bluuebunny/crossref_metadata_2025 huggingface dataset:
Provision of STD Services in Community Settings After the Loss and Return of State Funding to Support Service Provision: Observations From Select Providers in Massachusetts, 2010 and 2013
Authors: Loosier Penny S. , Carter Marion W. , Hsu Katherine K. , Doshi Sonal , Peterson Maddox Brandy L. , Kroeger Karen , Cranston Kevin
Published: November 2018

Context:

In 2008, the $1.2 M sexually transmitted disease (STD) services line item supporting STD clinical services by the Massachusetts Department of Public Health was eliminated, forcing the cessation of all state-supported STD service delivery.

Objective:

To determine the impact on community provision of STD services after the elimination of state funds supporting STD service provision.

Design and Setting:

Rapid ethnographic assessments were conducted in May 2010 and September 2013 to better understand the impact of budget cuts on STD services in Massachusetts. The rapid ethnographic assessment teams identified key informants through Massachusetts's STD and human immunodeficiency virus programs.

Participants:

Fifty providers/clinic administrators in 19 sites (15 unique) participated in a semistructured interview (community health centers [n = 10; 53%], hospitals [n = 4; 21%], and other clinical settings [n = 5; 26%]).

Results:

Results clustered under 3 themes: financial stability of agencies/clinics, the role insurance played in the provision of STD care, and perceived clinic capacity to offer appropriate STD services. Clinics faced hard choices about whether to provide care to patients or refer elsewhere patients who were unable or unwilling to use insurance. Clinics that decided to see patients regardless of ability to pay often found themselves absorbing costs that were then passed along to their parent agency; the difficulty and financial strain incurred by a clinic's parent agency by providing STD services without support by state grant dollars emerged as a primary concern. Meeting patient demand with staff with appropriate training and expertise remained a concern.

Conclusions:

Provision of public health by private health care providers may increase concern among some community provision sites about the sustainability of service provision absent external funds, either from the state or from the third-party billing. Resource constraints may be felt across clinic operations. Provision of public health in the for-profit health system involves close consideration of resources, including those: leveraged, used to provide uncompensated care, or available for collection through third-party billing.
Optimal Muscle Selection for OnabotulinumtoxinA Injections in Poststroke Lower-Limb Spasticity
Authors: Esquenazi Alberto , Wein Theodore H. , Ward Anthony B. , Geis Carolyn , Liu Chengcheng , Dimitrova Rozalina
Published: November 2018

Objective

The aim of the study was to identify optimal muscle selection patterns for onabotulinumtoxinA treatment of poststroke lower-limb spasticity.

Design

Adults with poststroke lower-limb spasticity (ankle Modified Ashworth Scale ≥3) were randomized to onabotulinumtoxinA (300 U, mandatory ankle plantar flexors; ≤100 U, optional lower-limb muscles) or placebo. Post hoc analysis assessed the impact of muscle selection patterns on ankle Modified Ashworth Scale and physician-assessed Clinical Global Impression of Change based on change from baseline to average of weeks 4/6 versus placebo.

Results

Among 468 patients randomized, onabotulinumtoxinA improved ankle Modified Ashworth Scale (−0.81 vs −0.61, P = 0.01) and Clinical Global Impression of Change (0.86 vs 0.65, P = 0.012) versus placebo. Injection of mandatory muscles alone was not sufficient in improving ankle Modified Ashworth Scale (P = 0.255) or Clinical Global Impression of Change (P = 0.576) versus placebo but was adequate 24 mos or less after stroke (Modified Ashworth Scale, −1.13 vs −0.62, P = 0.019; Clinical Global Impression of Change, 1.24 vs 0.68, P = 0.006). Additional injections into toe muscles (flexor digitorum longus, flexor hallucis longus) improved ankle Modified Ashworth Scale (−0.98 vs −0.52, P = 0.002) and Clinical Global Impression of Change (0.80 vs 0.38, P = 0.023) versus placebo regardless of time since stroke. OnabotulinumtoxinA was well tolerated, with no new safety findings.

Conclusions

Post hoc analyses suggested additional injections of onabotulinumtoxinA into toe flexors improved ankle Modified Ashworth Scale and Clinical Global Impression of Change scores versus mandatory muscles alone overall and with treatment initiation more than 24 mos after stroke.
Assessing Age as a Risk Factor for Complications in Autologous Breast Reconstruction
Authors: Torabi Radbeh , Stalder Mark W. , Tessler Oren , Bartow Matthew J. , Lam Jonathan , Patterson Charles , Wise M. Whitten , Dupin Charles L. , St. Hilaire Hugo
Published: November 2018

Background:

Breast cancer is primarily a diagnosis of older women. Many patients seeking breast reconstruction are elderly women (aged 65 years or older). However, many surgeons anecdotally believe that surgery in elderly patients is inherently dangerous, or at least prone to more complications.

Methods:

The authors conducted a retrospective cohort study composed of chart review of all deep inferior epigastric perforator flap breast reconstruction patients at a single institution divided into an elderly cohort (65 years or older) and a nonelderly cohort (younger than 65 years). Cohort was the primary predictor variable. Demographic and comorbidity data were secondary predictor variables. Primary outcomes were complete flap loss, partial flap loss, or need for flap reexploration. Secondary outcomes such as wound healing problems, seroma, and others were also assessed.

Results:

There were 285 flaps in the nonelderly cohort and 54 flaps in the elderly cohort. The elderly cohort had higher rates of diabetes, hypertension, and hyperlipidemia. Chi-square analysis showed no significant differences in primary outcomes between the two cohorts. Breast wound dehiscence was significantly higher in the elderly cohort (p < 0.01). On logistic regression, being elderly was seen as a significant risk factor for complete flap loss (OR, 10.92; 95 percent CI, 0.97 to 122.67; p = 0.05). The overall success rate for the nonelderly cohort was 99.6 percent, whereas the success rate for the nonelderly cohort was 96.3 percent.

Conclusions:

Elderly women desire breast reconstruction. Free flap breast reconstruction is a viable and safe procedure in these patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Smoking and Postoperative Complications in Plastic and General Surgical Procedures: A Propensity Score–Matched Analysis of 294,903 Patients from the National Surgical Quality Improvement Program Database from 2005 to 2014
Authors: Fu Rose H. , Toyoda Yoshiko , Li Lu , Baser Onur , Rohde Christine H. , Otterburn David M.
Published: November 2018

Background:

Smoking as a risk factor for postoperative complications is more relevant in elective plastic surgery than in urgent general surgery. From 2005 to 2014, the U.S. smoking rate decreased from 20.9 percent to 16.8 percent. This study compares smoking prevalence in plastic and general surgery patients, and postoperative complications when smoking is isolated as an independent risk factor.

Methods:

The American College of Surgeons National Surgical Quality Improvement Program database was used to examine smoking and 30-day postoperative complications for plastic and general surgery procedures. Patients were propensity score matched for demographics and comorbidities.

Results:

The authors examined 294,903 patients from 2005 to 2014. The smoking rates in general surgery mirrored national trends (R = −0.85), whereas those in plastic surgery were significantly lower (p < 0.01). General surgery smokers were more comorbid and experienced more superficial surgical-site infections, pulmonary embolism, and myocardial infarction (p < 0.02) than general surgery nonsmokers. Plastic surgery smokers were not significantly different than plastic surgery nonsmokers. The general surgery cohort was more comorbid than the plastic surgery cohort. All smokers had increased dehiscence, deep surgical-site infection, and reoperation (p ≤ 0.01). Plastic surgery patients suffered more wound complications and bleeding than general surgery patients (p < 0.01).

Conclusions:

This is the first propensity score–matched, large-scale database analysis isolating smoking as a risk factor for postoperative complications. Smoking may have different risk factor profiles for postoperative complications in plastic surgical versus general surgical patient populations, emphasizing the need for caution when generalizing general surgical evidence for use in the plastic surgical population.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
The Prognostic Value of 18F-FDG Uptake in the Supraclavicular Lymph Node (N3c) on PET/CT in Patients With Locally Advanced Breast Cancer With Clinical N3c
Authors: Lee Suk Hyun , Kim Sung Hoon , Park Hyung Seok , Kim Joo Heung , Kim Dongwoo , Cho Hojin , Yun Mijin
Published: November 2018

Purpose

We investigated the prognostic value of 18F-FDG uptake in the supraclavicular lymph node (SCLN) on PET/CT in breast cancer patients with clinical ipsilateral SCLN metastasis (cN3c).

Methods

Fifty-five female patients with initial 18F-FDG PET/CT were treated with curative intent. For semiquantitative analysis, the SUVmax of the primary tumor, axillary lymph node, and SCLN were normalized by the SUVmean of the liver (defined as SUVR-tumor, SUVR–axillary lymph node, and SUVR-SCLN, respectively). Cox proportional hazards models were used to predict disease-free survival (DFS) and overall survival (OS). Differences in DFS and OS were assessed by Kaplan-Meier analysis.

Results

Twenty-three patients (41.8%) experienced recurrence, and 13 (23.6%) died during follow-up (median, 70.0 months; range, 6–128 months). In multivariate analysis, SUVR-tumor greater than 3.26 (hazards ratio, 7.26; 95% confidence interval, 1.58–33.31; P = 0.01) and SUVR-SCLN greater than 1.05 (hazards ratio, 8.47; 95% confidence interval, 1.09–65.87; P = 0.04) were prognostic for OS. No clinicopathologic or PET/CT parameters were prognostic for DFS. The patients were divided into 3 groups: group 1 (n = 11, SUVR-tumor ≤3.26 and SUVR-SCLN ≤1.05); group 2 (n = 27, SUVR-tumor >3.26 or SUVR-SCLN >1.05); and group 3 (n = 17, SUVR-tumor >3.26 and SUVR-SCLN >1.05). The 5-year OS rates were 100% in group 1, 85.2% in group 2, and 51.0% in group 3. Group 3 showed worse prognosis than group 1 (P < 0.01) and group 2 (P < 0.01).

Conclusions

In addition to SUVR-tumor, SUVR-SCLN seemed to play an important role in selecting patients with the worst prognosis.
Prognostic Value and Clinical Impact of Pretreatment FDG PET in Pulmonary Lymphoepithelioma-Like Carcinoma
Authors: Su Tzu-Pei , Ho Kung-Chu , Wang Chih-Wei , Lin Chun-Yu , Liu Chien-Ying , Yang Cheng-Ta , Yen Tzu-Chen
Published: November 2018

Purpose

Compared with other forms of non–small cell lung cancer, pulmonary lymphoepithelioma-like carcinoma (LELC) is rarer and portends better outcomes. We sought to investigate the prognostic role and clinical impact of pretreatment 18F-FDG PET in pulmonary LELC.

Methods

A total of 71 patients with pulmonary LELC were identified through a retrospective review of clinical records. Of them, 41 underwent 18F-FDG PET for primary staging. Outcomes were assessed using the Kaplan-Meier method and Cox regression models with a forward stepwise selection procedure. Staging changes served as the main outcome measure for assessing the impact of 18F-FDG PET. For the purpose of analyses, all patients were restaged according the American Joint Committee on Cancer Staging Manual eighth edition.

Results

Stage and pretreatment 18F-FDG PET were significantly independent predictors of overall survival (OS) on multivariate analysis. Five-year OS rates for patients with stages I–II, III–IVA, and IVB were 92.3%, 70.4%, and 20.0%, respectively. The use of 18F-FDG PET for staging purposes was associated with a better OS (P = 0.003). Specifically, the 5-year OS rates for patients who were staged with and without 18F-FDG PET were 85.4% and 49.7%, respectively (P = 0.012). 18F-FDG PET resulted in a disease upstage in 28.6% of patients with CT-defined stages III–IVA; of them, 14.3% were upstaged to IVB disease.

Conclusions

The American Joint Committee on Cancer eighth edition stage and pretreatment 18F-FDG PET were independent prognostic factors for OS in patients with pulmonary LELC. 18F-FDG PET imaging resulted in a better disease staging with a corresponding optimization of therapeutic interventions, which ultimately improved survival outcomes.
Telbivudine-Induced Myopathy Incidentally Detected by FDG PET/CT Imaging in a Patient With History of Hepatocellular Carcinoma
Authors: Zou Sijuan , Cheng Zhaoting , Song Shuang , Zhu Dongling , Zhu Xiaohua
Published: November 2018

Myopathy is an adverse effect of telbivudine. We describe a case of telbivudine-induced myopathy visualized on FDG PET/CT in a 75-year-old man with history of chronic HBV infection and hepatocellular carcinoma. FDG PET/CT images demonstrate no abnormal uptake characteristic of hypermetabolic malignancy. However, intense hypermetabolic activity in muscles of the abdominal wall was noted. Three months after telbivudine withdrawal, a second FDG PET/CT showed normal muscle activity in the abdominal wall.
New Model for Predicting Malignancy in Patients With Intraductal Papillary Mucinous Neoplasm
Authors: Shimizu Yasuhiro , Hijioka Susumu , Hirono Seiko , Kin Toshifumi , Ohtsuka Takao , Kanno Atsushi , Koshita Shinsuke , Hanada Keiji , Kitano Masayuki , Inoue Hiroyuki , Itoi Takao , Ueki Toshiharu , Matsuo Keitaro , Yanagisawa Akio , Yamaue Hiroki , Sugiyama Masanori , Okazaki Kazuichi
Published: November 2018

Objective:

To create a simple, objective model to predict the presence of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN), which can be easily applied in daily practice and, importantly, adopted for any lesion types.

Background:

No predictive model for malignant IPMN has been widely applied in clinical practice.

Methods:

The clinical details of 466 patients with IPMN who underwent pancreatic resection at 3 hospitals were retrospectively analyzed for model development. Then, the model was validated in 664 surgically resected patients at 8 hospitals in Japan.

In the preoperative examination, endoscopic ultrasonography (EUS) was considered to be essential to observe mural nodules in both the model development and external validation sets. Malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma.

Results:

Of the 466 patients, 258 (55%) had malignant IPMNs (158 high-grade dysplasia, 100 invasive carcinoma), and 208 (45%) had benign IPMNs. Logistic regression analysis resulted in 3 variables (mural nodule size, main pancreatic duct diameter, and cyst size) being selected to construct the model. The area under the receiver operating characteristic curve (AUC) for the model was 0.763. In external validation sets, the pathological diagnosis was malignant and benign IPMN in 351 (53%) and 313 (47%) cases, respectively. For the external validation, the malignancy prediction ability of the model corresponded to an AUC of 0.725.

Conclusion:

This predictive model provides important information for physicians and patients in assessing an individual's risk for malignancy and may help to identify patients who need surgery.
Negative Pressure Wound Therapy Use to Decrease Surgical Nosocomial Events in Colorectal Resections (NEPTUNE)
Authors: Murphy Patrick B. , Knowles Sarah , Chadi Sami A. , Vogt Kelly , Brackstone Muriel , Koughnett Julie Ann Van , Ott Michael C.
Published: November 2018

Objective:

Determine if negative pressure wound therapy (NPWT) reduces surgical site infection (SSI) in primarily closed incision after open and laparoscopic-converted colorectal surgery.

Background:

SSIs after colorectal surgery are a common cause of morbidity. The prophylactic effect of NPWT has not been established. We undertook this study to evaluate if, among patients undergoing open colorectal resection, NPWT, as compared with standard postoperative dressings, is associated with a reduction in the rate of postoperative SSI.

Methods:

In a randomized, controlled trial, 300 patients undergoing elective open colorectal surgery were assigned to receive prophylactic NPWT or standard gauze dressing. The primary end-point was 30-day SSI, as assessed by wound care experts blinded to treatment arm. Secondary outcomes included length of stay. Statistical analysis was performed on an intention-to-treat basis. A priori subgroup analysis was planned for patients who received a stoma at the time of initial operation.

Results:

The incidence of SSI at 30-days postoperatively was no different between experimental and control groups (32% vs 34% respectively, P = 0.68). Length of stay was also no different at a median of 7 days (IQR 5) for both groups. Among patients receiving a stoma, there was also no difference in SSI between the experimental and control groups (38% vs 33% respectively, P = 0.66).

Conclusions:

Prophylactic use of NPWT on primarily closed incisions after open colorectal surgery was not associated with a decrease in SSI rate when compared with standard gauze dressing.

Trial Registration Number:

Clinicaltrials.gov (NCT02007018)
Is it time to measure complications from the National Trauma Data Bank? A longitudinal analysis of recent reporting trends
Authors: Robles Anamaria J. , Conroy Amanda S. , Cohen Mitchell J. , Callcut Rachael A.
Published: November 2018

BACKGROUND

Payers have approached select complications as never events, yet there is rationale that achieving a zero incidence of these events is impractical. Prior 2005 National Trauma Data Bank (NTDB) analysis showed high rates (37%) of centers reporting no complications data making national estimates for determining standardized complication rates difficult to ascertain.

METHODS

The 2008–2012 NTDB National Sample Program nationally weighted files were used to calculate yearly national estimates. Rates were compared in all centers and those reporting complications data. Hospital characteristics were compared using Student t test. In 2011, an other complication category was introduced; overall rates were calculated with and without this category. Yearly estimates were reported for patients receiving care within centers reporting complications data.

RESULTS

From 2008–2012 NTDB, there were raw data on 3,657,884 patients. A total of 594,894 patients (16.3%) experienced one or more complications (82.7% one complication; 17.3% two or more complications). Excluding the other complication category, the overall weighted rate was 8.4% to 9.2%. Pneumonia was the most common complication (2.7–3.0%), occurring at twice the 2005 rate. The number of centers reporting no complications data dropped to 8.1% in 2011 (2008, 14.5%; 2009, 18.2%; 2010, 15.9%; 2012, 8.9%). By 2012, nearly all level I centers reported complications, whereas 46.4% of level IVs reported none (I 0.5%, II 2.7%, III 8.5%, p = 0.04). Data were reported the least frequently in nonteaching hospitals (15.8%, p = 0.007), those in the South (19.6%, p = 0.007), and those with less than 200 beds (23.6%, p = 0.005).

CONCLUSION

Overall rates of complications from 2008 to 2012 were nearly twofold higher than 2005 data. Reporting has increased, and NTDB may provide a valuable platform for establishing rational and achievable measures for specific complications.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level IV.
An unambiguous definition of pediatric hypotension is still lacking: Gaps between two percentile-based definitions and Pediatric Advanced Life Support/Advanced Trauma Life Support guidelines
Authors: Sarganas Giselle , Schaffrath Rosario Angelika , Berger Steffen , Neuhauser Hannelore K.
Published: November 2018

BACKGROUND

Data are lacking to provide cutoffs for hypotension in children based on outcome studies and Pediatric Advanced Life Support (PALS), and Advanced Trauma Life Support (ATLS) definitions are based on normal populations. The goal of this study was to compare different normal population based cutoffs including fifth percentile of systolic blood pressure (P5-SBP) in children and adolescents from the German Health Examination Survey for Children and Adolescents (KiGGS), US population data (Fourth Report), and cutoffs from PALS and ATLS guidelines.

METHODS

Fifth percentile of systolic blood pressure according to age, sex, and height was modeled based on standardized resting oscillometric BP measurements (12,199 children aged 3–17 years) from KiGGS 2003–2006. In addition, we applied the age-adjusted pediatric shock index in the KiGGS study.

RESULTS

The KiGGS P5-SBP was on average 7 mm Hg higher than Fourth Report P5-SBP (5–10 mm Hg depending on age-sex group). For children aged 3 to 9 years, KIGGS P5-SBP at median height follows the formula 82 mm Hg + age; for age 10 to 17 years, the increase was not linear and is presented in a simplified table. Pediatric Advanced Life Support/ATLS thresholds were between KiGGS and Fourth Report until age of 11 years. The adult threshold of 90 mm Hg was reached by KiGGS P5-SBP median height at 8 years, PALS/ATLS at age of 10 years, and Fourth Report P5-SBP at 12 years. The pediatric shock index, which is supposed to identify severely injured children, was exceeded by 2.3% nonacutely ill KiGGS participants.

CONCLUSION

Our study shows that percentile cutoffs vary by reference population. The 90 mm Hg cutoff for adolescents targets only those in the less than 1% of the low SBP range and represents an undertriage compared with P5 at younger ages according to both KiGGS and Fourth Report. Finally, current pediatric shock index cutoffs when applied to a healthy cohort lead to a relevant percentage of false positives.

LEVEL OF EVIDENCE

Epidemiologic/prognostic, level III.
Persistent inflammation and anemia among critically ill septic patients
Authors: Loftus Tyler J. , Mira Juan C. , Stortz Julie A. , Ozrazgat-Baslanti Tezcan , Ghita Gabriella L. , Wang Zhongkai , Brumback Babette A. , Ungaro Ricardo F. , Bihorac Azra , Leeuwenburgh Christiaan , Moore Frederick A. , Moldawer Lyle L. , Brakenridge Scott C. , Efron Philip A. , Mohr Alicia M.
Published: November 2018

BACKGROUND

Associations among inflammatory cytokines, erythropoietin (EPO), and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased EPO would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume.

METHODS

Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ΔHb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ΔHb (AdjΔHb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with AdjΔHb of greater than 0 (positive AdjΔHb, n = 18) were compared with patients with AdjΔHb of less than or equal to 0 (negative AdjΔHb, n = 24).

RESULTS

Plasma tumor necrosis factor α, granulocyte colony-stimulating factor, interleukin (IL)-6, IL-8, EPO, erythrocyte mean corpuscular volume, and serum transferrin receptor were measured on days 0, 1, 4, 7, and 14. Patients with negative AdjΔHb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p < 0.05), IL-8 (39.1 vs. 18.2 pg/mL, p = 0.01), and granulocyte colony-stimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower AdjΔHb was associated with higher day 14 levels of IL-6 (r
2 = 0.22, p < 0.01), IL-8 (r
2 = 0.10, p = 0.04), stromal cell–derived factor 1 (r
2 = 0.14, p = 0.02), and tumor necrosis factor α (r
2 = 0.13, p = 0.02), but not EPO. Patients with negative AdjΔHb had significantly lower mean corpuscular volume on days 4 (89.6 vs. 93.2 fL/cell, p = 0.04), 7 (92.3 vs. 94.9 fL/cell, p = 0.04), and 14 (92.1 vs. 96.0 fL/cell, p = 0.03) but similar serum transferrin receptor levels.

CONCLUSION

Persistent elevation of inflammatory cytokines was associated with iron-restricted anemia among critically ill septic patients, occurring in the absence of systemic iron deficiency, independent of endogenous EPO.

LEVEL OF EVIDENCE

Prognostic study, level II.
Recurring emergency general surgery: Characterizing a vulnerable population
Authors: Lunardi Nicole , Mehta Ambar , Ezzeddine Hiba , Canner Joseph K. , Hamidi Mohammad , Jehan Faisal , Joseph Bellal A. , Nathens Avery B. , Efron David T. , Diaz Jose , Sakran Joseph V.
Published: November 2018

BACKGROUND

Limited data exist for long-term outcomes after emergency general surgeries (EGSs) in the United States. This study aimed to characterize the incidence of inpatient readmissions and additional operations within 6 months of an EGS procedure.

METHODS

In this retrospective observational study, we identified adults (≥18 years old) undergoing one of seven common EGS procedures (appendectomies, cholecystectomies, small bowel resections, large bowel resections, control of gastrointestinal [GI] ulcers and bleeding, peritoneal adhesiolysis, and exploratory laparotomies) who were discharged alive in the 2010–2015 National Readmissions Database. Outcomes included the rates of all-cause inpatient readmissions and of undergoing a second EGS procedure, both within 6 months. Multivariable logistic regression models identified risk factors of reoperation, adjusting for patient, clinical, and hospital factors.

RESULTS

Of 706,678 patients undergoing an EGS procedure 131,291 (18.6%) had an inpatient readmission within 6 months. Among those readmitted, 15,178 (11.6%) underwent a second EGS procedure, occurring at a median of 45 days (interquartile range, 15–95). After adjustment, notable predictors of reoperation included male sex (adjusted odds ratio [aOR], 1.06 [95% confidence interval, 1.01–1.10]); private, nonprofit hospitals (aOR, 1.09 [1.02–1.17]); private, investor-owned hospitals (aOR, 1.09 [1.00–1.85]); discharge to short-term hospital (aOR, 1.35 [1.04–1.74]); discharge with home health care (aOR, 1.19 [1.13–1.25]); and index procedure of control of GI ulcer and bleeding (aOR, 9.38 [8.75–10.05]), laparotomy (aOR, 7.62 [6.92–8.40]), or large bowel resection (aOR, 6.94 [6.44–7.47]).

CONCLUSION

One fifth of patients undergoing an EGS procedure had an inpatient readmission within 6 months, where one in nine of those underwent a second EGS procedure. As half of all second EGS procedures occurred within 6 weeks of the index procedure, identifying patients with the highest health care needs (index procedure type and discharge needs) may identify patients at risk for subsequent reoperation in nonemergency settings.

LEVEL OF EVIDENCE

Epidemiological, level III.
Favorable Kidney Function in Pediatric Liver Transplant Recipients: Results of a Single-center Cohort Study
Authors: Sato Mai , Kaneko Tetsuji , Ogura Masao , Kamei Koichi , Ito Shuichi , Fukuda Akinari , Sakamoto Seisuke , Kasahara Mureo , Ishikura Kenji
Published: November 2018

Background.

Although chronic kidney disease (CKD) is still a common complication, the prognosis of kidney function after liver transplantation (LT) is not well known. Moreover, kidney function after LT in children with renal involvement is unknown.

Methods.

We retrospectively analyzed patients aged <20 years who underwent LT between November 2005 and March 2015 at our institute.

Results.

The cohort included 313 pediatric LT recipients (135 males). The median age at LT was 1.1 years (interquartile range, 0.6 to 4.8 y), and the median duration of follow-up was 3.8 years (interquartile range, 1.7 to 6.2 y). We divided the patients by their primary disease into BA (biliary atresia), non-BA (other liver disease without primary renal involvement), or KD (patients with a pre-existing kidney disease) group, which comprised 141, 141, and 31 patients, respectively. Eight-year renal survival with stage 3 CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2) as the event was 99.2%, 92.4%, and 47.7% for the BA, non-BA, and KD group, respectively. Multivariate analysis disclosed primary kidney disease and multiple acute rejections as independent predictors of renal survival. The KD group showed no increase in the rate of kidney function deterioration after LT.

Conclusions.

Eight-year renal survival with stage 3 CKD, particularly in patients with non–pre-existing KD, exceeded 92.0%, and end-stage kidney disease developed in only one patient. Kidney function can be highly preserved following LT even in patients with KD, provided that LT is not contraindicated in patients with renal involvement receiving optimal immunosuppressive management.
New Daily Persistent Headache and OnabotulinumtoxinA Therapy
Authors: Ali Ashhar , Kriegler Jennifer , Tepper Stewart , Vij Brinder
Published: November 2018

Objective

The aim of the study was to determine whether onabotulinumtoxinA therapy is effective in the treatment of new daily persistent headache (NDPH).

Background

New daily persistent headache is a difficult to treat headache syndrome resistant to both conventional and unconventional headache therapies. New daily persistent headache was excluded in the registration trials for onabotunlinumtoxinA (onabot) in chronic migraine. Apart from case reports supporting its benefit, little is known about its therapeutic value in NDPH.

Design and Methods

We performed a single-center, retrospective chart review of patients with a diagnosis of NDPH who received onabot treatment for a 30-month period at the Cleveland Clinic Headache Center. Measures of interest were headache frequency and headache severity. All patients had received the Food and Drug Administration–approved PREEMPT Protocol.

Results

A decrease in headache frequency was noted in 8 (50.0%) of 16 patients at 6 months and 7 (63.6%) of 11 patients at 12 months. Headache severity improved in 5 (50.0%) of 10 patients at 6 months and in 7 (77.8%) of 9 patients at 12 months.

Conclusions

Most therapies are unable to break the unremitting course of NDPH. In our investigation, at 1 year (3–4 cycles of onabot treatment), approximately half of the patients treated showed a reduction in headache frequency and approximately 75% demonstrated some improvement in headache severity. Evidence from this small-scale retrospective study suggests that onabot shows strong promise for the treatment of NDPH, which currently is resistant to most therapies, but a randomized controlled study should be the next step in confirmation of this therapy.
Heart Rate Variability During Nocturnal Sleep and Daytime Naps in Patients With Narcolepsy Type 1 and Type 2
Authors: Aslan Sabina , Erbil Nurhan , Tezer F. Irsel
Published: November 2018

Purpose:

Heart rate variability is a noninvasive measure of autonomic function. The aim of this study was to determine the risk of cardiovascular autonomic dysfunction during sleep in patients with narcolepsy. The effect of daytime napping was also examined in patients with narcolepsy type 1 and type 2.

Methods:

Polysomnography recordings and multiple sleep latency tests from 11 patients with narcolepsy type 1 (N1) and 20 patients with narcolepsy type 2 (N2) were included and compared with 12 healthy controls. Heart rate variability values (measured by time- and frequency-domain parameters) were calculated using electrocardiography data from the polysomnography–multiple sleep latency test recordings.

Results:

As an indicator of increasing sympathovagal imbalance, the low-frequency/high-frequency ratio was higher in all patients than in controls during non–rapid eye movement (NREM)-2 stage sleep (P ≤ 0.01). The root mean square of successive RR interval differences was lower (indicating parasympathetic tone) in N1 patients compared with N2 patients during REM sleep (P ≤ 0.04). In addition, decreased heart rate variability values were observed during sleep-onset REM–negative multiple sleep latency test periods compared with sleep-onset REM–positive periods.

Conclusions:

Heart rate variability abnormalities during sleep and the role of these changes on the development of cardiovascular diseases must be investigated in prospective follow-up studies of patients with narcolepsy. Heart rate variability changes during night sleep, daytime napping, and presence of sleep-onset REM periods may affect the life-threatening events.
Beyond a ribosomal RNA methyltransferase, the wider role of MraW in DNA methylation, motility and colonization inEscherichia coliO157:H7
Authors: Xu Xuefang , Zhang Heng , Huang Ying , Zhang Yuan , Wang Xiaoyuan , Wang Dai , Pu Ji , Zhao Hongqing , Lu Xuancheng , Lu Shuangshuang , Xiong Yanwen , Ye Changyun , Dong Yuhui , Lan Ruiting , Xu Jianguo
Published: November 2018

MraW (RsmH) is an AdoMet-dependent 16S rRNA methyltransferase conserved in bacteria and plays a role in the fine-tuning of the ribosomal decoding center. It was recently found to contribute to the virulence ofStaphylococcus aureusin host animals. In this study, we examined the function of MraW inEscherichia coliO157:H7 and found that deletion ofmraWled to decreased motility and flagellar production. Whole-genome bisulfite sequencing showed genome wide decrease of methylation of 336 genes and 219 promoters in themraWmutant. The methylation level of 4 flagellar gene sequences were further confirmed by bisulfite PCR sequencing. Quantitative reverse transcription PCR results indicated the transcription of these genes was also affected. MraW was observed to directly bind to the four flagellar gene sequences by electrophoretic mobility shift assay (EMSA). A common motif in differentially methylated regions of promoters and coding regions of the 4 flagellar genes was identified. Reduced methylation was correlated with altered expression of 21 of the 24 genes tested. DNA methylation activity of MraW was confirmed by DNA methyltransferase (DNMT) activity assayin vitro. ThemraWmutant colonized poorer than wild type in mice. we further found that the expression ofmraZin themraWmutant was increased confirming the antagonistic effect ofmraWonmraZ. In conclusion,mraWwas found to be a DNA methylase and has a wide-ranging effect onE.coliO157:H7 including motility and virulencein vivovia genome wide methylation andmraZantagonism.

IMPORTANCE

MraW is a well-studied 16S rRNA methyltransferase and was recently found have an impact on bacterial virulence. Here we demonstrated its new function as a DNA methylase and effect on motility, colonization in mice, DNA methylation in genome wide and contribution to virulence. Its direct binding of differentially methylated flagellar-encoding DNA sequences was observed, indicating a correlation between DNA methylation and regulation of flagellar genes. In addition, the expression ofmraZwhich function as an antagonist ofmraWwas increased in themraWmutant.mraWplays an important role in gene regulation likely through DNA methylation. Clearly it plays a role in virulence inE. coliO157:H7. It also opens a new research field for virulence study in bacteria.
Very rapid flow cytometric assessment of antimicrobial susceptibility during the apparent lag phase of microbial (re)growth
Authors: Jindal Srijan , Thampy Harish , Day Philip J. , Kell Douglas B.
Published: November 2018

Cells ofE. coliwere grown in LB medium, taken from a stationary phase of 2-4h, and reinoculated into fresh media at a concentration (105.mL-1or lower) characteristic of bacteriuria. Flow cytometry was used to assess how quickly we could detect changes in cell size, number, membrane energisation (using a carbocyanine dye) and DNA distribution. It turned out that while the lag phase observable macroscopically via bulk OD measurements could be as long as 4h, the true lag phase could be less than 15-20 min, and was accompanied by many observable biochemical changes. Antibiotics to which the cells were sensitive affected these changes within 20 min of reinoculation, providing the possibility of a very rapid antibiotic susceptibility test, on a timescale compatible with a visit to a GP clinic. The strategy was applied successfully to genuine potential Urinary Tract Infection (UTI) samples taken from a doctor’s surgery. The methods developed could prove of considerable value in ensuring the correct prescription and thereby lowering the spread of antimicrobial resistance.
TET-catalyzed 5-carboxylcytosine promotes CTCF binding to suboptimal sequences genome-wide
Authors: Nanan Kyster K. , Sturgill David M. , Prigge Maria F. , Thenoz Morgan , Dillman Allissa A. , Mandler Mariana D. , Oberdoerffer Shalini
Published: November 2018

The mechanisms supporting dynamic regulation of CTCF binding sites remain poorly understood. Here we describe the TET-catalyzed 5-methylcytosine derivative, 5-carboxylcytosine (5caC) as a factor driving new CTCF binding within genomic DNA. Through a combination of in vivo and in vitro approaches, we reveal that 5caC generally strengthens CTCF association with DNA and facilitates binding to suboptimal sequences. Dramatically, profiling of CTCF binding in a cellular model that accumulates genomic 5caC identified ∼13,000 new CTCF sites. The new sites were enriched for overlapping 5caC and were marked by an overall reduction in CTCF motif strength. As CTCF has multiple roles in gene expression, these findings have wide-reaching implications and point to induced 5caC as a potential mechanism to achieve differential CTCF binding in cells.
Human Navigation Without and With Vision - the Role of Visual Experience and Visual Regions
Authors: Maidenbaum Shachar , Chebat Daniel-Robert , Amedi Amir
Published: November 2018

Human navigation relies on a wide range of visual retinotopic cortical regions yet the precise role that these regions play in navigation remains unclear. Are these regions mainly sensory input channels or also modality-independent spatial processing centers? Accordingly, will they be recruited for navigation also without vision, such as via audition? Will visual experience, or the lack thereof, affect this recruitment? Sighted, congenitally blind and sighted-blindfolded participants actively navigated virtual mazes during fMRI scanning before and after navigating them in the real world. Participants used the EyeCane visual-to-auditory navigation aid for non-visual navigation.

We found that retinotopic regions, including both dorsal stream regions (e.g. V6) and primary regions (e.g. peripheral V1), were selectively recruited for non-visual navigation only after the participants mastered the EyeCane demonstrating rapid plasticity for non-visual navigation. The hippocampus, considered the navigation network’s core, displayed negative BOLD in all groups.

Our results demonstrate the robustness of the retinotopic nodes modality-independent spatial role in non-visual human navigation to lifelong visual-deprivation, demonstrating that visual input during development is not required for their recruitment. Furthermore, our results with the blindfolded group demonstrate this recruitment’s robustness even to brief blindfolding, but only after brief training, demonstrating rapid task based plasticity. These results generalize the wider framework of task-selectivity rather than input-modality as a brain organization principle to dorsal-stream retinotopic areas and even for the first time to the primary visual cortex.

Highlights

Both visual and non-visual navigation recruit retinotopic regions

After training blindfolded subjects selectively recruit V1 & V6 for navigation

This holds also for participants with no visual experience (congenitally blind)

The medial temporal lobe showed non-selective Negative BOLD in all groups

Declaration of interests

All authors declare that they have no conflicts of interests.
A multi-site MicroLED Optrode Array for Neural Interfacing
Authors: McAlinden Niall , Cheng Yunzhou , Scharf Robert , Xie Enyuan , Gu Erdan , Dawson Martin D. , Reiche Christopher , Sharma Rohit , Tathireddy Prashant , Rieth Loren , Blair Steve , Mathieson Keith
Published: November 2018

We present an electrically addressable optrode array capable of delivering light to 181 sites in the brain, each providing sufficient light to optogenetically excite hundreds of neurons in vivo, developed with the aim to allow behavioural studies in large mammals. The device is a glass microneedle array directly integrated with a custom fabricated microLED device, which delivers light to 100 needle tips and 81 interstitial surface sites, giving 2-level optogenetic excitation of neurons in vivo. Light delivery and thermal properties are evaluated, with the device capable of peak irradiances > 80 mW/mm2 per needle at 50 ms pulse widths with tissue temperature increase less than 1 °C. Future designs are explored through optical and thermal modelling and benchmarked against the current device.
Flexible, fast and selective genetic manipulation of the vertebrate CNS with misPiggy
Authors: Slezak Michal , Vin Filip de , Shinmyo Yohei , Batiuk Mykhailo Y. , Rincon Melvin Y. , Pando Carmen Menacho , Urschitz Johann , Moisyadi Stefan , Schnütgen Frank , Kawasaki Hiroshi , Holt Matthew G.
Published: November 2018

In utero electroporation is increasingly used for manipulation of gene expression in the mammalian central nervous system. Here we created a transposon-based single plasmid system, that allows long-term conditional loss- and gain-of-function experiments across major CNS cell types. The system is widely applicable across species, allowing fast, flexible and cheap cell manipulation in previously non-transgenic species.
Non-uniform genetic effect sizes of variants associated with refractive error suggests gene-gene or gene-environment interactions are pervasive
Authors: Pozarickij Alfred , Williams Cathy , Hysi Pirro , Guggenheim Jeremy A. ,   the UK Biobank Eye and Vision Consortium
Published: November 2018

Refractive error is a complex ocular trait controlled by genetic and environmental factors. Genome-wide association studies (GWAS) have identified approximately 150 genetic variants associated with refractive error. Among the known environmental factors, education, near-work and time spent outdoors have been demonstrated to have the strongest associations. Currently, the extent of gene-environment or gene-gene interactions in myopia is unknown. Here we show that the majority of genetic variants associated with refractive error show evidence of effect size heterogeneity, which is a hallmark feature of genetic interactions. Using conditional quantile regression, we observed that 88% of genetic variants associated with refractive error have at least nominally-significant non-uniform, non-linear profiles across the refractive error distribution. SNP effects tend to be strongest at the phenotype extremes and have weaker effects in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in refractive error are pervasive.

Author summary

The prevalence of myopia (nearsightedness) in the United States and East Asia has almost doubled in the past 30 years. Such a rapid rise in prevalence cannot be explained by genetics, which implies that environmental (lifestyle) risk factors play a major role. Nevertheless, diverse approaches have suggested that genetics is also important, and indeed approximately 150 distinct genetic risk loci for myopia have been discovered to date. One attractive explanation for the evidence implicating both genes and environment in myopia is gene-environment (GxE) interaction (a difference in genetic effect in individuals exposed to a high vs. low level of an environmental risk factor). Past studies aiming to discover GxE interactions in myopia have met with limited success, perhaps because information on lifestyle exposures during childhood has rarely been available. Here we used an agnostic approach that does not require information about specific lifestyle exposures in order to detect ‘signatures’ of GxE interaction. We found compelling evidence for widespread genetic interactions in myopia, with 88% of 150 known myopia genetic susceptibility loci showing an interaction signature. These findings suggest that GxE interactions in myopia are pervasive.
Accelerated rates of large-scale mutations in the presence of copper and nickel
Authors: Chain Frédéric J.J. , Flynn Jullien M. , Bull James K. , Cristescu Melania E.
Published: November 2018

Mutation rate variation has been under intense investigation for decades. Despite these efforts, little is known about the extent to which environmental stressors accelerate mutation rates and influence the genetic load of populations. Moreover, most studies on stressors have focused on unicellular organisms and point mutations rather than large-scale deletions and duplications (copy number variations [CNVs]). We estimated mutation rates in Daphnia pulex exposed to low levels of environmental stressors as well as the effect of selection on de novo mutations. We conducted a mutation accumulation (MA) experiment in which selection was minimized, coupled with an experiment in which a population was propagated under competitive conditions in a benign environment. After an average of 103 generations of MA propagation, we sequenced 60 genomes and found significantly accelerated rates of deletions and duplications in MA lines exposed to ecologically relevant concentrations of metals. Whereas control lines had gene deletion and duplication rates comparable to other multicellular eukaryotes (1.8 × 10−6 per gene per generation), the presence of nickel and copper increased these rates fourfold. The realized mutation rate under selection was reduced to 0.4× that of control MA lines, providing evidence that CNVs contribute to mutational load. Our CNV breakpoint analysis revealed that nonhomologous recombination associated with regions of DNA fragility is the primary source of CNVs, plausibly linking metal-induced DNA strand breaks with higher CNV rates. Our findings suggest that environmental stress, in particular multiple stressors, can have profound effects on large-scale mutation rates and mutational load of multicellular organisms.
Synthesis and characterization of self-assembled inorganic–organic hybrid arsenotungstates
Authors: Parbhakar Swati , Kaushik Reetam , Hussain Firasat
Published: November 2018

A series of 12 inorganic–organic hybrid 4f-substituted arsenotungstates decorated with 3d-based complexes along with acetate bridging, viz. {[Cu2(H2O)(1,10-phen)2(μ-CH3COO)2]4[Ln2(H2O)2(μ-CH3COO)2(α-AsW11O39)2]}2− (LnIII = Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu), have been synthesized. These compounds were isolated using a one-pot synthetic strategy with copper, lanthanoid, trilacunary arsenotungstate and 1,10-phenanthroline as precursors. They were characterized using various analytical techniques, such as single-crystal X-ray diffraction (SC-XRD), powder XRD (PXRD), Fourier transform IR (FT–IR) spectroscopy, UV–Vis spectroscopy and thermogravimetric analysis (TGA). In all these compounds, a dinuclear Ln2(ac)2 moiety is sandwiched between two monolacunary [AsW11O39]7− polyoxometalates (POMs), where the Ln2(ac)2 moiety is comprised of two acetate ligands in a μ-κO,O′:κO fashion. Moreover, the anion is decorated by a copper–phenanthroline–acetate complex through a terminal O atom of the polyanion.