bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+ cell count and outcomes among HIV-infected compared with uninfected medical ICU survivors in a national cohort
Authors: Akgün Kathleen M. , Krishnan Supriya , Butt Adeel A. , Gibert Cynthia L. , Graber Christopher J. , Huang Laurence , Pisani Margaret A. , Rodriguez-Barradas Maria C. , Hoo Guy W. Soo , Justice Amy C. , Crothers Kristina , Tate Janet P. 
Published: July 2021

Background:
People with HIV (PWH) with access to antiretroviral therapy (ART) experience excess morbidity and mortality compared with uninfected patients, particularly those with persistent viremia and without CD4+ cell recovery. We compared outcomes for medical intensive care unit (MICU) survivors with unsuppressed (>500 copies/ml) and suppressed (≤500 copies/ml) HIV-1 RNA and HIV-uninfected survivors, adjusting for CD4+ cell count.

Setting:
We studied 4537 PWH [unsuppressed = 38%; suppressed = 62%; 72% Veterans Affairs-based (VA) and 10 531 (64% VA) uninfected Veterans who survived MICU admission after entering the Veterans Aging Cohort Study (VACS) between fiscal years 2001 and 2015.

Methods:
Primary outcomes were all-cause 30-day and 6-month readmission and mortality, adjusted for demographics, CD4+ cell category (≥350 (reference); 200–349; 50–199; <50), comorbidity and prior healthcare utilization using proportional hazards models. We also adjusted for severity of illness using discharge VACS Index (VI) 2.0 among VA-based survivors.

Results:
In adjusted models, CD4+ categories <350 cells/μl were associated with increased risk for both outcomes up to 6 months, and risk increased with lower CD4+ categories (e.g. 6-month mortality CD4+ 200–349 hazard ratio [HR] = 1.35 [1.12–1.63]; CD4+ <50 HR = 2.14 [1.72–2.66]); unsuppressed status was not associated with outcomes. After adjusting for VI in models stratified by HIV, VI quintiles were strongly associated with both outcomes at both time points.

Conclusion:
PWH who survive MICU admissions are at increased risk for worse outcomes compared with uninfected, especially those without CD4+ cell recovery. Severity of illness at discharge is the strongest predictor for outcomes regardless of HIV status. Strategies including intensive case management for HIV-specific and general organ dysfunction may improve outcomes for MICU survivors.
Antimicrobial-resistant bacteria in international travelers
Authors: Sridhar Sushmita , Turbett Sarah E. , Harris Jason B. , LaRocque Regina C. 
Published: July 2021

Purpose of review
Antimicrobial resistance (AMR) in bacteria poses a major risk to global public health, with many factors contributing to the observed increase in AMR. International travel is one recognized contributor. The purpose of this review is to summarize current knowledge regarding the acquisition, carriage and spread of AMR bacteria by international travelers.

Recent findings
Recent studies have highlighted that travel is an important risk factor for the acquisition of AMR bacteria, with approximately 30% of studied travelers returning with an acquired AMR bacterium. Epidemiological studies have shown there are three major risk factors for acquisition: travel destination, antimicrobial usage and travelers’ diarrhea (TD). Analyses have begun to illustrate the AMR genes that are acquired and spread by travelers, risk factors for acquisition and carriage of AMR bacteria, and local transmission of imported AMR organisms.

Summary
International travel is a contributor to the acquisition and dissemination of AMR organisms globally. Efforts to reduce the burden of AMR organisms should include a focus on international travelers. Routine genomic surveillance would further elucidate the role of international travel in the global spread of AMR bacteria.
Continuous versus intermittent infusion of antibiotics in Gram-negative multidrug-resistant infections
Authors: Gatti Milo , Pea Federico 
Published: July 2021

Purpose of review
The aim of this review was to perform a critical reappraisal of the real-world evidence supporting administration by prolonged infusion of novel beta-lactams for the management of multidrug-resistant Gram-negative infections.

Recent findings
Real-world evidence support the use of novel beta-lactams by prolonged infusion over intermittent infusion in terms of achieving aggressive pharmacokinetic/pharmacodynamic (PK/PD) target for either maximizing efficacy and clinical outcome or suppressing the emergence of resistance development. Continuous infusion of ceftolozane-tazobactam showed a marked superiority toward both intermittent and extended infusion (EI) in achieving a PK/PD target of 100%fT> 4 X MIC in infections caused by less-susceptible Pseudomonas aeruginosa isolates. No resistance development was found in critically ill or immunocompromised patients treated with EI ceftolozane-tazobactam compared to intermittent infusion. Prolonged infusion of ceftazidime-avibactam was negatively associated with mortality in patients affected by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infections. Different challenging scenarios (patients showing augmented renal clearance of affected by deep-seated infections) could benefit from prolonged infusion to optimize the efficacy of novel agents.

Summary
Although available data are still limited, real-world evidence regarding mainly ceftolozane-tazobactam and ceftazidime-avibactam could support the administration of novel beta-lactams by prolonged infusion in some specific scenarios in which achievement of aggressive PK/PD target is quite challenging.
Emerging treatment options for cryptosporidiosis
Authors: Love Melissa S. , Choy Robert K.M. 
Published: July 2021

Purpose of review
Substantial progress has been made recently on the development of new therapeutics for cryptosporidiosis, an infection by the protozoan parasite Cryptosporidium that is associated with diarrhea, malnutrition, growth stunting, cognitive deficits, and oral vaccine failure in children living in low-resource settings.

Recent findings
Various drug discovery approaches have generated promising lead candidates. The repurposed antimycobacterial drug clofazimine was tested in Malawian HIV patients with cryptosporidiosis but was ineffective. Target-based screens identified inhibitors of lysyl-tRNA synthetase, phenylalanyl-tRNA synthetase, methionyl-tRNA synthetase, and calcium-dependent protein kinase 1. Phenotypic screens led to discovery of a phosphatidylinositol 4-kinase inhibitor, the piperazine MMV665917, and the benzoxaborole AN7973. The relationship between pharmacokinetic properties and in-vivo efficacy is gradually emerging. A pathway to clinical trials, regulatory approval, and introduction has been proposed but additional work is needed to strengthen the route.

Summary
Several lead compounds with potent activity in animal models and a favorable safety profile have been identified. A sustained effort will be required to advance at least one to clinical proof-of-concept studies. The demonstrated risk of resistance indicates multiple candidates should be advanced as potential components of a combination therapy.
Coronavirus disease 2019 in children
Authors: Levy Emily R. , Blumenthal Jennifer , Chiotos Kathleen 
Published: July 2021

Purpose of review
Over the course of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that the clinical features, epidemiology, and outcomes of COVID-19 are distinct in children relative to adults. In this review, we will present recent pediatric studies informing our current understanding of COVID-19 in children, and review pediatric considerations surrounding disease transmission, currently available therapies, and vaccination.

Recent findings
Recent studies have shed light on the clinical epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, identifying a high prevalence of asymptomatic and mild infections, with severe COVID-19 infrequently reported. Several adult clinical trials have informed the use of remdesivir, anti-SARS-CoV-2 monoclonal antibodies, dexamethasone, and tocilizumab in the management of COVID-19. Associations between underlying comorbid medical conditions and severe outcomes, as well as transmission dynamics of SARS-CoV-2 in children, are complex and warrant further study. Finally, highly efficacious vaccines are available for adults and adolescents, with pediatric trials ongoing.

Summary
Children generally fare well with acute COVID-19 infection, though critical illness is possible. Future research should focus on clarifying the role of children in SARS-CoV-2 transmission and optimal prevention strategies, particularly in the school setting, as well as evaluating pediatric vaccine candidates.
Prevalence of Metabolic Syndrome in Psoriatic Arthritis
Authors: Urruticoechea-Arana Ana , Castañeda Santos , Otón Teresa , Benavent Diego , Loza Estíbaliz , Martín-Martínez María A. , González-Gay Miguel Ángel 
Published: July 2021

Objective
To analyze the prevalence of metabolic syndrome (MetS) in patients with psoriatic arthritis (PsA) in a systematic literature review (SLR) and in the Spanish CArdiovascular in RheuMAtology (CARMA) cohort.

Methods
A SLR and a subanalysis of the CARMA cohort were performed. In the SLR, PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov up to March 2019 were searched. Systematic literature reviews, clinical trials, and observational studies that analyzed the prevalence or frequency of MetS in PsA were analyzed. Two reviewers selected the articles, assessed the quality of the studies, and collected data, independently. In addition, data on sociodemographic characteristics and MetS in patients with PsA from the CARMA cohort were collected and analyzed. Comparative descriptive analysis was performed.

Results
The SLR included 18 articles, of moderate to high quality, with PsA patients of both sexes, with mean ages between 42 and 59 years. The rate of MetS varied from 23.5% to 62.9%. The most commonly used classification method was that of the National Cholesterol Education Program. Additionally, 724 PsA patients from the CARMA cohort were analyzed; 327 (45.4%) were women, 157 (21.8%) smokers, with a mean age of 51 years and a mean PsA disease duration of 9 years. Hypertension was the most common abnormal finding (66.8%), followed by hyperglycemia (42.6%) and hypertriglyceridemia (30.6%). Notably, 222 patients (30.6%) had MetS.

Conclusions
The prevalence of MetS in PsA varies, depending on the definition. Whereas 23.5% to 62.9% of PsA patients have MetS, in the CARMA cohort almost a third of patients with PsA have MetS.
Determination of Extra Craniofacial Abnormalities in Patients With Craniofacial Microsomia
Authors: Raposo Barbara Kawano , Ferreira Guilherme Bail , Silva Alfredo Benjamin Duarte e , Ono Maria Cecília Closs , de Souza Josiane , da Silva Freitas Renato 
Published: July 2021

Introduction:
Craniofacial microsomia (CFM) is caused by abnormalities in the development of the first and second pharyngeal arches. One-third to half of the patients with CFM also present with extra craniofacial (ECF) malformations. The knowledge of the visceral alteration related to CFM is vital for optimized care and a better prognosis.

Aim:
To describe the incidence of ECF malformations in patients with CFM and to infer if there was a correlation between CFM and ECF malformations.

Materials and Methods:
The authors analyzed medical records of patients diagnosed with CFM from 1996 to 2006. The data collected included age, gender, category of craniofacial alteration, and the type of ECF malformation when present. The sample was inspected to find possible correlations between craniofacial abnormalities and ECF malformations.

Results:
The sample included 102 patients, with a mean age of 7 years and a predominance of males (61.8%). Ear malformations (93.1%) followed by mandible (59.8%) and facial nerve (10.8%) abnormalities were the most common CFM. Among patients with CFM, 37.2% had ECF involvement, mainly in vertebrae (20%), heart (11%), and limbs (9.8%). Multivariate analysis revealed that the presence of ear malformations was related to a higher incidence of nonspecific visceral malformations (P = 0.034) and that mandible malformation was related to an increased incidence of vertebral malformations (P = 0.008).

Conclusion:
A significant percentage of patients with CFM presented associated ECF impairment. Ear and mandible involvement may be predictors of nonspecific visceral malformation and vertebral malformations, respectively.
Changes in Quality of Life After Secondary Closure of Palatal Defects: Prosthetic Obturation Versus Surgical Reconstruction
Authors: Matsumoto Hiroshi , Ota Tomoyuki , Takeda Seiko , Mizukawa Nobuyoshi , Kimata Yoshihiro 
Published: July 2021

Background:The closure of palatal defects after tumor resection or irradiation is performed with either a prosthesis or autogenous tissue; however, there are no clear criteria regarding selection of the method. Thus, this study aimed to investigate the real-world situation and problems of palatal closure using prostheses, and examined patient opinion on how palatal closure using autogenous tissue improved their postoperative quality of life (QOL).Methods:In 5 patients whose palatal defects resulted from treatment for head and neck cancer and were closed with a prosthesis, the palate was closed secondarily with autogenous tissue; a questionnaire on daily life was administered pre- and post-operatively.Results:Functional improvements in terms of speech and eating were achieved in all and in 4 of 5 cases, respectively. In all cases, the QOL was better for palatal closure with autogenous tissue than with the prosthesis.Conclusions:As postoperative QOL was considered to be better when reconstructing the palate with autogenous tissue than with the prosthesis, we recommend to actively select autogenous tissue for palate reconstruction.
Endoscopic Modified Medial Maxillectomy for Inverted Papilloma of the Maxillary Sinus
Authors: Liu Qinghua , Weng Cuilian , Zheng Hao , Wu Lihua , Huang Shaopeng 
Published: July 2021

Background:
Sinonasal inverted papilloma (SNIP) is a benign tumor that can be surgically managed by an endoscopic approach. However, SNIP has a high recurrence rate, mainly due to incomplete resection.

Aim:
This study aimed to analyze the outcomes of endoscopic modified medial maxillectomy in treating SINP originating from the maxillary sinus.

Methods:
The authors retrospectively analyzed 24 patients treated for SNIP via endoscopic modified medial maxillectomy at our institution between August 2014 and June 2019. During surgery, the mucosa involved in the tumor was stripped, and the bone underlying the tumor base was completely excised. Demographic data, surgical technique, location of SNIP attachment, complications, follow-up duration, and recurrence were recorded.

Results:
Twenty four patients with SNIP were identified (16 males). All patients had Krouse stage-III disease. Eleven patients presented with single attachment and 13 with multiple attachments. None of the patients had any complications during surgery. Four patients had postsurgical facial numbness around the cheek and upper lip. After a mean follow-up of 35.12 ± 14.98 months, no recurrence of SNIP was observed.

Conclusions and Significance:
Endoscopic modified medial maxillectomy is a safe and effective technique for treating SNIP. Recurrence can be reduced by complete excision of the attachment sites.
Age Related Changes of Superior Orbicularis Oris Muscle in Terms of Tone and Viscoelastic Properties
Authors: Ramazanoglu Engin , Turhan Begümhan , Usgu Serkan 
Published: July 2021

Objective:
To examine the age-related changes in the viscoelastic properties and tone of the superior orbicularis oris muscle by a portablehand-held myotonometer.

Methods:
A total of 128 individuals (65 female, 63 male) who met the inclusion criteria were evaluated. Individuals were divided into 2 groups as under 40 years old (Group 1), and above (Group 2). The viscoelastic properties and muscle tone of orbicularis oris muscle were evaluated bilaterally in supine position with the Myoton PRO (Myoton AS, Estonia) device from the skin overlying the orbicularis oris. The reference point is accepted as the right and left paramedial philtrum dimple. The statistical analysis was performed.

Results:
There was no statistically significant difference in the elasticity values of the right and left orbicularis oris muscles of the Group 1 and Group 2 individuals. There was a difference between the groups when the tone and stiffness values of both groups were compared. It was determined that individuals over the age of 40 had higher muscle tone and stiffness. All mechanical properties of the superior orbicularis oris muscle between the male and female individuals in Group 1 were different. The values are higher in the female gender. The elasticity values in both genders in Group 2 were similar. Tone and stiffness parameters were different between genders.

Conclusions:
Myoton PRO can be recommended as an alternative device in the quantitative evaluations of post-operative follow-ups, and pre/post rehabilitation in terms of viscoelastic parameters of the muscle.
Elevated Plasma Levels of Matrix Metalloproteinase-3 and Tissue-Inhibitor of Matrix Metalloproteinases-1 Associate With Organ Dysfunction and Mortality in Sepsis
Authors: Jones Tiffanie K. , Reilly John P. , Anderson Brian J. , Miano Todd A. , Dunn Thomas G. , Weisman Ariel R. , Agyekum Roseline , Feng Rui , Ittner Caroline A.G. , Shashaty Michael G.S. , Meyer Nuala J. 
Published: July 2021

ABSTRACT

Background:
Matrix Metalloproteinases (MMP) respond to tissue damage during sepsis. Higher plasma concentrations of MMPs and the tissue-inhibitor of matrix metalloproteinases (TIMP) have been reported in sepsis compared with healthy controls. The objective of this study was to examine if plasma levels of MMP-3, MMP-9, and TIMP-1 associate with mortality and organ dysfunction during sepsis.

Methods:
We conducted a prospective cohort study of critically ill patients with sepsis adjudicated per Sepsis-3 criteria at a tertiary academic medical center. We measured plasma concentrations of MMP-3, MMP-9, and TIMP-1 on intensive care unit admission. We phenotyped the subjects for shock, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality at 30 days. We used logistic regression to test the associations between the MMPs and TIMP-1 with shock, ARDS, AKI, and mortality.

Results:
Higher plasma TIMP-1 levels were associated with shock (odds ratio [OR] 1.51 per log increase [95% CI 1.25, 1.83]), ARDS (OR 1.24 [95% CI 1.05, 1.46]), AKI (OR 1.18 [95% CI 1.01, 1.38]), and mortality (OR 1.20 [95% CI 1.05, 1.46]. Higher plasma MMP-3 concentrations were associated with shock (OR 1.40 [95% CI 1.12, 1.75]) and mortality (OR 1.24 [95% CI 1.03, 1.48]) whereas MMP-9 levels were not associated with outcomes. Higher plasma TIMP-1 to MMP-3 ratios were associated with shock (OR 1.41 [95% CI 1.15, 1.72], P = 0.02).

Conclusion:
Elevated plasma concentrations of TIMP-1 associate with organ dysfunction and mortality in sepsis. Higher plasma levels of MMP-3 associate with shock and mortality. Plasma MMP and TIMP-1 may warrant further investigation as emerging sepsis theragnostic biomarkers.
Participation in a Chronic Limb Threatening Ischemia Randomized Trial Is Inversely Correlated With Regional Amputation Rate in Limb Threatening Ischemia Patients
Authors: Siracuse Jeffrey J. , Goodney Philip P. , Menard Matthew T. , Rosenfield Kenneth , Van Over Maxwell , Hamza Taye H. , Eid Mark , Villarreal Maria F. , Strong Michael B. , Farber Alik 
Published: July 2021

Objective:
The National Health Service demonstrated that regions of the United Kingdom with the highest number of patients enrolled in research studies had the lowest risk-adjusted mortality when patients were admitted to the hospital. Our goal was to investigate if this correlation was evident for patients with chronic limb threatening ischemia (CLI) treated in the United States (US). Accordingly, we examined correlations among sites participating in the Best Endovascular versus best Surgical Therapy in patients with Critical (BEST-CLI) trial, a multicenter, National Institute of Health-sponsored, international randomized controlled trial (RCT) comparing revascularization strategies in patients with CLI, and regional rates of major amputation from CLI.

Methods:
We measured regional participation in the BEST-CLI trial by evaluating trial participation and enrollment rosters. To determine regional rates of lower limb amputation, we queried the Medicare database (2007–2016) for patients with concurrent peripheral arterial disease (PAD) and diabetes, then assessed how many had lower extremity amputations. Correlation of regional amputation rates with distribution of BEST-CLI sites in four US geographical regions was calculated using Pearson's correlation coefficients. Simple regression equations were used to calculate the significance of these correlation coefficients.

Results:
Of 9,231,909 CLI patients, 342,406 underwent amputation in the Medicare dataset. Amputation rates per 1000 CLI patients differed by region (South 40.42, Midwest 40.12, West 34.81, Northeast 31.14). There were 116 US vascular centers, selected by volume and expertise that participated in BEST-CLI with the following distribution: South (n = 30, 26%), Midwest (n = 26, 22%), West (n = 29, 25%), and Northeast (n = 31, 27%). There was a negative correlation between the number of amputations per 1000 for Medicare CLI patients with diabetes and PAD and the number of BEST-CLI sites in the region which trended toward significance (Pearson R= −0.61, P = 0.39).

Conclusions:
Amputation rate among Medicare CLI patients is inversely correlated with US BEST-CLI site distribution. Higher participation in clinical research, especially within large RCTs, may be a marker of optimal PAD management.
National Institutes of Health Career Development (K) Awards to Young Surgeons
Authors: Mesquita-Neto Jose Wilson , Dailey William , Weaver Donald , Datta Jashodeep , Macedo Francis I. , Merchant Nipun B. 
Published: July 2021

Objective:
To assess contemporary trends in the National Institutes of Health (NIH) Career Development (K) Awards within the Departments of Surgery and its impact on the likelihood of achieving independent R01 grants.

Background:
The NIH provides K-type Career Development Awards to nurture young clinicians toward a productive academic career, thereby maintaining a pipeline of physician-scientists. However, the impact of K awards on career trajectory of surgeons remains unclear.

Methods:
The NIH grant data was queried for all new K08/K23 grants awarded to Departments of Surgery (1999–2019). Principal Investigators’ data and grant-related information was obtained.

Results:
The NIH awarded 298 K08/23 surgical grants ($41,893,170) over the last 2 decades. Median budget increased from $116,370 to $167,508 (P<0.001). Of grantees, 83.2% were MDs, 15.1% MD/PhD, and 1.7% PhDs, with 25.2% being women. Principal Investigators’ were mostly practicing surgeons (91.1%) with fellowship training (82.4%) and young in their careers {4 [interquartile ranges (IQR) 4] years of experience}. Vascular surgery (15.9%), Complex General Surgical Oncology (15.1%), and Trauma/Critical Care (14.6%) were the most frequent specialties. Awards were associated with 3,336 publications [median 8/project (IQR 13)]. The majority of K grantees (77.2%) currently hold an academic faculty position. Only 32.2% of awardees received independent R01 grant funding, at a median of 5.5 years (IQR 5) after their K awards. Sex (P = 0.71), previous fellowship training (P = 0.63), type of surgical specialty (P = 0.72), or MD/PhD degree (P = 0.75) were not associated with increased likelihood of achieving a subsequent R01 award.

Conclusion:
Although the majority of K awardees maintain an academic career, only a limited number of grantees progress to obtain NIH R01 funding. Increased mentorship, financial support, and infrastructure are needed to facilitate career development awardees opportunities to enhance their ability to achieve independent funding.