bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause
Authors: Labrie Fernand , Archer David F. , Koltun William , Vachon Andrée , Young Douglas , Frenette Louise , Portman David , Montesino Marlene , Côté Isabelle , Parent Julie , Lavoie Lyne , BSc Adam Beauregard , Martel Céline , Vaillancourt Mario , Balser John , Moyneur Érick
Published: October 2018

Objective:

The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM).

Methods:

In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively.

Results:

After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6% of the participants.

Conclusions:

The daily intravaginal administration of 0.50% (6.5 mg) DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.
A Situation-Specific Theory of Caregiver Contributions to Heart Failure Self-care
Authors: Vellone Ercole , Riegel Barbara , Alvaro Rosaria
Published: October 2018

Background

The literature on caregiver contributions to heart failure (HF) patient self-care has grown rapidly during the last few years, but theory guiding this growth is lacking.

Objective

The purpose of this article is to describe a Situation-Specific Theory of Caregiver Contributions to HF Self-care.

Results

We describe theoretical assumptions, the process by which caregivers contribute to HF self-care, factors influencing caregiver contributions to HF self-care, known predictors (caregiver, patient, and dyadic related) and outcomes of caregiver contributions to HF. These outcomes may be caregiver and patient related and positive and/or negative. Caregiver contributions to HF self-care include interacting processes of self-care maintenance, symptom monitoring and perception, and self-care management. Caregiver confidence and cultural values are discussed as important influences on caregiver contributions to HF self-care. Recursive pathways are hypothesized between processes and outcomes. Ten theoretical propositions are proposed.

Conclusions

The Situation-Specific Theory of Caregiver Contributions to HF Self-care is still in its infancy, and more research is needed to strengthen the evidence supporting the theory. But at this point, the theory may help to guide future studies addressing caregiver contributions to HF self-care and clinical practice aimed at improving caregiver and patient outcomes.
A Multicenter Study on the Utility of EBUS-TBNA and EUS-B-FNA in the Diagnosis of Mediastinal Lymphoma
Authors: Dhooria Sahajal , Mehta Ravindra M. , Madan Karan , Vishwanath Gella , Sehgal Inderpaul S. , Chhajed Prashant N. , Prakash Gaurav , Gupta Nalini , Bal Amanjit , Agarwal Ritesh
Published: October 2018

Background:

There is conflicting data on the utility of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) for the detection and subtyping of lymphomas. Herein, we present our experience with EBUS-TBNA in suspected lymphoma.

Methods:

This was a multicenter retrospective study of subjects with suspected lymphoma who underwent EBUS-TBNA (July 2011 to June 2017). The performance characteristics of EBUS-TBNA were calculated separately for suspected new-onset and recurrent lymphoma as well as for subtyping. We also analyzed the factors predicting the yield of EBUS-TBNA in suspected lymphoma.

Results:

Among the 4803 EBUS procedures performed, 92 (1.9%) subjects had either suspected or proven lymphoma; 48 were finally diagnosed to have lymphoma. The diagnostic sensitivities of EBUS-TBNA in new-onset and recurrent lymphomas were 72.7% and 73.3%, respectively. Only 24.2% (8/33) subjects with new-onset lymphoma could be appropriately subtyped. This low yield was possibly due to inadequate material for cell block in 10 subjects, and performance of immunophenotyping and flow cytometry in only 5 and 1 subjects, respectively. Among the suspected cases of recurrence, EBUS-TBNA was sufficient for management in 81.8% (18/22). On a multivariate analysis, no factor (rapid onsite evaluation, needle size, number of lymph nodes sampled, passes per node, and size of the largest lymph node sampled) predicted the diagnostic yield.

Conclusion:

EBUS-TBNA is a useful investigation in the diagnostic algorithm of suspected lymphoma as it helps avoid other invasive diagnostic procedures. The sensitivity of EBUS-TBNA in subtyping new-onset mediastinal lymphoma depends on the adequacy of cell aspirate and the judicious utilization of pathologic techniques.
Risk of Renal Injury After the Use of Polyethylene Glycol for Outpatient Colonoscopy
Authors: Cheng Chi-Liang , Liu Nai-Jen , Tang Jui-Hsiang , Kuo Yen-Lin , Lin Cheng-Hui , Lien Jau-Min , Tsui Yi-Ning , Lee Bai-Ping , Hung Hsiang-Ling
Published: October 2018

Goal:

The goal of this study was to estimate the risk of renal injury after the use of 3-L polyethylene glycol (PEG) before outpatient colonoscopy.

Background:

Population-based studies showed that the use of PEG was associated with renal injury, but this association has not been confirmed by prospective study.

Study:

Patients ≥40 years of age with an estimated glomerular filtration rate ≥30 mL/min were screened for enrollment. Laboratory data were collected before, during, and after the colonoscopies. Patients with a ≥30% increase in baseline serum creatinine levels were followed until a peak level was detected. Renal injury included acute renal dysfunction (ARD) and acute kidney injury (AKI), defined as a 30% to 49% increase and ≥50% increase in creatinine levels compared with the baseline, respectively.

Results:

A total of 1163 patients (mean age, 55.7 y) completed the study. Baseline and first postcolonoscopy laboratory data were obtained an average of 17.0 days before and 17.3 days after the colonoscopies were performed, respectively. Renal injury was identified in 32 patients; 26 patients (2.2%) had ARD, and 6 patients (0.5%) had AKI. All patients with renal injury recovered fully during follow-up. In the subgroup analysis, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) before colonoscopy was statistically associated with the development of AKI (odds ratio, 6.5; 95% confidence interval, 1.2-35.5; P=0.03).

Conclusions:

This prospective study showed that the use of PEG was associated with a small risk of renal injury. NSAIDs use was statistically associated with AKI in the context of colonoscopy for which PEG was used for bowel preparation.
Risk of sexually transmitted infections following depressive disorder
Authors: Huang Sheng-Yun , Hung Jeng-Hsiu , Hu Li-Yu , Huang Min-Wei , Lee Shyh-Chyang , Shen Cheng-Che
Published: October 2018

Depressive disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous papers in the literature investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial.

We explored the relationship between depressive disorder and the subsequent development of STIs including human immunodeficiency virus (HIV) infection, primary, secondary, and latent syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis.

We identified patients who were diagnosed with the depressive disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without the depressive disorder who were matched according to age and sex. The occurrence of subsequent new-onset STIs was evaluated in both cohorts.

The depression cohort consisted of 5959 patients, and the comparison cohort consisted of 23,836 matched control patients without depressive disorder. The incidence of subsequent STIs (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.34–1.76) was higher among the depressed patients than among the patients in the comparison cohort. Furthermore, female gender compared to male (HR 1.58, 95% CI 1.24–2.01) and young age <40-year-old (HR 1.79, 95% CI 1.38–2.32) are both risk factors for acquisition of STIs in depression patient. For individual STI, the results indicated that the patients with depressive disorder exhibited a markedly higher risk for subsequent STIs including HIV infection, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis.

Depressive disorder might increase the risk of subsequent newly diagnosed STIs including HIV infection, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis in Taiwan population. Clinicians should pay particular attention to STIs in depression patients. Depression patients, especially those with the history of high-risk sexual behaviors, should be routinely screened for STIs.
Pharmacologic prevention of postoperative delirium after on-pump cardiac surgery
Authors: Tao Rui , Wang Xiao-Wen , Pang Liang-Jun , Cheng Jun , Wang Yong-Mei , Gao Guo-Qing , Liu Yu , Wang Chao
Published: October 2018

Background:

Postoperative delirium is a prevalent and disabling mental disorder in patients undergoing on-pump cardiac surgery. There is some evidence that the use of pharmacological interventions may reduce the risk of developing of postoperative delirium. Therefore, the aim of this meta-analysis was to determine the effect of pharmacologic agents for the prevention postoperative delirium after cardiac surgery.

Methods:

Randomized controlled trials (RCTs) were identified through a systematic literature search of electronic databases and article references up to October 2016. End points included incidence of postoperative delirium, severity of postoperative delirium, cognitive disturbances of postoperative delirium, duration of postoperative delirium, length of stay in intensive care unit (ICU) and hospital, and short-term mortality.

Results:

A total of 14 RCTs with an aggregate of 14,139 patients were included. The results of the present meta-analysis show that pharmacologic agents significantly decrease postoperative delirium [relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.75–0.91, P < .00001] and duration of postoperative delirium (RR = −0.37, 95% CI = −0.47 to −0.27, P < .00001) after on-pump cardiac surgery. In addition, subgroup analysis shows that dexamethasone and dexamethasone were associated with a trend toward a reduction in postoperative delirium (RR, 0.45; 95% CI, 0.30–0.66, P < .0001; RR, 0.80; 95% CI, 0.68–0.93, P = .003, respectively). However, our results fail to support the assumption that pharmacologic prophylaxis is associated with a positively reduction in short-term mortality, length of ICU, or hospital stay.

Conclusion:

This meta-analysis suggests that the perioperative use of pharmacologic agents can prevent postoperative delirium development in patients undergoing cardiac surgery. However, there remain important gaps in the evidence base on a few small studies with multiple limitations. Further large-scale, high-quality RCTs are needed in this area.
Using an informatics education strategy to resolve the dilemma of teaching transplantation in medical institutions
Authors: Hsieh Ming H. , Shih Fu-Jong , Sheu Shuh-Jen , Wang Shoei-Shen , Shih Fu-Jin
Published: October 2018

In Taiwan, the current survival rate 1 year after transplantation exceeds 80%. However, the number of organ/tissue donors per year in Taiwan is extremely low, resulting in increased mortality. This is also true in Europe and in the United States. Recently, data from the Taiwan Organ Registry and Sharing Center showed that, although fundraising for organs/tissues slightly increased, the number of donors did not exhibit a corresponding growth trend. Identifying appropriate donors and the provision of good quality transplantation care by medical team members are current challenges. Hence, the application of information technology to in-service education for organ transplantation professionals has been suggested.

This was a qualitative study that employed qualitative content analysis with purposive and snowball sampling. The study participants (n = 8, mean age 39.88 ± 3.06 years) included medical staff involved in tissue/organ transplantation from 4 leading medical centers and 3 regional teaching hospitals, and those who participated in the informatics education system.

The interviewees from multidisciplinary medical teams showed the status of and dilemma in organ fundraising/donation/transplantation, noting 6 core themes. Regarding relevant education and training, 4 core themes were identified.

Current educational courses for organ fundraising/donation/transplantation are inadequate and seem to provide insufficient information to multidisciplinary medical teams. Hence, it is necessary to develop a theoretical construct to create a complete curriculum framework and to establish complete fit-in professional and ethical organ transplantation learning programs based on informatics technology to increase the interdisciplinary exchange of experience.
Hemichorea associated with cavernous angioma and a small errhysis
Authors: Qiu Jiqing , Cui Yu , Sun Lichao , Guo Yunbao , Zhu Zhanpeng
Published: October 2018

Rationale:

Chorea is a movement disorder characterized by randomly appearing involuntary movements of the face, neck, limbs, or trunk. Hemichorea is unilateral, involving one side of the body. Hemichorea is commonly caused by non-ketotic hyperglycemia and/or cerebrovascular injury to the contralateral basal ganglia.

Patient concerns:

Here, we report the case of a patient diagnosed with hemichorea who had diabetes, cavernous angioma, and a small intracranial errhysis. Routine testing showed the patient's blood glucose level was slightly higher than the normal range.

Interventions:

The errhysis was too small to be treated.

Diagnoses:

Brain magnetic resonance imaging showed a cavernous angioma with a small errhysis in the right putamen.

Outcomes:

Hemichorea was completely resolved after 4 months.

Lessons:

If diabetes is well controlled and imaging indicates brain lesions suggestive of a recent stroke, a diagnosis of post-stroke hemichorea should be considered.
Dysphagia with fatal choking in oculopharyngeal muscular dystrophy
Authors: Chen Andy Wei-Ge , Wu Shey-Lin , Cheng Wen-Ling , Chuang Chieh-Sen , Chen Chih-Hua , Chen Mu-Kuan , Liu Chin-San
Published: October 2018

Rationale:

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant late-onset progressive muscle disorder typically characterized by ptosis, difficulty in swallowing, and proximal limb weakness. Underdiagnosis of OPMD is common in Asian countries and results in delayed diagnoses and fatal events.

Patient concerns:

Here, we report the case of a 53-year-old female who suffered from progressive dysphagia and experienced several choking events involving solid material. An extensive family history of dysphagia was noted, and 2 family members had died as a result of aspiration.

Diagnoses:

PABPN1 genotyping and DNA sequence analysis revealed a heterozygous (GCG)10(GCA)3GCG mutation that led to the diagnosis of OPMD.

Interventions:

Rehabilitation exercises, namely, the Shaker exercise and the Masako maneuver, were suggested.

Outcomes:

Improved swallowing ability with safe food intake was noted after 2 months of training. Surgical intervention will be considered when progression of the disease is noted.

Lessons:

Underdiagnosis and a lack of awareness of OPMD may lead to choking, aspiration pneumonia, and death in multiple members of affected families. Currently, there is no definitive treatment for OPMD, but rehabilitation exercises and surgical intervention are helpful in relieving dysphagia.
Prevalence and outcome of acute gastrointestinal injury in critically ill patients
Authors: Zhang Dong , Li Yuting , Ding Lili , Fu Yao , Dong Xuechao , Li Hongxiang
Published: October 2018

Background:

The aim of the study was to investigate the prevalence and impact of acute gastrointestinal injury (AGI) on clinical outcomes in critically ill patients.

Methods:

The PubMed, Cochrane, and Embase databases were searched to identify trials that assessed gastrointestinal injury in critically ill patients. Outcome measures were prevalence of AGI among critically ill patients; incidence of mortality among critically ill patients with AGI, and incidence of mortality stratified by severity of AGI.

Results:

The meta-analysis included 14 studies. The prevalence of AGI in critically ill patients was 40% [95% confidence interval (CI), 27%–54%]; the incidence of mortality among critically ill patients with AGI was 33% (95% CI, 26%–41%). There was a higher risk of mortality in critically ill patients with AGI compared to those without AGI [risk ratio (RR) = 2.01; 95% CI 1.20–3.37, P = .008). Subgroup analyses of studies that defined AGI according to European Society of Intensive Care Medicine (ESICM) criteria confirmed these findings and showed that the risk of mortality was higher in critically ill patients with more severe AGI (ESICM grade III and IV vs grade II) [RR of 1.86 (95% CI 1.48–2.34), P < .00001].

Conclusion:

AGI is common in critically ill patients, mortality in critically ill patients with AGI is high, and severity of AGI is associated with mortality. The widespread clinical use of standard criteria with a severity gradation will facilitate the diagnosis and management of AGI in critically ill patients.
Performance of noninvasive laser Doppler flowmetry and laser speckle contrast imaging methods in diagnosis of Buerger disease
Authors: Omarjee Loukman , Larralde Antoine , Jaquinandi Vincent , Stivalet Olivier , Mahe Guillaume
Published: October 2018

Rationale:

Buerger disease (BD) is a nonatherosclerotic, inflammatory, segmental vascular occlusive disease, which affects small and medium-sized arteries and veins and is triggered by substantial tobacco exposure. Angiographic findings consistent with BD are required for diagnosis. Laser Doppler flowmetry (LDF) and laser speckle contrast imaging (LSCI) could represent potential noninvasive alternative techniques to angiography.

Patient concerns:

We report the case of a 49-year-old smoker who developed an ischemic ulcer in the distal segment of the second finger of the left hand. He had no medical history.

Diagnoses:

In our vascular center, LDF and LSCI are conducted routinely for digital artery disease diagnosis. LDF was indicative of digital obstructive artery disease (DOAD). Postocclusive reactive hyperemia, assessed by LCSI, demonstrated no skin blood flow (SBF) perfusion in the distal phalanx of the thumb, index, middle, and auricular fingers. Angiography confirmed BD, showing distally located multisegmental vessel occlusion and corkscrew collaterals in this patient's hands.

Interventions:

Ilomedine treatment was initiated and smoking cessation was definitive.

Outcomes:

Recently, the patient had an improvement in clinical condition despite the persistence of a small zone of necrosis of the left index finger 28 days post-treatment.

Lessons:

Our observation suggests that where suspicion of BD is based on clinical criteria, combining LDF and LSCI could represent a noninvasive, safe means of reaching BD diagnosis. Further clinical trials are necessary to confirm this novel observation.
Natural prognosis of carbapenem-resistant Acinetobacter baumannii bacteremia in patients who did not receive appropriate antibiotic treatment
Authors: Kim Tark , Lee Eun Jung , Park Seong Yeon , Yu Shi Nae , Lee Yu Mi , Park Ki-Ho , Park Se Yoon , Jeon Min Hyok , Choo Eun Ju , Kim Tae Hyong , Lee Mi Suk
Published: October 2018

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is a major issues in current era. The aim of study was to investigate the natural prognosis and prognostic factors associated with 28-day mortality in patients with CRAB bacteremia who were not receiving appropriate antibiotic treatment.

Adult patients with CRAB bacteremia were retrospectively identified between April 2012 and March 2015 at 5 tertiary hospitals in Republic of Korea. Patients who were transferred to another hospital within 28 days of onset of bacteremia and who receive appropriate antibiotics more than 48 hours were excluded. We investigated prognostic factors associated with 28-day mortality in patients with CRAB bacteremia without appropriate antibiotic treatment.

Of enrolled 205 patients, 143 (69.8%) patients died within 28 days after blood culture. Of patients with 28-day mortality, 88.9% (127/143) of patients died within 5 days. Of 78 patients who survived more than 5 days, the 28-day mortality was 20.5% (16/78). Diabetes mellitus (adjusted odds ratio [aOR] 3.81, 95% confidence interval [95% CI] 1.19–12.20), immunocompromised (aOR 8.72, 95% CI 2.62–29.70), sequential organ failure assessment (SOFA) ≥ 10 (aOR 13.87, 95% CI 3.70–51.96), vasopressor use (aOR 7.03, 95% CI 1.79–27.60), and pneumonia (aOR 4.44, 95% CI 1.67–11.78) were found to be the factors independently associated with the 28-day mortality.

The 28-day mortality in patients with CRAB bacteremia without appropriate treatment was high, although some patients could survive. Severity and underlying conditions were important prognostic factors in patients with CRAB bacteremia.
Epidemiology of Pediatric Acute Pancreatitis in Taiwan
Authors: Cheng Yu‐Jyun , Yang Hsin‐Yi , Tsai Ching‐Fang , Lin Jen‐Shyang , Lee Hung‐Chang , Yeung Chun‐Yan , Chen Solomon Chih‐Cheng
Published: October 2018

Objective:

Pediatric acute pancreatitis (AP) may be different from adult AP in various respects. This study focuses on the epidemiology and medical resource use of pediatric AP in Taiwan.

Methods:

Patients aged 0 to 18 years with AP were identified from the Taiwan National Health Insurance Research Database based on the International Classification of Diseases, Ninth Revision code of AP 577.0. The medical resource use was measured by length of hospital stay and hospital charges.

Results:

Between 2000 and 2013, a total of 2127 inpatient cases of pediatric AP were collected, which represented a hospitalization rate of 2.83 per 100,000 population. The incidence by age had 2 peaks, the first peak was at age 4 to 5 years old, and the second one started rising from 12 to 13 years old until adulthood. The incidence by year increased from 2.33 to 3.07 cases per 100,000 population during the study period. The average hospital stay is steady, but the medical cost is increasing. Girls have longer hospital stays, higher medical expenditures, more use of endoscopic retrograde cholangiopancreatography possibly due to more comorbidities with biliary tract diseases than boys (P < 0.05). The mortality in cases of AP is mostly associated with systemic diseases rather than AP itself.

Conclusions:

The incidence of pediatric AP in Taiwan is in a rising trend. There are gender differences in length of hospital stay, medical costs, use of endoscopic retrograde cholangiopancreatography and comorbidities.
Biliary Atresia Relevant Human Induced Pluripotent Stem Cells Recapitulate Key Disease Features in a Dish
Authors: Tian Lipeng , Ye Zhaohui , Kafka Kim , Stewart Dylan , Anders Robert , Schwarz Kathleen B. , Jang Yoon‐Young
Published: October 2018

Biliary atresia (BA) is the most common cause of pediatric end‐stage liver disease and the etiology is poorly understood. There is no effective therapy for BA partly due to lack of human BA models. Towards developing in vitro human models of BA, disease‐specific induced pluripotent stem cells (iPSCs) from 6 BA patients were generated using non‐integrating episomal plasmids. In addition, to determine the functional significance of BA‐susceptibility genes identified by genome‐wide association studies (GWAS) in biliary development, a genome‐editing approach was used to create iPSCs with defined mutations in these GWAS BA loci. Using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system, isogenic iPSCs deficient in BA‐associated genes (GPC1 and ADD3) were created from healthy iPSCs. Both the BA patient‐iPSCs and the knock out (KO) iPSCs were studied for their in vitro biliary differentiation potential. These BA‐specific iPSCs demonstrated significantly decreased formation of ductal structures, decreased expression of biliary markers including CK7, EpCAM, SOX9, CK19, AE2, and CFTR and increased fibrosis markers such as alpha smooth muscle actin, Loxl2, and Collagen1 compared to controls. Both the patient‐ and the KO‐iPSCs also showed increased yes‐associated protein (YAP, a marker of bile duct proliferation/fibrosis). Collagen and YAP were reduced by treatment with the anti‐fibrogenic drug pentoxifylline. In summary, these BA‐specific human iPSCs showed deficiency in biliary differentiation along with increased fibrosis, the 2 key disease features of BA. These iPSCs can provide new human BA models for understanding the molecular basis of abnormal biliary development and opportunities to identify drugs that have therapeutic effects on BA.
Unexpected PAX8 Immunoreactivity in Metastatic High-grade Breast Cancer
Authors: Kilgore Mark R. , Bosch Dustin E. , Adamson Kathi H. , Swanson Paul E. , Dintzis Suzanne M. , Rendi Mara H.
Published: October 2018

Immunohistochemistry (IHC) is often critical for distinction between metastatic carcinomas of Mullerian organ and breast origin. Paired box family protein 8 (PAX8) has been described as a transcription factor highly specific to neoplasms derived from Mullerian organs, thyroid, and kidney. PAX8 IHC with polyclonal and monoclonal antibody reagents was performed on 27 primary and 22 metastatic breast carcinomas. Eight of 27 primary breast carcinomas (30%) were positive for PAX8 with the monoclonal antibody reagent only; 0 of 22 were polyclonal anti-PAX8 immunoreactive. Substantial numbers of metastases had positive immunoreactivity for polyclonal anti-PAX8 (23%). Each of these metastases and additional cases (45% total) also had positive immunoreactivity for monoclonal anti-PAX8, including 5 of 7 brain metastases. IHC with monoclonal anti-PAX8 was positive on 6 of 7 primary breast carcinomas corresponding to PAX8-positive metastases. Together, these results indicate a significant fraction of breast carcinoma metastases and corresponding primary neoplasms have immunoreactivity for PAX8, and positivity rates depend on the antibody used. Diagnoses of metastatic breast carcinoma were achieved with the aid of clinical history and additional IHC in cases of PAX8 immunoreactivity. Contextual interpretation is imperative for PAX8 IHC, particularly when the differential diagnosis includes metastatic breast carcinoma with limited diagnostic material available.
Assessment of Proliferative Index Between the Tumor Margin, Center of Tumor, and the Invasive Tumor Front of Oral Squamous Cell Carcinoma With the Help of Mcm-2: An Immunohistochemical Study
Authors: Alrani Devendra , Niranjan Kochli C. , Sarathy Niharika A.
Published: October 2018

Aim:

The knowledge of cellular proteins that involves cell cycle and its control system is essential for understanding tumor biology. Minichromosome maintenance protein (Mcm-2), a component of prereplicative complex, essential for initiating DNA replication, is deregulated in different malignant lesions, and is expressed throughout the whole cell cycle including the G0 and G1 phases. This characteristic cell cycle event is not found in other proliferative markers such as geminin, AgNOR, Ki-67, and proliferating cell nuclear antigen. The aim of the present study was to analyze and compare the expression of Mcm-2 in normal oral mucosa (NM) and oral squamous cell carcinomas at tumor margins (TM), the tumor center (TC), and the invasive tumor front (ITF), with correlation of clinicopathologic features.

Materials and Methods:

Tissues from 50 oral squamous cell carcinomas and 10 NM were archived retrospectively and stained with an antibody directed against the Mcm-2 antigen. A quantitative method was used to score the Mcm-2 expression in NM, TM, TC, and ITF. Nuclei labeling index for each case was estimated as the percentage of immunoreactive nuclei among 500 cells separately for NM, TM, TC, and ITF.

Results:

Nuclei labeling index increases progressively from NM (49.08%), TM (67.79%), and TC (76.87%) to ITF (87.77%).

Conclusions:

Cell proliferation by Mcm-2 at the ITF had a strong positive relationship with TC, TM. Mcm-2, a pan-cell cycle marker, is more sensitive in comparison with other conventional proliferative markers, which can be a better prognostic indicator.
Cytologic Diagnosis of Oncocytic Neoplasms of the Thyroid Gland: The Importance of the Clinical Scenario
Authors: Straccia Patrizia , Santeusanio Giuseppe , Pierconti Francesco , Brunelli Chiara , Fadda Guido
Published: October 2018

It is a diagnostic challenge to differentiate benign and malignant thyroid neoplasms made up of Hürthle (or oncocytic) cells on cytologic material. They are large, polygonal cells with marked eosinophilic, granular cytoplasm reflective of overly abundant mitochondria. These cells commonly occur in nodular goiters and dominant adenomatous or hyperplastic nodules though they may also be the predominant component of neoplastic lesions. There are significant controversies concerning the optimal management of patients with oncocytic cell carcinoma. This review provides an overview of the most significant studies addressing the distinction between benign and malignant Hürthle cell lesions on cytology and histology.
Autologous Blood-Derived Products Compared With Corticosteroids for Treatment of Plantar Fasciopathy
Authors: Chen Yu-Jen , Wu Yi-Cheng , Tu Yu-Kang , Cheng Ju-Wen , Tsai Wen-Chung , Yu Tung-Yang
Published: October 2018

Objective

This review article evaluated the efficacy of autologous blood-derived products, including whole blood and platelet-rich plasma, in reducing pain and improving function compared with corticosteroids for plantar fasciopathy patients.

Design

Literature comparing autologous blood-derived product and corticosteroids for the treatment of plantar fasciopathy was systematically reviewed. Twelve randomized controlled trials and four quasi-experimental studies were included. The visual analog scale pain score and American Orthopedic Foot and Ankle Society hindfoot score were evaluated at 1.5, 3, and 6 mos' follow-up. Subgroup analyses were performed concerning platelet-rich plasma preparation techniques, injection regiments, and study designs.

Results

Corticosteroids were found to reduce pain more effectively than whole blood at 1.5 and 3 mos, but the effect disappeared at 6 mos. Platelet-rich plasma reduced pain more effectively at 6 mos' postinjection than corticosteroids. However, there was no significant difference in the American Orthopedic Foot and Ankle Society score between platelet-rich plasma and corticosteroids injections at any time point. In the subgroup analyses, pain was significantly reduced at 6 mos by self-prepared platelet-rich plasma, one-step separation platelet-rich plasma, platelet-rich plasma of more than 3 ml, and platelet-rich plasma without local analgesics.

Conclusions

The results of this meta-analysis suggest that platelet-rich plasma may provide a long-term effect in relieving pain in plantar fasciopathy patients.

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CME Objectives

Upon completion of this article, the reader should be able to: (1) Compare the efficacy of whole blood (WB), platelet-rich plasma (PRP), and corticosteroid (CS) in short-term pain reduction in patients with plantar fasciopathy (PF); (2) Compare the efficacy of WB, PRP, and CS in long-term pain reduction in patients with PF; (3) Identify the potential complication of corticosteroid injection for plantar fasciopathy; and (4) Identify the components of whole blood that might influence the growth factors in healing process.

Level

Advanced

Accreditation

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The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Conservative Management and Rehabilitation in the Older Runner With Knee Osteoarthritis
Authors: Castillo Brenda , Sepúlveda Fernando , Micheo William
Published: October 2018

Osteoarthritis is an age-related condition that commonly affects the middle-aged and elderly population including individuals who continue to pursue an active and athletic lifestyle. Running is an easily accessible activity with many health benefits; thus, it is becoming a popular form of exercise, even in older individuals. Studies evaluating the correlation between running and osteoarthritis show conflicting results; however, most studies show an increased risk of osteoarthritis in runners with a combination of modifiable and nonmodifiable risk factors. This study reviews the current literature to provide an overview of conservative (nonpharmacological and pharmacological) management strategies including patient education, therapeutic modalities and exercises, mechanical measures, dietary factors, oral and injectable pharmacotherapies, and orthobiologics. Rehabilitation considerations and return-to-sport guidelines are discussed, emphasizing the notion that a return to running activity requires reduction in mileage and formulation of a structured exercise program that includes strengthening, flexibility, and stability exercises, as well as modifications in the running technique.
Characterization of Perinatal Risk Factors and Complications Associated With Nonsyndromic Craniosynostosis
Authors: Sergesketter Amanda R. , Elsamadicy Aladine A. , Lubkin David T. , Krucoff Kate B. , Krucoff Max O. , Muh Carrie R.
Published: October 2018

Background:

Certain intrauterine risk factors are known to increase the risk of premature cranial suture fusion and may cause complications during birth. Some of these risk factors may be modifiable. Therefore, the authors sought to characterize the institutional patterns of prenatal risk factors and perinatal complications in nonsyndromic craniosynostosis patients compared to normal births from the surrounding area to identify areas for possible intervention or prevention.

Methods:

The medical records of all infants with nonsyndromic craniosynostosis and full birth records born at Duke University Health System from 2006 to 2017 were retrospectively reviewed. Maternal comorbidities, prenatal risk factors, and perinatal complications were collected. The North Carolina State Center for Health Statistics was queried for perinatal statistics from Durham county and the Northeastern Perinatal Care Region to represent a control cohort of normal births from the same time period and region. The primary outcome investigated was the incidence of prenatal risk factors and complications at birth associated with premature fusion of cranial sutures.

Results:

Eighty births with nonsyndromic craniosynostosis were included in this study. The majority of these patients were males (61.7%) and born via cesarean section (55.0%). Intrauterine growth restriction occurred in 10.0% and head trauma during delivery occurred in 2.5%. Twinning (14.8% vs 3.6%, P < 0.0001), cesarean births (55.5% vs 30.0%, P < 0.0001), and breech presentation (17.3% vs 3.2%, P < 0.0001) were significantly more common in craniosynostosis patients. Prenatally, mothers of craniosynostosis infants had higher incidence of gestational diabetes (13.5% vs 5.0%, P < 0.0001) and oligohydramnios (6.1% vs 1.3%, P < 0.0001) compared to regional controls.

Conclusion:

This study demonstrates that premature suture fusion is associated with prenatal risk factors such as gestational diabetes and oligohydramnios. Continued research into potentially modifiable prenatal risk factors and more refined prenatal diagnostic tools has the potential to reduce both the incidence of premature suture fusion and the sequelae of birth complications in this population.
Prehospital tourniquet use in penetrating extremity trauma: Decreased blood transfusions and limb complications
Authors: Smith Alison A. , Ochoa Joana E. , Wong Sunnie , Beatty Sydney , Elder Jeffrey , Guidry Chrissy , McGrew Patrick , McGinness Clifton , Duchesne Juan , Schroll Rebecca
Published: October 2018

BACKGROUND

Despite increasing popularity of prehospital tourniquet use in civilians, few studies have evaluated the efficacy and safety of tourniquet use. Furthermore, previous studies in civilian populations have focused on blunt trauma patients. The objective of this study was to determine if prehospital tourniquet use in patients with major penetrating trauma is associated with differences in outcomes compared to a matched control group.

METHODS

An 8-year retrospective analysis of adult patients with penetrating major extremity trauma amenable to tourniquet use (major vascular trauma, traumatic amputation and near-amputation) was performed at a Level I trauma center. Patients with prehospital tourniquet placement (TQ) were identified and compared to a matched group of patients without tourniquets (N-TQ). Univariate analysis was used to compare outcomes in the groups.

RESULTS

A total of 204 patients were matched with 127 (62.3%) in the prehospital TQ group. No differences in patient demographics or injury severity existed between the two groups. Average time from tourniquet application to arrival in the emergency department (ED) was 22.5 ± 1.3 minutes. Patients in the TQ group had higher average systolic blood pressure on arrival in the ED (120 ± 2 vs. 112 ± 2, p = 0.003). The TQ group required less total PRBCs (2.0 ± 0.1 vs. 9.3 ± 0.6, p < 0.001) and FFP (1.4 ± 0.08 vs. 6.2 ± 0.4, p < 0.001). Tourniquets were not associated with nerve palsy (p = 0.330) or secondary infection (p = 0.43). Fasciotomy was significantly higher in the N-TQ group (12.6% vs. 31.4%, p < 0.0001) as was limb amputation (0.8% vs. 9.1%, p = 0.005).

CONCLUSION

This study demonstrated that prehospital tourniquets could be safely used to control bleeding in major extremity penetrating trauma with no increased risk of major complications. Prehospital tourniquet use was also associated with increased systolic blood pressure on arrival to the ED, decreased blood product utilization and decreased incidence of limb related complications, which may lead to improved long-term outcomes and increased survival in trauma patients.

LEVEL OF EVIDENCE

Therapeutic, level IV.
IgA-deficient humans exhibit gut microbiota dysbiosis despite production of compensatory IgM
Authors: Catanzaro Jason R , Strauss Juliet D , Bielecka Agata , Porto Anthony F , Lobo Francis M , Urban Andrea , Schofield Whitman B , Palm Noah W
Published: October 2018

Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) is the most common primary immunodeficiency in humans and is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and IgA or IgM coating of the gut microbiota in 15 sIgAd subjects and 15 matched controls. Although sIgAd subjects secreted a significant amount of IgM into the intestinal lumen, this was insufficient to fully compensate for the lack of secretory IgA. Indeed, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls, which was characterized by a trend towards decreased overall microbial diversity and significant shifts in the relative abundances of specific microbial taxa. While IgA targets a defined subset of the microbiota via high-level coating, compensatory IgM binds a broader subset of the microbiota in a less targeted manner. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community that promotes human health, enhances resistance to infection, and is resilient to perturbation.
Reorganization of thalamocortical connections in congenitally blind humans
Authors: Marins Theo F. , Russo Maite , Rodrigues Erika C. , Monteiro Marina , Moll Jorge , Felix Daniel , Bouzas Julia , Arcanjo Helena , Vargas Claudia D. , Tovar-Moll Fernanda
Published: October 2018

Cross-modal plasticity in blind individuals has been reported over the past decades showing that non-visual information is carried and processed by ‘visual’ brain structures. However, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear despite multiple efforts. We mapped thalamocortical connectivity and assessed cortical thickness and integrity of white matter of ten congenitally blind individuals and ten sighted controls. We hypothesized an aberrant thalamocortical pattern of connectivity taking place in the absence of visual stimuli from birth as a potential mechanism of cross-modal plasticity. In addition to the increased cortical thickness of the primary visual cortex and reduced integrity of visual white matter bundles, we observed structural connectivity changes between the thalamus and occipital and temporal cortices. Specifically, the thalamic territory dedicated to connections with the occipital cortex was smaller and displayed weaker connectivity in congenitally blind individuals. In contrast, those connecting with the temporal cortex showed greater volume and increased connectivity compared to sighted controls. The abnormal pattern of thalamocortical connectivity included the lateral and medial geniculate nuclei and the pulvinar nucleus. For the first time in humans, a remapping of structural thalamocortical connections involving both unimodal and multimodal thalamic nuclei has been demonstrated, shedding light on the possible mechanisms of cross-modal plasticity in humans. The present findings may help understand the functional adaptations commonly observed in congenitally blind individuals.
On-ratio PDMS bonding for multilayer microfluidic device fabrication
Authors: Lai Andre , Altemose Nicolas , White Jonathan A. , Streets Aaron M.
Published: October 2018

Integrated elastomeric valves, also referred to as Quake valves, enable precise control and manipulation of fluid within microfluidic devices. Fabrication of such valves requires bonding of multiple layers of the silicone polymer polydimethylsiloxane (PDMS). The conventional method for PDMS-PDMS bonding is to use varied base to crosslinking agent ratios between layers, typically 20:1 and 5:1. This bonding technique, known as “off-ratio bonding,” provides strong, effective PDMS-PDMS bonding for multi-layer soft-lithography, but it can yield adverse PDMS material properties and can be wasteful of PDMS. Here we demonstrate the effectiveness of on-ratio PDMS bonding for multilayer soft lithography. We show the efficacy of this technique among common variants of PDMS: Sylgard 184, RTV 615, and Sylgard 182.
Comparative mode of action of antimicrobial peptide melimine and its derivative Mel4 against Pseudomonas aeruginosa
Authors: Yasir Muhammad , Dutta Debarun , Willcox Mark DP
Published: October 2018

Melimine and Mel4 are chimeric cationic peptides with broad spectrum antimicrobial activity, and recent investigations have shown that they are highly biocompatible with animal model and human clinical trials. The current study examined the mechanism of action of these two antimicrobial peptides against P. aeruginosa with a series of investigations. Antimicrobial activities were determined by MIC and MBC. Endotoxin neutralization was determined using the LAL assay, effect on the cytoplasmic membrane was evaluated using DiSC(3)-5 and Sytox green stains, and Syto-9 and PI dyes using flow cytometry. Release of cytoplasmic materials (ATP and DNA/RNA) were determined using ATP luminescence and increase in OD260nm. The ability to lyse bacteria was studied by measuring a decrease in OD620nm. The MIC of the peptides remained low against P. aeruginosa strains, which showed efficient neutralization of LPS, indicating their role in the anti-pseudomonas and LPS binding activities. Both AMPs rapidly (starting at 30 seconds) depolarized P. aeruginosa cytoplasmic membrane leading to reduction in viability. Melimine was responsible for more ATP release (75%) compared to Mel4 (36%) (P<0.001) following two minutes exposure. For both peptides, Sytox green entered cells after five minutes of incubation. Flow cytometry demonstrated that both the AMPs permeabilized the cell membrane at 30 minutes and followed by increasing permeability. Similar results were found with DNA/RNA release experiments. Overall, melimine showed higher ability of membrane disruption, cell lysis compared to Mel4 (P<0.001). Knowledge regarding mechanism of action of these two AMPs would be helpful in making them as anti-pseudomonas drug.