bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obstructive sleep apnea and CPAP therapy alter distinct transcriptional programs in subcutaneous fat tissue
Authors: Gharib Sina A , Hurley Amanda L , Rosen Michael J , Spilsbury James C , Schell Amy E , Mehra Reena , Patel Sanjay R 
Published: December 2019

Abstract
Obstructive sleep apnea (OSA) has been linked to dysregulated metabolic states, and treatment of sleep apnea may improve these conditions. Subcutaneous adipose tissue is a readily samplable fat depot that plays an important role in regulating metabolism. However, neither the pathophysiologic consequences of OSA nor the effects of continuous positive airway pressure (CPAP) in altering this compartment’s molecular pathways are understood. This study aimed to systematically identify subcutaneous adipose tissue transcriptional programs modulated in OSA and in response to its effective treatment with CPAP. Two subject groups were investigated: Study Group 1 was comprised of 10 OSA and 8 controls; Study Group 2 included 24 individuals with OSA studied at baseline and following CPAP. For each subject, genome-wide gene expression measurement of subcutaneous fat was performed. Differentially activated pathways elicited by OSA (Group 1) and in response to its treatment (Group 2) were determined using network and Gene Set Enrichment Analysis (GSEA). In Group 2, treatment of OSA with CPAP improved apnea-hypopnea index, daytime sleepiness, and blood pressure, but not anthropometric measures. In Group 1, GSEA revealed many up-regulated gene sets in OSA subjects, most of which were involved in immuno-inflammatory (e.g. interferon-γ signaling), transcription, and metabolic processes such as adipogenesis. Unexpectedly, CPAP therapy in Group 2 subjects was also associated with up-regulation of several immune pathways as well as cholesterol biosynthesis. Collectively, our findings demonstrate that OSA alters distinct inflammatory and metabolic programs in subcutaneous fat, but these transcriptional signatures are not reversed with short-term effective therapy.
Grain supplementation of calves as an alternative beef production system to pasture-finished steers in Chilean Patagonia: meat quality and fatty acid composition
Authors: Sales Francisco , Bravo-Lamas Leire , Realini Carolina E , Lira Raúl , Aldai Noelia , Morales Rodrigo 
Published: December 2019

AbstractBeef production in Chilean Patagonia is based on steer finishing on pastures with low nutritive value. Grain supplementation for finishing calves on pasture arises as an attractive alternative to shorten the finishing phase and improve the production efficiency of the traditional system. The aim of this study was to compare meat quality and fatty acid (FA) composition of beef from steers and calves. Forty Angus cross steers were raised on pasture and slaughtered at 18 to 20 mo of age (448 ± 31.7 kg body weight). An additional group of 10 calves from similar genetics was weaned at 9 mo of age (303 ± 8.0 kg) and subsequently supplemented with 2.5 kg corn plus 1.0 kg commercial concentrate daily while on pasture during 47 d, until they reached slaughter weight (316 ± 13.9 kg). All animals were slaughtered on the same day and the Longissimus thoracis muscle was removed from each carcass for meat quality and FA profile analysis. Hot carcass weight from calves was lighter than steers (174 ± 7.9 vs. 224 ± 17.5 kg, P ≤ 0.001). Meat from calves was lighter (higher L*) and less red (lower a*). In addition, meat from calves showed lower level of yellow pigments in subcutaneous fat (lower b*) compared with meat from steers (P ≤ 0.001). Meat from calves was more tender than meat from steers (P ≤ 0.05), although both shear force values were low and within recommendations for high consumer acceptability. Meat from both production systems showed fat content and FA profiles within dietary recommendations for a healthy diet. However, meat from calves was leaner (1.10 ± 0.29 vs. 2.00 ± 0.72% fat, P ≤ 0.001). Meat from calves showed lower percentages of saturated (P ≤ 0.05) and monounsaturated (P ≤ 0.001) FAs and higher percentages of polyunsaturated and n-3 (P ≤ 0.001) FAs and conjugated linoleic acid (total and 9c,11t-18:2 isomer, P ≤ 0.001) than meat from steers. Grain supplementation of calves on pasture can reduce the finishing period by 8 to 10 mo at the expense of lighter carcasses with similar or improved meat quality characteristics compared with the traditional finishing of steers on pasture. Implementation of the alternative production system will depend mainly on feed costs and target carcass weights for specific markets.
Insights into basic science: what basic science can teach us about iron homeostasis in trauma patients
Authors: Bartnikas Thomas B. , Steinbicker Andrea U. , Enns Caroline A. 
Published: December 2019

Purpose of reviewThis review summarizes recent basic science studies on homeostasis of iron, an essential dietary nutrient and potentially toxic metal, and explores the relevance of these studies to our understanding of trauma and related severe, acute events.Recent findingsRecent studies in experimental models of iron homeostasis have added to our understanding of how iron levels are regulated in the body and how iron levels and iron-dependent biological processes contribute to trauma and related events. Iron deficiency, a common nutritional disorder, can impair critical organ function and wound and injury repair. Iron excess, typically because of genetic defects, can cause toxicity to tissues and, like iron deficiency, impair wound and injury repair. Finally, pharmacologic inhibition of ferroptosis, a novel form of iron-dependent cell death, is beneficial in animal models of cardiac, hepatic, and intestinal injury and intracerebral hemorrhage, suggesting that ferroptosis inhibitors could serve as novel therapeutic agents for trauma and related events.SummaryPerturbations in iron homeostasis can contribute significantly to an individual's predisposition to trauma and their ability to recover posttrauma, whereas pharmacologic targeting of ferroptosis may attenuate severity of trauma-induced organ dysfunction.
Comorbidities in gout and hyperuricemia: causality or epiphenomena?
Authors: Sumpter Nicholas A. , Saag Kenneth G. , Reynolds Richard J. , Merriman Tony R. 
Published: December 2019

Purpose of reviewTo review advances in the understanding of potentially causal relationships between gout, hyperuricemia and comorbidities.Recent findingsObservational studies reveal 4–5 comorbidity clusters in gout patients. There tend to be gout alone, gout with chronic kidney disease and gout with other metabolic comorbidities. However, heterogeneous study populations and confounding make inference difficult for causal relationships. Mendelian randomization leverages genetic information as an instrumental variable to indicate putatively causal relationships between traits of epidemiological interest. Thus far, Mendelian randomization has not indicated widespread causal relationships of serum urate for comorbid traits. However, BMI has a small causal effect on serum urate, which may partially explain the increased prevalence of metabolic syndrome and cardiovascular disease among those with gout and hyperuricemia. There is a lack of robust and sufficiently powered Mendelian randomization studies for many serum urate-associated traits, such as hypertension. No adequately powered studies have been completed for gout and its comorbidities.SummaryAlthough observational studies indicate putative causal effects of serum urate on comorbidities, Mendelian randomization studies suggest that serum urate does not have a causal role on the various tested comorbidities. There remains work to be done in clarifying the causal role of gout per se on the same traits.
Management of Fasciotomy Incisions After Acute Compartment Syndrome: Is Delayed Primary Closure More Feasible in Children Compared With Adults?
Authors: Rademacher Emily , Miller Patricia E. , Jordan Eric , May Collin J. , Glotzbecker Michael P. , Bae Donald S. , Hedequist Daniel J. , Shore Benjamin J. 
Published: December 2019

Background:
Recent adult literature has demonstrated that in the setting of acute compartment syndrome (ACS), if fasciotomy wounds are not closed after the first debridement, they are unlikely to be closed via delayed primary closure (DPC). The purpose of this study was to report the success of DPC through serial debridement in children with fasciotomy wounds secondary to ACS and to determine whether length of hospital stay is negatively affected by adopting a DPC strategy.

Methods:
We identified all patients treated with fasciotomy for ACS (aged 0 to18 y). Patient, injury, and treatment characteristics were summarized by fasciotomy treatment type. Patients were grouped as: primary closure, DPC, and flap or skin graft (F/SG). For patients who required additional debridements after initial fasciotomy, treatment success was defined as closure by DPC (without requiring F/SG). Multivariable logistic regression was used to determine factors associated with additional surgeries, complications, and treatment success.

Results:
A total of 82 children underwent fasciotomies for ACS. Fifteen (18%) patients were treated with primary closure at the time of their initial fasciotomy and were excluded from the remainder of the analysis, 48 (59%) patients underwent DPC, and 19 (23%) patients were treated with F/SG. The majority of delayed fasciotomy wounds were successfully closed by DPC (48/67, 72%) and the rate of successful closure remained consistent with each successive operative debridement. There were no differences across DPC and F/SG groups with respect to age, method of injury, or injury severity. Patients who underwent F/SG remained in the hospital for an average of 12 days compared with 8 days for those who underwent DPC (P<0.001).

Conclusions:
In the setting of ACS, pediatric fasciotomy wounds that are not closed after the first postfasciotomy debridement still have a high likelihood of being closed through DPC with serial surgical debridement. In children, persisting with DPC strategy for fasciotomy closure after ACS is more successful than it is in adults.

Level of Evidence:
Level III.
Clinical Documentation for Intensivists: The Impact of Diagnosis Documentation
Authors: Sanderson Amy L. , Burns Jeffrey P. 
Published: December 2019

Objectives:
The aim of this review is to describe the interaction of clinical documentation with patient care, measures of patient acuity, quality metrics, research database accuracy, and healthcare reimbursement in order to highlight potential areas of improvement for intensivists.

Data Sources:
An online search of PubMed was undertaken as well as review of resources published by the American Academy of Pediatrics, the Society of Critical Care Medicine, the American Medical Association, and the Association of Clinical Documentation Improvement Specialists.

Study Selection:
Selected publications included those that described coding, medical record documentation, healthcare reimbursement, quality metrics, administrative databases, Clinical Documentation Improvement programs, medical scribe programs, and various payment models.

Data Extraction:
Relevant information was extracted to highlight the impact of diagnosis documentation on patient care, perceived patient severity of illness, quality metrics, and healthcare reimbursement. Query data from our hospital’s Clinical Documentation Improvement program were reviewed to highlight areas of improvement within our own Division of Critical Care Medicine. Additionally, interventions to improve clinical documentation were incorporated into this review.

Data Synthesis:
Available data in the literature indicate that documentation of precise diagnoses in the medical record has a positive impact on quality metrics, accuracy of administrative databases, hospital reimbursement, and perceived patient complexity. However, there is insufficient data to make conclusions regarding documentation of specific diagnoses and effects on patient care. Administrative responsibilities associated with documentation have been increasing, especially with the introduction of electronic medical records.

Conclusions:
Documentation of specific diagnoses in the medical record is important in the broad context of our existing medical system but there is an associated burden in doing so. Widespread implementation of electronic medical record systems has inadvertently led to clinician dissatisfaction and burnout. Research is needed to further evaluate the impact of documentation on patient care as well as steps to decrease the associated burden.
Association Between Consecutive Days Worked by Intensivists and Outcomes for Critically Ill Patients
Authors: Gershengorn Hayley B. , Pilcher David V. , Litton Edward , Anstey Matthew , Garland Allan , Wunsch Hannah 
Published: December 2019

Objective:
To evaluate the association between consecutive days worked by intensivists and ICU patient outcomes.

Design:
Retrospective cohort study linked with survey data.

Setting:
Australia and New Zealand ICUs.

Patients:
Adults (16+ yr old) admitted to ICU in the Australia New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Registries (July 1, 2016, to June 30, 2018).

Interventions:
None.

Measurements and Main Results:
We linked data on staffing schedules for each unit from the Critical Care Resources Registry 2016–2017 annual survey with patient-level data from the Adult Patient Database. The a priori chosen primary outcome was ICU length of stay. Secondary outcomes included hospital length of stay, ICU readmissions, and mortality (ICU and hospital). We used multilevel multivariable regression modeling to assess the association between days of consecutive intensivist service and patient outcomes; the predicted probability of death was included as a covariate and individual ICU as a random effect. The cohort included 225,034 patients in 109 ICUs. Intensivists were scheduled for seven or more consecutive days in 43 (39.4%) ICUs; 27 (24.7%) scheduled intensivists for 5 days, 22 (20.1%) for 4 days, seven (6.4%) for 3 days, four (3.7%) for 2 days, and six (5.5%) for less than or equal to 1 day. Compared with care by intensivists working 7+ consecutive days (adjusted ICU length of stay = 2.85 d), care by an intensivist working 3 or fewer consecutive days was associated with shorter ICU length of stay (3 consecutive days: 0.46 d fewer, p = 0.010; 2 consecutive days: 0.77 d fewer, p < 0.001; ≤ 1 consecutive days: 0.68 d fewer, p < 0.001). Shorter schedules of consecutive intensivist days worked were also associated with trends toward shorter hospital length of stay without increases in ICU readmissions or hospital mortality.

Conclusions:
Care by intensivists working fewer consecutive days is associated with reduced ICU length of stay without negatively impacting mortality.
Relative Hypoglycemia in Diabetic Patients With Critical Illness
Authors: Kwan Timothy N. , Zwakman-Hessels Lara , Marhoon Nada , Robbins Ray , Mårtensson Johan , Ekinci Elif , Bellomo Rinaldo 
Published: December 2019

Objectives:
Relative hypoglycemia is a decrease in glucose greater than or equal to 30% below prehospital admission levels (estimated by hemoglobin A1C) but not to absolute hypoglycemia levels. It is a recognized pathophysiologic phenomenon in ambulant poorly controlled diabetic patients but remains unexamined during critical illness. We examined the frequency, characteristics, and outcome associations of relative hypoglycemia in diabetic patients with critical illness.

Design:
Retrospective cohort study.

Setting:
ICU of a tertiary hospital.

Patients:
One-thousand five-hundred ninety-two critically ill diabetic patients between January 2013 and December 2017.

Interventions:
None.

Measurements and Main Results:
The median age of patients was 67 years (interquartile range, 60–75 yr). The median Acute Physiology and Chronic Health Evaluation III score was 53 (interquartile range, 40–68). Thirty-four percent of patients with diabetes experienced relative hypoglycemia (exposure) during their ICU admission. Such patients had higher glycemic lability, hemoglobin A1C levels, and Acute Physiology and Chronic Health Evaluation III scores. The hazard ratio for 28-day mortality of diabetic patients, censored at hospital discharge, for patients with relative hypoglycemia was 1.9 (95% CI, 1.3–2.8) and was essentially unchanged after adjustment for episodes of absolute hypoglycemia. After an episode of relative hypoglycemia, the hazard ratio for subsequent absolute hypoglycemia in the ICU was 3.5 (95% CI, 2.3–5.3).

Conclusions:
In ICU patients with diabetes, relative hypoglycemia is common, increases with higher hemoglobin A1C levels, and is a modifiable risk factor for both mortality and subsequent absolute hypoglycemia. These findings provide the rationale for future interventional studies to explore new blood glucose management strategies and to substantiate the clinical relevance of relative hypoglycemia.
Immune checkpoint inhibitors in melanoma in the metastatic, neoadjuvant, and adjuvant setting
Authors: Herrscher Hugo , Robert Caroline 
Published: December 2019

Purpose of reviewImmune checkpoint inhibitors (ICI) are now standards of care in metastatic melanoma. We highlight here the dramatic improvement that these drugs brought in the history of melanoma care.Recent findingsThe monoclonal antibody directed against cytotoxic T-lymphocyte-associated protein 4, ipilimumab, was approved in 2011. Antiprogramed death cell protein 1 antibodies, nivolumab and pembrolizumab, were developed afterward and approved in 2014, demonstrating an improved efficacy/safety ratio as compared with ipilimumab. The association of ipilimumab and nivolumab now appears as the most efficient immunotherapy but the toxicity of this regimen is a limitation. These drugs have also been evaluated in the adjuvant setting for patients with stage III or IV resected melanoma where they have shown a significant benefit in terms of relapse-free survival.SummaryICI-based immunotherapy radically modified melanoma management and now appear as the most efficient treatment for patients with metastatic melanoma with characterized by long-lasting cancer remissions, and a distinct spectrum of immune-related adverse events. Their efficacy is now also established in the adjuvant setting and they are now actively evaluated as neoadjuvant treatment with promising early results.Intensive translational work is ongoing to identify predictive biomarkers of efficacy and toxicity to improve ICI benefit/risk ratio.
Increased Risk of Acute Myelogenous Leukemia After Early Onset but Not Late-Onset Colorectal Cancer
Authors: Lehrer Steven , Rheinstein Peter H. 
Published: December 2019

Background:
Early onset colorectal cancer in persons younger than 50 years is increasingly common. Clinical and molecular characterizations reveal a distinctive disease. Thirty percent of patients have mutations of hereditary cancer syndromes, especially Lynch syndrome. A recent analysis, testing germline DNA for mutations in 25 cancer susceptibility genes, showed that some patients younger than 50 years had mutations of high-penetrance colorectal cancer genes such as APC (adenopolyposis coli). Others had mutations in high-penetrance or moderate-penetrance genes not traditionally associated with colorectal cancer, such as ATM (ataxia telangiectasia mutated), whereas still others had low penetrance colorectal cancer genes. In the current study, we examined the incidence of second cancers following early onset (age less than 50 y) colorectal cancer.

Methods:
The initial study population was assembled using records from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The SEER*Stat MP-SIR (multiple primary-standardized incidence ratio) tool was used to calculate SIRs and excess risk for second primary malignancies. The SIR is expressed as the ratio of observed-to-expected (O/E) cases. We used The Cancer Genome Atlas (TCGA) and AACR Project Genie for genetic analysis. The data were accessed with the online Xena Browser and cBioportal.

Results:
Acute myelogenous leukemia (AML) O/E ratios were significantly >1 in patients aged less than 50 years, at 12 to 59 months after colorectal cancer. In patients aged 50 years and older, O/E ratios were equal to 1 or quite close at 12 to 59 months after colorectal cancer. Alterations in 3 AML genes, CEBPA-AS1, MLLT1, and MLLT6, affected the prognosis of colorectal cancer patients less than 50 years but not older than 50 years. One AML gene, FLT3, had the highest copy number alteration frequency of any gene in 1438 colorectal patients 18 to 48 years of age. Genetic alterations of FLT3/TP53 were mutually exclusive. Genetic alterations of FLT3/JAK2 and JAK2/CTNNB1 were co-occurrent.

Conclusion:
These observations suggest that early onset colorectal cancer and AML may be related diseases.
What is the collective effect of aging and HIV on the gut microbiome?
Authors: Dillon Stephanie M. , Wilson Cara C. 
Published: December 2019

Purpose of review
Aging and HIV share features of intestinal damage and alterations in the communities of enteric bacteria, termed dysbiosis. The purpose of this review is to highlight the various features of the gut microbiome in aging and in people with HIV (PWH) and to discuss how aging and HIV converge to impact the gut microbiome. The term microbiome reflects the combined genetic material of micro-organisms present including bacteria, viruses, bacteriophages, and fungi. To date, the majority of studies investigating the impact of aging and HIV on the gut microbiome have focused on bacteria, and therefore, for the purposes of this review, the term ‘microbiome’ is used to reflect enteric bacterial communities.

Recent findings
Aging is associated with alterations in the gut bacterial microbiome. Although changes vary by the age of the population, lifestyle (diet, physical activity) and geographic location, the age-associated dysbiosis is typically characterized by an increase in facultative anaerobes with inflammatory properties and a decrease in obligate anaerobes that play critical roles in maintaining intestinal homeostasis and in regulating host immunity. PWH also have dysbiotic gut microbiomes, many features of which reflect those observed in elderly persons. In one study, the age effect on the gut microbiome differed based on HIV serostatus in older adults.

Summary
HIV and age may interact to shape the gut microbiome. Future studies should investigate relationships between the gut microbiome and age-associated comorbidities in older PWH populations. Identifying these links will provide new avenues for treatments and interventions to improve the healthspan and lifespan of older PWH.