: December 2023

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in neonates, infants, and children worldwide. The virus is estimated to infect 97% of this population in the United States by the age of 2 years, leading to hospitalization for severe lower respiratory tract disease in 2–3% of infants younger than age 6 months. Two preventive options, prenatal administration of a maternal vaccine and administration of a long-acting monoclonal antibody to the infant, are now available for the prevention of RSV-associated lower respiratory tract infection in infants in the United States. The U.S. Food and Drug Administration (FDA) has approved and the Centers for Disease Control and Prevention (CDC) has recommended a new maternal vaccination, RSVPreF, to be administered between 32 0/7 and 36 6/7 weeks of gestation to reduce the risk of RSV-associated lower respiratory tract infection in infants in the first 6 months of life. The monoclonal antibody nirsevimab was approved by the FDA and recommended by the CDC for prevention of RSV-associated lower respiratory tract infection in infants younger than age 8 months who are born during or entering their first RSV season and for infants and children aged 8–19 months who are at high risk for RSV-associated lower respiratory tract infection and entering their second RSV season. Either maternal vaccination during pregnancy or monoclonal antibody administration to the infant is recommended to prevent RSV-associated lower respiratory tract infection among infants, but both are not needed for most infants. Given that the availability of these products may vary as these recommendations are implemented, it is important that obstetricians and other prenatal practitioners have the information they need to counsel their pregnant patients about both options. We review the safety and efficacy of these products, current recommendations for their use, and relative advantages and disadvantages of both newly approved options for the prevention of RSV-associated lower respiratory tract infection in infants to assist obstetricians and other prenatal practitioners in their counseling of pregnant patients.
Oxygenation During Venoarterial Extracorporeal Membrane Oxygenation: Physiology, Current Evidence, and a Pragmatic Approach to Oxygen Titration
Authors: Premraj Lavienraj , Brown Alastair , Fraser John F. , Pellegrino Vincent , Pilcher David , Burrell Aidan
Published: December 2023

OBJECTIVES:

This review aims to: 1) identify the key circuit and patient factors affecting systemic oxygenation, 2) summarize the literature reporting the association between hyperoxia and patient outcomes, and 3) provide a pragmatic approach to oxygen titration, in patients undergoing peripheral venoarterial extracorporeal membrane oxygenation (ECMO).

DATA SOURCES:

Searches were performed using PubMed, SCOPUS, Medline, and Google Scholar.

STUDY SELECTION:

All observational and interventional studies investigating the association between hyperoxia, and clinical outcomes were included, as well as guidelines from the Extracorporeal Life Support Organization.

DATA EXTRACTION:

Data from relevant literature was extracted, summarized, and integrated into a concise narrative review. For ease of reference a summary of relevant studies was also produced.

DATA SYNTHESIS:

The extracorporeal circuit and the native cardiorespiratory circuit both contribute to systemic oxygenation during venoarterial ECMO. The ECMO circuit’s contribution to systemic oxygenation is, in practice, largely determined by the ECMO blood flow, whereas the native component of systemic oxygenation derives from native cardiac output and residual respiratory function. Interactions between ECMO outflow and native cardiac output (as in differential hypoxia), the presence of respiratory support, and physiologic parameters affecting blood oxygen carriage also modulate overall oxygen exposure during venoarterial ECMO. Physiologically those requiring venoarterial ECMO are prone to hyperoxia. Hyperoxia has a variety of definitions, most commonly Pao
2 greater than 150 mm Hg. Severe hypoxia (Pao
2 > 300 mm Hg) is common, seen in 20%. Early severe hyperoxia, as well as cumulative hyperoxia exposure was associated with in-hospital mortality, even after adjustment for disease severity in both venoarterial ECMO and extracorporeal cardiopulmonary resuscitation. A pragmatic approach to oxygenation during peripheral venoarterial ECMO involves targeting a right radial oxygen saturation target of 94–98%, and in selected patients, titration of the fraction of oxygen in the mixture via the air-oxygen blender to target postoxygenator Pao
2 of 150–300 mm Hg.

CONCLUSIONS:

Hyperoxia results from a range of ECMO circuit and patient-related factors. It is common during peripheral venoarterial ECMO, and its presence is associated with poor outcome. A pragmatic approach that avoids hyperoxia, while also preventing hypoxia has been described for patients receiving peripheral venoarterial ECMO.
Incidence, clinical characteristics, and risk factors associated with recurrent alcohol-associated hepatitis
Authors: Patidar Kavish R. , Guarnizo Ortiz Maria , Slaven James E. , Nephew Lauren D. , Vilar Gomez Eduardo , Kettler Carla D. , Ghabril Marwan S. , Desai Archita P. , Orman Eric S. , Chalasani Naga , Gawrieh Samer
Published: December 2023

Background:

Alcohol relapse occurs frequently in alcohol-associated hepatitis (AH) survivors, but data on the frequency and course of recurrent alcohol-associated hepatitis (rAH) are sparse. We investigated the incidence, risk factors, and outcomes of rAH.

Methods:

Hospitalized patients with AH from 2010 to 2020 at a large health care system were followed until death/liver transplant, last follow-up, or end of study (December 31, 2021). AH was defined by NIAAA Alcoholic Hepatitis Consortium criteria; rAH was defined a priori as a discrete AH episode >6 months from index AH hospitalization with interim >50% improvement or normalization of total bilirubin. Multivariable competing risk analysis was performed to identify factors associated with rAH. Landmark Kaplan-Meier analysis was performed to compare survival between patients who did versus those who did not develop rAH.

Results:

Of 1504 hospitalized patients with AH, 1317 (87.6%) survived and were analyzed. During a 3055 person‐year follow‐up, 116 (8.8%) developed rAH at an annual incidence rate of 3.8% (95% CI: 2.8–4.8). On multivariable competing risk analysis, marital status [sub-HR 0.54 (95% CI: 0.34, 0.92), p=0.01] and medications for alcohol use disorder [sub-HR 0.56 (95% CI: 0.34, 0.91), p=0.02] were associated with a lower risk for rAH. On landmark Kaplan-Meier analysis, the cumulative proportion surviving at 1 year (75% vs. 90%) and 3 years (50% vs. 78%) was significantly lower in patients who developed rAH compared to those who did not develop rAH (log-rank p<0.001).

Conclusions:

rAH develops in ~1 in 10 AH survivors and is associated with lower long-term survival. Medications for alcohol use disorder lower the risk for rAH and, therefore, could be a key preventative strategy to improve outcomes.
Racial and Ethnic Disparities in Home Health Referral Among Adult Medicare Patients
Authors: Yakusheva Olga , Lee Kathryn A. , Keller Abiola , Weiss Marianne E.
Published: December 2023

Background:

Home health care (HHC) services following hospital discharge provide essential continuity of care to mitigate risks of posthospitalization adverse outcomes and readmissions, yet patients from racial and ethnic minority groups are less likely to receive HHC visits.

Objective:

To examine how the association of nurse assessments of patients’ readiness for discharge with referral to HHC services at the time of hospital discharge differs by race and ethnic minority group.

Research Design:

Secondary data analysis from a multisite study of the implementation of discharge readiness assessments in 31 US hospitals (READI Randomized Clinical Trial: 09/15/2014–03/31/2017), using linear and logistic models adjusted for patient demographic/clinical characteristics and hospital fixed effects.

Subjects:

All Medicare patients in the study’s intervention arm (n=14,684).

Measures:

Patient’s race/ethnicity and discharge disposition code for referral to HHC (vs. home) from electronic health records. Patient’s Readiness for Hospital Discharge Scale (RHDS) score (0–10 scale) assessed by the discharging nurse on the day of discharge.

Results:

Adjusted RHDS scores were similar for non-Hispanic White (8.21; 95% CI: 8.18–8.24), non-Hispanic Black (8.20; 95% CI: 8.12–8.28), Hispanic (7.92; 95% CI: 7.81–8.02), and other race/ethnicity patients (8.09; 95% CI: 8.01–8.17). Non-Hispanic Black patients with low RHDS scores (6 or less) were less likely than non-Hispanic White patients to be discharged with an HHC referral (Black: 26.8%, 95% CI: 23.3–30.3; White: 32.6%, 95% CI: 31.1–34.1).

Conclusions:

Despite similar RHDS scores, Black patients were less likely to be discharged with HHC. A better understanding of root causes is needed to address systemic structural injustice in health care settings.
Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop
Authors: Jackson Shawn S. , Lee Jennifer J. , Jackson William M. , Price Jerri C. , Beers Sue R. , Berkenbosch John W. , Biagas Katherine V. , Dworkin Robert H. , Houck Constance S. , Li Guohua , Smith Heidi A. B. , Ward Denham S. , Zimmerman Kanecia O. , Curley Martha A. Q. , Horvat Christopher M. , Huang David T. , Pinto Neethi P. , Salorio Cynthia F. , Slater Rebeccah , Slomine Beth S. , West Leanne L. , Wypij David , Yeates Keith O. , Sun Lena S.
Published: December 2023

OBJECTIVES:

Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia.

DESIGN:

Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions.

SETTING:

A virtual meeting was held on March 2–3, 2022, followed by an in-person meeting in Washington, DC, on June 15–16, 2022. Subsequent iterative online meetings were held to achieve consensus.

SUBJECTS:

Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium.

CONCLUSIONS:

These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.
Use of a machine learning model to predict retention in care in an urban HIV clinic
Authors: Schmalzle Sarah A. , Maroosis Demetri , Masur Henry , Kottilil Shyam , Mathur Poonam
Published: December 2023

Identifying barriers to retention in care (RIC) is critical to ending the HIV epidemic in the United States. Therefore, we developed a machine learning model (MLM) to identify predictive factors for RIC in an urban HIV clinic. Our MLM yielded a positive predictive value of 84%, higher than previously reported MLMs. We found that MLM can be used to develop interventional strategies to enhance RIC in HIV care.
Minimizing Metabolic and Cardiac Risk Factors to Maximize Outcomes After Liver Transplantation
Authors: Schmidt Kathryn , Spann Ashley , Khan Mohammad Qasim , Izzy Manhal , Watt Kymberly D.
Published: December 2023

Cardiovascular disease (CVD) is a leading complication after liver transplantation and has a significant impact on patients’ outcomes posttransplant. The major risk factors for post–liver transplant CVD are age, preexisting CVD, nonalcoholic fatty liver disease, chronic kidney disease, and metabolic syndrome. This review explores the contemporary strategies and approaches to minimizing cardiometabolic disease burden in liver transplant recipients. We highlight areas for potential intervention to reduce the mortality of patients with metabolic syndrome and CVD after liver transplantation.
Is a Preservation Solution for Living Donor Liver Transplantation Needed? Adding a New Chapter in LDLT!
Authors: Dogar Abdul Wahab , Ullah Kaleem , Shams-ud-din  , Abbas Syed Hasnain , Hussain Azhar , Ghaffar Abdul , Bilal Hafiz , Siraj-ud-din  , Shoaib Azam , Ahmed Bilal , Raza Hamid , Hamza Ameer , Hafeez Bhatti Abu Bakar , Gupta Subash , Black Sylvester M. , Mumtaz Khalid
Published: December 2023

Background.

Preservation solutions are required for organ viability in deceased donor liver transplantation (LT). However, their role in live donor LT (LDLT) has not been standardized.

Methods.

Eighty adult recipients who underwent right lobe LDLT at the Department of Liver Transplantation Surgery, Gambat, Pakistan, were studied. Based on shorter cold ischemia time and no back table reconstruction work, recipients were assigned to receive “no preservation solution” (cases/non–histidine-tryptophan-ketoglutarate group; n = 40) or “HTK group” (controls; n = 40). Early allograft dysfunction (bilirubin, transaminases, and international normalized ratio), postoperative complications (biliary and vascular), hospital stay, and 1-y survival were reported. The direct cost was also reported.

Results.

Demographics and clinical characteristics were comparable in the 2 groups. Comparing cases versus controls, mean bilirubin, alanine aminotransferase, aspartate aminotransferase, and international normalized ratio on postoperative day 7 were similar in the 2 groups. Five (12.5%) cases and 4 (10%) controls developed early allograft dysfunction (P = 0.72). Post-LT complications (biliary leak 2.5% in cases versus 0 in control), strictures (15% in cases versus 17.5% in controls), hepatic artery thrombosis (2.5% versus 00%)‚ and portal vein thrombosis (0 versus 2.5%) were comparable. Mean hospital stay (10.80 + 2.36 and 11.78 + 2.91 d) and 30 d mortality (2.5% versus 5%) were also comparable. Finally, 1-y survival based on Kaplan-Meier analysis was comparable in both groups (ie, 92.5%; non-HTK group versus 90%; HTK group) (P = 0.71). The direct cost of using a non-HTK–based approach was less than the HTK solution.

Conclusion.

In a selected cohort of right lobe LDLT recipients, preservation solutions can be avoided safely with comparable outcomes.
Hymenobacter endophyticus sp. nov., isolated from wheat leaf tissue
Authors: Zhang Xue , Duan Xue-Mei , Cheng Jin , Qiao Hong-Jiao , Dai Yu-Mei
Published: December 2023

A bacterium, designated strain ZK17L-C2T, was isolated from the leaf tissues of wheat (Triticum aestivum) collected in Chengdu, Sichuan Province, PR China. It is aerobic, non-motile, Gram-negative, rod-shaped and red-to-pink in colour. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZK17L-C2T belonged to the genus

Hymenobacter

and was most closely related to

Hymenobacter rigui

KCTC 12533T (98.68 %) and

Hymenobacter metallilatus

9PBR-2T (98.19 %). Digital DNA–DNA hybridization (dDDH) values between strain ZK17L-C2T and these two type strains were 26.6 and 26.5 %, and average nucleotide identity (ANI) values were 84.9 and 84.8 %, respectively; these values are lower than the proposed and generally accepted species boundaries for dDDH and ANI. The genomic DNA G+C content of strain ZK17L-C2T was 59.4 mol%. It can grow at pH 5.5–7.5 and 15–30 °C, which is different from the closely related type strains. The major fatty acids of strain ZK17L-C2T were iso-C15 : 0, C16 : 0 and C18 : 0. Overall, the results from biochemical, chemical taxonomy and phylogenetic analyses indicate that strain ZK17L-C2T (=CGMCC 1.19373T=KCTC 92184 T) represents a new species of the genus

Hymenobacter

, for which the name Hymenobacter endophyticus sp. nov. is proposed.
Molecular and Structural Basis of Oligopeptide Recognition and Transport by the Ami Transporter System in Pneumococci
Authors: Alcorlo Martín , Abdullah Mohammed R. , Steil Leif , Sotomayor Francisco , Oro Laura López-de , de Castro Sonia , Velázquez Sonsoles , Kohler Thomas P. , Jiménez Elisabet , Medina Ana , Usón Isabel , Keller Lance E. , Bradshaw Jessica L. , McDaniel Larry S. , Camarasa María-José , Völker Uwe , Hammerschmidt Sven , Hermoso Juan A.
Published: December 2023

ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiontStreptococcus pneumoniae(pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids. The system comprises five exposed Oligopeptide Binding Proteins (OBPs) and four proteins building the ABC transporter channel. Here, we present a structural analysis of all the OBPs in this system. Multiple crystallographic structures, capturing both open and closed conformations along with complexes involving chemically synthesized peptides, have been solved at high resolution providing insights into the molecular basis of their diverse peptide specificities. Mass spectrometry analysis of oligopeptides demonstrates the remarkable promiscuity of some of these proteins when expressed inEscherichia coli, displaying affinity for a wide range of peptides. Finally, a model is proposed for the complete Ami transport system in complex with its various OBPs. We further disclosed some essential structural changes facilitating oligopeptide transport into the cellular cytoplasm. Thus, the structural analysis of the Ami system provides valuable insights into the mechanism and specificity of oligopeptide binding by the different OBPs, shedding light on the intricacies of the uptake mechanism.

Author Summary

The uptake of diverse oligopeptides enables pneumococcal growth despite auxotrophies and functions as a critical sensor for assessing the composition of the local environment. The identification of additional OBPs in non-encapsulatedS. pneumoniaestrains suggests their involvement in sensing a broader spectrum of bacterial competitors coexisting with the highly commensal pneumococcus. This study presents a comprehensive analysis of the initial phase of peptide transport mediated by OBPs within the pneumococcal Ami permease system. We disclose a common mechanism for oligopeptide recognition that is modulated in each OBP to accommodate a diverse array of oligopeptides. Understanding how pneumococcus perceives external stimuli and responds to them is imperative for unraveling the transition from a commensal to a pathogenic state.
The effect of gravity on hand spatio-temporal kinematic features during functional movements
Authors: Bucchieri Anna , Tessari Federico , Buccelli Stefano , De Momi Elena , Laffranchi Matteo , De Michieli Lorenzo
Published: December 2023

Exploring the impact of gravity on daily upper-limb movements is crucial for comprehending the complexities of upper-limb impairments. The present study delves into the relationship between the gravitational force and the functional aspects of upper-limb mobility. Starting from 9 pick-and-place tasks, hand trajectories of 24 healthy subjects were acquired using a motion capture system. Five in-use and two novel kinematic metrics were calculated by such trends and tested across conditions. Results suggest movements performed against and propelled by gravity lead to statistically significant changes in motor behaviour in terms of planning, smoothness, efficiency, and accuracy of the movement, underlining the need of differentiating the study of such movements in impaired subjects.
Algorithm for selecting potential SARS-CoV-2 dominant variants based on POS-NT frequency
Authors: Kang Eunhee , Ahn TaeJin , Park Taesung
Published: December 2023

COVID-19, currently prevalent worldwide, is caused by a novel coronavirus, SARS-CoV-2. Similar to other RNA viruses, SARS-CoV-2 continues to evolve through random mutations, creating numerous variants, such as Alpha, Beta, and Delta. It is, therefore, necessary to predict the mutations constituting the dominant variant before they are generated. This can be achieved by continuously monitoring the mutation trends and patterns. Hence, in the current study, we sought to design a dominant variant candidate (DVC) selection algorithm. To this end, we obtained COVID-19 sequence data from GISAID and extracted position-nucleotide (POS-NT) frequency ratio data by country and date through data preprocessing. We then defined the dominant dates for each variant in the USA and developed a frequency ratio prediction model for each POS-NT. Based on this model, we applied DVC criteria to develop the selection algorithm, verified for Delta and Omicron. Using Condition 3 as the DVC criterion, 69 and 102 DVC POS-NTs were identified for Delta and Omicron an average of 47 and 82 days before the dominant dates, respectively. Moreover, 13 and 44 Delta- and Omicron-defining POS-NTs were recognized 18 and 25 days before the dominant dates, respectively. We identified all DVC POS-NTs before the dominant dates, including soaring and gently increasing POS-NTs. Considering that we successfully defined all POS-NT mutations for Delta and Omicron, the DVC algorithm may represent a valuable tool for providing early predictions regarding future variants, helping improve global health.

Author Summary
Kv4.2 regulates baseline synaptic strength by inhibiting R-type channel-mediated calcium signaling in the hippocampus
Authors: Lee Seung Yeon , Kwon Minjeong , Ho Won Kyung , Lee Suk-Ho
Published: December 2023

Kv4.2 channels, which mediate A-type K+current, exert significant influence on synaptic input signals and synaptic plasticity in the principal cells of the hippocampus. While their influence on activity-dependent regulation of synaptic response is well-established, the impact of Kv4.2 channels on baseline synaptic strength remains elusive. To investigate this, we selectively inhibited postsynaptic Kv4.2 by introducing Kv4.2 antibodies into the hippocampal granule cells and evaluated its impact on the baseline synaptic transmission. Our results demonstrated that Kv4.2 inhibitions led to notable increase in the amplitude of AMPA receptor (AMPAR)-mediated synaptic currents, and this effect was in parallel with the Kv4.2 expression level at dendritic regions. This Kv4.2-dependent synaptic potentiation was effectively abolished by intracellular 10 mM BAPTA or block of R-type calcium channels (RTCC) and downstream signaling molecules including protein kinase A (PKA) and protein kinase C (PKC). Importantly, Kv4.2 inhibitions did not occlude further synaptic strengthening high frequency stimulation, suggesting that synaptic strength regulation by Kv4.2 s distinct from the mechanism of long-term potentiation. Our study highlights the role of Kv4.2 in regulating the baseline synaptic strength, where Kv4.2-mediated inhibition of RTCC is crucial.
Dynamics of brainstem arousal systems and pupil size predict cortical interactions for flexible decision-making
Authors: van den Brink R.L. , Hagena K. , Wilming N. , Murphy P.R. , Calder-Travis J. , Finsterbusch J. , Büchel C. , Donner T.H.
Published: December 2023

Most perceptual decisions entail a flexible mapping from sensory input to motor output. Flexible input-output mapping is reflected in correlated variability within the cortical network involved in perceptual decisions. Here, we tested the idea that brainstem arousal systems are involved in flexible input-output mapping and changes in cortical correlated variability. We combined brainstem fMRI, pupillometry, and time-resolved assessment of the intrinsic correlations between cortical population codes for stimulus and action. Human participants reported the orientation of visual stimuli by button presses, while the required stimulus-response mapping rule could undergo hidden and unpredictable changes. Rule switches evoked brainstem and pupil responses as well as changes in computational model-inferred, latent variables. These variables governed participants’ rule-switching behavior and pupil responses. Brainstem activity and pupil dilation preceded increases in the strength of correlations between cortical stimulus and action codes. Brainstem arousal systems may promote the reorganization of sensorimotor cortical pathways for flexible decisions.