bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Course of Frailty in Survivors of Critical Illness*
Authors: Brummel Nathan E. , Girard Timothy D. , Pandharipande Pratik P. , Thompson Jennifer L. , Jarrett Ryan T. , Raman Rameela , Hughes Christopher G. , Patel Mayur B. , Morandi Alessandro , Gill Thomas M. , Ely E. Wesley 
Published: July 2020

Objectives:
Little is known about frailty that develops following critical illness. We sought to describe the prevalence of newly acquired frailty, its clinical course, and the co-occurrence of frailty with disability and cognitive impairment in survivors of critical illness.

Design:
Longitudinal prospective cohort study.

Setting:
Medical and surgical ICUs at five U.S. centers.

Patients:
Adult patients treated for respiratory failure and/or shock.

Measurements and Main Results:
We measured frailty with the Clinical Frailty Scale at baseline (i.e., study enrollment) and at 3 and 12 months postdischarge. We constructed alluvial diagrams to describe the course of frailty and Venn diagrams to describe the overlap of frailty with disability in activities of daily living and cognitive impairment. We included 567 participants a median (interquartile range) of 61 years old (51–70 yr old) with a high severity of illness (Acute Physiology and Chronic Health Evaluation II of 23). Frailty (Clinical Frailty Scale scores ≥ 5) was present in 135 of 567 (24%) at baseline, 239 of 530 (45%) at 3 months, and 163 of 445 (37%) at 12 months. Of those with frailty at 3- or 12-month follow-up, 61% were not frail at baseline. Transition to a worse frailty state occurred in 242 of 530 of patients (46%) between baseline and 3 months and in 179 of 445 of patients (40%) between baseline and 12 months. There were 376 patients with frailty, disability, or cognitive impairment at 3-month follow-up. Of these, 53 (14%) had frailty alone. At 12 months, 276 patients had frailty, disability, or cognitive impairment, 37 (13%) of whom had frailty alone.

Conclusions:
Frailty is common among survivors of critical illness. In the majority, frailty is newly acquired. Roughly one in seven had frailty without co-occurring disability or cognitive impairment. Studies to understand outcomes of frailty that develops as the result of a critical illness and to identify modifiable risk factors for this potentially reversible syndrome are needed.
A Comparison of Sepsis-2 (Systemic Inflammatory Response Syndrome Based) to Sepsis-3 (Sequential Organ Failure Assessment Based) Definitions—A Multicenter Retrospective Study*
Authors: Engoren Milo , Seelhammer Troy , Freundlich Robert E. , Maile Michael D. , Sigakis Matthew J. G. , Schwann Thomas A. 
Published: July 2020

Objectives:
Recently, the definition of sepsis has changed from a physiologic derangement (Sepsis-1 and -2) to organ dysfunction (Sepsis-3) based. We sought to determine the concordance between the different sepsis phenotypes and how that affected mortality.

Design:
Retrospective, multicenter study.

Setting:
Three academic medical centers.

Patients:
29,459 patients who had suspected infection, defined as obtaining blood cultures and receiving antibiotics: 18,183 (62%) had either Sepsis-2 or Sepsis-3.

Measurements and Main Results:
Kappa was used to show agreement between phenotypes. Conditional logistic regression was used to create models of associations between factors and phenotypes and between factors and mortality. About 12,981 patients had Sepsis-2; 12,043 had Sepsis-3; and 6,841 patients had both Sepsis-2 and Sepsis-3. Fifty-three percent of Sepsis-2 patients also had Sepsis-3, whereas 57% of Sepsis-3 patients also had Sepsis-2. Agreement between the two phenotypes was poor: kappa = 0.213 ± 0.006. Mortality was 6% in patients with only Sepsis-2, 10% with only Sepsis-3, and 18% in patients who had both phenotypes. Combining the variables in Sepsis-2 and Sepsis-3 improved the discrimination (C-statistic = 0.742 ± 0.005, p < 0.001) of mortality.

Conclusions:
We found that Sepsis-2 and Sepsis-3-based sepsis diagnoses represent separate phenotypes with poor agreement. Patients who have both phenotypes are at increased risk of mortality compared with having either phenotype alone. Inclusion of both systemic inflammatory response syndrome and Sequential Organ Failure Assessment criteria in the same model improves the discrimination of mortality.
Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria
Authors: Ouma Benson J. , Ssenkusu John M. , Shabani Estela , Datta Dibyadyuti , Opoka Robert O. , Idro Richard , Bangirana Paul , Park Gregory , Joloba Moses L. , Kain Kevin C. , John Chandy C. , Conroy Andrea L. 
Published: July 2020

Objectives:
Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors.

Design:
Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children.

Setting:
Mulago National Referral Hospital in Kampala, Uganda.

Subjects:
Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months.

Interventions:
None.

Measurements and Main Results:
Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β –0.42, 95% CI, –0.69 to –0.15, p = 0.002; children ≥ 5, β –0.39, 95% CI, –0.67 to –0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau).

Conclusions:
These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.
Folliculocystic and Collagen Hamartoma: A Distinct Hamartoma Associated With Tuberous Sclerosis Complex
Authors: Cardona Rocio , Cancel-Artau Karina J. , Carrasquillo Osward Y. , Martin-Garcia Rafael F. 
Published: July 2020

Abstract:
Tuberous sclerosis complex (TSC) is a neurocutaneous disease characterized by cutaneous and extracutaneous hamartomas. Dermatologic evaluation is critical for early diagnosis because mucocutaneous manifestations account for 4 of 11 major and 3 of 6 minor diagnostic criteria. Folliculocystic and collagen hamartoma (FCCH) is a recently described entity associated with TSC. We herein describe the case of a 28-year-old woman with a history of TSC who presented with a scalp lesion present since childhood. Physical examination revealed a solitary, well-circumscribed exophytic tumor over the occipital scalp measuring 9 × 8 cm and covered with comedones and cyst-like structures. Biopsy of the lesion demonstrated thickening of the collagen bundles throughout the dermis, concentric perifollicular and perivascular fibrosis, an increased number of dilated vessels, and keratin-filled cysts lined by the infundibular epithelium. Clinicopathologic correlation was diagnostic for FCCH. The patient was referred for surgical excision. In addition, we review 11 other cases of FCCH previously reported in the literature.
Unusual Presentations of Primary and Metastatic Adenoid Cystic Carcinoma Involving the Skin
Authors: Collins Katrina , Prieto Victor G. , Aung Phyu P. 
Published: July 2020

Abstract:
Adenoid cystic carcinoma (ACC) is most commonly seen in the salivary glands but may occur at other sites. Primary or metastatic involvement of the skin is unusual. We report 2 cases of ACC with unusual presentation. In the first case, a 55-year-old woman presented with a cutaneous lesion on the right shin, and final pathology showed ACC. An extracutaneous origin was excluded by clinical and imaging studies. In the second case, a 49-year-old woman presented with a nodule on the breast, and biopsy confirmed high-grade ACC (>30% solid areas). She underwent lumpectomy and subsequent mastectomy after recurrence. Sixteen months after the initial diagnosis of ACC of the breast, distant metastases at multiple sites, including the skin, were identified. This report will increase awareness of these rare presentations of cutaneous ACC and allow correct diagnosis and appropriate management of such cases.
Coronavirus (COVID-19) Infection–Induced Chilblains: A Brisk Perieccrine Inflammatory Response
Authors: Wargo Jeffrey J. , Weir Nathan M. , Shamma H. Nicholas 
Published: July 2020

Abstract:
The varying cutaneous and pathological manifestations of coronavirus 2 (SARS-CoV-2 or COVID-19) may have prognostic implications. Acral ischemic findings present with a hypercoagulable state in critically ill COVID-19 patients. Pathologically confirmed varicella-like exanthem and perniosis COVID-19 cases have correlated with paucisymptomatic and asymptomatic patients in previous reports. We present the second case of biopsy-proven COVID-19 infection–induced chilblains (pernio) in a paucisymptomatic patient with a brisk perieccrine lymphocytic response. Based on an antecedent pathological study, we know coronavirus particles have been seen in the eccrine gland associated with a brisk peri-inflammatory response. The prominent perieccrine inflammation is helpful in the diagnosis of COVID-19 infections. Currently, nonischemic pathological findings correlate with a good prognosis based on the paucisymptomatic or asymptomatic nature of their disease courses. Patients presenting with suspected COVID-19 infection–induced chilblains who are paucisymptomatic or asymptomatic should be isolated and immediately tested with polymerase chain reaction (PCR) testing (as there is a delay in diagnosis based on the poor sensitivity of the current rapid test). We continue to stress the importance of early diagnosis and quarantining to prevent spread to the older and immunocompromised patients.
The Impact of Vaccination Efforts on the Spatiotemporal Patterns of the Hepatitis A Outbreak in Michigan, 2016–2018
Authors: Brouwer Andrew F. , Zelner Jonathan L. , Eisenberg Marisa C. , Kimmins Lynsey , Ladisky Macey , Collins Jim , Eisenberg Joseph N. S. 
Published: July 2020

Background:
The United States is currently experiencing the largest hepatitis A virus (HAV) outbreak since the introduction of a vaccine in 1996. More than 31,000 cases have been reported since 2016. Although HAV had largely been considered a foodborne pathogen in recent years, this outbreak has been spread primarily through person-to-person transmission in urban settings and has been associated with homelessness and substance use. Michigan was one of the first states to report an outbreak, with 910 reported cases between August 2016 and December 2018.

Methods:
We analyzed surveillance and vaccination data from Michigan using a disease transmission model to investigate how vaccine timing and coverage influenced the spatiotemporal patterns of the outbreak, distinguishing between Southeast Michigan, where the outbreak began, and the rest of the state.

Results:
We estimated that vaccination had little impact in Southeast Michigan (3% cases averted [95% confidence interval (CI) = 1%, 8%]) but had a substantial impact in the rest of the state, preventing a larger outbreak (91% cases averted [95% CI = 85%, 97%]) lasting several more years.

Conclusions:
Our results emphasize the value of targeting populations where local transmission is not yet sustained rather than populations where transmission is already waning. Simulation modeling can aid in proactive rather than reactive decision-making and may help direct the response to outbreaks emerging in other states. See video abstract: http://links.lww.com/EDE/B704.
Prospective Association Between Manganese in Early Pregnancy and the Risk of Preeclampsia
Authors: Liu Tiange , Hivert Marie-France , Rifas-Shiman Sheryl L. , Rahman Mohammad L. , Oken Emily , Cardenas Andres , Mueller Noel T. 
Published: July 2020

Background:
Manganese, an essential micronutrient, has been found in lower concentrations among women with preeclampsia in cross-sectional and case–control studies without establishment of a temporal relationship.

Methods:
We evaluated the prospective association of manganese (in red blood cells) in first trimester of pregnancy with incidence of preeclampsia (ascertained by reviewing medical records) among 1,312 women in eastern Massachusetts (Project Viva, 1999–2002). We used log-binomial regression to examine the manganese–preeclampsia relationship, adjusting for maternal age, race/ethnicity, parity, prepregnancy body mass index, blood pressure, and hematocrit.

Results:
The median (25th, 75th percentile) manganese concentrationin red blood cells was 16.2 ng/g (13.1, 20.4) and 48 (4%) women developed preeclampsia. We observed an inverse dose–response relationship between manganese and preeclampsia. Compared with women in the lowest tertile, women in the middle manganese tertile had 0.81 times the risk of preeclampsia (95% CI: 0.43, 1.5) and those in the highest tertile had 0.50 (95% CI: 0.25, 0.99) times the risk.

Conclusions:
Our results provide insight into a potentially modifiable way to prevent preeclampsia.
Porcine Urinary Bladder Extracellular Matrix for Treatment of Periocular Skin Defects
Authors: Law James J. , Baker Laura X. , Chen Qingxia , Mawn Louise A. , Barahimi Behin , Kupcha Anna C. , Alford Mark A. , Sobel Rachel K. 
Published: July 2020

Purpose:
To describe the experience of 4 oculoplastic surgeons with porcine bladder matrix for periocular anterior lamella and donor site skin defects either as stand-alone treatment or in conjunction with other reconstructive procedures. The authors hypothesized that defect size and location influence the requirement for additional matrix treatments or ancillary procedures.

Methods:
Following the Institutional Review Board approval, the authors conducted a retrospective review of 17 patients treated with porcine bladder matrix at 2 oculoplastic practices between 2016 and 2018. Powdered matrix was applied to the skin defect and overlaid with a matrix sheet. Subsequent rounds of matrix treatment or other reconstructive procedures were performed as necessary. Defect size and location were correlated to the number of ancillary matrix treatments or surgical procedures via univariate analysis.

Results:
Twenty-five sites (21 primary and 4 donor) in 17 individuals (8–95 years, M = 58.8 years, 10 males) were treated with porcine bladder matrix. All wounds healed successfully. Additional matrix treatments were administered at 5 sites. Ancillary procedures were performed for 7 sites. Upper lid involvement and larger defect size tended to require additional ancillary procedures (p = 0.006), while lower eyelid and other periocular defects required fewer procedures (p < 0.001).

Conclusion:
Porcine bladder matrices are useful adjuncts to healing periocular anterior lamella defects in various settings. Such repairs are useful in nonsurgical candidates, but must take into account varying levels of complexity based on lesion location. Smaller defects are more conducive to application of matrices as stand-alone treatment, while larger or upper eyelid defects often require additional procedures.
The Ophthalmology Surgical Competency Assessment Rubric for External Dacryocystorhinostomy Surgery
Authors: Juniat Valerie , Saleh George M. , Naik Milind , Nerad Jeffrey , Gauba Vinod , Devoto Martin H. , Pakdel Farzad , Golnik Karl C. 
Published: July 2020

Purpose:
The International Council of Ophthalmology (ICO) is currently developing a series of standardized, internationally validated, teaching tool for key ophthalmic surgical procedures called the Ophthalmology Surgical Competency Assessment Rubrics (OSCARs). This study aims to develop an OSCAR for external dacryocystorhinostomy (ExDCR).

Methods:
An international panel of content experts, representing Argentina, India, U.A.E., United Kingdom, and the U.S.A. was established and worked to develop the rubric using a range of online collaboration tools. The team used the standardized OSCAR template as a baseline, developing explicit behavioral descriptors (the behavior and performance expected for each step) that were reviewed and modified with successive models. Learners were scored on a modified 4-point Dreyfus scale of skill acquisition (novice, beginner, advanced beginner, competent) with the removal of the expert domain. The tool was then reviewed by a secondary panel of international content experts, representing Brazil, India, Iran, Singapore, United Kingdom, and the U.S.A.

Results:
The final OSCAR ExDCR tool was developed in alignment with the ICO-OSCAR standard. Nineteen agreed and weighted stems were produced. Specific comments with regards to the parameters and wording were incorporated to formulate the final rubric, which was internationally agreed and demonstrated face and content validity.

Conclusions:
The OSCAR ExDCR is skill and behavior based, has ICO agreed standards for assessment, and provides learners with specific targets for improvement. Although the OSCAR tool has face and content validity, further development could better elucidate its precise role.
Factors Associated With Physician Empowerment and Well-being at an Academic Medical Center
Authors: Yakes Elizabeth Ann , Dean Stephanie , Labadie Robert F. , Byrne Daniel , Estrada Cristina , Thompson Reid , Kendall James , Yarbrough Mary 
Published: July 2020

Objective:
This study reports an institutional approach to rapidly measure burnout and gather physicians’ opinions on workplace factors that empower well-being.

Methods:
In July 2017, physicians at Vanderbilt University Medical Center were invited to participate in a two-question survey measuring self-reported burnout and providing an opportunity to describe structures that empower well-being. Free-text responses were analyzed and a linear regression model assessed factors associated with well-being.

Results:
A total of 1135 physicians responded (43.3% response rate) with a mean well-being score of 56 (scale 0 to 100). Higher scores were associated with clinical fellow status (P = 0.002), male sex (P = 0.008), less allocation of time to clinical care (P < 0.001), and not commenting on “leadership” and “autonomy” in the free-text response.

Conclusions:
Brief surveys collecting perspectives on well-being can help employers identify high-risk groups and provide a roadmap for institutional change.
Fecal microbial transplant for inflammatory bowel disease
Authors: Claytor Jennifer D. , El-Nachef Najwa 
Published: July 2020

Purpose of review
The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis.

Recent findings
Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation.

Summary
The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.
Trigeminal Neuralgia With Extraoral Trigger Zone Successfully Treated With Intraoral Injections of Botulinum Toxin: A Case Report
Authors: Dinan John E. , Smith Alexander , Hawkins James M. 
Published: July 2020

Abstract
Trigeminal neuralgia is a pain condition that is frequently misdiagnosed and challenging to manage. We present the case of a patient with trigeminal neuralgia with multiple misdiagnoses and poorly managed pain. Despite the presence of trigger zones both inside and outside her mouth, complete symptom resolution was ultimately achieved through onabotulinumtoxinA injections, delivered solely intraorally.
Compliance to Individualized Recommendations Based on an Evidence-Based Algorithm for Behavioral Management of Lower Urinary Tract Symptoms
Authors: Gammie Andrew 
Published: July 2020

PURPOSE:
The aim of this study was to evaluate patient compliance to individualized recommendations for self-management of fluid intake, bladder irritants, and timing of fluid consumption.

DESIGN:
Single-group, before-after pilot study.

SUBJECTS AND SETTING:
The sample comprised 22 patients (17 male and 5 females, mean age 62 years, age range 27-84 years). The study setting was the uroflow clinic at Southmead Hospital, Bristol, UK, a tertiary level referral hospital for complex evaluation and treatment of urological patients.

METHODS:
Patients were given a bladder diary to complete after 2 weeks, which was compared with the bladder diary they had originally brought to clinic, to see whether the advice was followed. The bladder diary used required the patient to document the times and volumes of urination over a period of 3 days, magnitude of urinary urgency felt at the time, along with fluid intake timing, amount, and type of beverage. The study was not designed to measure changes in symptoms, but observed changes recorded in the bladder diaries are reported.

RESULTS:
All 6 of the 22 participants who were advised to increase the volume of fluid intake complied, with an increased average intake of a mean of 520 mL (range 100-1450 mL). Similarly, one participant advised to reduce fluid intake decreased their fluid intake by 1800 mL per day. Thirteen out of 16 patients (81%) who were advised to remove caffeine, alcohol, or artificial sweeteners from their diet complied, indicated by no bladder irritant being recorded on their bladder diary. Nine out of 12 patients (75%) advised to reduce fluid intake in the evenings complied, decreased fluid intake after 6 pm by an average of 240 mL (range 100-550 mL less).

CONCLUSIONS:
A majority of participants given fluid intake advice that is specific to their symptoms and lifestyle complied with recommendations. Simple guidance could usefully be given to patients before they are referred to specialist urological care or undergo urodynamic testing.