bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential thrombocytosis with recurrent spontaneous abortion in the mid trimester
Authors: Yu Yang , Zhang Xinyue , Shi Qingyang , Wang Meiyan , Jing Jili , Liu Yanhong
Published: June 2019

Rationale:

Essential thrombocytosis (ET) is a myeloproliferative neoplasm characterized by clonal proliferation of the megakaryocytic lineage within the bone marrow and phenotypically by an elevated platelet count in peripheral blood. Common vascular complications include thrombosis, microvascular disturbances, and hemorrhage. ET with recurrent spontaneous abortion as the primary symptom is rare.

Patient concerns:

A 30-year-old pregnant woman (gestational age: 8 weeks) with a history of recurrent spontaneous abortion in the mid trimester was admitted to our hospital for further management.

Diagnosis:

The diagnosis of ET was made based on the platelet count, bone marrow biopsy, and molecular biology testing.

Interventions:

The patient was treated with interferon, heparin, and aspirin.

Outcomes:

The infant was delivered by cesarean section without complication at 28 weeks gestation due to placental abruption. The child remained healthy with no developmental abnormalities during follow-up for 2 years.

Lessons:

Recurrent spontaneous abortion in the mid trimester might be associated with ET. Thus, a detailed investigation including blood routine examination to identify an abnormal platelet count is warranted for pregnant patients with such a history in order to facilitate timely treatment.
Nomograms to predict survival of stage IV tongue squamous cell carcinoma after surgery
Authors: Sun Wei , Cheng Minghua , Zhuang Shaohui , Chen Huimin , Yang Shaohui , Qiu Zeting
Published: June 2019

To develop clinical nomograms for prediction of overall survival (OS) and cancer-specific survival (CSS) in patients with stage IV tongue squamous cell carcinoma (TSCC) after surgery based on the Surveillance, Epidemiology, and End Results (SEER) program database.

We collected data of resected stage IV TSCC patients from the SEER database, and divided them into the training set and validation set by 7:3 randomly. Kaplan–Meier analysis and Cox regression analysis were adopted to distinguish independent risk factors for OS and CSS. Clinical nomograms were constructed to predict the 3-year and 5-year probabilities of OS and CSS for individual patients. Calibration curves and Harrell C-indices were used for internal and external validation.

A total of 1550 patients with resected stage IV TSCC were identified. No statistical differences were detected between the training and validation sets. Age, race, marital status, tumor site, AJCC T/N/M status, and radiotherapy were recognized as independent prognostic factors associated with OS as well as CSS. Then nomograms were developed based on these variables. The calibration curves displayed a good agreement between the predicted and actual values of 3-year and 5-year probabilities for OS and CSS. The C-indices predicting OS were corrected as 0.705 in the training set, and 0.664 in the validation set. As for CSS, corrected C-indices were 0.708 in the training set and 0.663 in the validation set.

The established nomograms in this study exhibited good accuracy and effectiveness to predict 3-year and 5-year probabilities of OS and CSS in resected stage IV TSCC patients. They are useful tools to evaluate survival outcomes and helped choose appropriate treatment strategies.
Mesothelin expression and its prognostic role according to microsatellite instability status in colorectal adenocarcinoma
Authors: Kim Hyunsung , Chung Yumin , Paik Seung Sam , Jang Kiseok , Shin Su-Jin
Published: June 2019

The cell-surface glycoprotein, mesothelin, is normally present on mesothelial cells. Overexpression of mesothelin has been reported in many tumors and is correlated with poor outcome. We investigated the clinicopathologic significance of mesothelin expression in colorectal adenocarcinoma with microsatellites instability (MSI) status.

Mesothelin expression was evaluated immunohistochemically in tissue microarray blocks from 390 colorectal adenocarcinoma samples. Mesothelin expression was interpreted according to the intensity and extent. A score of 2 was considered high expression. We analyzed the correlation between mesothelin expression and clinicopathologic characteristics.

High mesothelin expression was observed in 177 (45.4%) out of 390 colorectal adenocarcinoma samples and was significantly associated with high histologic grade (P = .037), lymphatic invasion (P = .028), lymph node metastasis (P = .028), and high AJCC stage (P = .026). Kaplan–Meier survival curves revealed no significant difference between patients with high mesothelin expression and patients with low mesothelin expression in both recurrence-free survival (RFS) and cancer-specific survival (P = .609 and P = .167, respectively). In subgroup survival analyses, high mesothelin expression was associated with poor RFS in the MSI-High group of colorectal adenocarcinoma (P 
= .004).

High mesothelin expression was significantly associated with aggressive phenotypes and poor patient outcome in MSI-High colorectal adenocarcinoma.
Effect of paternal age on intracytoplasmic sperm injection outcomes in cryptozoospermic men
Authors: Yu Yang , Wang Ruixue , Xi Qi , Zhang Hongguo , Jiang Yuting , Li Leilei , Liu Ruizhi , Zhang Xinyue
Published: June 2019

It is not clear whether age has any influence on the outcomes for sperm used for assisted reproductive technology in cryptozoospermic men. We evaluated intracytoplasmic sperm injection (ICSI) outcomes using ejaculated or testicular sperm in men with cryptozoospermia from different paternal age ranges.

We conducted a retrospective observational study of 35 men with cryptozoospermia who underwent ICSI from 2010 to 2018. They were classified into 2 groups based on male age, namely < 35 years and ≥ 35 years. Each group was further divided into 2 subgroups according to the origin of sperm (ejaculated or testicular).

In the <35 years group, the normal fertilization and high-quality embryo rates for ejaculated sperm were significantly higher than with testicular sperm (74.7% vs. 62.4%, P = .02; 50.5% vs. 36.6%, P = .03, respectively). However, in the ≥35 years group, the high-quality embryo and clinical pregnancy rates were significantly lower in the ejaculated sperm subgroup than in the testicular sperm subgroup (26.2% vs. 63%, P = .002; 12.5% vs. 71.4%, P = .04, respectively).

This study indicates that ICSI should be performed as soon as possible for men with cryptozoospermia. When the paternal age ≥35 years, testicular sperm should be used for ICSI, as this offers better high-quality embryo and clinical pregnancy rates.
Efficacy and safety of Tripterygium wilfordii Hook F preparations for the treatment of Crohn disease
Authors: Zhang Jianying , Han Gang , Yu Zhenwei
Published: June 2019

Background:

Crohn disease (CD) is associated with substantial healthcare related costs and impairment of quality of life. Tripterygium wilfordii Hook F (TwHF) is proved to be effective for CD in animal and human. However, there is no systemic review and meta-analysis regarding the clinical efficacy and safety of TwHF preparation for the treatment of CD.

Methods:

Six electronic databases (Medline, EMBASE, Cochrane database, Chinese National Knowledge Infrastructure, Wanfang Database and Chongqing VIP Database) will be searched for eligibility studies. Data from the included studies will be extracted and the quality of studies will be assessed. Data synthesis will be performed using Review Manager software. Sensitivity analysis and publication bias assessment will also be carried out.

Results:

This systemic review and meta-analysis will provide synthesized result of clinical efficacy and safety of TwHF preparation for the treatment of CD.

Conclusion:

This research will determine the clinical efficacy and safety of TwHF preparation for the treatment of CD.

Registration: PROSPERO CRD42019127893
Efficacy and safety of glucocorticoids in the treatment of severe community-acquired pneumonia
Authors: Jiang Shan , Liu Tiecheng , Hu Yuxin , Li Ranwei , Di Xin , Jin Xin , Wang Yanqiao , Wang Ke
Published: June 2019

Background:

Recent clinical trials have shown that adjunctive glucocorticoids is associated with inhibiting excessive inflammatory response and modulating cytokines release offering several advantages over conventional therapy on relieving clinical symptoms, reducing mortality, and improving prognosis. However, given the severe complications triggered by glucocorticosteroid, whether similar benefits may be achieved by patients undergoing glucocorticosteroid intervention remains controversial. Our meta-analysis aimed to investigate the efficacy and safety of adjunctive glucocorticoids in the treatment of severe community acquired pneumonia.

Methods:

A search of PubMed, EMBASE, Cochrane Library, EBASO, Medline, Google Scholar, Science Dicet, CBM, and CNKI databases was performed to analyze all relevant randomized controlled trials (RCTs) of corticosteroids in patients with severe community acquired pneumonia (CAP) up to January 2018. All-cause mortality, C-reactive protein (CRP) level, incidence of septic shock, and requirement of mechanical ventilation were selected as efficacy outcomes. Major adverse events involving super infection, upper gastrointestinal bleeding, and hyperglycemia were safety outcomes. Meta-analysis was conducted with RevMan 5.3 software.

Results:

A total of 10 RCTs comprising 665 patients were included for analysis. Regarding efficacy outcomes, adjunctive corticosteroid seemed to be superior compared with conventional treatment in terms of all-cause mortality (relative risk [RR]: 0.47, 95% confidence interval [CI], 0.3–0.74, P = .001), CRP level on day 8 after administration (standard mean difference [SMD]: −0.8, 95% CI, −1.11 to −0.5, P < .001), incidence of septic shock (odds ratio [OR] 0.15, 95% CI, 0.07–0.29, P < .001) and requirement for mechanical ventilation (OR: 0.32, 95% CI, 0.20–0.52, P < .001). Meanwhile, we found that low dose (≤86 mg) (RR: 0.41, 95% CI, 0.21–0.82, P = .01) and prolonged (>5 days) (RR: 0.35, 95% CI, 0.15–0.81, P = .01) use of corticosteroids in dosage modus of a maintenance dose after a bolus (RR: 0.28, 95% CI, 0.14–0.55, P = .002) obtained better results in death through subgroup analysis. Regarding safety outcomes, no difference was observed between 2 groups in terms of upper gastrointestinal bleeding (OR: 0.83, 95% CI, 0.27–2.52, P = .74), hyperglycemia (OR: 1.3, 95% CI, 0.68–2.49, P = .42), and super infection (OR: 1.11, 95% CI, 0.14–9.13, P = .92).

Conclusion:

Adjunctive corticosteroid yielded favorable outcomes in the treatment of severe community acquired pneumonia (SCAP) as evidenced by decreased all-cause mortality, incidence of septic shock, and requirement for mechanical ventilation without increasing risk of adverse events. Low dose (≤86 mg/d), prolonged use (>5 days) of corticosteroid in dosage modus of a maintenance dose after a bolus can be recommended as preferred regimen to guard against SCAP.
Pediatric eosinophilic esophagitis effectively treated with a short-term 6-food-group elimination diet and reintroduction therapy
Authors: Kakiuchi Toshihiko , Nakayama Aiko , Matsuo Muneaki
Published: June 2019

Rationale:

Eosinophilic esophagitis (EoE) is an inflammatory disease diagnosed based on clinical symptoms and pathological findings. EoE is treated with proton pump inhibitors (PPIs), topical steroids, and elimination diet-reintroduction therapy. After remission is achieved with the elimination diet, foods can be reintroduced sequentially to identify specific food triggers; however, this reintroduction method was not previously standardized.

Patient concerns:

A 12-year-old girl presented to our hospital with a 3-year history of epigastric pain. Esophagogastroduodenoscopy revealed linear furrows, esophageal rings, white exudates, and pallor throughout the esophagus. Histopathological findings revealed eosinophilic infiltration >15 eos/hpf on esophageal biopsy. There were no obvious abnormal findings in the stomach and duodenum.

Diagnoses:

EoE

Interventions and outcomes:

Because PPI was ineffective, we proposed a 6-food-group elimination diet (SFGED) and reintroduction therapy for EoE, which was initially planned out over a 6-week interval. However, a 5-day interval of SFGED and reintroduction therapy was performed instead. The treatment was effective and causative food antigens (egg and nuts) were identified. Since her symptoms recovered following short-term treatment, the nutritional impact was minimized, as was the duration of her hospitalization. Consequently, the patient's quality of life was well-preserved.

Lessons:

SFGED and reintroduction therapy for EoE may be effective even for short-term treatments involving 5-day intervals.
Challenges in diagnosing community-acquired carbapenem-susceptible Acinetobacter baumannii enterogenic sepsis
Authors: Ye Gongjie , Ye Longqiang , Zhou Jianqing , Shi Linhui , Yang Lei , Dong Zhouzhou
Published: June 2019

Introduction:

Community-acquired (CA) carbapenem-susceptible Acinetobacter baumannii (CSAB) enterogenic sepsis is very rare but has a high mortality. Although CA A. baumannii bloodstream infections have been known to develop from respiratory tract, urinary tract, and intravenous device-related infections, CA A. baumannii bloodstream infections from the gastrointestinal tract have not yet been reported.

Patient concerns:

A 73-year-old male with the chief presentation of gastrointestinal symptoms was initially diagnosed with acute gastroenteritis and showed poor clinical response to empirical antibiotic therapy.

Diagnoses:

The diagnosis of CSAB enterogenic sepsis was established based on results of blood culture, elevated serum procalcitonin level, and specific hemodynamic changes related to septic shock.

Interventions:

The patient initially received empirical antibiotic treatment (cefodizime 2.0 q12 hours plus moxifloxacin 0.4 qd); then, treatment was changed to the conventional dose of carbapenem (imipenem 0.5 q6 hour).

Outcomes:

Finally, CSAB was eliminated from the bloodstream, and the patient was discharged.

Lessons:

Although severe, CA CSAB enterogenic sepsis is often misdiagnosed because of its clinical rarity. Early diagnosis and appropriate initial empirical antibiotic therapy are crucial for treating such cases.
Real-world observational experience with direct-acting antivirals for hepatitis C: baseline resistance, efficacy, and need for long-term surveillance
Authors: Loo Nicole , Hanysak Bryan , Mann Jena , Ramirez Ruben , Kim Jae , Mitchell Robert , Van Frank Timothy , Guerrero Richard , Hinojosa Kim , Christensen Kimberley , Pedicone Lisa D. , Alkhouri Naim , Wells Jennifer , Landaverde Carmen , Rodas Fabian , Lawitz Eric , Poordad Fred
Published: June 2019

The aim of this study was to obtain real-world, US, observational data on the effect of baseline resistance-associated substitutions (RASs) on achieving sustained virologic response (SVR) in hepatitis C (HCV) patients treated with direct-acting antiviral (DAA) regimens; the need for long-term follow-up in post-SVR patients.

It is uncertain if the presence of RASs limits efficacy to DAAs. Once SVR is achieved, society guidelines recommend long-term surveillance for hepatocellular carcinoma in certain patients. Real-world data are limited on these topics.

Adult patients treated with DAAs at community hepatitis clinics between January 2015 and April 2017 were included in this study. Baseline resistance testing was performed before treatment. Per guidelines, post-SVR long-term monitoring was required in patients with F3 to F4 fibrosis before treatment or with elevated ALT levels (>19 U/L females; >30 U/L males).

A total of 875 chronic, mostly GT1a (60%) HCV patients were treated with an approved DAA regimen. Average baseline AST and ALT were 75 and 67 U/L, respectively, and 47% had F3 to F4 fibrosis at baseline. SVR was achieved in 863 (98.6%) patients despite a high presence of baseline RASs (61%). Long-term monitoring was required post-SVR in 539 patients (62%).

In a real-life, US cohort of HCV-infected patients, nearly all patients achieved SVR with available DAA regimens regardless of baseline RASs. Approximately two-thirds of these patients required long-term follow-up, despite viral eradication.
The effects of hip strengthening exercises in a patient with plantar fasciitis
Authors: Lee Jin Hyuck , Park Jong Hoon , Jang Woo Young
Published: June 2019

Rationale:

Plantar fasciitis is a common cause of foot pain presenting with morning stiffness and plantar area pain. This case study is to optimize the management in patient with plantar fasciitis accompanied by apparent high-arch foot.

Patient concerns:

A 55-year-old women presented with plantar fasciitis accompanied by apparent high-arch foot. The pain presents for the heel and pelvic areas with long-distance walking.

Diagnoses:

She was diagnosed with plantar fasciitis accompanied by apparent high-arch foot for physical examination and plain radiographs. In muscle performance and dynamic postural stability tests, indicated the muscle weakness and postural instability.

Interventions:

The patient was treated with manual therapy such as joint and soft tissue mobilization interventions including plantar fascia and gastrocnemius stretching, but the heel and pelvic pain were aggravated during long-distance walking. After hip strengthening exercises, the heel and pelvic pain significantly improved.

Outcomes:

The 3-month follow-up revealed that the heel and pelvic pain did not occur in the long-distance walking, and there was no pain and discomfort at one year follow-up.

Lessons:

To optimize the management in patient with plantar fasciitis accompanied by apparent high-arch deformity, clinicians should try to identify the hip abductor muscles weakness, and therapists should consider incorporating hip strengthening exercises.
Comparison of 2 curative treatment options for very early hepatocellular carcinoma
Authors: Kim Tae Hyung , Chang Jung Mi , Um Soon Ho , Jee Heejung , Lee Yoo Ra , Lee Han Ah , Yim Sun Young , Han Na Yeon , Lee Jae Min , Choi Hyuk Soon , Kim Eun Sun , Yu Young-Dong , Keum Bora , Kim Min Ju , An Hyunggin , Park Beom Jin , Seo Yeon Seok , Kim Dong-Sik , Yim Hyung Joon , Cho Sung Bum , Jeen Yoon Tae , Lee Hong Sik , Chun Hoon Jai , Kim Yun Hwan , Kim Chang Duck
Published: June 2019

Curative treatments for very early-stage hepatocellular carcinoma (HCC), defined as single HCC with a maximum diameter of <2 cm in patients with well-preserved liver function, consist of surgical resection or radiofrequency ablation (RFA). In this retrospective study, we compared the efficacy of both treatments in 154 patients with very early-stage HCCs who underwent resection or RFA as initial therapy and were followed up for a median of 56.8 months. Propensity score matching analysis was also conducted. Overall survival was comparable between treatment groups (median survival time of 143 vs 97 months for resection and RFA, respectively; P = .132). Resection group; however, demonstrated a significantly lower recurrence rate after initial therapy than RFA group (42.3% vs 65.7%; P = .006) with a longer median recurrence-free survival time (66.7 vs 33.8 months; P = .002), which was confirmed even after matching (P = .04). In contrast, the recurrence pattern in advanced-stage (9.6% vs 1.0%; P = .01) or incurable recurrences (19% vs 13%; P = .04) was more frequent following resection than RFA. Recurrent lesions were comparatively more curable in RFA group than in resection group (80% vs 54.5%; P = .02). The recurrence of HCC was independently associated with lower serum albumin level (P = .027), the presence of comorbid diabetes mellitus (P = .010), and RFA (P = .034). In conclusion, in patients with very early-stage HCC, surgical resection has achieved significantly better recurrence-free survival than RFA. A closer follow-up is required after resection.
Non-syndromic occurrence of true generalized microdontia with hypodontia
Authors: Chen Yuan , Zhou Fangjie , Peng Yiran , Chen Luxian , Wang Yan
Published: June 2019

Rational:

Dental abnormalities can occur at any stage of tooth development. Of these abnormalities, true generalized microdontia is a rare condition in which all teeth are smaller than normal, while hypodontia is defined as the absence of 1 to 5 teeth. As far as we are aware, no article has reported a case of the non-syndromic occurrence of true generalized microdontia with hypodontia.

Patient concerns:

A 9-year-old girl who had no systemic diseases presented with congenital absence of maxillary lateral incisors bilaterally and small teeth involving the whole dentition.

Diagnoses:

Based on intraoral examinations and panoramic radiograph, the patient was diagnosed with the simultaneous occurrence of true generalized microdontia, hypodontia, and a variation of maxillary 1st molar with a single root and single canal. Also, the patient had premature loss of mandibular molars and canines, periapical periodontitis in the mandible left 1st primary molar and deep caries in mandible left secondary primary molar.

Interventions:

A removable appliance to hold space for early loss of mandibular molars and canines was made at the present stage. The mandible left 1st primary molar had periapical periodontitis and the affected tooth was extracted. Furthermore, the distal surface of the mandible left 2nd primary molar was filled with complex resin materials. A multi-disciplinary therapy plan was carefully designed including orthodontics, dental implants and esthetic restoration in the future.

Outcomes:

The patient complied well with instructions for wearing the removable space maintainer, which helps prevent mesial migration of the permanent 1st molars, at the current stage. The therapeutic efficiency on periapical periodontitis and caries lesions was also good.

Lessons:

The non-syndromic presence of true generalized microdontia is extremely rare. A personalized treatment plan with multi-disciplinary considerations should be given for these patients. The pathogenesis remains unclear but may be related to genetic as well as environmental factors. More studies are urgently needed to explore the pathogenesis and treatment options for the future.
Sustained Remission After Maintenance Irinotecan in Patient With Multiply Relapsed Hepatoblastoma
Authors: Natarajan Eesha , Auerbach Claudia , Cheron Rebecca , Pashankar Farzana
Published: June 2019

Children with recurrent hepatoblastoma have a poor prognosis and limited treatment options. The authors describe a child with metastatic hepatoblastoma who had multiple relapses. He was treated with surgical resection and adjuvant chemotherapy at first relapse. At second relapse, he had progressive disease postresection. He was treated with ifosfamide/carboplatin/etoposide chemotherapy followed by maintenance irinotecan and achieved long-term disease-free survival. Irinotecan as maintenance should be explored in recurrent hepatoblastoma.
A Cross-sectional Analysis of Compassion Fatigue, Burnout, and Compassion Satisfaction in Pediatric Hematology-Oncology Physicians in the United States
Authors: Weintraub Andrea S. , Sarosi Alex , Goldberg Eliana , Waldman Elisha D.
Published: June 2019

Compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS) are interrelated phenomena that impact personal and professional performance. The CF and Satisfaction Self-Test and a demographic questionnaire were distributed electronically to pediatric hematology-oncology physicians nationally. Linear regression models for CF, BO, and CS as a function of potential predictors were constructed. Survey response rate was 28%. Female sex, BO score, distress about a “clinical situation,” and “teaching” were associated with higher CF scores. “Administrative activities” were associated with lower CF scores. CF score, and distress about “administrative burden/academic stress” and “coworkers” were associated with higher BO scores. CS score and “socializing” were associated with lower BO scores. “Exercise,” “socializing,” and “talking with partner” were associated with higher CS scores. CF and BO scores, emotional depletion, and distress about the “work environment” and “administrative/academic burden” were associated with lower CS scores. Our data highlights the importance of strong social connections at work and at home to decrease BO and enhance CS. Professional development in leadership, communication, and conflict resolution, as well as “team building” events may perpetuate coworker relationships. Education about the importance of connectedness and self-care should begin early in medical education to cultivate robust coping mechanisms in trainees.
Beware of Osteogenesis Imperfecta
Authors: Dinca Eduard B. , Carron Romain
Published: June 2019

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by disruption of normal collagen formation resulting in varying degrees of ligamentous laxity and skeletal vulnerability; the low bleeding potential is easily overlooked. Subdural hematoma (SDH) is a common neurosurgical condition, classically related to the rupture of bridging cortico-dural veins after trauma. In the pediatric population, the age distribution shows a massive preponderance for children in their early first decade. We report a very unusual case of SDH in a 10-year-old boy with OI type I, with history of minor trauma. SDH remains exceedingly rare in OI, and its pathophysiology is unclear. To the best of our knowledge, this is the first report of a unilateral subacute SDH associated with OI in a child of such advanced age. These cases may also carry legal ramifications, including misdiagnosis of child abuse in ambiguous situations that are not thoroughly investigated.
An Integrative Review of the Barriers to Job Acquisition for People With Severe Mental Illnesses
Authors: Charette-Dussault Élyse , Corbière Marc
Published: June 2019

This integrative review analyses and synthesizes specialized literature of 20 years up to 2017 studying barriers/obstacles to employment for people with severe mental illnesses. The inclusion and exclusion criteria led to 35 experimental and nonexperimental studies. Results of the prospective studies were analyzed with the evidence synthesis method to isolate the most salient obstacles. Six main themes emerged from the findings, grouped into personal and environmental barriers. Environmental barriers were related to disability benefits and other physical resources, to stigma and social support, and to vocational services. Individual barriers included those related to illness, to work experience and skills, and to self-perception, fears, and motivation. The most prominent obstacles are lack of work experience and lack of use of effective strategies toward employment. Systematically identifying barriers to employment for people with severe mental illnesses will enable employment specialists to better support their clients in overcoming them, thus facilitating their work integration.
A Simplified Cost-Utility Analysis of Inpatient Flap Monitoring after Microsurgical Breast Reconstruction and Implications for Hospital Length of Stay
Authors: Jablonka Eric M. , Lamelas Andreas M. , Kanchwala Suhail K. , Rhemtulla Irfan , Smith Mark L.
Published: June 2019

Background:

The number of free flap take-backs and successful salvages following microsurgical breast reconstruction decreases as time from surgery increases. As a result, the cost of extended inpatient monitoring to achieve a successful flap salvage rises rapidly with each postoperative day. This study introduces a simplified cost-utility model of inpatient flap monitoring and identifies when cost-utility exceeds the thresholds established for other medical treatments.

Methods:

A retrospective review of a prospectively maintained database was performed of patients who underwent microsurgical breast reconstruction to identify flap take-back and salvage rates by postoperative day. The number of patients and flaps that needed to be kept on an inpatient basis each day for monitoring to salvage a single failing flap was determined. Quality-of-life measures and incremental cost-effectiveness ratios for inpatient flap monitoring following microsurgical breast reconstruction were calculated and plotted against a $100,000/quality-adjusted life-year threshold.

Results:

A total of 1813 patients (2847 flaps) were included. Overall flap take-back and salvage rates were 2.4 percent and 52.3 percent, respectively. Of the flaps taken back, the daily take-back and salvage rates were 56.8 and 60.0 percent (postoperative day 0 to 1), 13.6 and 83.3 percent (postoperative day 2), 11.4 and 40.0 percent (postoperative day 3), 9.1 and 25.0 percent (postoperative day 4), and 9.1 and 0.0 percent (>postoperative day 4), respectively. To salvage a single failing flap each day, the number of flaps that needed to be monitored were 121 (postoperative day 0 to 1), 363 (postoperative day 2), 907 (postoperative day 3), 1813 (postoperative day 4), and innumerable for days beyond postoperative day 4. The incremental cost-effectiveness ratio of inpatient flap monitoring begins to exceed a willingness-to-pay threshold of $100,000/quality-adjusted life-year by postoperative day 2.

Conclusion:

The health care cost associated with inpatient flap monitoring following microsurgical breast reconstruction begins to rise rapidly after postoperative day 2.
Preoperative Perforator Mapping in SGAP Flap: Does Magnetic Resonance Imaging Make the Difference?
Authors: Zoccali Giovanni , Mughal Maleeha , Roblin Paul , Farhadi Jian
Published: June 2019

Background:

Preoperative vascular mapping has emerged as an excellent adjunct to perforator flap surgery, improving operative time while aiding the surgeon in the selection of the ideal perforator. This study evaluated the effect of preoperative vascular mapping by magnetic resonance imaging to identify tissue for a superior gluteal artery perforator (SGAP) flap on total operative time and compared radiologic mapping by magnetic resonance imaging with Doppler ultrasonography for perforator localization. The authors also investigated whether drawing the flap according to magnetic resonance imaging perforator localization or tissue availability affected the outcome of the donor site.

Methods:

A prospective study was performed on patients undergoing SGAP flap breast reconstruction. Patients were randomized into two groups. One group received preoperative magnetic resonance imaging for flap tissue planning based on localization of the perforator. The other group received flap planning based on tissue availability and then underwent external Doppler ultrasonography to identify the dominant perforator. An ad hoc outcome scale was created to evaluate outcomes of the donor sites.

Results:

Preoperative vascular mapping by magnetic resonance imaging or external Doppler ultrasonography was performed the day of surgery on 35 and 27 patients, respectively. The mean flap elevation times of the imaging patients versus the ultrasonography patients were 252 and 228 minutes, respectively. The differences between flap elevation times and cosmetic outcomes for the two patient groups were not significant.

Conclusion:

The authors’ findings indicate that the use of magnetic resonance imaging for SGAP flap planning did not reduce operative time, and that donor-site outcomes were not affected by the modality used for preoperative perforator mapping.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Identification of Fibrinogen as a Key Anti-Apoptotic Factor in Human Fresh Frozen Plasma for Protecting Endothelial Cells In Vitro
Authors: Yu Qiang , Yang Baibing , Davis Joy M. , Ghosn Jean , Deng Xiyun , Doursout Marie-Francoise , Dong Jing-fei , Wang Run , Holcomb John B. , Wade Charles E. , Ko Tien C. , Cao Yanna
Published: June 2019

Resuscitation with human fresh frozen plasma (FFP) in hemorrhagic shock (HS) patients is associated with improved clinical outcomes. Our group has demonstrated that the beneficial effect of FFP is due to its blockade on endothelial hyperpermeability, thereby improving vascular barrier function. The current study aimed to investigate HS-induced endothelial cell apoptosis, a potential major contributor to the endothelial hyperpermeability, and to determine the effect and the key components/factors of FFP on protecting endothelial cells from apoptosis. We first measured and demonstrated an increase in apoptotic endothelial microparticles (CD146+AnnexinV+) in patients in shock compared to normal subjects, indicating the induction of endothelial cell activation and apoptosis in shock patients. We then transfused HS rats with FFP and showed that FFP blocked HS-induced endothelial cell apoptosis in gut tissue. To identify the anti-apoptotic factors in FFP, we utilized high-performance liquid chromatography, fractionated FFP, and screened the fractions in vitro for the anti-apoptotic effects. We selected the most effective fractions, performed mass spectrometry, and identified fibrinogen as a potent anti-apoptotic factor. Taken together, our findings suggest that HS-induced endothelial apoptosis may constitute a major mechanism underlying the vascular hyperpermeability. Furthermore, the identified anti-apoptotic factor fibrinogen may contribute to the beneficial effects of FFP resuscitation, and therefore, may have therapeutic potential for HS.
Endoscopic Ultrasound in Pediatric Patients With Pancreatobiliary Disease
Authors: Téllez-Ávila Félix I. , Duarte-Medrano Gilberto , Herrera-Mora David , Lopez-Arce Gustavo , Leal-García Mariana , Ramírez-Martínez Maribel , Ramírez-Luna Miguel
Published: June 2019

Background:

Endoscopic ultrasound (EUS) is one of the greatest advances of the last few decades for the diagnostic and therapeutic approach of gastrointestinal diseases in adults. However, there are limitations to the application of the procedure in the pediatric population. The aim of this study was to describe the diagnostic yield and therapeutic role of EUS in pediatric patients with pancreatobiliary disease.

Materials and Methods:

A retrospective study was performed on a prospective database of pediatric patients who underwent diagnostic and therapeutic endosonographic procedures. All patients seen in a 12-year period were included.

Results:

A total of 54 patients were included, including 32 (59.3%) female individuals, with an average age of 16 (9 to 17) years. EUS was abnormal in 46 (85%) patients. Of the abnormal procedures, 4 (7.4%) corresponded to therapeutic ones. The main indication of the study was recurrent acute pancreatitis in 29 (54%). The main endosonographic findings were microlithiasis in 14 (25.9%), chronic pancreatitis in 9 (16.7%), and pancreatic tumors in 6 (11.1%) patients. Follow-up was performed in 31 (57.4%) patients, 19/31 patients underwent surgery, and 4/31 patients had endoscopic retrograde cholangiopancreatography. The median follow-up was 910 (2 to 3916) days. In 100% of the patients with follow-up, the initial diagnosis of EUS was confirmed.

Conclusion:

EUS is a useful and safe tool in the pediatric population with pancreatobiliary diseases.
Ectopic Opening of the Common Bile Duct into the Duodenal Bulb: Diagnosis and Therapeutic Management and Considerations for Timing of Surgery and Duration of Follow-up After Initial Endoscopic Retrograde Cholangiopancreatography
Authors: Muhammedoğlu Bahtiyar
Published: June 2019

Introduction:

Ectopic opening of the common bile duct (EO-CBD) is a rare pathology, and its management is important. To date, only a few studies have been conducted for EO-CBD due to its low incidence.

Materials and Methods:

A retrospective review was conducted on 54 patients with available prospective data. Among them, 30 patients (group 1) underwent choledochoduodenostomy for reasons other than anomalous opening, and 24 patients (group 2) had an EO-CBD.

Results:

Endoscopic retrograde cholangiopancreatography (ERCP) was performed for 24 patients with duodenal deformity and apical stenosis. EO-CBD was detected in 2.72% of all patients who underwent ERCP (24/880 ERCPs). The occurrence of hyperbilirubinemia (total bilirubin >1.2 mg/dL) was not significantly different between groups: 3.83±4.57 mg/dL for group 1 and 2.26±2.17 mg/dL for group 2.

Conclusions:

Failed ERCP, giant stones, and recurrent episodes (>2) of cholangitis requiring ERCP constitute indications for surgical treatment in cases of EO-CBD into the duodenum.
A Pseudoaneurysm of Aberrant Right Subclavian Artery Caused by Esophageal Stent Placement Because of Esophageal Stricture After Endoscopic Submucosal Dissection
Authors: Zheng Shiqin , Wang Xiaosong , Chen Shuang , Wei Jianming , Wei Zhiqing , Miao Lin , Zhang Xiuhua
Published: June 2019

A 67-year-old man who received endoscopic submucosal dissection for an early squamous esophageal cancer was hospitalized for dysphagia. The mucosal defect was over three quarters of the circumference, and the distal edge of the resection scar formed the stenosis after 8 months. After experiencing conservative treatment, probe expansion, and esophageal stent placement, the symptom of deglutition disorder in the patient was improved, but persistent hemorrhage and progressive anemia occurred in the short term. An enhanced neck and chest computed tomography (CT) showed a contrast agent leaked from the aberrant right subclavian artery to the esophagus. A pseudoaneurysm of the aberrant right subclavian artery and subclavian artery-esophageal fistula were diagnosed by CT angiography. Although false aneurysms developing after iatrogenic injury and trauma have been reported, those caused by esophageal stent placement because of esophageal stricture after endoscopic submucosal dissection have not. When persistent hemorrhage and progressive anemia develop after esophageal stent placement, an enhanced CT should be performed to exclude the false aneurysm.
Development and Validation of a 49-Item Sports Nutrition Knowledge Instrument (49-SNKI) for Adult Athletes
Authors: Karpinski Christine A. , Dolins Karen Reznik , Bachman Jessica
Published: June 2019

The purpose of this project was to develop and validate an instrument to assess the sports nutrition knowledge of adult athletes. An evidence-based, mixed-methods process was employed to establish face/content validity (expert review), construct validity, (Independent t test and Mann-Whitney U test), internal consistency (Cronbach α), and test-retest reliability (Pearson ρ). Results confirmed content and construct validity (mean total score for registered dietitian nutritionists compared with the athletes 38.5 ± 5.3 vs 15.9 ± 9.2; P < .001), internal consistency (0.843), and reliability (r = 0.951; P < .001). The 49-item Sports Nutrition Knowledge Instrument (49-SNKI) can be a valid and reliable instrument used to measure sports nutrition knowledge of adult athletes.
Comparison of the Identification of Malnutrition by Subjective Global Assessment and the A.S.P.E.N./Academy Malnutrition Diagnostic Framework Among Adults on Maintenance Hemodialysis
Authors: Schwartz Emily , Brody Rebecca A. , Parrott J. Scott , Peters Emily , Byham-Gray Laura
Published: June 2019

The aim of this study was to determine the level of agreement between Subjective Global Assessment (SGA) and the A.S.P.E.N./Academy framework (AAF) in identifying malnutrition among adults on maintenance hemodialysis. In a secondary analysis, participants (N = 80) were evaluated using surrogate markers for the AAF and results were compared with SGA scores. Malnutrition prevalence identified by the AAF and SGA was 25% (n = 20) and 78.8% (n = 63), respectively. A κ value of 0.131 indicated only slight agreement between the 2 tools. Prospective trials should be conducted that compare malnutrition identification by using the 2 tools.
Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels
Authors: Kanavy Dona M. , McNulty Shannon M. , Jairath Meera K. , Brnich Sarah E. , Bizon Chris , Powell Bradford C. , Berg Jonathan S.
Published: June 2019

Background

The 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines for clinical sequence variant interpretation state that “well-established” functional studies can be used as evidence in variant classification. These guidelines articulated key attributes of functional data, including that assays should reflect the biological environment and be analytically sound; however, details of how to evaluate these attributes were left to expert judgment. The Clinical Genome Resource (ClinGen) designates Variant Curation Expert Panels (VCEPs) in specific disease areas to make gene-centric specifications to the ACMG/AMP guidelines, including more specific definitions of appropriate functional assays. We set out to evaluate the existing VCEP guidelines for functional assays.

Methods

We evaluated the functional criteria (PS3/BS3) of six VCEPs (CDH1, Hearing Loss, Inherited Cardiomyopathy-MYH7, PAH, PTEN, RASopathy). We then established criteria for evaluating functional studies based on disease mechanism, general class of assay, and the characteristics of specific assay instances described in primary literature. Using these criteria, we extensively curated assay instances cited by each VCEP in their pilot variant classification to analyze VCEP recommendations and their use in the interpretation of functional studies.

Results

Unsurprisingly, our analysis highlighted the breadth of VCEP-approved assays, reflecting the diversity of disease mechanisms among VCEPs. We also noted substantial variability between VCEPs in the method used to select these assays and in the approach used to specify strength modifications, as well as differences in suggested validation parameters. Importantly, we observed discrepancies between the parameters VCEPs specified as required for approved assay instances and the fulfillment of these requirements in the individual assays cited in pilot variant interpretation.

Conclusions

Interpretation of the intricacies of functional assays often requires expert-level knowledge of the gene and disease and current VCEP recommendations for functional assay evidence are a useful tool to improve the accessibility of functional data. However, our analysis suggests that further guidance is needed to standardize this process and ensure consistency in the application of functional evidence.
Nutritional Supplementation during Pulmonary Rehabilitation in COPD: A Systematic Review
Authors: Aldhahir Abdulelah M , Al Rajah Ahmed M , Aldabayan Yousef S , Drammeh Salifu , Subbu Vanitha , Alqahtani Jaber S , Hurst John R , Mandal Swapna
Published: June 2019

Background

Uptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use. Our objective were to report and summarise the current evidence supporting use of nutritional supplementation to improve outcomes during pulmonary rehabilitation in stable COPD patients.

Methods

A systematic search was conducted up to May 7th, 2019 (registration number CRD42018089142). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online (Medline), Allied and Complementary Medicine Database (AMED), the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE (Embase), Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Web of Science.

Results

This systematic search generated 580 initial matches, of which 24 studies (1035 COPD participants) met the pre-specified criteria and were included. Our analysis does not confirm an impact of nutritional supplementation during PR, but studies, supplements and PR programmes were heterogeneous in nature.

Conclusion

There is currently insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD. Therefore, controversy remains and further research is needed.
Fast Klebsiella pneumoniae typing for outbreak reconstruction: an highly discriminatory HRM protocol on wzi capsular gene developed using EasyPrimer tool
Authors: Perini Matteo , Piazza Aurora , Panelli Simona , Carlo Domenico Di , Corbella Marta , Gona Floriana , Vailati Francesca , Marone Piero , Cirillo Daniela Maria , Farina Claudio , Zuccotti Gian Vincenzo , Comandatore Francesco
Published: June 2019

In this work we present EasyPrimer, a user-friendly online tool developed to assist pan-PCR and High Resolution Melting (HRM) primer design. The tool finds the most suitable regions for primer design in a gene alignment and returns a clear graphical representation of their positions on the gene. EasyPrimer is particularly useful in difficult contexts, e.g. on gene alignments of hundreds of sequences and/or on highly variable genes. HRM analysis is an emerging method for fast and cost saving bacterial typing and an HRM scheme of six primer sets on five Multi-Locus Sequence Type (MLST) genes is already available for Klebsiella pneumoniae. We validated the tool designing a scheme of two HRM primer sets on the hypervariable gene wzi of Klebsiella pneumoniae and compared the two schemes. The wzi scheme resulted to have a discriminatory power comparable to the HRM MLST scheme, using only one third of primer sets. Then we successfully used the wzi HRM primer scheme to reconstruct a Klebsiella pneumoniae nosocomial outbreak in few hours. The use of hypervariable genes reduces the number of HRM primer sets required for bacterial typing allowing to perform cost saving, large-scale surveillance programs.
3D imaging of undissected optically clearedAnopheles stephensimosquitoes infected withPlasmodiumparasites
Authors: De Niz Mariana , Kehrer Jessica , Brancucci Nicolas M.B. , Moalli Federica , Reynaud Emmanuel G. , Stein Jens V. , Frischknecht Friedrich
Published: June 2019

Malaria is a life-threatening disease, caused by Apicomplexan parasites of thePlasmodiumgenus. TheAnophelesmosquito is necessary for the sexual replication of these parasites and for their transmission to vertebrate hosts, including humans. Imaging of the parasite within the insect vector has been attempted using multiple microscopy methods, most of which are hampered by the presence of the light scattering opaque cuticle of the mosquito. So far, imaging of thePlasmodiummosquito stages depended on either sectioning or surgical dissection of important anatomical sites, such as the midgut and the salivary glands. Optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) enable imaging fields of view in the centimeter scale whilst providing micrometer resolution. In this paper, we present reconstructions of the whole body ofPlasmodium-infected, optically clearedAnopheles stephensimosquitoes and their midguts. The 3D-reconstructions from OPT imaging show detailed features of the mosquito anatomy and enable overall localization of parasites in midguts. Additionally, LSFM imaging of mosquito midguts shows detailed distribution of oocysts in extracted midguts.
Humans are primarily model-based learners in the two-stage task
Authors: da Silva Carolina Feher , Hare Todd A.
Published: June 2019

Distinct model-free and model-based learning processes are thought to drive both typical and dysfunctional behaviours. Data from two-stage decision tasks have seemingly shown that human behaviour is driven by both processes operating in parallel. However, in this study, we show that more detailed task instructions lead participants to make primarily model-based choices that have little, if any, simple model-free influence. We also demonstrate that behaviour in the two-stage task may falsely appear to be driven by a combination of simple model-free and model-based learning if purely model-based agents form inaccurate models of the task because of misconceptions. Furthermore, we report evidence that many participants do misconceive the task in important ways. Overall, we argue that humans formulate a wide variety of learning models. Consequently, the simple dichotomy of model-free versus model-based learning is inadequate to explain behaviour in the two-stage task and connections between reward learning, habit formation, and compulsivity.