bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of noninvasive scores for the diagnosis of advanced liver fibrosis in morbidly obese with nonalcoholic fatty liver disease
Authors: de Carli Maria AL , de Carli Luiz A. , Correa Marcos B. , Junqueira Gerson , Tovo Cristiane Valle , Coral Gabriela P.
Published: August 2019

Objectives

Liver fibrosis is one of the most important predictors of mortality related to nonalcoholic fatty liver disease (NAFLD). The use of noninvasive markers has the advantage of a simple and low-cost evaluation. The aim of this study was to evaluate the performance of six noninvasive scores for the diagnosis of advanced liver fibrosis in morbidly obese patients.

Material and methods

A retrospective study validation included 323 morbidly obese patients undergoing bariatric surgery. Advance fibrosis was defined as stage 3 and 4 (septal fibrosis or cirrhosis). Accuracy, sensitivity, specificity, positive (PPV) or negative (NPV) predictive value, and positive (PLR) or negative (NLR) likelihood ratio test of the following noninvasive liver fibrosis scores were evaluated: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR); AST to platelet ratio index (APRI); BARD; FIB4, NAFLD fibrosis score (NFS) and BAAT, which were compared with the histological findings of the intraoperative liver biopsy. The cutoff points established in the validation studies were used: AAR  >  1; APRL  >  0.98; BARD  ≥  2; FIB4  >  2.67; NFS  >  0.676 and BAAT  >  1.

Results

Twenty-nine patients (8.97%) presented advanced fibrosis. APRI presented the higher specificity (99.61%), PPV (85.71%), PLR (62.5) and accuracy (0.93). FIB4 was the second test in accuracy (0.9) and in PLR (10.53). BAAT presented the highest sensitivity (73.08%) and NPV (94.78%); NFS the lowest sensitivity (12,5%), and BARD the lowest accuracy (0.44).

Conclusion

APRI and FIB-4 were the tests with best performance to predict advanced fibrosis.
Safety of variceal band ligation in patients with cirrhosis and portal vein thrombosis treated with anticoagulant therapy: A retrospective study
Authors: Ponthus Simon , Spahr Laurent , Casini Alessandro , Berney Thierry , Frossard Jean-Louis , Majno Pietro , Elkrief Laure
Published: August 2019

Background and aims

Anticoagulant therapy has been recommended in patients with cirrhosis and portal vein thrombosis especially in candidates for liver transplantation. These patients are also likely to need variceal band ligation. This study aimed to assess the incidence of upper gastrointestinal bleeding after elective variceal band ligation in patients with cirrhosis receiving anticoagulant therapy for portal vein thrombosis.

Methods

Patients with cirrhosis and nontumoral portal vein thrombosis treated with anticoagulant therapy undergoing elective variceal band ligation were retrospectively included. We recorded upper gastrointestinal bleeding events occurring within two weeks after variceal band ligation. Postvariceal band ligation bleeding was defined as active bleeding on at least one site of previous ligation at endoscopy.

Results

Between 2014 and 2017, 32 patients with cirrhosis had scheduled variceal band ligations while on anticoagulant therapy [men 75%; median age 59 years; aetiology of cirrhosis: alcohol (50%), viral (34%), alcohol and viral (16%); and Child-Pugh score: A (31%), B (44%), and C (25%)]. Three (9%) patients presented postvariceal band ligation bleeding during the follow-up. None of these events led to haemorrhagic shock or death. Factors associated with postvariceal band ligation bleeding included variceal band ligation performed as secondary prophylaxis (P = 0.05) and previous decompensation of cirrhosis (P = 0.03).

Conclusion

In this small group of patients under anticoagulation therapy undergoing variceal band ligation, only a minority presented postendoscopic bleeding of minor importance. Nevertheless, particular attention should be paid to patients with previous decompensation of cirrhosis.
The 7-day mortality associated with an early warning score varies between age groups in a cohort of adult Danish emergency department patients
Authors: Dynesen Jacob , Skov Maj J. , Mackenhauer Julie , Jessen Marie K. , Liesanth Janet Y. , Ebdrup Lotte , Kirkegaard Hans
Published: August 2019

Introduction:

Early warning scores are designed for monitoring hospitalized patients and enable a timely response to deviating vital signs. The aim of this study was to examine whether 7-day mortality, associated with an initial early warning score, differs between age groups. Our hypothesis was that elderly patients are at greater risk of dying compared to a younger patient with a similar early warning score.

Methods:

This observational cohort study included adult emergency department patients from five hospitals in Denmark over three consecutive months in 2015. Logistic regression was used to examine the relationship between patients’ initial early warning scores category (0, 1–2, 3–4, 5–6, 7+) and 7-day mortality in different age groups (16–59 years, 60–79 years, 80+ years). Mortality rates in each early warning scores category are compared between the youngest patients (16–59 years, reference group) and the two older age groups (60–79 years and 80+ years).

Results:

A total of 19 123 emergency patients were included. The senior age groups (60–79 years and 80+ years) both displayed significantly higher 7-day mortality, in all early warning score categories, when compared to the youngest patients (16–59 years). The mortality difference between the youngest (16–59 years) and oldest age group (80+ years) remained significant in all early warning scores categories after adjusting for comorbidity.

Conclusion:

Our findings show that the oldest emergency department patients (80+ years) have a higher 7-day mortality compared to young patients (16–59 years) with a similar initial early warning score.
Persistently elevated early warning scores and lactate identifies patients at high risk of mortality in suspected sepsis
Authors: Hargreaves Duncan Sebastian , de Carvalho Joshua Lucas Jarman , Smith Laura , Picton Graham , Venn Richard , Hodgson Luke Eliot
Published: August 2019

Objective

In the UK, the National Early Warning Score (NEWS) is recommended as part of screening for suspicion of sepsis. Is a change in NEWS a better predictor of mortality than an isolated score when screening for suspicion of sepsis?.

Methods

A prospectively gathered cohort of 1233 adults brought in by ambulance to two UK nonspecialist hospitals, with suspicion of sepsis at emergency department (ED) triage (2015–2017) was analysed. Associations with 30-day mortality and ICU admission rate were compared between groups with an isolated NEWS ≥5 points prehospital and those with persistently elevated NEWS prehospital, in ED and at ward admission. The effect of adding the ED (venous or arterial) lactate was also assessed.

Results

Mortality increased if the NEWS persisted ≥5 at ED arrival 22.1% vs. 10.2% [odds ratio (OR) 2.5 (1.6–4.0); P < 0.001]. Adding an ED lactate ≥2 mmol/L was associated with an increase in mortality greater than for NEWS alone [32.2% vs. 13.3%, OR 3.1 (2.2–4.1); P < 0.001], and increased ICU admission [13.9% vs. 3.7%, OR 3.1 (2.2–4.3); P < 0.001]. If NEWS remained ≥5 at ward admission (predominantly within 4 h of ED arrival), mortality was 32.1% vs. 14.3%, [OR 2.8 (2.1–3.9); P < 0.001] and still higher if accompanied by an elevated ED lactate [42.1% vs. 16.4%, OR 3.7 (2.6–5.3); P < 0.001].

Conclusion

Persistently elevated NEWS, from prehospital through the ED to the time of ward admission, combined with an elevated ED lactate identifies patients with suspicion of sepsis at highest risk of in-hospital mortality.
New immunodeficiency syndromes that help us understand the IFN-mediated antiviral immune response
Authors: Jing Huie , Su Helen C.
Published: August 2019

Purpose of review

Studying primary immunodeficiencies (PIDs) provides insights into human antiviral immunity in the natural infectious environment. This review describes new PIDs with genetic defects that impair innate antiviral responses.

Recent findings

New genetic defects in the interferon (IFN) signaling pathway include IFNAR1 deficiency, which causes uncontrolled infections with measles-mumps-rubella or yellow fever vaccines, and possibly also cytomegalovirus (CMV); and IRF9 deficiency, which results in influenza virus susceptibility. Genetic defects in several pattern recognition receptors include MDA5 deficiency, which impairs viral RNA sensing and confers human rhinovirus susceptibility; RNA polymerase III haploinsufficiency, which impairs sensing of A:T-rich virus DNA and confers VZV susceptibility; and TLR3 deficiency, which causes HSV-1 encephalitis (HSE) or influenza virus pneumonitis. Defects in RNA metabolism, such as that caused by Debranching enzyme 1 deficiency, can cause virus meningoencephalitis. Finally, defects in host restriction factors for virus replication, such as in CIB1 deficiency, contribute to uncontrolled β-HPV infections.

Several new PIDs highlight the role of type I/III IFN signaling pathway, virus sensors, and host virus restriction factors in human antiviral immunity.
Nurses' Short Peripheral Catheter Flushing Practices: Implications for Patient Care, Nursing Education, and Policy
Authors: Norton Crystal B. , Alico Lauria Heather , Baker David , Hauser Paloma , Smith-Miller Cheryl A.
Published: August 2019

Nursing practice and institutional policies regarding short peripheral catheter (SPC) flushing vary. These variations result in a lack of understanding about the factors that influence nurses' SPC flushing practices and leave their effect on outcomes unexplored–information that could potentially enhance nurses' clinical education, institutional policy efforts, and patient care. Using a mixed-methods design, this study examined SPC flushing practices and outcomes among a cohort of medical-surgical nurses and explored their rationale for flushing. Trends were noted in the timing of flushes, and the factors that influenced nurses' SPC flushing practices included patient acuity, experience, and workload.
Improving Lower Extremity Bypass Patient Outcomes
Authors: Guthrie Meredith P. , Xhaja Anisa , Beck Adam W.
Published: August 2019

Background:

Care variation is associated with poor quality outcomes. Clinical practice guideline implementation is one method to decrease care variation and improve outcomes. Enhanced Recovery After Surgery (ERAS) is a clinical pathway encompassing best practices across the surgical patient care continuum.

Local Problem:

The lower extremity bypass (LEB) population had high length of stay (LOS), readmissions, and surgical site infections.

Methods:

A comprehensive and systematic project management process was utilized to implement the ERAS pathway in the LEB population with the help of an interdisciplinary team.

Interventions:

Clinical practice guidelines were created to integrate ERAS elements into the LEB population care continuum. Patient education was revised or created to ensure standardized information was communicated to patients from consultation through discharge and early follow-up.

Results:

Preliminary data show 4.57 mean LOS (n = 21) compared with the prior year's mean of 6.81 (n = 53).

Conclusion:

ERAS pathway introduction to the LEB population is suggestive of improved outcomes based on preliminary data.
Reducing Missed Appointments for Patients With HIV
Authors: Adams Judith Ann , Whiteman Kimberly , McGraw Samantha
Published: August 2019

Background:

High rates of missed appointments for routine HIV care are associated with unsuppressed viremia, increasing morbidity.

Local Problem:

The Clinic no-show rate ranged between 30% and 35%, and only 69% of patients were considered retained in care within a 24-month time frame.

Methods:

The Woodward Risk Prediction Tool was completed on all patients to stratify patient risk for missing the next appointment.

Interventions:

All patients were offered text message along with standard phone message appointment reminders, and patients who missed appointments were called within 24 hours to reschedule. Medium-risk patients received a previsit planning call to remove barriers to appointment attendance, and high-risk patients received a home visit from the peer navigator.

Results:

The project resulted in a 3.8% reduction rate in the overall no-show rate in the first 5 months of implementation. Using risk stratification and targeted interventions allowed valuable resources to be allocated where they were needed.
Maximizing the Benefit of Quality Improvement Activities
Authors: Wolak Erica , Overman Angela , Willis Beth , Hedges Christine , Spivak Glen F.
Published: August 2019

Background:

Many organizations struggle to efficiently and effectively spread improvement activities. This article presents findings from a model developed to standardize the sharing of innovative ideas within nursing at an academic medical center.

Problem:

Quality improvement activities were occurring in many nursing units but often did not spread beyond the originating unit. Challenges included variability in operationalizing initiatives, inconsistent understanding of project goals, and the lack of a dissemination process.

Approach:

The Spread of Innovations Model was developed to ensure structure and resources are in place to spread successful initiatives. The model uses Lean problem-solving and engages frontline nurses with senior leadership when spreading internally developed best practices.

Outcomes:

The model was piloted by spreading a catheter-associated urinary tract infection (CAUTI) prevention project throughout nursing. Using the model led to significantly decreased CAUTIs.

Conclusions:

Improvement efforts without a process for spreading can lead to inefficiencies and variable outcomes.
Modern-Day Relics of Psychiatry
Authors: Tripathi Samidha , Messias Erick , Spollen John , Salomon Ronald M.
Published: August 2019

Constantly shifting cultural views influence public perceptions of psychiatric diagnoses, sometimes accommodated by changes in diagnostic terminology. Evolving scientific knowledge of the era is at times used to justify and support mental illnesses. Too often, however, remasked nomenclatures fail to alter social stigma, in part because political arguments are used. Scientific validations of variant behaviors as symptoms with a pathologic status are unfortunately overshadowed. Examples of cultural bias effects on recurring diagnostic challenges illustrate a need for scientific validation. Renaming fails to improve stigma or diagnostic clarity. For example, neurasthenia, or nervous exhaustion, was attributed to fast-paced urban life through the late 1970s. Its symptoms are now largely, to no real advantage, retitled as chronic fatigue syndrome. Diagnoses like “hysteria” have evolved into histrionic personality disorder and somatoform spectrum disorders, although less as a result of demonic possession or a “wandering uterus.” Decriminalized and depathologized homosexuality remains a political football, where religious “sin” conceptualizations have not been displaced by studies documenting healthy adjustments among groups with diverse sexual orientations and preferences. Each of these remains severely socially stigmatized. The pseudoscience of “drapetomania,” once used to rationalize and pathologize a slave's freedom, is perceived now as psychiatric incarcerations of mentally healthy individuals, more commonly in totalitarian regimes—a politicization of stigma. Research reviews and funding efforts need to emphasize a sound basis for individuals caught in perpetuated diagnostic challenges, not remedied by simple shifts in nomenclature.
Determinants of Acquisition and Clearance of Human Papillomavirus Infection in Previously Unexposed Young Women
Authors: El-Zein Mariam , Ramanakumar Agnihotram V. , Naud Paulo , Roteli-Martins Cecilia M. , de Carvalho Newton S. , Colares de Borba Paola , Teixeira Julio C. , Moscicki Anna-Barbara , Harper Diane M. , Tyring Stephen K. , Ramjattan Brian , Dubin Gary , Franco Eduardo L.
Published: August 2019

Background

Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV.

Methods

Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000–September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time.

Results

On short-term follow-up (0–27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64–34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37–3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19–3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0–76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08–1.78) and black women (RR, 1.64; 95% CI, 1.04–2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43–0.98).

Conclusions

We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.
Pediatric Exposures Reported to the Toxicology Investigators Consortium, 2010–2015
Authors: Desai Neil M. , Mistry Rakesh D. , Brou Lina , Boehnke Maren E. , Lee Jeffrey S. , Wang George S. ,   on behalf of the Toxicology Investigators Consortium
Published: August 2019

Background and Objective

Poisoning is the leading cause of injury death in pediatric patients. Hospital and provider readiness, including pharmacy stocking, depends on reliable surveillance data describing local patterns of age-specific clinically significant exposures and the therapeutic modalities employed in their treatment. We aimed to characterize trends in clinically significant toxic exposures and their management.

Methods

We performed a retrospective review of patients 18 years or younger in the American College of Medical Toxicology's Toxicology Investigators Consortium (ToxIC) Registry, a self-reporting database completed by bedside consulting medical toxicologists. We reviewed cases from January 1, 2010, through December 31, 2015. In 2015, ToxIC included 101 health care facilities. Data collected included demographics, geographic region, encounter and exposure details, survival, and therapeutic modalities employed, including antidotes, antivenoms, gastric decontamination, enhanced elimination, hyperbaric oxygen therapy, and extracorporeal membrane oxygenation.

Results

From 2010 to 2015, 11,616 consults were recorded in ToxIC. Pediatric consultations increased from 934 (23.7%) in 2010 to 2425 (29.9%) in 2015 (P < 0.001). Exposures were most commonly reported in females (57.8%) and adolescents (59.4%). Intentional ingestions (55.5%) comprised the majority of cases. The most frequent agents of exposure were analgesics (21.0%). There were 38 deaths reported (0.9%). The antidote used most commonly was N-acetylcysteine (11.0%). Geographic variation was demonstrated in prevalence of envenomations and heavy metal exposures, their respective treatments, and overall use of decontamination.

Conclusions

Toxicology consultations for pediatric exposures increased from 2010 to 2015. Understanding which pediatric exposures require toxicologist management, the therapies most frequently employed, and geographical patterns is paramount to facility-level planning, pharmacy stocking, and provider education.
Management and Outcomes of Spontaneous Pneumomediastinum in Children
Authors: Noorbakhsh Kathleen A. , Williams Allison E. , Langham Joseph J.W. , Wu Liwen , Krafty Robert T. , Furtado Andre D. , Zuckerbraun Noel S. , Manole Mioara D.
Published: August 2019

Objectives

Management of spontaneous pneumomediastinum in the pediatric population is highly variable. There are limited data on the use of diagnostic tests and the need for admission. Our objectives were to characterize the management of pediatric spontaneous pneumomediastinum, determine the diagnostic yield of advanced imaging, and describe the patients' outcomes.

Methods

This is a retrospective cohort study of all patients presenting to a single tertiary pediatric emergency department between January 2008 and February 2015 diagnosed with pneumomediastinum. Patients were identified using 2 complementary strategies: International Classification of Diseases, Ninth Revision billing codes and a keyword search of the hospital radiology database.

Results

We identified 183 patients with spontaneous pneumomediastinum. The mean age was 12.8 ± 4.8 years. Diagnosis was established by chest radiograph (CXR) in 165 (90%) patients, chest computed tomography in 15 (8%), neck imaging in 2 (1%), and abdominal imaging in 1. After diagnosis, many patients underwent additional studies: repeat CXR (99, 54%), chest computed tomography (53, 29%), esophagram (45, 25%), and laryngoscopy (15, 8%). Seventy-eight percent of patients (n = 142) were admitted with a median length of stay of 27 hours (18.4–45.6 hours). Six patients returned to the emergency department within 96 hours for persistent chest pain; 2 were admitted, and 1 was found to have worsening pneumomediastinum on CXR. We performed a secondary analysis on 3 key subgroups: primary spontaneous pneumomediastinum (64, 35%), secondary gastrointestinal-associated pneumomediastinum (31, 17%), and secondary respiratory-associated pneumomediastinum (88, 48%). No patients in the study received an invasive intervention for pneumomediastinum. In all patients, further studies did not yield additional diagnostic information.

Conclusions

Our data suggest that patients with spontaneous pneumomediastinum who are clinically well appearing can be managed conservatively with clinical observation, avoiding exposure to radiation and invasive procedures.
A Pediatric Patient With Ascites, Proteinuria, and Thrombocytopenia
Authors: Simpson Samantha L. , Clarkston Kathryn , Wurster Ovalle Victoria M. , Reed Jennifer L.
Published: August 2019

A 7-year-old female patient presented to our pediatric emergency department with 5 days of fever, sore throat, abdominal pain, vomiting, headache, and 2 days of periorbital swelling. Her initial laboratory evaluation revealed a negative monospot test, neutropenia, atypical lymphocytosis, and thrombocytopenia in addition to transaminitis and proteinuria. An abdominal ultrasound obtained identified hepatosplenomegaly, moderate ascites, acalculous cholecystitis, and a distended appendix with periappendiceal fluid. She was admitted to gastroenterology for further management with antibiotics and surgery and hematology consults. Ultimately, Epstein-Barr virus polymerase chain reaction was positive. This case highlights an atypical presentation of Epstein-Barr virus and the collaborative approach to diagnosis.
A Clinical Vignette of Insidious Shoulder Pain and Weakness
Authors: Wong Ashley , Cleland Travis
Published: August 2019

We present a case of a 53-yr-old woman presenting with insidious shoulder pain and weakness. This case will go through the physical examination of the shoulder, a broad differential diagnosis, and analysis of appropriate imaging and tests to culminate in determining the final diagnosis. The objective of this clinical vignette was to highlight the importance of obtaining an extensive differential for shoulder pain and give readers a chance to critically analyze the case findings through electromyography interpretation, evaluating neurological signs and identifying key points in history taking. In addition, readers will also learn the evidence behind the available treatment options.
Patient-Reported Satisfaction and Quality of Life in Obese Patients: A Comparison between Microsurgical and Prosthetic Implant Recipients
Authors: Kamel George N. , Mehta Karan , Nash David , Jacobson Joshua , Berk Robin , Rizzo Amanda M. , Greige Nicolas , Benacquista Teresa , Garfein Evan S. , Weichman Katie E.
Published: August 2019

Background:

Patients undergoing autologous breast reconstruction have higher rates of patient-reported satisfaction compared to patients undergoing prosthetic reconstruction. Obesity has been shown to increase postoperative complications in both microsurgical and implant reconstructions. The authors evaluated the effects of microsurgical breast reconstruction and prosthetic breast reconstruction on patient-reported outcomes and quality of life in obese patients.

Methods:

A retrospective review of obese patients who underwent breast reconstruction from January of 2009 to December of 2017 was conducted. Patients were divided into two cohorts: microsurgical and two-stage tissue expander/implant-based reconstruction. BREAST-Q survey response, demographic information, complications, and need for revision procedures were analyzed.

Results:

One hundred fifty-five patients met the inclusion criteria: 75 (48.4 percent) underwent microsurgical breast reconstruction and 80 (51.6 percent) underwent implant-based reconstruction. Cohorts were similar in body mass index, mean mastectomy specimen weight, laterality, indication for surgery, smoking status, and postoperative complications. Microsurgical reconstruction patients were younger (49.0 years versus 53.0 years; p = 0.02) and more likely to have delayed reconstruction [n = 70 (64.2 percent) versus n = 0 (0.0 percent); p = 0.0001]. BREAST-Q responses showed that microsurgery patients were more satisfied with their breasts (Q-Score of 63.4 ± 6.9 versus 50.8 ± 12.8; p = 0.0001), overall outcome (Q-Score 70.5 ± 13.0 versus 60.3 ± 10.8; p = 0.0001), and chest physical well-being (Q-Score of 69.1 ± 10.9 versus 63.8 ± 8.2; p = 0.01).

Conclusions:

Microsurgical breast reconstruction in obese patients yields higher satisfaction with breasts, overall outcomes, and chest physical well-being than implant-based reconstruction. Despite increased postoperative complications associated with obesity, microsurgical breast reconstruction appears to be a good choice for women who understand its risks and benefits and choose to proceed with it.
Infections following Immediate Implant-Based Breast Reconstruction: A Case-Control Study over 11 Years
Authors: Banuelos Joseph , Sabbagh M. Diya , Roh Si-Gyun , Nguyen Minh-Doan T. , Lemaine Valerie , Tran Nho V. , Jacobson Steven R. , Boughey Judy C. , Jakub James W. , Hieken Tina J. , Degnim Amy C. , Mandrekar Jay , Berbari Elie , Sharaf Basel
Published: August 2019

Background:

Surgical-site infection after implant-based breast reconstruction adversely affects surgical outcomes and increases health care costs. This 11-year case-control study examines risk factors specific for surgical-site infection after immediate tissue expander/implant-based breast reconstruction.

Methods:

The authors performed a retrospective review to identify all consecutive patients with breast implant infections between 2006 and 2016. Patients who developed surgical-site infection after immediate tissue expander/implant-based breast reconstruction were included. Surgical-site infection was defined using the Centers for Disease Control and Prevention criteria; specifically, infections requiring hospital admission, intravenous antibiotics, or surgical intervention were included. The authors matched a control patient to each infection case by patient age and date of surgery. Patient demographics, medical comorbidities, and perioperative surgical variables were examined. Univariate and multivariable conditional logistic regression models were constructed.

Results:

A total of 270 breasts in 252 patients were evaluated. On multivariate analysis, patients with a higher body mass index (OR, 1.1 per 1 body mass index point increase; 95 percent CI, 1.0 to 1.2; p = 0.02), hypertension (OR, 6.5; 95 percent CI, 1.9 to 22.3; p = 0.002), neoadjuvant chemotherapy (OR, 2.6; 95 percent CI, 1.0 to 6.3; p = 0.04), axillary lymph node dissection (OR, 7.1; 95 percent CI, 1.7 to 29.2; p = 0.006), seroma formation (OR, 15.34; 95 percent CI, 3.7 to 62.5; p = 0.0001), and wound healing complications (OR, 23.91; 95 percent CI, 6.1 to 93.4; p < 0.0001) were significantly associated with surgical-site infection.

Conclusions:

Women with obesity, women with hypertension, and those treated with neoadjuvant chemotherapy are at increased risk of surgical-site infection. Further risks are also associated with postoperative seroma and wound complications. This may help patient selection and counseling, adjusted based on risk factors regarding complications of immediate implant-based breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Systematic Review of the Impact of Acellular Dermal Matrix on Aesthetics and Patient Satisfaction in Tissue Expander-to-Implant Breast Reconstructions
Authors: DeLong Michael R. , Tandon Vickram J. , Farajzadeh Matthew , Berlin Nicholas L. , MacEachern Mark P. , Rudkin George H. , Da Lio Andrew L. , Cederna Paul S.
Published: August 2019

Background:

Acellular dermal matrix is used in most postmastectomy implant-based breast reconstructions in the United States. It is believed to be safe, despite a slightly increased complication rate. Although never established in a unifying study, the primary advantage of acellular dermal matrix is believed to be an enhanced aesthetic result, thus justifying the added expense. The purpose of this study was to assess the aesthetic benefits of acellular dermal matrix in expander-to-implant breast reconstruction.

Methods:

A systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was performed including all original studies examining aesthetic outcomes of expander-to-implant breast reconstructions with acellular dermal matrix compared to muscular coverage. Direct-to-implant and prepectoral studies were excluded from the evaluation. The results were aggregated and reported as a summary.

Results:

Among 883 studies identified, 49 full-text articles were reviewed and nine articles ultimately met inclusion criteria. All nine studies were not randomized. Of these, three articles (1448 total patients) evaluated reconstruction aesthetic outcomes by patient satisfaction, whereas six articles evaluated the aesthetic outcomes by external observer (504 total patients). None of the articles evaluating patient satisfaction reported a difference between acellular dermal matrix and muscular reconstruction. Five of the six articles using objective outcomes demonstrated significant improvement in aesthetic outcome in the acellular dermal matrix group.

Conclusions:

Although little evidence exists evaluating the aesthetic benefits of acellular dermal matrix for expander-to-implant breast reconstruction, the data suggest that objective observers consider acellular dermal matrix–assisted expander-to-implant breast reconstructions aesthetically superior to reconstruction with only muscular coverage, but patients appear to be equally satisfied with both reconstructive options.
Preliminary Results Supporting the Bacterial Hypothesis in Red Breast Syndrome following Postmastectomy Acellular Dermal Matrix– and Implant-Based Reconstructions
Authors: Danino Michel A. , El Khatib Arij M. , Doucet Ophélie , Dao Lan , Efanov Johnny I. , Bou-Merhi Joseph S. , Iliescu-Nelea Monica
Published: August 2019

Acellular dermal matrices have become a mandatory tool in reconstructive breast surgery. Since their introduction, they have been considered to be nonreactive and nonimmunogenic scaffolds. However, some patients who undergo implant-based breast reconstruction with acellular dermal matrices develop postoperative cutaneous erythema overlying their matrices, a condition commonly referred to as red breast syndrome. The aim of this study was to gain a better understanding of this phenomenon. An analysis was conducted on consecutive patients who underwent acellular dermal matrix– and implant-based breast reconstructions and developed red breast syndrome that was treated surgically between April of 2017 and June of 2018 at the authors’ institution. During surgery, 1-cm2 specimens of acellular dermal matrix were sampled and analyzed by scanning electron microscopy. Observations were charted to score and record the presence and thickness of biofilm, and for identification of bacteria. These measurements were performed using Adobe Photoshop CS6 Extended software. Six postmastectomy breast reconstruction patients were included, all with AlloDerm Ready-to-Use–based reconstructions. All specimens were colonized by various bacteria ranging from Gram-negative bacilli to Gram-positive microorganisms. Biofilm was present in all studied specimens. The cause of skin erythema overlying acellular dermal matrix grafts, and the so-called red breast syndrome, may be related to contamination with various bacteria. Although contamination was omnipresent in analyzed samples, its clinical significance is variable. Even if acellular dermal matrix–based reconstructions are salvaged, this could come at the price of chronic local inflammation.
Morphological Characteristics and Individual Differences of Palatal Rugae
Authors: Gezer Rabia , Deniz Mustafa , Uslu Ayşe Imge
Published: August 2019

Purpose:

This study aims to determine the number, symmetry, shape and individual characteristic of palatal rugae.

Methods:

In our study, we performed on subjects ages 16 to 57 (23.01 ± 7.12), ranging from a total of 230 (108 female and 122 male). Alginant impression material from each took dimensions of the upper jaw. Then casts were obtained by pouring hard casts. The shapes, lengths, and directions of rugae measured on these casts. The palatine photos were taken by using a mobile phone-Samsung brand with 12 MP camera and an orthodontic mirror. The casts and photographs were selected at random belonging to 100 subjects. Selected at random 10 photographs were matched among 100 casts. The ratios of correct matches were determined.

Results:

In our study, the total number of palatal rugae was found as 9.49 ± 1.87 in females and 9.42 ± 1.92 in males. The most detected rugae pattern was wavy on both females and males. The most rarely seen rugae pattern was converged in the males and circular in the females. Regarding lengths of rugae, the most detected rugae pattern was the primary one. Regarding the direction of rugae pattern, positive-sided one was the most dominant in both genders. We determined the ratio of matching the casts belonging to Palatine with the photos as 63.5%. The number of rugae aged under 18 and above 41 was found to be statistically significant (P = 0.003), but the number of curved and positive-sided rugae in older ages was not found to be statistically significant.

Conclusions:

Compared with data from earlier studies, the shapes, length, and direction of palatal rugae were seen specific in every individual, and it was seen to have discriminating characteristics among different populations. The possible differences in individual specific palatal rugae require further studies involving larger samples.
Variability of Consecutive Lumbar Puncture Opening Pressures
Authors: Kilgore Khin P. , Bhatti M. Tariq , Cutsforth-Gregory Jeremy K. , Hodge David O. , Chen John J.
Published: August 2019

Background:

Lumbar puncture (LP) opening pressures (OPs) are known to fluctuate based on diurnal, environmental, and pathologic conditions. Despite their dynamic nature, single OPs are often deemed sufficient for diagnosis of elevated intracranial pressures (ICPs) in nonspecialists' hands. The purpose of this study was to determine the variability of consecutive LP OPs at a large referral center to determine the potential range of variability for a given LP OP.

Methods:

In this retrospective cohort study, medical records of all patients seen at Mayo Clinic, Rochester, MN, from January 1, 2001, through June 1, 2016, were screened for ≥2 LP OPs within 30 days of each other. Patients with pathologic conditions known to influence ICP were excluded.

Results:

There were 148 eligible patients (39.2% female) with mean age of 63.5 ± 15.5 years and mean body mass index (BMI) 28.0 ± 6.0. The LPs were a mean of 10 ± 9 days apart. Mean OP for the first and second LP was 149 ± 51 mm H2O and 148 ± 48 mm H2O (P = 0.78), respectively, with a mean difference of 1 mm H2O, providing an overall coefficient of repeatability (CR) of 86.4 between consecutive LPs. There was a significant correlation between initial OP and BMI (r = 0.39, P < 0.001). OP >200 mm H2O had a significantly higher CR of 111.4, compared to OP <200 mm H2O, with CR 74.6 (P = 0.006). CRs were also higher for patients with diagnoses of headache (P = 0.002) or anxiety (P = 0.03).

Conclusions:

Higher initial LP OP, headache, and anxiety were associated with greater variability on subsequent LPs. OPs that are not consistent with the patients' clinical signs and symptoms should therefore be interpreted with caution.
Motif elucidation in ChIP-seq datasets with a knockout control
Authors: Denisko Danielle , Viner Coby , Hoffman Michael M.
Published: August 2019

Chromatin immunoprecipitation-sequencing (ChIP-seq) is widely used to find transcription factor binding sites, but suffers from various sources of noise. Knocking out the target factor mitigates noise by acting as a negative control. Paired wild-type and knockout experiments can generate improved motifs but require optimal differential analysis. We introduce peaKO—a computational method to automatically optimize motif analyses with knockout controls, which we compare to two other methods. PeaKO often improves elucidation of the target factor and highlights the benefits of knockout controls, which far outperform input controls. It is freely available at https://peako.hoffmanlab.org.
Shielding working memory from distraction is more effortful than flexible updating
Authors: Papadopetraki Danae , Froböse Monja I. , Westbrook Andrew , Zandbelt Bram B. , Cools Roshan
Published: August 2019

Exerting cognitive control is known to carry a subjective effort cost and people are generally biased to avoid it. Recent theorizing suggests that the cost of cognitive effort serves as a motivational signal to bias people away from excessive focusing and towards more cognitive flexibility. We asked whether the effort cost of stable distractor resistance is higher than that of flexible updating of working memory representations. We tested this prediction by using (i) a delayed response paradigm in which we manipulate demands for distractor resistance and flexible updating, as well as (ii) a subsequent cognitive effort discounting paradigm that allows us to quantify subjective effort costs. We demonstrate, in two different samples (28 and 62 participants) that participants discount tasks both high in distractor resistance and flexible updating when comparing with taking a break. As predicted, when directly contrasting distractor resistance and flexible updating the subjective cost of performing a task requiring distractor resistance is higher than that requiring flexible updating.
High-performance chemical and light-inducible recombinases in mammalian cells and mice
Authors: Weinberg Benjamin H. , Cho Jang Hwan , Agarwal Yash , Pham N. T. Hang , Caraballo Leidy D. , Walkosz Maciej , Ortega Charina , Trexler Micaela , Tague Nathan , Law Billy , Benman William K. J. , Letendre Justin , Beal Jacob , Wong Wilson W.
Published: August 2019

Site-specific DNA recombinases are some of the most powerful genome engineering tools in biology. Chemical and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, the availability of inducible recombinases is scarce due to the challenge of engineering high performance systems with low basal activity and sufficient dynamic range. This limitation constrains the sophistication of genetic circuits and animal models that can be created. To expand the number of available inducible recombinases, here we present a library of >20 orthogonal split recombinases that can be inducibly dimerized and activated by various small molecules, light, and temperature in mammalian cells and mice.

Furthermore, we have engineered inducible split Cre systems with better performance than existing inducible Cre systems. Using our orthogonal inducible recombinases, we created a “genetic switchboard” that can independently regulate the expression of 3 different cytokines in the same cell. To demonstrate novel capability with our split recombinases, we created a tripartite inducible Flp and a 4-Input AND gate. We have performed extensive quantitative characterization of the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs in terms of signal-to-noise ratio (SNR). To facilitate sharing of this set of reagents, we have deposited our library to Addgene. This library thus significantly expands capabilities for precise and multiplexed mammalian gene expression control.
Somatic Mutations in Clonally Expanded T-lymphocytes in Patients with Chronic Graft-Versus-Host Disease
Authors: Park Giljun , Kim Daehong , Huuhtanen Jani , Lundgren Sofie , Khajuria Rajiv K. , Hurtado Ana M. , Muñoz-Calleja Cecilia , Cardeñoso Laura , Gómez-García de Soria Valle , Chen-Liang Tzu Hua , Eldfors Samuli , Ellonen Pekka , Hannula Sari , Bruck Oscar , Kreutzman Anna , Salmenniemi Urpu , Lönnberg Tapio , Jerez Andres , Itälä-Remes Maija , Keränen Mikko A. I. , Mustjoki Satu
Published: August 2019

Graft-versus-host-disease (GvHD) is the main complication of allogeneic hematopoietic stem cell transplantation. GvHD patients have aberrant T cell expansions, which are thought to drive pathological immune activation. Here we report mechanistic insights that somatic mutations may account for persistent clonal T cell expansions in chronic GvHD (cGvHD). In an index patient suffering from cGVHD, we discovered persisting somaticMTOR,NFKB2, andTLR2mutations in an expanded CD4+ T clone. In the screening cohort (n=135), theMTOR P2229Rkinase domain mutation was detected in two additional cGvHD patients, but not in controls. Functional analysis of the discoveredMTORmutation indicated a gain-of-function alteration in translational regulation yielding in up-regulation of phosphorylated S6K1, S6, and AKT. Paired single-cell RNA and T cell receptor alpha and beta sequencing strongly supported cytotoxicity and abnormal proliferation of the clonally expanded CD4+ T cells. Real-time impedance measurements indicated increased cytotoxicity of mutated CD4 + T cells against the patient’s fibroblasts. High throughput drug-sensitivity testing suggested that mutations induce resistance to mTOR inhibitors but increase sensitivity for HSP90 inhibitors. Our findings suggest a novel explanation for the aberrant, persistent T cell activation in cGvHD, and pave the way for novel targeted therapies.
Improved motion correction of submillimetre 7T fMRI time series with boundary-based registration (BBR)
Authors: Huang Pei , Carlin Johan D. , Henson Richard N. , Correia Marta M.
Published: August 2019

Ultra-high field functional magnetic resonance imaging (fMRI) has allowed us to acquire images with submillimetre voxels. However, in order to interpret the data clearly, we need to accurately correct head motion and the resultant distortions. Here, we present a novel application of Boundary Based Registration (BBR) to realign functional Magnetic Resonance Imaging (fMRI) data and evaluate its effectiveness on a set of 7T submillimetre data, as well as millimetre 3T data for comparison. BBR utilizes the boundary information from high contrast present in structural data to drive registration of functional data to the structural data. In our application, we realign each functional volume individually to the structural data, effectively realigning them to each other. In addition, this realignment method removes the need for a secondary aligning of functional data to structural data for purposes such as laminar segmentation or registration to data from other scanners. We demonstrate that BBR realignment outperforms standard realignment methods across a variety of data analysis methods. Further analysis shows that this benefit is an inherent property of the BBR cost function and not due to the difference in target volume. Our results show that BBR realignment is able to accurately correct head motion in 7T data and can be utilized in preprocessing pipelines to improve the quality of 7T data.
Heart Disease in a Mutant Mouse Model of Spontaneous Eosinophilic Myocarditis Maps to Three Highly Significant Loci
Authors: Zimmermann Nives , Gibbons William J. , Homan Shelli M. , Prows Daniel R.
Published: August 2019

Background

Heart disease (HD) is the major cause of morbidity and mortality in patients with hypereosinophilic diseases. Due to a lack of adequate animal models, our understanding of the pathophysiology of eosinophil-mediated diseases with heart complications is limited. We have discovered a mouse mutant, now maintained on an A/J inbred background, that spontaneously develops hypereosinophilia in multiple organs. Cellular infiltration into the heart causes an eosinophilic myocarditis, with affected mice of the mutant line (i.e.,A/JHD) demonstrating extensive myocardial damage and remodeling that leads to HD and premature death, usually by 15-weeks old. Maintaining the A/JHDline for many generations established that the HD trait was heritable and implied the mode of inheritance was not too complex. Backcross and intercross populations generated from mating A/JHDmales with females from four different inbred strains produced recombinant populations with highly variable rates of affected offspring, ranging from none in C57BL/6J intercrosses, to a few mice with HD using 129S1/SvImJ intercrosses and C57BL/6J backcrosses, but nearly 8% of intercrosses and >17% of backcrosses from SJL/J related populations developed HD. Linkage analyses of these SJL/J derived recombinants identified three highly significant loci: a recessive locus mapping to distal chromosome 5 (LOD=4.88; namedEmhd1foreosinophilicmyocarditis toheartdisease-1); and two dominant variants mapping to chromosome 17, one (Emhd2; LOD=7.51) proximal to the major histocompatibility complex, and a second (Emhd3; LOD=6.89) that includes the major histocompatibility region. Haplotype analysis identified the specific crossovers that defined theEmhd1(2.65Mb),Emhd2(8.46Mb) andEmhd3(14.59Mb) intervals. These results indicate the HD trait in this mutant mouse model of eosinophilic myocarditis is oligogenic with reduced penetrance, due to multiple segregating variants and possibly additional genetic or nongenetic factors. The A/JHDmouse model represents a unique and valuable tool to understand the interplay of causal factors that underlie the pathology of this newly discovered eosinophil-associated disease with cardiac complications.