bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of Keratoconus Management: Review of the Past 20 Years' Contemporary Treatment Modalities
Authors: Mandathara Preeji S. , Stapleton Fiona J. , Willcox Mark D. P.
Published: May 2016

Objectives:

To describe the past 20 years' contemporary management modalities for keratoconus (KC) and their outcomes and failures and to propose recommendations in reporting their outcomes.

Methods:

A systematic review of the literature on KC management options for the last 20 years was performed. Original articles that reported the outcome of any form of KC management other than full-thickness or lamellar corneal graft were reviewed to collect information on their outcomes and complications and the level of scientific evidence of the study.

Results:

A total of 1,147 articles retrieved and of those, 241 satisfied the inclusion criteria, and 41.1% of them were prospective case series. The higher level of evidence studies, that is, randomized controlled trials (RCTs), were limited to only one intervention, that is, corneal collagen cross-linking (CXL). However, the quality of most RCTs was limited because of performance and detection bias. Contact lenses (CLs) remain the mainstream of KC management and were associated with reversible and non–sight-threatening complications. Surgical options such as intracorneal segment implantation and phakic intraocular lens are considered in the visual rehabilitation of CL intolerants, and CXL is the only available option to stop or delay the disease progression. Generally, these surgical procedures are associated with transient inflammatory events and permanent sequelae.

Conclusions:

The published studies on KC management options varied significantly with respect to the study population, age of participants, severity of KC, clinical outcome measurements, and follow-up period. High-quality longer follow-up RCTs are required to evaluate the long-term effects of KC interventions.
Blood Glucose Control in Noncritically Ill Patients Is Associated With a Decreased Length of Stay, Readmission Rate, and Hospital Mortality
Authors: Ables Adrienne Z. , Bouknight Patricia J. , Bendyk Heather , Beagle Rebecca , Alsip Rebecca , Williams Jill
Published: May 2016

Purpose:

Multiple studies have shown that hyperglycemia correlates with mortality and morbidity in critically ill patients. This has not been demonstrated in noncritically hospitalized patients. The primary objective of this study was to determine whether glycemic control shortens the length of stay (LOS). Secondary objectives included assessing readmissions, in-hospital mortality, and rates of hypoglycemia.

Methods:

A retrospective review of hospitalized patients admitted between 2008 and 2012 with fingerstick blood sugar (FSBS) was performed. Patients were divided into two groups: “controlled” FSBS (≥80% of FSBS were <180 mg/dL) and “uncontrolled” FSBS (<80% of FSBS were <180 mg/dL). The average LOS (ALOS) in days, in-hospital mortality, readmission rates, and rates of hypoglycemia was compared.

Results:

A total of 32,851 patient records were reviewed. ALOS for patients with controlled and uncontrolled FSBS was 5.86 and 6.17 days, respectively (p < .0001). Readmission within 30 days and hospital mortality were significantly lower in patients with controlled FSBS (p = .0000, .00001), whereas rates of hypoglycemia were significantly higher in the uncontrolled group (p = .00000).

Conclusions:

Glycemic control was associated with decreased LOS, hospital mortality, and 30-day readmission rate in noncritically ill patients regardless of the presence or absence of diabetes.
An Analysis of the Daily Work-Rounding Process in a Pediatric Intensive Care Unit
Authors: Gangadharan Sandeep , Belpanno Brian , Silver Peter
Published: May 2016

Objective:

To complete an objective analysis of the activities that occur during the course of daily rounds in a high acuity academic tertiary care pediatric intensive care unit (PICU).

Design:

Prospective observational work sampling design.

Setting:

Tertiary care academic Children's Hospital Pediatric Intensive Care Unit.

Subjects:

Multidisciplinary PICU teams.

Interventions:

None.

Methods:

Intensive care unit rounds were observed as part of an initiative to improve efficiency over a 2-month period. The number of observations required was determined by Neibel's work sampling method. Rounds were broken into various constituent events and then later classified as “value-added/essential,” “value-added/nonessential,” and “nonessential” based on whether the observed event was essential to the core mission of PICU rounds.

Results:

The mean time spent per patient for all observed teams was 17.9 min (SD 1.3 min). Teams spent 64% of their time doing value-added/essential tasks (11.2 min, SD 2.2 min) and 13% of their time doing value-added/nonessential tasks (2.4 min, SD 0.9 min). Teams spent 23% of their time on non–value-added activities (4.1 min, SD 2.3 min). The top three non–value-added activities conducted during rounds were travel, waiting, and interruptions regarding care of other patients. Given the consistency of time spent on value-added activities among attendings, these non–value-added activities might explain the significant variability observed among attendings in total time spent rounding.

Conclusions:

This was an observational study to characterize the activities that occur during the course of a routine PICU work rounds. Although there was significant consistency in the time spent per patient in value-added activities, there was significant disparity in time spent on nonessential activities, such as travel and waiting. A dedicated attempt to reduce time spent on nonessential activities can substantially reduce rounding times and improve the efficiency and value of rounds.
Feasibility and Efficacy of Function-Focused Care for Orthopedic Trauma Patients
Authors: Resnick Barbara , Wells Chris , Galik Elizabeth , Holtzman Lauren , Zhu Shijun , Gamertsfelder Elise , Laidlow Terry , Boltz Marie
Published: May 2016

To overcome challenges associated with optimizing function and physical activity among hospitalized older adults, we developed function-focused care for acute care (FFC-AC). The purpose of this study was to test the feasibility and preliminary effectiveness of this intervention. We hypothesized that hospitalized trauma patients exposed to FFC-AC would (1) maintain or improve function, spend more time in physical activity, and have fewer adverse events between admission and discharge; and (2) maintain or improve function, have less fear of falling, fewer depressive symptoms, less pain, be more physically resilient, and be less likely to experience adverse events at 1 month postdischarge compared with those exposed to FFC-education only (EO). FFC-AC was implemented by a research function-focused care nurse who worked on the participating units for 20 hr a week for 16 months to implement the three components of FFC-AC. The sample included 89 older orthopedic trauma patients the majority of whom were female (N = 59, 66%), white (N = 82, 92%), and not married (N = 53, 59%). At discharge and/or 30 days postdischarge, participants in the treatment site showed greater improvement in function, less fear of falling, and better physical resilience when compared with those in the FFC-EO site. Future research is needed to continue to work on engaging staff in function-focused care approaches and optimizing the hospital environment and policies to support nurses in this type of care approach.
Mycoplasmataceae Colonizations in Women With Urethral Pain Syndrome: A Case-Control Study
Authors: Kyndel Anna , Elmér Caroline , Källman Owe , Altman Daniel
Published: May 2016

Objectives

To determine if Mycoplasma genitalium, Ureaplasma urealyticum, and Ureaplasma parvum are more common in premenopausal women with urethral pain syndrome than in asymptomatic controls.

Methods

We used a case-control study design to compare the prevalence of M. genitalium, U. urealyticum, and U. parvum using polymerase chain reaction (PCR) analysis in urine. Urethral pain syndrome was defined as localized urethral pain with or without accompanying lower urinary tract symptoms during the past month or longer and at least one negative urine culture.

Results

Among the 28 cases, 46% carried Ureaplasma species compared with 64% of the 92 controls overall (P = 0.09). There were no significant differences in the prevalence of U. parvum and U. urealyticum among controls than in patients with urethral pain syndrome (P = 0.35 and P = 0.33, respectively). Co-colonization with U. parvum and urealyticum was infrequent, and there was only one case of M. genitalium colonization, which occurred among the controls. The symptomatic profile of Ureaplasma carriers with urethral pain syndrome was heterogeneous with no clear pattern and did not differ significantly compared with patients negative for Ureaplasma.

Conclusions

We found no evidence to support the notion that M. genitalium, U. parvum, and U. urealyticum are more prevalent in women with urethral pain syndrome than in women without lower urinary tract symptoms.
Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts
Authors: Trahanas John M. , Witer Lucas J. , Alghanem Fares , Bryner Benjamin S. , Iyengar Amit , Hirschl Jacob R. , Hoenerhoff Mark J. , Potkay Joseph A. , Bartlett Robert H. , Rojas-Pena Alvaro , Owens Gabe E. , Bocks Martin L.
Published: May 2016

Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12 hour experiments demonstrated lower potassium (4.3 ± 0.8 vs. 5.0 ± 1.2 mmol/L; p = 0.018) and lactate (3.5 ± 2.8 vs. 4.5 ± 2.9 mmol/L; p = 0.139) levels, and histopathology revealed less tissue damage (p = 0.003) and less weight gain (p = 0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.
Outcome of the Z-expandable metallic stent for Budd–Chiari syndrome and segmental obstruction of the inferior vena cava
Authors: Ding Peng-Xu , Li Zhen , Zhang Shui-Jun , Han Xin-Wei , Wu Yan , Wang Zhong-Gao , Fu Ming-Ti
Published: May 2016

Objective

Treatment of segmental obstruction of the inferior vena cava (SOIVC) with Z-expandable metallic stents (Z-EMS) is controversial and data on long-term follow-up are lacking. We aimed to evaluate the long-term outcomes of the use of a Z-EMS for Budd–Chiari syndrome (BCS) patients with SOIVC.

Materials and methods

Between August 2004 and December 2014, 37 consecutive BCS patients with SOIVC were referred for Z-EMS treatment and subsequently underwent follow-up in our department. Data were collected retrospectively and follow-up observations were made 1, 2, 2–5, and 5–10 years postoperatively.

Results

Percutaneous transluminal balloon angioplasty and Z-EMS placement were technically successful in all patients. Major procedure-related complications occurred in four of 37 patients (10.81%). Follow-up for 61.89±41.45 months in 37 patients indicated portal hypertension in one patient 4 months after stent placement and symptoms were resolved by transjugular intrahepatic portosystemic stent shunting. Hepatocellular carcinoma was observed in four patients and five patients died during follow-up. Reocclusion of the inferior vena cava occurred in four patients (10.81%, 4/41) and all reocclusions were managed by percutaneous transluminal balloon angioplasty. Cumulative 1-, 2-, 2–5-, and 5–10-year primary patency rates were 94.60% (35/37), 93.33% (28/30), 88.89% (24/27), and 85.0% (17/20), respectively. Cumulative 1-, 2-, 2–5-, and 5–10-year secondary patency rates were 100% at all time-points.

Conclusion

These data suggest that Z-EMS implantation is an efficacious, safe, and curative approach for BCS with SOIVC because satisfactory long-term outcomes were achieved. Long-term follow-up is required to ascertain stent patency and hepatocellular carcinoma occurrence.
Missing rate for gastric cancer during upper gastrointestinal endoscopy: a systematic review and meta-analysis
Authors: Pimenta-Melo Ana Rita , Monteiro-Soares Matilde , Libânio Diogo , Dinis-Ribeiro Mário
Published: May 2016

Objectives

Esophagogastroduodenoscopy (EGD) is considered a very effective method to identify gastric cancer (GC). However, the existence of missed lesions has been frequently discussed. This systematic review and meta-analysis aimed at assessing the magnitude of missing GC diagnosis with EGD and its predictive factors.

Methods

MEDLINE was searched to identify all studies assessing and reporting the proportion of missed GC diagnosis with EGD. Pooled proportion and negative predictive values were computed using the random-effects model and heterogeneity was assessed using the Cochrane Q-test and I
2.

Results

The studies included (n=22) were grouped by study design. The pooled negative predictive value was 99.7% (95% confidence interval 99.6–99.9%). Missed GCs proportion was 9.4% (95% confidence interval 5.7–13.1%), being 10.0% in studies including patients with negative EGD followed over time, 8.3% in studies including patients with GC, and 23.3% in studies evaluating the proportion of missed synchronous lesions. Mainly, missed cancers were located in the gastric body both in Eastern and in Western studies (39 and 47%, respectively). The majority of missed GCs were adenocarcinomas. Younger age (<55 years), female sex, marked gastric atrophy, gastric adenoma or ulcer, and inadequate number of biopsy fragments were reported as predictive factors for diagnostic failure.

Conclusion

EGD is a very effective method to rule out GC. However, missing GC with EGD is not uncommon, with one out of 10 cancers being potentially missed. Interestingly, lesions were more often missed in the body and therefore a more rigorous protocol for endoscopy and biopsy should be implemented worldwide.
Actinomycosis of hand: a case report
Authors: Mousavi Seyed Alireza , Mojahed Masudah , Shahcheraghi Seyed Hossein
Published: May 2016

Actinomycosis is a chronic, suppurative and granulomatous infection. Gram-positive, nonsporeforming anaerobic or microaerophilic rods, primarily from the genusActinomyces, are the responsible agents. We present a case report of actinomycosis of the hand.
The Application of an Evidence-Based Clinical Nursing Path for Improving the Preoperative and Postoperative Quality of Care of Pediatric Retroperitoneal Neuroblastoma Patients
Authors: Liu Yang , Mo Lin , Tang Yan , Wang Qiuhong , Huang Xiaoyan
Published: May 2016

Background:

A clinical nursing path (CNP) that encourages patients and their families to become actively involved in healthcare decision-making processes may improve outcomes of pediatric retroperitoneal neuroblastoma (NB) patients.

Objective:

The aim of this study was to evaluate the utility and value of an evidence-based CNP provided to pediatric retroperitoneal NB patients undergoing resection surgery.

Methods:

One hundred twenty NB cases were assigned to a control group or a CNP group. The control group was provided with standard nursing care. The CNP group was provided with nursing care in accordance with an evidence-based CNP. The utility and value of the CNP were compared with standard nursing care. Outcome measures included rates of postoperative complications, lengths of hospital stay, and cost of hospitalization, as well as preoperative and postoperative quality of care and patient satisfaction with care.

Results:

The rates of postoperative complications, length of preoperative hospitalization, total length of hospital stay, and costs of hospitalization were significantly lower for patients receiving the CNP compared with the control group. Preoperative and postoperative quality of care and patient satisfaction with care were significantly higher in patients receiving the CNP compared with the control group.

Conclusion:

Adoption of a CNP for preoperative and postoperative care of pediatric retroperitoneal NB patients undergoing resection surgery improves clinical outcomes and patient satisfaction with care.

Implications for Practice:

A CNP can increase families’ participation in a patient’s recovery process, enhance nurses’ understanding of the services they are providing, and improve the quality of healthcare received by patients.
Palliative Cancer Care in Brazil
Authors: da Silva Marcelle M. , Büscher Andreas , Moreira Marléa Chagas
Published: May 2016

Background:

Palliative care is a recent development in health worldwide. In Brazil, a growing number of people with cancer require palliative care, emphasizing the need for investment in this aspect of health to increase the quality of life of patients during the dying process. As a developing country, Brazil lacks knowledge regarding the themes, material and financial resources, and policies of palliative care.

Objective:

The aim of this study was to provide insights into the Brazilian palliative care system from the perspectives of nurses and physicians.

Methods:

This was a descriptive and qualitative study, conducted at the palliative care unit of the Instituto Nacional de Câncer in Brazil. Twelve professionals, among them 8 nurses and 4 physicians, were interviewed in November 2013. The data were analyzed using the thematic analysis method. Ethical aspects were respected.

Results:

The perspectives of the participants were characterized by 3 themes regarding the initial phase of development of palliative cancer care in Brazil: (1) controversies about when palliative cancer care should be initiated, (2) the World Health Organization recommendations and current practices, and (3) the need to invest in palliative cancer care education in Brazil.

Conclusions:

The development of palliative care is in the initial stages, and there is a possibility for growth due to recent advances.

Implications for Practice:

Knowledge about these challenges to palliative care could contribute to the development of strategies, such as the establishment of service organizations and networks, as well as educational and political investments for the advancement of palliative care.
Relationship Between Patient SWAP-200 Personality Characteristics and Therapist-Rated Therapeutic Alliance Early in Treatment
Authors: Smith Scott W. , Levy Saryn R. , Hilsenroth Mark J. , Fiori Katherine , Bornstein Robert F.
Published: May 2016

In the present study, we assess the extent to which patient personality features and prototypes are associated with early treatment therapist-rated alliance. The study sample consisted of 94 patients receiving psychodynamic psychotherapy at an outpatient clinic. Clinicians completed the Working Alliance Inventory (J Couns Psychol 36:223–233; Psychother Res 9:405–423) to assess their views of early alliance and the Shedler-Westen Assessment Procedure 200 (SWAP-200; Assessment 5:333–353, Am J Psychiatry 161:1350–1365, 1743–1754; Am J Psychiatry 156:258–272, 273–285) to assess patient personality. The SWAP-200 Narcissistic Clinical Prototype, Dysphoric Q-Factor, and Dysphoric/High-Functioning Neurotic Q-Subfactor significantly correlated with early therapist-rated alliance. Correlations that trended toward significance were also found. Also identified were specific SWAP-200 items that were found to relate to high early therapist-rated alliance scores. These results demonstrate some relationship, albeit small, between patient personality characteristics and therapists’ views of the alliance that may serve to further a conceptual understanding of the alliance, specific personality syndromes, and the associated impact on the therapeutic interaction.
Suicide as a Distorted Goal-Directed Process
Authors: Valach Ladislav , Michel Konrad , Young Richard A.
Published: May 2016

It has been suggested that suicidal persons engage in distorted thinking. We propose that suicide can be understood as a distorted goal-directed action. The purpose of this qualitative study was to identify the specific distortions in the goal-directed processes of suicide as indicated in suicide narratives of 40 persons after a suicide attempt. The findings indicate action distortions such as the disconnect between the wish to die, the action of killing oneself, and the experience of being killed. Furthermore, we found a lack of long-term nonsuicidal pursuits, missing or incomplete action monitoring, and control and regulation processes. The implications for suicide prevention are discussed, and the procedure of self-confrontation interview is suggested as a helpful intervention.
The Effects of “Physical Activity on Prescription” in Persons With Transient Ischemic Attack: A Randomized Controlled Study
Authors: Morén Carina , Welmer Anna-Karin , Hagströmer Maria , Karlsson Emelie , Sommerfeld Disa K.
Published: May 2016

Background and Purpose:

Transient ischemic attack (TIA) is a strong predictor of stroke, and physical inactivity is one risk factor for TIA/stroke. “Physical activity on Prescription” (PaP) can increase physical activity, but the effect of PaP after TIA has not been described. Our goal was to objectively measure the effect of PaP on physical activity and physical capacity, as well as self-rated health at 3 and 6 months after TIA.

Methods:

The primary outcome was moderate to vigorous intensities of physical activity objectively assessed by accelerometry. Secondary outcomes were steps per day assessed by accelerometry, physical capacity assessed by the 6-minute walk test, and self-rated health assessed by EQ-5D VAS.

Results:

Eighty-eight individuals with TIA were randomized to an intervention group (n = 44) that received conventional treatment and PaP or to a control group (n = 44) that received conventional treatment alone. There was a 30% dropout among the participants at 6 months. No significant differences between groups were found in physical activity at 3 and 6 months. At 6 months, participants in the intervention group were significantly more likely to have improved their physical capacity than the control group. There was no significant difference between groups in self-rated health.

Discussion and Conclusions:

PaP did not increase physical activity after TIA; however, there was an increase in physical capacity. The nonsignificant results for physical activity may be the result of a relatively high baseline physical activity level. The results may also indicate that prior studies suggesting that PaP increases physical activity overestimated effects because of the self-reported nature of the previous outcomes.

Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A134).
A Case of Sinonasal Melanoma With Unusual Primary Exon 17 KIT D820G Mutation
Authors: Pilozzi Emanuela , Bartolazzi Armando , Fochetti Flavio , Duranti Enrico , Scarpino Stefania , Valeriani Maurizio , Moriconi Piero , Ruco Luigi
Published: May 2016

Sinonasal melanomas are rare neoplasms with poor prognosis that may harbor KIT and NRAS genes mutations. Molecular alterations represent possible targets of tailored therapeutic approaches. We describe the case of a 74-year-old patient with primary melanoma of the nasal cavity. Mutational analysis of KIT demonstrated a point missense mutation D820G in exon 17. This represents, to our knowledge, the first case of sinonasal melanoma harboring this specific KIT mutation. Although KIT mutations confer sensibility to thyrosine-kinase inhibitor, it has been proved that this is strongly dependent on the region in which this alteration occurs. Thus it seems very important to perform an accurate gene mutational analysis to provide a biological rationale to the tailored therapy.
HER2 Status in Gastroesophageal Adenocarcinomas: Correlation Between Immunohistochemistry and Fluorescence In Situ Hybridization Methodologies
Authors: Robertson Scott A. , Cimino-Mathews Ashley , Cornish Toby C.
Published: May 2016

Semiquantitative immunohistochemistry (IHC) is commonly used in combination with fluorescence in situ hybridization (FISH) to detect HER2 amplification in gastroesophageal adenocarcinomas. Most laboratories apply these tests in a sequential algorithm, using IHC as a frontline test and reserving FISH for IHC-equivocal cases. To gain a better understanding of the concordance of IHC and FISH results at our institution, we identified all gastroesophageal adenocarcinomas at our institution tested for HER2 (n=125). Matched IHC and FISH were available for 116 cases (94%). Cases consisted of adenocarcinoma of the distal esophagus (22%), gastroesophageal junction (24%), stomach (43%), and metastatic sites (12%). A total of 88 cases (70%) were biopsies, whereas 37 cases (30%) were resections. Overall, 15 cases (13%) were HER2 positive (IHC 3+ and/or FISH amplified). A total of 60 cases (52%) were IHC score 0; none of these were HER2 amplified by FISH. A total of 30 cases (26%) were IHC 1+; 5 (17%) of these cases were HER2 amplified by FISH. A total of 20 cases (17%) were IHC 2+; 4 (20%) of these cases were HER2 amplified by FISH. A total of 6 cases were IHC score 3+; all of these were HER2 amplified by FISH. Although there was a high overall concordance between IHC and FISH results (96%), a subset (17%) of IHC-negative cases (score 1+) were HER2 amplified as evaluated by FISH, representing 33% of all HER2 amplified cases. This suggests that the common practice of limited FISH testing to IHC 2+ cases will miss a significant number of HER2 amplified cases.
Unexpected Death Due to Acute Gastric Dilatation and Gastric Necrosis in an 11-Year-Old Boy
Authors: Kocaoglu Canan , Akillioglu Ishak , Gunduz Metin , Sekmenli Tamer
Published: May 2016

This report is related to the unusual case of an 11-year-old boy presenting with acute gastric dilatation after the intake of excessive food and carbonated beverages after a 12-hour fasting who died of complications of acute reperfusion syndrome after decompression of the stomach with gastrotomy. An enormously distended stomach was encountered without volvulus and obstruction in the operation. Autopsy and histological findings revealed a severely distended stomach, the walls of which were notably thin and displayed transmural necrosis. The reported case demonstrated that enormous food and beverage intake may cause acute gastric dilatation and gastric necrosis, and subsequently, sudden death may develop in children. The subject reported here is the youngest child in literature dying from acute gastric dilatation and necrosis without any underlying disorders and exposed to autopsy.
Synchronous Ileal Neuroendocrine Tumor and Ovarian Steroid Cell Tumor Present in a Female With Hyperandrogenism
Authors: Gray Stephanie , Chen Yongxin , Litton Tyler , Jallad Bassel , Poddar Nishant , Hoff John T. , Schroeder Katie , Taylor Jason , Veerapong Jula , Lai Jin-Ping
Published: May 2016

Well-differentiated neuroendocrine tumors (NET) of the ileum are generally slow-growing tumors with metastatic potential that may cause systemic symptoms from the secretion of serotonin, cortisol, and other biologically active substances. Likewise, steroid cell tumors of the ovary are slow-growing tumors that cause systemic symptoms from the functional production of androgens, estrogens, and other hormones. To the best of our knowledge, synchronous ileal NET and ovarian steroid cell tumors have not been previously reported in the English literature. We present a case of a 59-yr-old woman with 2 primary tumors that were found incidentally: a Stage III (T2N1M0) 1.6 cm well-differentiated NET (NET G2) of the terminal ileum with metastasis to a mesenteric lymph node and a 2.4 cm steroid cell tumor of the left ovary. The patient had suffered from hyperandrogenism for several years before diagnosis of an ovarian steroid cell tumor, but had no symptoms attributable to the NET. From review of the literature, this is the first case description of these 2 primaries arising in the same individual.
Immunohistochemical Profiling of Endometrial Serous Carcinoma
Authors: Chen Wenqian , Husain Arjumand , Nelson Gregg S. , Rambau Peter F. , Liu Shuhong , Lee Cheng-Han , Lee Sandra , Duggan Máire A. , Köbel Martin
Published: May 2016

Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%–98%] and specificity of 87.8% (95% CI, 75%–95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%–99%) and specificity of 72.2% (95% CI, 46%–90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%–79%) and specificity of 98.0% (95% CI, 94%–99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.
IgG4-related Disease of the Ovary: A First Description
Authors: Sekulic Miroslav , Pichler Sekulic Simona , Movahedi-Lankarani Saeid
Published: May 2016

IgG4-related disease has been previously described to involve numerous organs and anatomic sites, however, involvement of the ovary has not yet been reported in the literature. In this case report we describe an ovary involved with an inflammatory process with histopathologic features supportive of involvement by IgG4-related disease: a dense lymphoplasmacytic infiltrate with an eosinophilic component, obliterative phlebitis, and a prominent proportion of IgG-positive cells with IgG4 expression by immunohistochemistry (40%–50%). The differential diagnosis for this case would include eosinophilic perifolliculitis involving the ovary, another rare entity that shares the eosinophilic component of IgG4-related disease. In short, we present the first description of IgG4-related disease of the ovary providing morphologic characterization and immunohistochemical studies supporting the diagnosis.
Antegrade Peroneal Flap through the Interosseous Membrane for Knee and Distal Femur Coverage
Authors: Angrigiani Claudio , Artero Guillermo , Neligan Peter C. , Escudero Ezequiel , Sereday Carlos , Khouri Roger K.
Published: May 2016

Background:

Antegrade peroneal flaps can be rotated around the fibula to cover defects in the lower leg and lateral knee. However, these flaps cannot reliably cover the distal femur and anterior and medial knee. In the present article, the authors describe a novel technical modification that involves creating a tunnel through the interosseous membrane, through which the flap can be passed, circumventing the need to rotate around the fibula, allowing it to reach the entire knee and distal femur.

Methods:

An anatomical study was performed in five cadaveric specimens to measure the gain in pedicle reaching distance when the flap is tunneled compared to transferred around the fibula. A clinical study in 12 patients was also performed to measure the gain in pedicle reaching distance and the long-term viability of the tunneled interosseous flap.

Results:

In the anatomical study, the mean reaching distance was 7.4 ± 0.9 cm for the flaps rotated around the fibula and 17.0 ± 1.6 for the tunneled interosseous flaps (p< 0.001). In the clinical study, the mean reaching distance was 2.6 ± 1.4 cm for the flaps rotated around the fibula and 11.4 ± 2.4 for the tunneled interosseous flaps (p< 0.0000000001). Patients were followed for up to 4 years (mean, 2.5 years). All flaps survived completely, and there were no complications.

Conclusion:

By passing the antegrade peroneal flap through the interosseous membrane, instead of around the fibula, the flap reaching distance can be increased by approximately 8 cm, allowing for effective coverage of distal femur and knee defects.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Classification System for Individualized Treatment of Adult Buried Penis Syndrome
Authors: Tausch Timothy J. , Tachibana Isamu , Siegel Jordan A. , Hoxworth Ronald , Scott Jeremy M. , Morey Allen F.
Published: May 2016

Background:

The authors present their experience with reconstructive strategies for men with various manifestations of adult buried penis syndrome, and propose a comprehensive anatomical classification system and treatment algorithm based on pathologic changes in the penile skin and involvement of neighboring abdominal and/or scrotal components.

Methods:

The authors reviewed all patients who underwent reconstruction of adult buried penis syndrome at their referral center between 2007 and 2015. Patients were stratified by location and severity of involved anatomical components. Procedures performed, demographics, comorbidities, and clinical outcomes were reviewed.

Results:

Fifty-six patients underwent reconstruction of buried penis at the authors’ center from 2007 to 2015. All procedures began with a ventral penile release. If the uncovered penile skin was determined to be viable, a phalloplasty was performed by anchoring penoscrotal skin to the proximal shaft, and the ventral shaft skin defect was closed with scrotal flaps. In more complex patients with circumferential nonviable penile skin, the penile skin was completely excised and replaced with a split-thickness skin graft. Complex patients with severe abdominal lipodystrophy required adjacent tissue transfer. For cases of genital lymphedema, the procedure involved complete excision of the lymphedematous tissue, and primary closure with or without a split-thickness skin graft, also often involving the scrotum. The authors’ overall success rate was 88 percent (49 of 56), defined as resolution of symptoms without the need for additional procedures.

Conclusion:

Successful correction of adult buried penis often necessitates an interdisciplinary, multimodal approach.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Pharmacokinetics of Total and Unbound Etravirine in HIV-1–Infected Pregnant Women
Authors: Ramgopal Moti , Osiyemi Olayemi , Zorrilla Carmen , Crauwels Herta M. , Ryan Robert , Brown Kimberley , Hillewaert Vera , Baugh Bryan
Published: May 2016

Background:

Treatment of HIV-1–infected women during pregnancy protects maternal health and reduces the risk of perinatal transmission of HIV-1. However, physiologic changes that occur during pregnancy may affect drug pharmacokinetics. This phase IIIb, open-label study evaluated the effects of pregnancy on the pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor etravirine.

Methods:

Eligible HIV-1–infected pregnant women (18–26 weeks gestation) on an individualized, highly active antiretroviral therapy regimen including etravirine 200 mg twice daily were enrolled. Blood samples to assess the pharmacokinetics of total and unbound etravirine were obtained at clinic visits during the second and third trimesters (24- to 28-weeks and 34- to 38-weeks gestation, respectively) and 6–12 weeks postpartum. At each time point, plasma concentrations were measured over 12 hours (12-hour time point was obtained before the second daily dose of etravirine); pharmacokinetic parameters were derived using noncompartmental analysis and were compared between pregnancy and postpartum using general linear models. Antiviral and immunologic response and safety were assessed at each visit.

Results:

Etravirine pharmacokinetic profiles were available for 13 of 15 enrolled women. Exposure to total etravirine was generally higher during pregnancy compared with 6–12 weeks postpartum (1.2- to 1.4-fold); the differences were less pronounced for unbound (pharmacodynamically active) etravirine. Virologic response was generally preserved throughout the study, and no perinatal transmission was observed. Etravirine was generally safe and well tolerated.

Conclusions:

Etravirine 200 mg twice daily, as part of individualized combination antiretroviral therapy, may be a treatment option for HIV-1–infected pregnant women.
Weight Gain and Incident Diabetes Among HIV-Infected Veterans Initiating Antiretroviral Therapy Compared With Uninfected Individuals
Authors: Herrin Melissa , Tate Janet P. , Akgün Kathleen M. , Butt Adeel A. , Crothers Kristina , Freiberg Matthew S. , Gibert Cynthia L. , Leaf David A. , Rimland David , Rodriguez-Barradas Maria C. , Ruser Chris B. , Herold Kevan C. , Justice Amy C.
Published: May 2016

Background:

The health implications of weight gain after antiretroviral therapy (ART) for HIV infection are not well characterized and may differ from weight gain among uninfected individuals. We use data from the Veterans Aging Cohort Study to determine whether weight gain after ART has a similar association with incident type 2 diabetes mellitus (DM) as weight gained among HIV-uninfected (uninfected) individuals.

Methods:

We explored associations of weight gain and incident diabetes (A1c ≥ 6.5%), in the Veterans Aging Cohort Study, a national observational study of HIV-infected (HIV+) individuals demographically matched 1:2 to uninfected controls. From 2000 to 2011, weight change was assessed in the year following ART initiation for HIV+ individuals and date of first available body mass index for uninfected individuals. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for baseline body mass index using Cox regression.

Results:

HIV+ individuals had lower prevalence of DM at baseline (12% HIV+, 23% uninfected) and lower incident diabetes (5% HIV+, 11% uninfected). The association of weight gain with risk of DM was linear for HIV+ and uninfected but the slope of the association was steeper for HIV+. For each 5 pounds of weight gained, HIV+ had 14% increased risk of DM (HR, 1.14; 95% CI: 1.10 to 1.17) and uninfected individuals had 8% increased risk (HR, 1.08; 95% CI: 1.07 to 1.10) (P < 0.01 for interaction).

Conclusions:

Weight gained in the first year after ART initiation is associated with greater risk of DM than that among uninfected individuals. HIV+ individuals initiating ART who are not underweight should avoid substantial weight gain.
Prevalence, Awareness, and Understanding of Pelvic Floor Disorders in Adolescent and Young Women
Authors: Parden Alison M. , Griffin Russell L. , Hoover Kimberly , Ellington David R. , Gleason Jonathan L. , Burgio Kathryn L. , Richter Holly E.
Published: May 2016

Objectives

The objective of this study was to characterize symptom prevalence, awareness of pelvic floor disorders (PFDs) in family/friends, and understanding of factors contributing to the development of PFDs in women aged 19 to 30 years.

Methods

This study is a cross-sectional study via online questionnaire survey of female students aged 19 to 30 years enrolled at the University of Alabama at Birmingham. Results of “adolescent women” aged 19 to 24 years were compared with “young women” aged 25 to 30 years.

Results

A total of 1092 questionnaires were completed with the mean age being 23.5 ± 3.1 years. The overall rate of urinary incontinence (UI) was 10.3% without a difference between adolescent and young women (P = 0.61). There were no differences in rates of urgency UI (P = 0.061), stress UI (P = 0.29), or pelvic organ prolapse (POP) symptoms (P = 0.56) between groups. There was no difference between groups in awareness of family members with UI, fecal incontinence (FI), or POP symptoms (P ≥ 0.24). However, logistic regression showed that the young women were more likely to have received education regarding UI (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 1.8–3.6), FI (aOR, 3.3; 95% CI, 2.2–4.8), POP (aOR, 2.9; 95% CI, 2.1–4.2), and have greater understanding regarding causes of UI (aOR, 2.9; 95% CI, 1.7–4.8), FI (aOR, 1.6; 95% CI, 1.1–2.3), and POP (aOR, 1.9; 95% CI, 1.3–2.9).

Conclusions

Women aged 25 to 30 years had more awareness and understanding of PFDs compared with adolescent women. These data may have implications for primary prevention strategies of PFDs.
Rescuing perishable neuroanatomical information from a threatened biodiversity hotspot: Remote field methods for brain tissue preservation validated by cytoarchitectonic analysis, immunohistochemistry, and X-ray microcomputed tomography
Authors: Hughes Daniel F. , Walker Ellen M. , Gignac Paul M. , Martinez Anais , Negishi Kenichiro , Lieb Carl S. , Greenbaum Eli , Khan Arshad M.
Published: May 2016

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot.

First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull.

In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity.
Self-Driven Jamming in Growing Microbial Populations
Authors: Delarue Morgan , Hartung Jörn , Schreck Carl , Gniewek Pawel , Hu Lucy , Herminghaus Stephan , Hallatschek Oskar
Published: May 2016

In natural settings, microbes tend to grow in dense populations [1–4] where they need to push against their surroundings to accommodate space for new cells. The associated contact forces play a critical role in a variety of population-level processes, including biofilm formation [5–7], the colonization of porous media [8, 9], and the invasion of biological tissues [10–12]. Although mechanical forces have been characterized at the single cell level [13–16], it remains elusive how collective pushing forces result from the combination of single cell forces. Here, we reveal a collective mechanism of confinement, which we call self-driven jamming, that promotes the build-up of large mechanical pressures in microbial populations. Microfluidic experiments on budding yeast populations in space-limited environments show that self-driven jamming arises from the gradual formation and sudden collapse of force chains driven by microbial proliferation, extending the framework of driven granular matter [17–20]. The resulting contact pressures can become large enough to slow down cell growth by delaying the cell cycle in the G1 phase and to strain or even destroy the microenvironment through crack propagation. Our results suggest that self-driven jamming and build-up of large mechanical pressures is a natural tendency of microbes growing in confined spaces, contributing to microbial pathogenesis and biofouling [21–26].
The relative values of the turnover number and the dissociation rate constant determine the definition of the Michaelis-constant
Authors: Nazzal Gassan
Published: May 2016

In this work, we attempt to determine the assumptions of each case of the QSSA. We came to the conclusion that for an enzyme with average kinetics parameters the REA is a good approximation to derive the rate equation and the Km value tends to equal the dissociation constant Kd. The active site classifies the population of the substrate into two energy states, the ground state, and the transition state. The ratio Km/Kdis equal to the partition function of the assumed two-state-system. For the average enzyme, the partition function of the transition tends to equal 1 thus the majority of the substrate molecules are in the ground state and the assumption kcat << k−1is valid hence Km ≈ Kd. In contrast, when the enzyme is diffusion controlled, the Km value is equal to the productive dissociation rate kcat/k1. We have also redefined the Km value as the equivalence point of the reaction rates, namely, the effective diffusion rate and the maximal catalytic rate, which reflects more clearly the transition from the bimolecular reaction to the unimolecular reaction in the saturation curve.