bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI in Postreduction Evaluation of Developmental Dysplasia of the Hip: Our Experience
Authors: Dibello Daniela , Odoni Luca , Pederiva Federica , Di Carlo Valentina
Published: June 2017

Background:

Developmental dysplasia of the hip (DDH) is one of the most common congenital defects in the newborn. When its severe form is not corrected, it is associated with long-term morbidity. Closed reduction with casting is the standard primary treatment and reduction is confirmed by magnetic resonance imaging (MRI). We reported our experience on the reliability of MRI in postreduction assessment of DDH.

Methods:

All children who underwent closed reduction for Graf type IV DDH at our institution between September 2010 and June 2016 were retrospectively reviewed. Since 2010 we assessed postreduction position of the femoral head by performing a MRI.

Results:

Twenty-five (5 male, 20 female) patients presented with 29 (15 left sided, 6 right sided, 4 bilateral) Graf type IV DDH and underwent closed reduction at a mean age of 3.4 months. In all patients MRI studies performed within 24 hours were diagnostic, showing a concentric reduction of the femoral head within the acetabulum in 24/25 patients. In the patient with persistent hip instability, a subsequent open reduction was performed. In all the cases, there was no need of any contention or sedation during MRI.

Conclusions:

On the basis of our experience, MRI is an excellent, safe and, reliable modality to confirm maintenance of adequate femoral head position and to evaluate soft tissue interposition. We agree that MRI is the gold standard to early depict dislocation after closed reduction of DDH.
Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU
Authors: Ravn Bo , Prowle John R. , Mårtensson Johan , Martling Claes-Roland , Bell Max
Published: June 2017

Objectives:

Renal outcomes after critical illness are seldom assessed despite strong correlation between chronic kidney disease and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin C than by creatinine. The relationship between creatinine and longer term mortality might be particularly weak in survivors of critical illness.

Design:

Retrospective observational cohort study.

Patients:

In 3,077 adult ICU survivors, we compared ICU discharge cystatin C and creatinine and their association with 1-year mortality. Exclusions were death within 72 hours of ICU discharge, ICU stay less than 24 hours, and end-stage renal disease.

Interventions:

None.

Measurements and Main Results:

During ICU admission, serum cystatin C and creatinine diverged, so that by ICU discharge, almost twice as many patients had glomerular filtration rate less than 60 mL/min/1.73 m2 when estimated from cystatin C compared with glomerular filtration rate estimated from creatinine, 44% versus 26%. In 743 patients without acute kidney injury, where ICU discharge renal function should reflect ongoing baseline, discharge glomerular filtration rate estimated from creatinine consistently overestimated follow-up glomerular filtration rate estimated from creatinine, whereas ICU discharge glomerular filtration rate estimated from cystatin C well matched follow-up chronic kidney disease status. By 1 year, 535 (17.4%) had died. In survival analysis adjusted for age, sex, and comorbidity, cystatin C was near-linearly associated with increased mortality, hazard ratio equals to 1.78 (95% CI, 1.46–2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J-shaped relationship with mortality, so that in the majority of patients, there was no significant association with survival, hazard ratio equals to 1.03 (0.87–1.2), 75th versus 25th centile. After adjustment for both creatinine and cystatin C levels, higher discharge creatinine was then associated with lower long-term mortality.

Conclusions:

In contrast to creatinine, cystatin C consistently associated with long-term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin C appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin C warrants further investigation as a more meaningful measure of renal function after critical illness.
Sedation Management in Children Supported on Extracorporeal Membrane Oxygenation for Acute Respiratory Failure*
Authors: Schneider James B. , Sweberg Todd , Asaro Lisa A. , Kirby Aileen , Wypij David , Thiagarajan Ravi R. , Curley Martha A. Q.
Published: June 2017

Objectives:

To describe sedation management in children supported on extracorporeal membrane oxygenation for acute respiratory failure.

Design:

Secondary analysis of prospectively collected data from a multicenter randomized trial of sedation (Randomized Evaluation of Sedation Titration for Respiratory Failure).

Setting:

Twenty-one U.S. PICUs.

Patients:

One thousand two hundred fifty-five children, 2 weeks to 17 years old, with moderate/severe pediatric acute respiratory distress syndrome.

Interventions:

Sedation managed per usual care or Randomized Evaluation of Sedation Titration for Respiratory Failure protocol.

Measurements and Main Results:

Sixty-one Randomized Evaluation of Sedation Titration for Respiratory Failure patients (5%) with moderate/severe pediatric acute respiratory distress syndrome were supported on extracorporeal membrane oxygenation, including 29 managed per Randomized Evaluation of Sedation Titration for Respiratory Failure protocol. Most extracorporeal membrane oxygenation patients received neuromuscular blockade (46%) or were heavily sedated with State Behavioral Scale scores –3/–2 (34%) by extracorporeal membrane oxygenation day 3. Median opioid and benzodiazepine doses on the day of cannulation, 0.15 mg/kg/hr (3.7 mg/kg/d) and 0.11 mg/kg/hr (2.8 mg/kg/d), increased by 36% and 58%, respectively, by extracorporeal membrane oxygenation day 3. In the 41 patients successfully decannulated prior to study discharge, patients were receiving 0.40 mg/kg/hr opioids (9.7 mg/kg/d) and 0.39 mg/kg/hr benzodiazepines (9.4 mg/kg/d) at decannulation, an increase from cannulation of 108% and 192%, respectively (both p < 0.001). Extracorporeal membrane oxygenation patients experienced more clinically significant iatrogenic withdrawal than moderate/severe pediatric acute respiratory distress syndrome patients managed without extracorporeal membrane oxygenation support (p < 0.001). Compared to extracorporeal membrane oxygenation patients managed per Randomized Evaluation of Sedation Titration for Respiratory Failure protocol, usual care extracorporeal membrane oxygenation patients received more opioids during the study period (mean cumulative dose of 183.0 vs 89.8 mg/kg; p = 0.02), over 6.5 greater exposure days (p = 0.002) with no differences in wakefulness or agitation.

Conclusions:

In children, the initiation of extracorporeal membrane oxygenation support is associated with deep sedation, substantial sedative exposure, and increased frequency of iatrogenic withdrawal syndrome. A standardized, goal-directed, nurse-driven sedation protocol may help mitigate these effects.
Seven years after Meaningful Use: Physicians’ and nurses’ experiences with electronic health records
Authors: Rathert Cheryl , Porter Tracy H. , Mittler Jessica N. , Fleig-Palmer Michelle
Published: June 2017

Although the federal government’s Meaningful Use electronic health record (EHR) implementation program resulted in some successes, there have been many challenges. The purpose of this study was to obtain detailed empirical data to better understand physicians’ and nurses’ experiences with EHRs. We conducted in-depth interviews with 30 physicians and nurses from two large health systems that were focused on attaining Stage 3 Meaningful Use criteria. Thematic framework analysis identified themes related to perceived benefits and challenges with EHR use. Participants appreciated benefits such as real-time patient data and easier access to information. Challenges included lack of interoperability across units, and this seemed to underlie many other noted challenges such as increased workload, insufficient training, and the perceived need for workarounds. Two key findings included mixed messages about trust in the EHR’s information and its interference with interpersonal relationships. Results suggest that conservation of resources theory may be a useful strategy for understanding behaviors that enhance or undermine effective EHR use. Implications for policy and practice are discussed.
The role of organizational context in the implementation of a statewide initiative to integrate mental health services into pediatric primary care
Authors: King Melissa A. , Wissow Lawrence S. , Baum Rebecca A.
Published: June 2017

Background:

Although there is evidence that mental health services can be delivered in pediatric primary care with good outcomes, few changes in service delivery have been seen over the past decade. Practices face a number of barriers, making interventions that address determinants of change at multiple levels a promising solution. However, these interventions may need appropriate organizational contexts in place to be successfully implemented.

Purpose:

The objective of this study was to test whether organizational context (culture, climate, structures/processes, and technologies) influenced uptake of a complex intervention to implement mental health services in pediatric primary care.

Methodology/Approach:

We incorporated our research into the implementation and evaluation of Ohio Building Mental Wellness Wave 3, a learning collaborative with on-site trainings and technical assistance supporting key drivers of mental health care implementation. Simple linear regression was used to test the effects of organizational context and external or fixed organizational characteristics on program uptake.

Results:

Culture, structure/processes, and technologies scores indicating a more positive organizational context for mental health at the project’s start, as well as general cultural values that were more group/developmental, were positively associated with uptake. Patient-centered medical home certification and use of electronic medical records were also associated with greater uptake. Changes in context over the course of Building Mental Wellness did not influence uptake.

Conclusion:

Organizational culture, structures/processes, and technologies are important determinants of the uptake of activities to implement mental health services in pediatric primary care. Interventions may be able to change these aspects of context to make them more favorable to integration, but baseline characteristics more heavily influence the more proximal uptake of program activities.

Practice Implications:

Pediatric primary care practices would benefit from assessing their organizational context and taking steps to address it prior to or in a phased approach with mental health service implementation.
The Role of the Back Plate in Angle Anatomy with the Boston Type I Keratoprosthesis
Authors: Taniguchi Elise V. , Paschalis Eleftherios I. , Crnej Alja , Ren Ai , Colby Kathryn A. , Chodosh James , Pasquale Louis R. , Shen Lucy Q. , Dohlman Claes H. , Cruzat Andrea
Published: June 2017

Purpose:

To quantitatively evaluate the angle anatomy in eyes with the Boston type I keratoprosthesis (B-KPro) differing in the back plate (BP) material and size using anterior segment optical coherence tomography.

Methods:

B-KPro eyes with poly(methyl methacrylate) (PMMA) (7.0 and 8.5 mm) and titanium (7.0, 8.5, and 9.5 mm) BPs were imaged with anterior segment optical coherence tomography. The angle opening distance at 500 μm from the scleral spur (AOD500), trabecular iris surface area at 500 μm from the scleral spur (TISA500), and trabecular iris angle at 500 μm from the scleral spur (TIA500) were measured. Among the visible quadrants, the average, the temporal, the widest, and the narrowest angle of each eye were included in the analysis. Average time between B-KPro implantation and imaging was 7.5 ± 1.4 years for a PMMA BP and 2.4 ± 2.3 years for a titanium BP (P < 0.0001).

Results:

We analyzed 17 B-KPro eyes with PMMA BPs and 24 B-KPro eyes with titanium BPs. The average AOD500 (394.1 ± 226.9 vs. 454.5 ± 255.6 μm, P = 0.44), average TIA500 (26.2 ± 14.2 vs. 29.8 ± 13.9 degrees, P = 0.43), and average TISA500 (0.15 ± 0.08 vs. 0.17 ± 0.10 μm2, P = 0.52) were not statistically different between eyes with PMMA and titanium BPs, nor were the temporal, the narrowest, and the widest angle measurements of each eye (all P > 0.05). Similarly, no significant differences were found between the angle measurements of B-KPro eyes with a titanium BP diameter of 8.5 or 9.5 mm (all P > 0.05).

Conclusions:

We successfully visualized the angle anatomy in 66.1% of the imaged eyes, including all BPs studied. Neither the material nor the size of the B-KPro BP had a significant impact on the angle anatomy.
Nonisolated Small Bowel Gastrointestinal Angiodysplasias are Associated With Higher Rebleeding Rates When Compared With Isolated Small Bowel Gastrointestinal Angiodysplasia on Video Capsule Endoscopy
Authors: Mai Stephanie H. , Chao Daniel C. , Liao Shu-Yi , Jackson Christian S.
Published: June 2017

Background:

Gastrointestinal angiodysplasias (GIAD) are commonly diagnosed in the small bowel but can be located in other areas of the gastrointestinal tract. About half of patients diagnosed with GIAD have more than 1 lesion and 20% of patients have GIAD in both the small bowel and a source outside of the small bowel (nonisolated to small bowel GIAD or NISGIAD). The remaining patients with GIAD have lesions isolated to the small bowel (ISGIAD). Complications including rebleeding, hospitalization and mortality rates have not been previously analyzed between these 2 groups.

Aim:

To compare rebleeding, hospitalization and mortality rates between ISGIAD and NISGIAD. The secondary goals were to evaluate comorbidities that may be associated with ISGIAD and/or NISGIAD, and to determine if any of these comorbidities are associated with a higher risk of rebleeding from GIAD.

Materials and Methods:

This was a retrospective study that included 425 patients who underwent video capsule endoscopy between 2006 and 2013. Patients underwent esophagogastroduodenoscopy and colonoscopy before video capsule endoscopy. The primary indications for workup included obscure gastrointestinal bleeding. After exclusion criteria, 87 patients diagnosed with GIAD remained, 57 patients with ISGIAD and 30 with NISGIAD. Categorical variables were compared by the Fisher exact test or χ2 test and continuous data were compared using the Student T test.

Results:

Risk factors associated with rebleeding rates included coronary artery disease, chronic kidney disease, and congestive heart failure on multivariate analysis. Odds ratios for rebleeding was found in patients with NISGIAD (odds ratio, 4.222; P=0.036). There was no difference in hospitalization rates between patients with ISGIAD and NISGIAD. There was no statistically significant difference in mortality from any cause at 30, 60, and 90 days in patients with ISGIAD and NISGIAD.

Conclusions:

In this retrospective analysis of GIAD at a single institution, patients with NISGIAD compared with ISGIAD had a 4 times odds of rebleeding within 1 year after capsule endoscopy. This is a novel study, as the distribution of GIAD has not been previously described as being a risk factor for rebleeding.
Hepatitis C Virus Prevalence in Egyptian Americans in Southern California
Authors: Saab Sammy , Viramontes Matthew R. , Chalifoux Sara L. , Craw Chris J. , Ramirez Samantha D. , Bau Sherona N. , Arevalo Diana G. , Saab Elena G. , Saab Clara E. , Craw Chloe S. , Estafanous Abram , Messiah Ramy , Messiah Waleed , El Kabany Mohamed
Published: June 2017

Background:

Hepatitis C virus (HCV) is a global medical health concern. Egypt has the highest HCV prevalence. Few studies have assessed the HCV prevalence rates among Egyptian-born expatriates. We sought to define the HCV prevalence Egyptian-born individuals residing in the Southern California area.

Patients and Methods:

We screened Egyptian-born individuals in houses of worship in the Southern California area using a point of care test HCV antibody test. Results were confirmed by testing the blood for viral load. Demographic information including risk factors were also collected. Individuals were contacted with their results, and those found to be detectable HCV antibodies were referred for further testing and additional care.

Results:

Three hundred twenty-six Egyptian expatriates from 7 houses of worship in Southern California were screened for the HCV infection. Most of the participants were screened at Coptic Churches. Nine of these individuals were found to be HCV infected (2.8%). We found an increased HCV seroprevalence in subjects were male and born in Egyptian urban areas. Five of the 9 subjects (56%) who tested positive were not baby boomers and only 2 of these 9 subjects (22%) had recognized Center for Disease Control risk factors.

Conclusions:

The HCV prevalence rate of Egyptian-born individuals living in the Southern California area was lower compared with the prevalence rate in the general Egyptian population, but higher than that seen in the general US population. The utility of using Center for Disease Control risk factors to define individuals at risk of HCV among Egyptian expatriates is not applicable.
Spontaneous fungal peritonitis: a rare but severe complication of liver cirrhosis
Authors: Gravito-Soares Marta , Gravito-Soares Elisa , Lopes Sandra , Ribeiro Graça , Figueiredo Pedro
Published: June 2017

Introduction and aim

Spontaneous bacterial peritonitis is the most common infectious complication in cirrhosis. Spontaneous fungal peritonitis is rare and remains unknown. In this work, spontaneous fungal peritonitis as well as risk factors and prognosis are characterized.

Patients and methods

A retrospective case–control study of 253 consecutive admissions by peritonitis in cirrhotic patients was carried out between 2006 and 2015. Comparison of patients with spontaneous fungal peritonitis (cases) and spontaneous bacterial peritonitis with positive microbiologic ascitic fluid culture (controls) was performed. Variables such as sociodemographic and clinical features, cirrhosis etiology, liver dysfunction scores, ascitic and laboratory parameters, invasive procedures, and prognosis were evaluated.

Results

Of the 231 patients, eight (3.5%) developed spontaneous fungal peritonitis, 62.5% of cases being coinfected with bacteria. Candida spp. was isolated in 87.5% of cases, mainly Candida albicans (37.5%) and C. krusei (25.0%). Patients with spontaneous fungal peritonitis had higher ascitic fluid lactate dehydrogenase (288.4±266.6 vs. 161.0±179.5; P=0.011), blood leukocyte count (15187.5±5432.3 vs. 10969.8±6949.5; P=0.028), blood urea nitrogen (69.8±3.1 vs. 36.3±25.5; P=0.001), higher number of invasive procedures (colonoscopy: 25.0 vs. 0.8%, P=0.001; urinary catheterization: 87.5 vs. 49.6%, P=0.038; nasogastric intubation: 87.5 vs. 26.9%, P=0.001), and longer duration of hospital stay (30.0±32.9 vs. 18.9±17.0 days; P=0.031). No statistical difference was found between the two groups for Model for End-Stage Liver Disease, Model for End-Stage Liver Disease–sodium, and Child–Pugh scores. Spontaneous fungal peritonitis was associated with a worse prognosis, particularly severe sepsis/septic shock (87.5 vs. 42.8%, P=0.023), admission in the gastroenterology intensive care unit (87.5 vs. 24.4%; P=0.001), and overall (62.5 vs. 31.9%; P=0.039) or 30-day mortality (50.0 vs. 24.4%; P=0.034), with a mean diagnosis-death time of 17.6±11.5 days.

Conclusion

Despite being a rare condition, spontaneous fungal peritonitis was associated with worse prognosis and higher mortality than SBP. The ascitic fluid lactate dehydrogenase, blood leukocyte count and urea nitrogen, invasive procedures, and longer admission time were independent risk factors for spontaneous fungal peritonitis.
Survey Instruments to Assess Patient Experiences With Access and Coordination Across Health Care Settings
Authors: Quinn Martha , Robinson Claire , Forman Jane , Krein Sarah L. , Rosland Ann-Marie
Published: June 2017

Background:

Improving access can increase the providers a patient sees, and cause coordination challenges. For initiatives that increase care across health care settings, measuring patient experiences with access and care coordination will be crucial.

Objectives:

Map existing survey measures of patient experiences with access and care coordination expected to be relevant to patients accessing care across settings. Preliminarily examine whether aspects of access and care coordination important to patients are represented by existing measures.

Research Design:

Structured literature review of domains and existing survey measures related to access and care coordination across settings. Survey measures, and preliminary themes from semistructured interviews of 10 patients offered VA-purchased Community Care, were mapped to identified domains.

Results:

We identified 31 existing survey instruments with 279 items representing 6 access and 5 care coordination domains relevant to cross-system care. Domains frequently assessed by existing measures included follow-up coordination, primary care access, cross-setting coordination, and continuity. Preliminary issues identified in interviews, but not commonly assessed by existing measures included: (1) acceptability of distance to care site given patient’s clinical situation; (2) burden on patients to access and coordinate care and billing; (3) provider familiarity with Veteran culture and VA processes.

Conclusions:

Existing survey instruments assess many aspects of patient experiences with access and care coordination in cross-system care. Systems assessing cross-system care should consider whether patient surveys accurately reflect the level of patients’ concerns with burden to access and coordinate care, and adequately reflect the impact of clinical severity and cultural familiarity on patient preferences.
Spectrum of Changes in Anogenital Mammary-like Glands in Primary Extramammary (Anogenital) Paget Disease and Their Possible Role in the Pathogenesis of the Disease
Authors: Konstantinova Anastasia M. , Spagnolo Dominic V. , Stewart Colin J.R. , Kacerovska Denisa , Shelekhova Ksenya V. , Plaza Jose A. , Suster Saul , Bouda Jiri , Kyrpychova Liubov , Michal Michal , Belousova Irena E. , Kerl Katrin , Kazakov Dmitry V.
Published: June 2017

To determine whether a subset of primary extramammary Paget disease (EMPD) may originate in anogenital mammary-like glands (AGMLG), the authors studied 181 specimens of EMPD, detailing alterations in AGMLG. The latter were identified in 33 specimens from 31 patients. All patients were women, ranging in age from 38 to 93 years (median, 65 y). In all cases, lesions involved the vulva and in 1 patient the perianal skin was affected. Histopathologically, AGMLG manifested changes identical to columnar cell change (CCC) (87.1%), usual ductal hyperplasia (22.6%), columnar cell hyperplasia (CCH) (9.7%), oxyphilic (apocrine) metaplasia (6.5%), and atypical duct hyperplasia (3.2%). Four cases (12.9%), in addition to intraepidermal carcinoma, harbored invasive carcinoma. In all 4 of these, AGMLG displayed a range of alterations including ductal carcinoma in situ, CCC, and CCH. Three further cases (9.7%) showed ductal carcinoma in situ without any definite invasive carcinoma. Colonization of AGMLG by neoplastic Paget cells was noted in 6 cases. As CCC and CCH may be encountered in normal AGMLG, these alterations are unlikely to play a significant role in the pathogenesis of the disease. However, by analogy with mammary Paget disease, rare cases of primary EMPD may originate in AGMLG with a subsequent upward migration of the neoplastic cells into the epidermis and possible later breach through the basal membrane. Usual ductal hyperplasia and atypical duct hyperplasia can then be regarded as earlier precursor lesions, linking both ends of the spectrum.
WNT Pathway Gene Mutations Are Associated With the Presence of Dysplasia in Colorectal Sessile Serrated Adenoma/Polyps
Authors: Hashimoto Taiki , Yamashita Satoshi , Yoshida Hiroshi , Taniguchi Hirokazu , Ushijima Toshikazu , Yamada Tesshi , Saito Yutaka , Ochiai Atsushi , Sekine Shigeki , Hiraoka Nobuyoshi
Published: June 2017

Sessile serrated adenoma/polyps (SSA/Ps) are believed to be the major precursor of serrated pathway-derived colorectal carcinomas. To better characterize the process of progression from SSA/Ps to carcinomas, we analyzed 46 SSA/Ps with dysplasia and 45 SSA/Ps without dysplasia using targeted next-generation sequencing and immunohistochemistry. Among the WNT pathway genes analyzed, protein-truncating mutations of RNF43, APC, and ZNRF3 were identified in 23 (50%), 4 (9%), and 3 (7%) SSA/Ps with dysplasia, respectively. In contrast, SSA/Ps without dysplasia rarely had WNT pathway gene mutations, except for 3 lesions with RNF43 mutations (7%). None of the SSA/Ps had CTNNB1 mutations or RSPO fusions. Thus, WNT pathway gene mutations were more common in SSA/Ps with dysplasia than in SSA/Ps without dysplasia (P=3.0×10−8). Consistently, nuclear β-catenin accumulation and MYC overexpression, indicative of active WNT signaling, were present in most of the SSA/Ps with dysplasia, but were rare in those without dysplasia. BRAF (86%) or KRAS mutations (7%) were identified in the majority of SSA/Ps, regardless of the presence or absence of dysplasia. MLH1 expression was lost in 14 SSA/Ps with dysplasia (30%). The majority of MLH1-deficient SSA/Ps with dysplasia had RNF43 mutations (86%), most of which were frameshift mutations involving mononucleotide repeats. In contrast, MLH1-retained lesions had less frequent RNF43 mutations with no hot spots (34%), and 4 had APC mutations (13%). These results suggest that WNT pathway gene mutations are involved in the development of dysplasia in SSA/Ps and that MLH1-deficient and MLH1-retained SSA/Ps with dysplasia exhibit distinct mutation profiles of WNT pathway genes.
Pathologic Separation of Chronic Hypersensitivity Pneumonitis From Fibrotic Connective Tissue Disease–associated Interstitial Lung Disease
Authors: Churg Andrew , Wright Joanne L. , Ryerson Christopher J.
Published: June 2017

Chronic (fibrotic) hypersensitivity pneumonitis (HP) and fibrosing interstitial pneumonias associated with connective tissue disease (CTD-ILD) can be difficult to distinguish in biopsy specimens. To investigate features that might separate these entities, 2 pathologists blinded to the diagnoses reviewed 16 cases of chronic HP and 12 cases of CTD-ILD. Fifteen predefined parameters were examined by morphometric point counting, analysis/cm2 of lung tissue, or presence/absence. Germinal centers were present in a minority of patients, but favored a diagnosis of CTD-ILD (7/12 CTD vs. 2/16 HP; odds ratio, 9.80 [95% confidence interval, 1.50-63.4]; P=0.02). The number of lymphoid aggregates/cm2 (4.4±3.1 vs. 1.4±1.0; P=0.001), volume proportion of plasma cells (0.076±0.058 vs. 0.031±0.023; P=0.031), and plasma cell: lymphocyte ratio (1.03±0.71 vs. 0.35±0.22; P=0.001) were all significantly higher in CTD compared with HP. A diagnosis of HP was more common in the presence of peribronchiolar metaplasia (12/16 HP vs. 4/12 CTD; odds ratio, 6.00 [95% confidence interval, 1.15-31.2]; P=0.033) and in patients with a greater fraction of bronchioles showing peribronchiolar metaplasia (0.41±0.33 vs. 0.16±0.27; P<0.001). Number of fibroblast foci/cm2, distribution of fibroblast foci, pattern of fibrosis, presence of giant cells/granulomas, and volume proportion of lymphocytes or eosinophils did not distinguish chronic HP from CTD-ILD. We conclude that no single morphologic measure definitively separates chronic HP from CTD-ILD lung biopsies, but numerous foci of peribronchiolar metaplasia favor HP, while the presence of germinal centers, large numbers of lymphoid aggregates, or a high plasma cell: lymphocyte ratio suggests CTD-ILD. Multidisciplinary discussion is often necessary for accurate classification inthis setting.
Prognostic Significance of New AJCC Tumor Stage in Patients With Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant Therapy
Authors: Chatterjee Deyali , Katz Matthew H. , Foo Wai Chin , Sundar Manonmani , Wang Hua , Varadhachary Gauri R. , Wolff Robert A. , Lee Jeffrey E. , Maitra Anirban , Fleming Jason B. , Rashid Asif , Wang Huamin
Published: June 2017

The American Joint Committee for Cancer has adopted a size-based T stage system (eighth edition) for pancreatic ductal adenocarcinoma (PDAC), defined as follows: pT1≤2 cm (pT1a≤0.5 cm, pT1b>0.5 and<1 cm, and pT1c 1-2 cm); pT2>2 and ≤4 cm; and pT3> 4 cm. However, the prognostic value of this new T staging system has not been validated in patients who underwent pancreaticoduodenectomy (PD) after neoadjuvant therapy. In this study, we analyzed 398 PDAC patients who underwent neoadjuvant therapy and PD at our institution from 1999 to 2012. The results were correlated with clinicopathologic parameters and survival. The new T stage correlated with lymph nodes metastasis (P<0.001), tumor response grade (P<0.001), disease-free survival (DFS, P<0.001) and overall survival (OS, P<0.001). None of the patients with ypT0 had recurrence or died of disease. Among the patients with ypT1 disease, patients with ypT1a and ypT1b had better DFS (P=0.046) and OS (P=0.03) than those with ypT1c. However, there was no significant difference in either DFS or OS between ypT1c and ypT2 or between ypT2 and ypT3 groups (P>0.05). In multivariate analysis, new ypT3 stage was associated with shorter OS (P=0.04), but not DFS (P=0.16). Our results show that the new ypT stage better stratify survival than the ypT stage in American Joint Committee for Cancer seventh edition for PDAC patients who received PD after neoadjuvant therapy, and that tumor size cutoff of 1.0 cm work better for ypT2 than the proposed tumor size cutoff of 2.0 cm in this group of patients.
Mixed Gonadal Germ Cell Tumor Composed of a Spermatocytic Tumor-Like Component and Germinoma Arising in Gonadoblastoma in a Phenotypic Woman With a 46, XX Peripheral Karyotype
Authors: Gru Alejandro A. , Williams Eli S. , Cao Dengfeng
Published: June 2017

We report a unique case of gonadal mixed germ cell tumor (GCT) composed of a predominantly spermatocytic tumor (ST)-like component and a minor component of germinoma arising in gonadoblastoma in a phenotypic woman with a 46, XX peripheral karotype. The patient was a 24-year-old woman (gravida 2, para 1) found to have a 7 cm pelvic mass during routine obstetric ultrasound examination at 20 weeks gestational age. She underwent a left salpingo-gonadectomy at gestational age 23 and 2/7 weeks. She recovered well and delivered a healthy baby at full term. The resected gonadal tumor measured 7.5 cm and microscopically was composed of 3 morphologically distinct components: gonadoblastoma (1%), germinoma (1%) and a ST-like component (98%). The ST-like component was composed of 3 populations of tumor cells: small cells, intermediate and large sized cells, similar to testicular ST. Scattered binucleated and multinucleated cells were present. Immunohistochemically the ST-like component was positive for pan-GCT markers SALL4 and LIN28 but with weaker staining than the germinoma. It was negative for OCT4 and TCL1. Only rare tumor cells were positive for SOX17. In contrast, the germinoma cells were diffusely and strongly positive for SALL4, LIN28, OCT4, SOX17, and TCL1. CD117 was positive in both the germinoma and ST-like component but with fewer tumor cells positive in the latter. Flurorescence in situ hybridization study demonstrated isochromosome 12p in the germinoma component but not in the gonadoblastoma and ST-like component. This patient did not receive further chemoradiation therapy after the surgery. She has been free of disease for 10 years and 1 month since her surgery. To our knowledge, this is the first case report of a ST-like GCT in a phenotypic female.
Phosphaturic Mesenchymal Tumors
Authors: Agaimy Abbas , Michal Michael , Chiosea Simion , Petersson Fredrik , Hadravsky Ladislav , Kristiansen Glenn , Horch Raymund E. , Schmolders Jan , Hartmann Arndt , Haller Florian , Michal Michal
Published: June 2017

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm of uncertain histogenesis that has been linked to tumor-induced osteomalacia (TIO) since 1959. The neoplastic cells produce increased amount of FGF23 which results in TIO via uncontrolled renal loss of phosphate (phosphaturia), and consequently diminished bone mineralization. To date, ∼300 cases have been reported. Although there is increasing evidence that PMT can be diagnosed by reproducible histopathologic features, firm diagnosis has been often restricted to cases associated with TIO and, hence, diagnosis of “nonphosphaturic variants” remained challenging. Recently, FGFR1/FN1 gene fusions were detected in roughly half of cases. We herein reviewed the clinicopathologic features of 22 PMTs (15 cases not published before), stained them with an extended immunohistochemical marker panel and examined them by fluorescence in situ hybridization for FGFR1 gene fusions. Patients were 12 males and 9 females (one of unknown sex) aged 33 to 83 years (median: 52 y). Lesions affected the soft tissues (n=11), bones (n=6), sinonasal tract (n=4), and unspecified site (n=1). Most lesions originated in the extremities (9 in the lower and 4 in the upper extremities). Acral sites were involved in 10 patients (6 foot/heel, 3 fingers/hands, and 1 in unspecified digit). Phosphaturia and TIO were recorded in 10/11 and 9/14 patients with detailed clinical data, respectively. Limited follow-up (5 mo to 14 y; median: 16 mo) was available for 14 patients. Local recurrence was noted in one patient and metastasis in another patient. Histologically, 11 tumors were purely of conventional mixed connective tissue type, 3 were chondromyxoid fibroma-like, 2 were hemangio-/glomangiopericytoma-like with giant cells, and 1 case each angiomyolipoma-like and reparative giant cell granuloma-like. Four tumors contained admixture of patterns (predominantly cellular with variable conventional component). Immunohistochemistry showed consistent expression of CD56 (11/11; 100%), ERG (19/21; 90%), SATB2 (19/21; 90%), and somatostatin receptor 2A (15/19; 79%), while other markers tested negative: DOG1 (0/17), beta-catenin (0/14), S100 protein (0/14), and STAT6 (0/7). FGFR1 fluorescence in situ hybridization was positive in 8/17 (47%) evaluable cases. These results add to the phenotypic delineation of PMT reporting for the first time consistent expression of SATB2 and excluding any phenotypic overlap with solitary fibrous tumor or sinonasal glomangiopericytoma. The unifying immunophenotype of the neoplastic cells irrespective of the histologic pattern suggests a specific disease entity with diverse morphotypes/variants rather than different neoplasms unified by TIO.
Nonhuman Primate (Rhesus Macaque) Models of Severe Pressure-Targeted Hemorrhagic and Polytraumatic Hemorrhagic Shock
Authors: Sheppard Forest R. , Macko Antoni R. , Glaser Jacob J. , Vernon Philip J. , Burdette Alexander J. , Paredes Ruth Madelaine , Koeller Craig A. , Pusateri Anthony E. , Tadaki Douglas K. , Cardin Sylvain
Published: June 2017

Background:

We endeavored to develop clinically translatable nonhuman primate (NHP) models of severe polytraumatic hemorrhagic shock.

Methods:

NHPs were randomized into five severe pressure-targeted hemorrhagic shock (PTHS) ± additional injuries scenarios: 30-min PTHS (PTHS-30), 60-min PTHS (PTHS-60), PTHS-60 + soft tissue injury (PTHS-60+ST), PTHS-60+ST + femur fracture (PTHS-60+ST+FF), and decompensated PTHS+ST+FF (PTHS-D). Physiologic parameters were recorded and blood samples collected at five time points with animal observation through T = 24 h. Results presented as mean ± SEM; statistics: log transformation followed by two-way ANOVA with Bonferroni multiple comparisons, Wilcoxon nonparametric test for comparisons, and the Friedmans’ one-way ANOVA; significance: P < 0.05.

Results:

Percent blood loss was 40% ± 2, 59% ± 3, 52% ± 3, 49% ± 2, and 54% ± 2 for PTHS-30, PTHS-60, PTHS-60+ST, PTHS-60+ST+FF, and PTHS-D, respectively. All animals survived to T = 24 h except one in each of the PTHS-60 and PTHS-60+ST+FF groups and seven in the PTHS-D group. Physiologic, coagulation, and inflammatory parameters demonstrated increasing derangements with increasing model severity.

Conclusion:

NHPs exhibit a high degree of resilience to hemorrhagic shock and polytrauma as evidenced by moderate perturbations in metabolic, coagulation, and immunologic outcomes with up to 60 min of profound hypotension regardless of injury pattern. Extending the duration of PTHS to the point of decompensation in combination with polytraumatic injury, evoked derangements consistent with those observed in severely injured trauma patients which would require ICU care. Thus, we have successfully established a clinically translatable NHP trauma model for use in testing therapeutic interventions to trauma.
Guillain–Barré syndrome and Zika virus outbreaks
Authors: Nascimento Osvaldo J.M. , da Silva Ivan R.F.
Published: June 2017

Purpose of review

Arboviruses have been associated with central and peripheral nervous system injuries, in special the flaviviruses. Guillain–Barré syndrome (GBS), transverse myelitis, meningoencephalitis, ophthalmological manifestations, and other neurological complications have been recently associated to Zika virus (ZIKV) infection. In this review, we aim to analyze the epidemiological aspects, possible pathophysiology, and what we have learned about the clinical and laboratory findings, as well as treatment of patients with ZIKV-associated neurological complications.

Recent findings

In the last decades, case series have suggested a possible link between flaviviruses and development of GBS. Recently, large outbreaks of ZIKV infection in Asia and the Americas have led to an increased incidence of GBS in these territories. Rapidly, several case reports and case series have reported an increase of all clinical forms and electrophysiological patterns of GBS, also including cases with associated central nervous system involvement. Finally, cases suggestive of acute transient polyneuritis, as well as acute and progressive postinfectious neuropathies associated to ZIKV infection have been reported, questioning the usually implicated mechanisms of neuronal injury.

The recent ZIKV outbreaks have triggered the occurrence of a myriad of neurological manifestations likely associated to this arbovirosis, in special GBS and its variants.
Klaus Friedrich Roth. 29 October 1925 — 10 November 2015
Authors: Chen William , Vaughan Robert
Published: June 2017

Klaus Friedrich Roth, who died in Inverness on 10 November 2015 aged 90, made fundamental contributions to different areas of number theory, including diophantine approximation, the large sieve, irregularities of distribution and what is nowadays known as arithmetic combinatorics. He was the first British winner of the Fields Medal, awarded in 1958 for his solution in 1955 of the famous Siegel conjecture concerning approximation of algebraic numbers by rationals. He was elected a Fellow of the Royal Society in 1960, and received its Sylvester Medal in 1991. He was also awarded the De Morgan Medal of the London Mathematical Society in 1983, and elected Fellow of University College London in 1979, Honorary Fellow of Peterhouse in 1989, Honorary Fellow of the Royal Society of Edinburgh in 1993 and Fellow of Imperial College London in 1999.
A Bayesian approach to estimating hidden variables as well as missing and wrong molecular interactions in ordinary differential equation-based mathematical models
Authors: Engelhardt Benjamin , Kschischo Maik , Fröhlich Holger
Published: June 2017

Ordinary differential equations (ODEs) are a popular approach to quantitatively model molecular networks based on biological knowledge. However, such knowledge is typically restricted. Wrongly modelled biological mechanisms as well as relevant external influence factors that are not included into the model are likely to manifest in major discrepancies between model predictions and experimental data. Finding the exact reasons for such observed discrepancies can be quite challenging in practice. In order to address this issue, we suggest a Bayesian approach to estimate hidden influences in ODE-based models. The method can distinguish between exogenous and endogenous hidden influences. Thus, we can detect wrongly specified as well as missed molecular interactions in the model. We demonstrate the performance of our Bayesian dynamic elastic-net with several ordinary differential equation models from the literature, such as human JAK–STAT signalling, information processing at the erythropoietin receptor, isomerization of liquid
α
-Pinene, G protein cycling in yeast and UV-B triggered signalling in plants. Moreover, we investigate a set of commonly known network motifs and a gene-regulatory network. Altogether our method supports the modeller in an algorithmic manner to identify possible sources of errors in ODE-based models on the basis of experimental data.
Forkhead box transcription factor L2 activates
Fcp3C
to regulate insect chorion formation
Authors: Ye Yu-Xuan , Pan Peng-Lu , Xu Ji-Yu , Shen Zhang-Fei , Kang Dong , Lu Jia-Bao , Hu Qing-Lin , Huang Hai-Jian , Lou Yi-Han , Zhou Nai-Ming , Zhang Chuan-Xi
Published: June 2017

Most animals are oviparous. However, the genes regulating egg shell formation remain not very clear. In this study, we found that
Nilaparvata lugens
Forkhead box transcription factor L2 (
Nl
FoxL2) directly activated follicle cell protein 3C (
NlFcp3C
) to regulate chorion formation.
NlFoxL2
and
NlFcp3C
had a similar expression pattern, both highly expressed in the follicular cells of female adults. Knockdown of
NlFoxL2
or
NlFcp3C
also resulted in the same phenotypes: obesity and female infertility. RNA interference (RNAi) results suggested that
NlFcp3C
is a downstream gene of
NlFoxL2
. Furthermore, transient expression showed that
Nl
FoxL2 could directly activate the
NlFcp3C
promoter. These results suggest that
NlFcp3C
is a direct target gene of
Nl
FoxL2. Depletion of
NlFoxL2
or
NlFcp3C
prevented normal chorion formation. Our results first revealed the functions of Fcp3C and FoxL2 in regulation of oocyte maturation in an oviparous animal.
A quantum Samaritan’s dilemma cellular automaton
Authors: Alonso-Sanz Ramón , Situ Haozhen
Published: June 2017

The dynamics of a spatial quantum formulation of the iterated Samaritan’s dilemma game with variable entangling is studied in this work. The game is played in the cellular automata manner, i.e. with local and synchronous interaction. The game is assessed in fair and unfair contests, in noiseless scenarios and with disrupting quantum noise.
On the regularization of impact without collision: the Painlevé paradox and compliance
Authors: Hogan S. J. , Kristiansen K. Uldall
Published: June 2017

We consider the problem of a rigid body, subject to a unilateral constraint, in the presence of Coulomb friction. We regularize the problem by assuming compliance (with both stiffness and damping) at the point of contact, for a general class of normal reaction forces. Using a rigorous mathematical approach, we recover impact without collision (IWC) in both the inconsistent and the indeterminate Painlevé paradoxes, in the latter case giving an exact formula for conditions that separate IWC and lift-off. We solve the problem for arbitrary values of the compliance damping and give explicit asymptotic expressions in the limiting cases of small and large damping, all for a large class of rigid bodies.
Experimental evidence that primate trichromacy is well suited for detecting primate social colour signals
Authors: Hiramatsu Chihiro , Melin Amanda D. , Allen William L. , Dubuc Constance , Higham James P.
Published: June 2017

Primate trichromatic colour vision has been hypothesized to be well tuned for detecting variation in facial coloration, which could be due to selection on either signal wavelengths or the sensitivities of the photoreceptors themselves. We provide one of the first empirical tests of this idea by asking whether, when compared with other visual systems, the information obtained through primate trichromatic vision confers an improved ability to detect the changes in facial colour that female macaque monkeys exhibit when they are proceptive. We presented pairs of digital images of faces of the same monkey to human observers and asked them to select the proceptive face. We tested images that simulated what would be seen by common catarrhine trichromatic vision, two additional trichromatic conditions and three dichromatic conditions. Performance under conditions of common catarrhine trichromacy, and trichromacy with narrowly separated LM cone pigments (common in female platyrrhines), was better than for evenly spaced trichromacy or for any of the dichromatic conditions. These results suggest that primate trichromatic colour vision confers excellent ability to detect meaningful variation in primate face colour. This is consistent with the hypothesis that social information detection has acted on either primate signal spectral reflectance or photoreceptor spectral tuning, or both.
Antagonistically pleiotropic allele increases lifespan and late-life reproduction at the cost of early-life reproduction and individual fitness
Authors: Maklakov Alexei A. , Carlsson Hanne , Denbaum Philip , Lind Martin I. , Mautz Brian , Hinas Andrea , Immler Simone
Published: June 2017

Evolutionary theory of ageing maintains that increased allocation to early-life reproduction results in reduced somatic maintenance, which is predicted to compromise longevity and late-life reproduction. This prediction has been challenged by the discovery of long-lived mutants with no loss of fecundity. The first such long-lived mutant was found in the nematode worm
Caenorhabditis elegans
. Specifically, partial loss-of-function mutation in the
age-1
gene, involved in the nutrient-sensing insulin/insulin-like growth factor signalling pathway, confers longevity, as well as increased resistance to pathogens and to temperature stress without appreciable fitness detriment. Here, we show that the long-lived
age-1
(
hx546
) mutant has reduced fecundity and offspring production in early-life, but increased fecundity, hatching success, and offspring production in late-life compared with wild-type worms under standard conditions. However, reduced early-life performance of long-lived mutant animals was not fully compensated by improved performance in late-life and resulted in reduced individual fitness. These results suggest that the
age-1
(
hx546
) allele has opposing effects on early-life versus late-life fitness in accordance with antagonistic pleiotropy (AP) and disposable soma theories of ageing. These findings support the theoretical conjecture that experimental studies based on standing genetic variation underestimate the importance of AP in the evolution of ageing.