bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the collective effect of aging and HIV on the gut microbiome?
Authors: Dillon Stephanie M. , Wilson Cara C.
Published: December 2019

Purpose of review

Aging and HIV share features of intestinal damage and alterations in the communities of enteric bacteria, termed dysbiosis. The purpose of this review is to highlight the various features of the gut microbiome in aging and in people with HIV (PWH) and to discuss how aging and HIV converge to impact the gut microbiome. The term microbiome reflects the combined genetic material of micro-organisms present including bacteria, viruses, bacteriophages, and fungi. To date, the majority of studies investigating the impact of aging and HIV on the gut microbiome have focused on bacteria, and therefore, for the purposes of this review, the term ‘microbiome’ is used to reflect enteric bacterial communities.

Recent findings

Aging is associated with alterations in the gut bacterial microbiome. Although changes vary by the age of the population, lifestyle (diet, physical activity) and geographic location, the age-associated dysbiosis is typically characterized by an increase in facultative anaerobes with inflammatory properties and a decrease in obligate anaerobes that play critical roles in maintaining intestinal homeostasis and in regulating host immunity. PWH also have dysbiotic gut microbiomes, many features of which reflect those observed in elderly persons. In one study, the age effect on the gut microbiome differed based on HIV serostatus in older adults.

HIV and age may interact to shape the gut microbiome. Future studies should investigate relationships between the gut microbiome and age-associated comorbidities in older PWH populations. Identifying these links will provide new avenues for treatments and interventions to improve the healthspan and lifespan of older PWH.
Association of circulating Progesterone Receptor Membrane Component-1 (PGRMC1) with breast tumor characteristics and comparison with known tumor markers
Authors: Ruan Xiangyan , Cai Guiju , Wei Yun , Gu Muqing , Zhang Ying , Zhao Yue , Mueck Alfred O.
Published: December 2019

Objectives:

Progesterone receptor membrane component-1 (PGRMC1) expressed in breast cancer tissue has been suggested to predict a worse prognosis. The aim of this study was to assess for the first time if blood concentrations of PGRMC1 are also associated with receptor status, tumor diameter, grading, and lymphatic status. The second aim was comparison with known tumor markers.

Methods:

A total of 372 women, including 278 patients with invasive breast cancer, 65 with benign breast disease, and 29 healthy women (control), were recruited. PGRMC1 blood concentrations were measured by a recently developed enzyme-linked immunosorbant assay, and were correlated to predictive tumor characteristics and compared with serum carcinoembryonic antigen (CEA), CA125, and CA153.

Results:

PGRMC1 levels in the cancer group were significantly higher than in the control and benign group and increased with higher cancer stages (P < 0.05). PGRMC1 concentrations in the estrogen receptor (ER)+/progesterone receptor (PR)+ group were higher than in the ER−/PR− group, related to larger tumor diameter and the presence of lymph node metastasis (P < 0.05). Multivariable linear regression analysis was used to control the confounding factors. Tumor diameter, lymphatic metastasis, and ER (but not PR) were positively associated with PGRMC1 (P < 0.05). The receiver-operating characteristic curve (ROC) analysis was used to assess area under the curve (AUC). AUC was 87.9% for stages III+IV and 80.8% for stages I+II (P < 0.01). ROC did not find significant effects on AUC for CA125, only significant for CEA and CA153 for stages III+IV.

Conclusion:

As PGRMC1 levels are positively associated with breast tumor characteristics known to predict a worse diagnosis, PGRMC1 may be valuable as a new tumor marker, and superior to CEA, C125, and CA153. Because of the positive association with ER-expression, PGRMC1 may interact with this receptor.
MANAGEMENT OF REFRACTORY LARGE MACULAR HOLE WITH AUTOLOGOUS NEUROSENSORY RETINAL FREE FLAP TRANSPLANTATION
Authors: Chang Yo-Chen , Liu Pei-Kang , Kao Tzu-En , Chen Kuo-Jen , Chen Yi-Hsien , Chiu Wei-Jun , Wu Kwou-Yeung , Wu Wen-Chuan
Published: December 2019

Purpose:

To investigate the morphological and functional outcome of refractory large macular hole (MH) with autologous neurosensory retinal free flap transplantation.

Methods:

This case series enrolled 10 patients suffering from refractory large MH at Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. All eyes underwent pars plana vitrectomy, a neurosensory retinal free flap with a 1.5 to 2-MH diameter was harvested. We used an adhesive agent such as whole blood or Viscoat to assist the stabilization of the retinal free flap and then use tamponade silicone oil to tamponade the vitreous cavity. Silicone oil was removed 6 months postoperatively. Main outcome measures including closure of MH and change in best-corrected visual acuity change were recorded.

Results:

The mean age was 64.9 ± 11.5 years. Before presentation, all cases had received at least two vitreoretinal procedures including vitrectomy, internal limiting membrane peeling, and fluid–gas exchange. At last visit, closure of the MH was achieved in 9 of 10 (90%) cases. The mean preoperative best-corrected visual acuity and that after 12 months of surgery improved from 1.65 ± 0.43 logarithm of minimum angle of resolution to 0.88 ± 0.49 logarithm of minimum angle of resolution (P < 0.001).

Conclusion:

For eyes with refractory or large MH, autologous neurosensory retinal free flap under silicone oil tamponade may provide a new option to improve the anatomical and function outcome, especially in cases where insufficient internal limiting membrane is left.
Double-Session Micropulse Transscleral Laser (CYCLO G6) as a Primary Surgical Procedure for Glaucoma
Authors: Magacho Leopoldo , Lima Francisco E. , Ávila Marcos P.
Published: December 2019

Précis:

Double-session micropulse transscleral laser was an effective and safe treatment strategy for eyes that have not undergone glaucoma surgery previously.

Purpose:

To evaluate the safety and effectiveness of double-session micropulse transscleral laser (MP3) as a primary treatment modality for glaucoma.

Materials and Methods:

Patients who underwent MP3 therapy with double sessions in each hemifield, with a follow-up period of at least 6 months, were retrospectively considered. Patients were categorized into 2 groups: GI (no previous glaucoma surgery) and GII (with previous glaucoma surgery). Success was defined by either achieving a final intraocular pressure (IOP) between 6 and 18 mm Hg and an IOP reduction of >20%, or a minimum 50% reduction in the number of glaucoma medications, at the last visit, without any serious complications.

Results:

Eighty-four eyes were included in the GI group and 101 in the GII group, with the latter demonstrating relatively higher preoperative IOP (31.1±5.4 vs. 26.2±6.9 mm Hg, P<0.001). Final IOP (14.9±5.2 vs. 13.6±4.1 mm Hg, P=0.06), average MP3 treatment time (358.0±50.7 vs. 362.7±67.8 s, P=0.5), and follow-up duration (10.8±5.1 vs. 12.3±5.4 mo, P=0.06) were similar between the groups. The percentage reduction with regard to glaucoma medication was higher in GI than in GII (49.1±28.8 vs. 38.8±30.1%, P=0.02). GI underwent fewer MP3 procedures than GII (1.2±0.5 vs. 1.5±0.8, P=0.002). No hypotony or phthisis bulbi was observed in GI (1 and 2 in GII, respectively). Procedural success was noted in 92.9% of the cases in GI and 87.1% in GII.

Conclusions:

Double-session MP3 therapy could be considered as a safe and effective procedure to treat glaucoma in eyes that have not undergone any previous glaucoma surgery. Primary eyes achieved a success-rate similar to those with refractory glaucoma with fewer MP3 procedures and fewer glaucoma medications.
Albumin supplementation may have limited effects on prolonged hypoalbuminemia in major burn patients: An outcome and prognostic factor analysis
Authors: Chen Yi-Fan , Ma Hsu , Perng Cherng-Kang , Liao Wen-Chieh , Shih Yu-Chung , Lin Chih-Hsun , Chen Mei-Chun , Hsiao Fu-Yin , Wang Tien-Hsiang
Published: December 2019

Background:

Burns that affect ≥20% of the total body surface area (TBSA) trigger a major inflammatory response in addition to capillary leakage and loss of serum proteins including albumin. Persistent hypoalbuminemia is therefore common in major burn patients. The purpose of this study was to determine whether human albumin solutions can benefit major burn patients with persistent hypoalbuminemia.

Methods:

We conducted a retrospective review of major burn patients with ≥20% of TBSA involved at Taipei Veterans General Hospital between January 2007 and December 2018. Thirty-eight patients were enrolled. Patient demographics, burn characteristics, fluid balance, laboratory results, and outcomes were recorded through chart review.

Result:

No significant differences were found in the baseline characteristics of patients who received <25 mg/kg/%TBSA/day of human albumin solutions and those who received more than this amount. Renal replacement therapy, duration of mechanical ventilation, length of stay in the burn unit, and in-hospital mortality rate were not statistically different between the two groups. The serum C-reactive protein/albumin ratio was associated with in-hospital mortality (p = 0.036).

Conclusion:

The administration of large amounts of albumin supplements for the correction of prolonged hypoalbuminemia in major burn patients had no significant benefits on mortality.
Fiberoptic bronchoesophagoscopy-assisted evaluation and prognostic factor analysis in children with congenital esophageal atresia and tracheoesophageal fistula
Authors: Chou Chia-Sui , Soong Wen-Jue , Lee Yu-Sheng , Tsao Pei-Chen , Chen Wei-Yu , Chen Szu-Jung , Liu Chin-Su , Jeng Mei-Jy
Published: December 2019

Background:

Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are serious congenital anomalies with high morbidity and mortality. Diagnostic and therapeutic fiberoptic endoscopy has been used in children to evaluate and manage trachea-esophageal anomalies. This study aimed to evaluate the prognostic factors and the role of fiberoptic bronchoesophagoscopy (FB) in managing children with EA and TEF.

Methods:

From 2000 to 2017, hospitalized children with suspected EA and TEF were enrolled in the study. All associated medical records were retrospectively reviewed. Basic characteristics, diagnoses, age of surgical reconstruction, FB findings, associated anomalies, and survival durations were reviewed. Prognostic factors associated with the patients’ mortality were analyzed.

Results:

A total of 33 children were enrolled, and 91% of them were type C. The median age at the time of hospitalization was 26 days (range, birth to 9 years), including 20 (61%) low-birth-weight infants and 26 (79 %) referred patients. FB was performed in patients preoperatively (39%) and postoperatively (96.8%). Among them, 28 patients (85%) had associated anomalies, including 17 (52%) cardiac and 23 (70%) airway anomalies. The median age of 31 patients who underwent surgical reconstruction was 3 (range, 0–39) days. Esophageal anastomotic stricture (21/31, 67.7%) was the most common postsurgical complication. Twenty-three patients (74.2%) received postoperative FB-guided interventions, including balloon dilatation, laser therapy, and stent implantation. Among the 9 mortality cases, the median age at death was 270 (range, 4–3246) days. Significant factor associated with mortality was delayed (> 48 h old) or no surgical reconstruction (p = 0.030).

Conclusion:

Delayed (>48-hour old) or no surgical reconstruction was significantly related to mortality in children with congenital EA and TEF. Preoperative and postoperative FB evaluations helped to facilitate diagnoses and nonsurgical managements and resolve the patients’ tracheoesophageal problems.
Experiences of First Insulin-Treated Patients (1922–1923)
Authors: de Leiva-Hidalgo Alberto , de Leiva-Pérez Alejandra
Published: December 2019

Background:

Historical description of first insulin trials just after its discovery.

Areas of Uncertainty:

The review includes first initiatives of insulin treatment. The probability of other trials, not reported to the Insulin Committee of the University of Toronto and conducted in the years 1922 and 1923, is quite low.

Data Sources:

(1) Archival Collections, University of Toronto: Insulin Discovery and Early Developments of Insulin (University of Toronto Libraries digital special collection, with a particular section entitled “From a Patient's Point of View” containing letters, patient charts, newspaper clippings, and photographs). (2) Thomas Fisher Rare Book Library: Academy of Medicine Collection, F. G. Banting Papers, C. H. Best Papers, J. B.Collip Papers, W. R. Feasby Papers, E. Hugues Papers, J. J. R. Macleod Papers. (3) National Library of Medicine: PubMed search for the topic of history of insulin, History of Medicine-on syllabus archive. (4) Selected Journals for History of Medicine: Bulletin of the History of Medicine, Journal of the History of Medicine and Allied Sciences, Medical History. (5) Selected books: The Discovery of Insulin (M. Bliss); Diabetes, Its Medical and Cultural History (D. von Engelhardt); H. C. Hagedorn and Danish Insulin (T.Deckert), Continuing Quest (W. A. Tomkins).

Therapeutic Advances:

This historical review shows the quick progress from impure pancreatic extract to the selective isoelectric precipitation of the hormone, which made possible the introduction of insulin in the clinic.

Conclusions:

The coordination between the Departments of Physiology (Connaught Laboratories) and Medicine (Toronto General Hospital) was essential for the discovery and implementation of insulin therapy. The Insulin Committee was decisive for the negotiation with the pharmaceutical industry, the purification, grand-scale production, patents' achievement, and provision of licenses to expert clinicians and prestigious health centers. At the end of the year 1923, insulin treatment was already extended to Europe (mainly Scandinavia, Great Britain, and Spain). Insulin discovery and treatment changed the clinical spectrum of diabetes.
Drivers of High-cost Medical Complexity in a Medicaid Population
Authors: Labby David , Wright Bill , Broffman Lauren , Holtorf Megan
Published: December 2019

Background:

Efforts to improve outcomes for the 10% of patients using two thirds of health care expenditures increasingly include addressing social determinants. Empiric evidence is needed to identify the highest impact nonmedical drivers of medical complexity and cost.

Objectives:

This study examines whether complex, highest cost patients have different patterns of critical life adversity than those with better health and lower utilization.

Research Design:

Using a validated algorithm we constructed a complexity/cost risk patient profile. We developed and fielded a life experience survey (Supplemental Digital Content 1, http://links.lww.com/MLR/B920) to a representative sample, then examined how the prevalence of specific adversities varied between complex, high-cost individuals, and others.

Subjects:

Surveys were sent to 9176 adult Medicaid members in Portland, Oregon.

Measures:

Our primary variable was high medical complexity health cost risk; an alternative specification combined health cost risk and actual utilization/cost. Our survey instrument measured exposure to early and later-life adversities.

Results:

Compared with healthy individuals in our population, medically complex individuals had significantly higher rates of adversity. The greatest risk of medical complexity and cost was associated with substance use [odds ratio (OR), 4.1], homelessness (OR, 3.0), childhood maltreatment (OR, 2.8), and incarceration (OR 2.4). Those with the highest prior year acute care utilization and cost had the highest rates of these same factors: substance use (62.5%), homelessness (61.7%), childhood maltreatment (55.5%), and incarceration (52.1%).

Conclusion:

Clinical and policy strategies that mitigate high-impact social drivers of poor outcomes are likely critical for improving both health and costs for complex, high-needs patients.
What’s Happening at Home
Authors: Harrison Krista L. , Leff Bruce , Altan Aylin , Dunning Stephan , Patterson Casey R. , Ritchie Christine S.
Published: December 2019

Background:

Home clinical care (HCC) includes home-based medical care (HBMC—medical visits in the home) and skilled home health care (skilled nursing or therapy visits). Over 7 million older adults would benefit from HCC; however, we know surprisingly little about homebound older adults and HCC.

Objective:

To describe HCC received by older adults using claims data within the OptumLabs Data Warehouse.

Research Design:

Using administrative claims data for commercial and Medicare Advantage enrollees, we describe morbidity profiles, health service use, and care coordination (operationalized as care plan oversight [CPO]) for people receiving HCC and the subgroup receiving HBMC.

Participants:

Three million adults (3,027,247) age ≥65 with 12 months of continuous enrollment 2013–2014.

Measures:

CPT or HCPCS codes delineated HCC, HBMC, and CPO recipients and care site, frequency, and provider type. Other measures included demographic characteristics, clinical characteristics, and health care utilization.

Results:

Overall, 5% of the study population (n=161,801) received 2+ months of HCC visits; of these, 46% also received 2+ HBMC visits (n=73,638) while 54% received only skilled home health (n=88,163 HCC but no HBMC). HBMC-recipients had high comorbidity burden (Charlson score 4.3), dementia (35%), and ambulance trips (58%), but few nursing facility admissions (4.9%). Evidence of care coordination (CPO claims) occurred in 30% of the HCC population, 46% of HBMC, and 17% of the skilled home health care only.

Conclusions:

Approximately 1 of 20 older adults in this study received HCC; 30% or less have a claim for care coordination by their primary care provider.
WT1-Mutant Wilms Tumor Progression Is Associated With Diverting Clonal Mutations of CTNNB1
Authors: Duhme Constanze , Busch Maike , Heine Eva , de Torres Carmen , Mora Jaume , Royer-Pokora Brigitte
Published: December 2019

WT1-mutant Wilms tumors exhibit a high rate of concomitant CTNNB1 mutations, associated with activated Wnt signaling. Here, we show by laser and manual microdissection of different histologic cell types from 6 WT1-mutant tumor samples that 1 patient’s tumor can contain up to 4 distinct mutations in CTNNB1 and/or WTX. Consecutive sections may also harbor different CTNNB1 mutations. The variability of activating CTNNB1 mutations demonstrates the multifocal nature of WT1-mutant Wilms tumors. As multiple independent tumors can occur in patients with constitutional WT1 mutations, they need to be surveyed more closely for tumor development.
Neutropenia and Life-threatening Agranulocytosis Among Children With β-Thalassemia Treated With Oral Iron Chelators in a Community With Background of Ethnic Neutropenia
Authors: Nazir Hanan F. , Alshizawi Maryam
Published: December 2019

Introduction:

Neutropenia and agranulocytosis are rare side effects of deferiprone (DFP) in patients treated for iron overload. Unfortunately, no study directly addressed special risks in countries with a background of ethnic neutropenia, such as Oman.

Aim:

The aim of this study was to report the incidence of neutropenia in Omani children with β-thalassemia treated with different iron chelators.

Methods/Design:

This was a retrospective study that included 179 Omani pediatric patients. For patients who developed neutropenia, demographic data, iron-chelating agent, clinical presentation, management, and outcome were recorded. Detailed clinical, laboratory±radiologic information was added for patients with agranulocytosis.

Results:

Neutropenia was encountered in 43.6% of patients: severe neutropenia in 10 patients, moderate in 29, and mild in 69 patients. Severe and moderate neutropenia had similar incidence among DFP-exposed and DFP-naive patients (P=0.515 and 0.421, respectively), while mild neutropenia was common among DFP-naive patients (P=0.0001). A higher incidence of DFP-related agranulocytosis (4.1%) was noted compared with previous reports, but none had a fatal outcome.

Conclusions:

In a community with ethnic neutropenia, mild to moderate neutropenia is common. Higher incidence of severe neutropenia and agranulocytosis mandates careful monitoring and rational modification of iron-chelating agents to avoid life-threatening complications.
Antibacterial effects of local analgesics and anesthetics
Authors: Imani Farnad , Mubarak Shaden M.H. , Mostafavi Seyyed Khalil Shokouhi , Khoda-Bakhshi Marjan , Bojary Mohammad R. , Ghasemian Abdolmajid
Published: December 2019

Objective:

The findings of a multitude of both animal and human studies could substantiate an additive role of both local and general anesthetic agents in inhibiting bacterial growth. The present study attempted to assess antimicrobial effects of local analgesics and general anesthetics including lidocaine, bupivacaine, pethidine, midazolam, and sufentanyl citrate.

Methods:

A bacterial suspension with opacity equal to the half Mac Farland containing of studied nine bacterial species [Escherichia coli ATCC25922, Staphylococcus aureus ATCC25923, Pseudomonas aeruginosa ATCC27853, Staphylococcus epidermidis ATCC12228, Streptococcus pneumoniae ATCC49619, group A Streptococcus (clinical), Bacillus cereus ATCC11778, Acinetobacter baumannii (clinical), and Enterococcus faecalis ATCC29212] was prepared. The bacterial growth was assessed via culturing each solution (containing bacterial suspension and anesthetic drug) on culture media. Antibacterial characteristics of anesthetics were evaluated at various time points of culturing the bacterial solution (exposure to anesthetics) and countering the bacterial colonies and compared with the controls.

Results:

We observed high efficacy of Sufentanil Citrate (50 μg/ml) on reducing colony count of Staph. aureus and also Strep. pneumoniae with high response rate within 24 h of exposure to antibiotic. Also, midazolam (1 mg/ml) could effectively reduce colony count of Staph. aureus and Strep. pneumoniae. Moreover, by exposing pethidine with the dose of 50 mg/ml, the count of P. aeruginosa and E. faecalis was successfully reduced in media. Bacterial viability in various time points after exposure to lidocaine 1% and also bupivacaine 0.5% showed inhibited growth of all bacterial species viable cells with high response rate.

Conclusion:

Sufentanil Citrate, midazolam, and pethidine exerted efficient inhibitory effect on Staph. aureus, Strep. pneumoniae, P. aeruginosa and E. faecalis. Lidocaine and bupivacaine had a strong inhibitory effect on growth of nine standard bacterial species in our survey.
Pain Perception of a Structured Vascular Access Team Approach to Short Peripheral Catheter (SPC) Placement Compared to SPC Placement by Bedside Nurses
Authors: Fujioka Genichiro , Newcomb Patricia , Hunchusky Cindy , Myers Helen , Behan Deborah
Published: December 2019

This study investigates the use of a structured protocol by vascular access team (VAT) nurses compared with the practice of bedside nurses to minimize patient pain related to short peripheral catheter (SPC) insertion. During this quantitative study, 201 adults were randomly assigned to have their SPC placed either by the VAT or by bedside nurses. Results showed significantly lower pain scores with the VAT SPC placement (P = .026), and patients were significantly more likely to report the experience as better than their previous SPC placement experiences (χ2 = 7.8; P = .005). Therefore, the use of a VAT would be worthwhile to improve patient satisfaction.
Hazardous Drug Residues in the Home Setting
Authors: Huff Cynthia
Published: December 2019

Safety concerns have existed for more than 40 years about how hazardous drug (HD) exposure contributes to adverse health outcomes in health care workers. Careless handling causes toxic HD residues to infiltrate hospital and ambulatory care settings and can even be tracked to patient homes. Little is known about the adverse health outcomes experienced by exposed caregivers. The December 1, 2019, release of new regulations will enforce health care organizations to minimize risk to all health care workers by implementing the US Pharmacopeia (USP) General Chapter<800>Hazardous Drugs—Handling in Healthcare Settings safety standards. Worker safety measures include wearing personal protective equipment, even in home care settings.
USP General Chapter <800> and Its Impact on Nursing Practice
Authors: Kleppin Susan
Published: December 2019

EDITOR'S NOTE

The Infusion Nurses Society (INS) and the Journal of Infusion Nursing (JIN) editors are pleased to debut Pharmacology Report, a recurring bimonthly column authored by Susan Kleppin, RPh, FASHP. Susan is an accomplished pharmacist in health-system pharmacy with significant experience in infusion therapy. Her column will discuss relevant pharmacology topics, including medications new to market, safe handling for hazardous drugs, and managing drug shortages. INS and JIN extend Susan a warm welcome.
Myasthenia Gravis Crisis and Atrial Fibrillation
Authors: Jacobs Daniel H.
Published: December 2019

Introduction:

Myasthenia gravis (MG) crisis has no specific reported correlation with atrial fibrillation (AF). We present a series of patients observed from a single general neurologist’s outpatient and inpatient practice over a 9-year period who experienced the combination of MG crisis and AF.

Case Report:

Retrospective chart review of patients within 1 neurologist’s inpatient and outpatient practice was done. Charts were selected based on the occurrence of newly diagnosed AF during MG crisis over a 9-year period. Most patients were diagnosed in the hospital and then followed as outpatients. Charts were reviewed to determine factors that may have played a role in the co-occurrence of these 2 conditions. Eight patients were identified that had co-occurring MG crisis and AF. All patients had very active MG, and were in or had recently been in MG crisis at the time their AF was discovered. Patients tended to have late-onset MG to be male, to be acetylcholinesterase receptor antibody positive, and to have improvement or remission of their AF once the MG achieved better clinical control.

Conclusion:

New-onset AF can occur during MG crisis. The cardiac outcome improves with treatment of the underlying disease, after initial cardiac stabilization.
Clinical Usefulness of Cell-Free DNA as a Prognostic Marker in Acute Ischemic Stroke
Authors: Vajpeyee Atulabh , Wijatmiko Teddy , Vajpeyee Manisha , Taywade Onjal , Pandey Swapnil , Chauhan Puneet S.
Published: December 2019

Objective:

Stroke has become the second most common cause of death. Several biomarkers have been detected in the peripheral blood from stroke patients, but none has found a place in clinical practice. Cell-free DNA (cf-DNA) liberated into the blood soon after the onset of stroke might be useful for assessing disease severity and prognosis.

Study Design and Methods:

A total of 54 patients presenting with ischemic stroke were recruited consecutively with the exclusion of patients having trauma, tumor, infections, and organ failure. The cf-DNA was extracted by circulating nucleic acid kit from Qiagen and measured by real-time quantitative polymerase chain reaction assay for β-globin gene. The primary outcome measure was poststroke modified Rankin scale Score at 3 months after the onset of symptoms.

Results:

Higher cf-DNA levels were associated with severity at the time of admission measured by National Institutes of Health Stroke Scale (P=0.003) and poor outcome as measured by modified Rankin scale 3-month scores (P=0.001). Therapeutic intervention in the form of a mechanical thrombectomy or IV thrombolysis was associated with improved outcome in patients with cf-DNA<10,000 kilogenome-equivalents/L (P≤0.01).

Conclusions:

cf-DNA level correlates well with the severity of stroke at admission and long-term prognosis. It can be used as an additional marker to predict the outcome of therapeutic intervention.
A Probable Case of Recurrent Bickerstaff Brainstem Encephalitis With Fulminant Course in a Pediatric Patient
Authors: Chamsi Basha Amjad , Kolko Naser , Santoro Jonathan D. , Alomani Hakem
Published: December 2019

Introduction:

Bickerstaff brainstem encephalitis is a rare, often postinfectious, syndrome characterized by the clinical triad of ophthalmoplegia, ataxia, and altered consciousness. Here, we present a probable case of recurrent, pediatric Bickerstaff encephalitis, whereby the patient acutely developed loss of consciousness and eventually brain death despite optimal management.

Case Report:

A 3-year-old male patient initially presented to the emergency department with progressive ataxia, following history of upper respiratory tract infection. He deteriorated within 12 hours of hospitalization, requiring cardiopulmonary resuscitation. The patient had decreased consciousness thereafter, showing minimal signs of brain activity. He was then deemed to be suffering a second episode of Bickerstaff encephalitis, the first being a year prior, and intravenous immunoglobulins were administered immediately. Magnetic resonance imaging of the brain on day 2 of admission showed signs of diffuse, bilateral encephalitis in the brainstem, thalami, and basal ganglia. Brain death was confirmed on day 11 of admission, following 2 brain death examinations.

Conclusion:

Although Bickerstaff brainstem encephalitis tends to involve the brainstem, outcomes of brain death have been rarely reported, even more so in the pediatric age group. This case report sheds light on, possibly, the first reported fatality of Bickerstaff encephalitis among children.
Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract
Authors: Kim Isaac E. , Amin Ali , Wang Li Juan , Cheng Liang , Perrino Carmen M.
Published: December 2019

Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: no staining; 1: weak; 2: moderate; 3: strong) and proportion of cells stained (0: 0%; 1: >0% to ≤25%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.
Immunohistochemical Expression Analysis of EpCAM in Hepatoblastomas
Authors: Lopez-Nunez Oscar , Ranganathan Sarangarajan
Published: December 2019

The epithelial cell adhesion molecule (EpCAM) is involved in oncogenesis of hepatoblastomas (HBs). Prior genomic profiling studies showed higher EpCAM expression and worse prognosis in HBs containing primitive histotypes, however, this has not been fully addressed from an immunohistochemical perspective. Our goal is to characterize differential EpCAM immunohistochemistry (EpCAM-IHC) among HBs histotypes. We retrieved 62 HBs from 52 patients. EpCAM-IHC was performed (anti-MOC-31, 1:50 dilution; Cell Marque Corporation, Rocklin, CA) and graded in histotypes using the immunoreactive score. The median age of patients was 2 years (range: 0.4 to 9 y) with a M:F ratio of 1.9. Outcome information was available in 38 patients (alive=30, alive with disease=3, and deceased=5) with median follow-up of 60 months (range: 2 to 171 mo). EpCAM-IHC showed notable overexpression (immunoreactive score >4) in embryonal (89%) and crowded fetal (74%) in contrast to glandular (33%), well-differentiated fetal (32%), and small cell undifferentiated/blastemal (3%) components. Mesenchymal elements were negative. In summary, EpCAM-IHC is helpful to distinguish between epithelial components as it is progressively lost in the transition from embryonal to crowded fetal and into well-differentiated fetal histotypes. Its preferential expression among primitive HBs might have therapeutic and prognostic implications. The significance of its largely negative expression in small cell undifferentiated/blastema is interesting despite its presumed immaturity, deserving further studies.
Clinicopathologic Characterization of Hidradenoma on Acral Sites
Authors: Wiedemeyer Katharina , Gill Pavandeep , Schneider Michelle , Kind Peter , Brenn Thomas
Published: December 2019

Hidradenomas are benign sweat gland tumors that typically present as small nodules in adulthood. Their anatomic distribution is wide and rarely includes acral sites. In this setting, reliable separation from digital papillary adenocarcinoma is important, but notoriously difficult. Hematoxylin and eosin–stained sections of 25 hidradenomas on acral skin were retrieved. The clinical presenting features and morphologic findings were recorded, and follow-up was obtained. Immunohistochemistry was performed for AE1/3, CK5/6, EMA, CEA, SMA, S100, p40, and p63. The tumors presented as solitary nodules on the hands (n=17) and feet (n=8) of adults (age range: 20 to 81 y; median: 50 y), with an equal sex distribution. Histologically, the well-circumscribed tumors were lobular, with a solid and cystic growth within dermis. Duct and squamous differentiation and vascularized hyaline stroma were frequent. The majority (n=18) were poroid hidradenomas. Scattered cytologic atypia and mitotic activity (median: 2/10 HPF) were common, and a pseudoinfiltrative growth of strands in a hyaline to sclerotic matrix was noted in 5 tumors. No papillary structures, atypical mitoses, or tumor necrosis were present. Immunohistochemically, all tumors expressed AE1/3, CK5/6, p40, and p63 strongly and diffusely. Luminal differentiation was highlighted by epithelial membrane antigen and carcinoembryonic antigen staining. S100 and SMA staining was absent. Follow-up (1 to 288 mo; median: 61 mo), available for 20 patients, showed no local recurrences and no disease-related mortality. Acral hidradenomas and digital papillary adenocarcinomas share a well-circumscribed dermal growth pattern containing solid, cystic, and tubular areas with mitotic activity and at least focal cytologic atypia. Lack of papillary structures and the diffuse positivity for p40 and p63 in the absence of S100 and SMA expression are helpful features in favor of acral hidradenoma.
Trans-Right–Ventricle and Transpulmonary MicroRNA Gradients in Human Pulmonary Arterial Hypertension*
Authors: Chouvarine Philippe , Geldner Jonas , Giagnorio Roberto , Legchenko Ekaterina , Bertram Harald , Hansmann Georg
Published: December 2019

Objectives:

We investigated whether concentrations of circulating microRNAs differ across the hypertensive right ventricle and pulmonary circulation, and correlate with hemodynamic/echocardiographic variables in patients with pulmonary arterial hypertension versus nonpulmonary arterial hypertension controls.

Design:

Prospective blood collection during cardiac catheterization from the superior vena cava, pulmonary artery, and ascending aorta in 12 children with pulmonary arterial hypertension and nine matched nonpulmonary arterial hypertension controls, followed by an unbiased quantitative polymerase chain reaction array screen for 754 microRNAs in plasma.

Setting:

Children’s hospital at a medical school.

Patients:

Twelve pulmonary arterial hypertension patients included as follows: idiopathic pulmonary arterial hypertension (5), pulmonary arterial hypertension (2), pulmonary arterial hypertension-repaired congenital heart disease (4), portopulmonary pulmonary hypertension (1). Nine nonpulmonary arterial hypertension controls included as follows: mild/moderate left ventricular outflow tract obstruction (7), mediastinal teratoma (1), portal vein stenosis (1).

Interventions:

Standard pulmonary arterial hypertension treatment.

Measurements and Main Results:

Analysis of differential concentrations (false discovery rate < 0.05) revealed two trans-right–ventricle microRNA gradients (pulmonary artery vs superior vena cava): miR-193a-5p (step-up in pulmonary arterial hypertension and step-down in control) and miR-423-5p (step-down in pulmonary arterial hypertension and step-up in control) and two transpulmonary microRNA gradients (ascending aorta vs pulmonary artery): miR-26b-5p (step-down only in control) and miR-331-3p (step-up only in pulmonary arterial hypertension). Between-group comparison revealed miR-29a-3p, miR-26a-5p, miR-590-5p, and miR-200c-3p as upregulated in pulmonary arterial hypertension-superior vena cava and miR-99a-5p as downregulated in pulmonary arterial hypertension–pulmonary artery. The differential microRNA-concentrations correlated with prognostic hemodynamic variables (pulmonary vascular resistance, tricuspid annular plane systolic excursion, etc.).

Conclusions:

We identified for the first time in human disease (pulmonary arterial hypertension) trans-right–ventricle and transpulmonary microRNA gradients in blood plasma. Several of these microRNAs regulate transcripts that drive cardiac remodeling and pulmonary arterial hypertension and are now emerging as epigenetic pulmonary arterial hypertension biomarkers and targets for therapy.
Botulinum Toxin A Salvage of Ischemic Hand Trauma
Authors: Laarakker Avra S. , Borah Gregory
Published: December 2019

Posttraumatic hand injuries from crush injury, infusion, or iatrogenic vascular cannulation can cause ischemic finger damage that can progress to necrosis and digital amputation. Botulinum toxin type A (Botox) improves blood flow in chronic vasospastic disorders of the hand. Botox’s efficacy in salvaging ischemic loss in digits in acute traumatic and iatrogenic injury has not been previously reported. From February of 2015 to December of 2016, 11 patients at a Level I trauma center (West Virginia University) presented to the hand surgery service with early ischemic injury and vascular compromise to hand and fingers as a result of crush, direct drug injection, or proximal arterial injury from drug injection or catheterization. Before 2015, all patients with vascular compromise were treated with standard protocol. After January of 2016, patients were treated with additional injection of 80 to 100 U of Botox into the palm and wrist. Before administration of Botox, six patients with vascular compromise of one or more fingers were treated with a conservative protocol and 83 percent had amputation of necrotic digits. After January of 2016, five patients with ischemia were treated with Botox into the palm and proximal arteries. All Botox-treated digits were preserved (100 percent salvage). Pain scores were lower in Botox-treated fingers. We conclude that (1) in the acute traumatic vascular hand injury, early Botox injection markedly increases digital salvage; (2) direct nerve effects after Botox injections improve postinjury pain scores; and (3) early use of Botox in finger injuries is our standard approach to impending ischemia in the hand.
Genital Gender-Affirming Surgery in Transgender Men in The Netherlands from 1989 to 2018: The Evolution of Surgical Care
Authors: Al-Tamimi Muhammed , Pigot Garry L. , Elfering Lian , Özer Müjde , de Haseth Kristin , van de Grift Tim C. , Mullender Margriet G. , Bouman Mark-Bram , Van der Sluis Wouter B.
Published: December 2019

Background:

The number of individuals with gender identity incongruence seeking treatment, including genital gender-affirming surgery, has increased over the past decade. Surgical techniques for genital gender-affirming surgery in transgender men have evolved considerably. The aim of this study was to present an overview of the evolution of genital gender-affirming surgery for transgender men in a single, high-volume center.

Methods:

The authors performed a retrospective analysis of medical records of all transgender men who underwent genital gender-affirming surgery from January of 1989 to January of 2018 at their institution. Subject demographics, type of surgery, and surgical techniques were recorded.

Results:

Over time, four hundred transgender men underwent genital gender-affirming surgery. Metoidioplasty was performed in 222 patients (56 percent) and phalloplasty in 178 patients (44 percent). Before 2010, the majority of patients underwent metoidioplasty, whereas since 2010, phalloplasty has been performed in most patients. Of 400 patients, 332 (83 percent) underwent urethral lengthening. The option to undergo genital surgery without urethral lengthening was offered from 2004. Since then, 68 (34 percent) patients chose to undergo genital gender-affirming surgery without urethral lengthening. The choice of surgical options for genital gender-affirming surgery in transgender men has grown from five in 1989 to 12 techniques currently. The variety and combination of flaps used for phalloplasty has increased over time. Conversely, the use of some flaps has been abandoned, whereas other flaps have reemerged.

Conclusions:

Genital gender-affirming surgery has developed over time in line with reconstructive surgical innovations. Despite technical advancements, there is no one ideal technique, and every technique has specific advantages and disadvantages. With the increase in surgical options, shared decision-making and a shift from surgeon-centered toward more patient-centered care are required.
Face Lifting in Bald Male Patients: New Trends and Specific Needs
Authors: Pascali Michele , Botti Chiara , Botti Giovanni
Published: December 2019

Background:

Aesthetic surgery has recently become popular also among men. The ever-increasing number of bald men wishing to undergo facial surgery represents a challenge for the surgeon, as the scars cannot be hidden in the hair and must therefore be as short as possible. The authors present their experience in face lifting in bald male patients and propose an innovative technique to handle the skin excess to achieve practically invisible scars.

Methods:

A 10-year observational study was carried out on 68 bald male face-lift patients. All patients underwent deep plane lifting with a specific method for handling skin excess. This technique is the innovation presented in this article. Subjective and objective methods were used to evaluate the results. The well-known FACE-Q questionnaire was sent to all the patients together with an explanatory letter. Three ad hoc questions were added to the questionnaire to assess the degree of satisfaction with the scars. The objective method involved the evaluation of preoperative and postoperative photographs by a three-member jury. The average follow-up period was 12 months.

Results:

All patients showed a high degree of satisfaction with the final appearance of the surgical scars and appreciation of the overall quality of the result, 1 year after face-lift surgery. No patient expressed regret about choosing to undergo this type of surgery. Very high scores were registered for the overall facial appearance and for the various critical areas examined, including scars, from patients and experts alike.

Conclusion:

The face-lifting technique for bald men proposed by the authors, involving a peculiar and innovative way of handling the skin excess, has proven to be reliably effective in obtaining virtually invisible scars.
Measured Levels of Human Adipose Tissue–Derived Stem Cells in Adipose Tissue Is Strongly Dependent on Harvesting Method and Stem Cell Isolation Technique
Authors: Alstrup Toke , Eijken Marco , Brunbjerg Mette Eline , Hammer-Hansen Niels , Møller Bjarne K. , Damsgaard Tine Engberg
Published: December 2019

Background:

Adipose tissue–derived stem cells are of great interest because of their properties of immune modulation, tissue regeneration, and multipotent differentiation. To advance development of stem cell–based treatments, determination of the physiologic concentration of adipose tissue–derived stem cells in human adipose tissue is relevant for proper guidance of stem cell treatment dosage, oncologic safety, and evaluation of efficacy.

Methods:

A prospective comparative case-control study of 20 patients was conducted to determine the yield of adipose tissue–derived stem cells in periumbilical adipose tissue harvested by the widely used method of aspiration and in structurally intact adipose tissue harvested by excision. Stem cells were isolated using conventional enzymatic digestion and by a method combining enzymatic digestion with mechanical distortion. Stem cell yield was quantified by multicolor flow cytometry and colony-forming capacity.

Results:

When only the conventional enzymatic digestion was used, no significant difference in adipose tissue–derived stem cell yield was observed. However, when enzymatic digestion was combined with mechanical distortion, twice as many stem cells were isolated from excised adipose tissue compared to aspirated adipose tissue. Inclusion of mechanical distortion significantly increased yield 5-fold in excised adipose tissue and 2-fold in aspirated adipose tissue. Combining enzymatic digestion and mechanical distortion, measured levels of excised adipose tissue reached 140 × 103 (95 percent CI, 62 to 220 × 103) adipose tissue–derived stem cells per gram of adipose tissue that corresponded to 26 × 103 (95 percent CI, 18 to 33 × 103) colony-forming units per gram.

Conclusions:

The study indicates that harvesting by aspiration halves the concentration of adipose tissue–derived stem cells in adipose tissue samples when compared to structural intact adipose tissue. Furthermore, the study presents stem cell yield higher than previously described in the current literature.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.