bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Gender Influence Outcome in Cartilage Repair Surgery? An Analysis of 4,968 Consecutive Patients from the German Cartilage Registry (Knorpel Register DGOU)
Authors: Faber Svea , Zinser Wolfgang , Angele Peter , Spahn Gunter , Löer Ingo , Zellner Johannes , Hochrein Alfred , Niemeyer Philipp
Published: June 2020

The goal was to examine gender differences of patient characteristics and outcome after cartilage repair based on a collective of nearly 5,000 patients. Patient characteristics, accompanying therapies, and outcome (Knee Injury and Osteoarthritis Outcome Score [KOOS], reoperations, patient satisfaction) of 4,986 patients of the German cartilage register DGOU were assessed by t test for possible gender differences. P values <0.05 were considered statistically significant. Women were older than men (38.07 ± 12.54 vs. 26.94 ± 12.394 years, P = 0.002), more often preoperated (0.30 ± 0.63 vs. 0.24 ± 0.55, P = 0.001), and had a longer symptom duration (25.22 ± 41.20 vs. 20.67 ± 35.32 months, P < 0.001). Men had greater mean leg axis malalignment than women (3.24° ± 3.26° vs. 2.67° ± 3.06°, P < 0.001), less favorable meniscal status ( P = 0.001), worse defect stage ( P = 0.006), and a more severely damaged corresponding articular surface ( P = 0.042). At baseline (59.84 ± 17.49 vs. 52.10 ± 17.77, P < 0.001), after 6 months (72.83 ± 15.56 vs. 66.56 ± 17.66, P < 0.001), after 12 months (77.88 ± 15.95 vs. 73.07 ± 18.12, P < 0.001), and after 24 months (79.311 ± 15.94 vs. 74.39 ± 18.81, P < 0.001), men had better absolute KOOS values, but women had better relative KOOS increases 6 months (14.59 ± 17.31 vs. 12.49 ± 16.3, P = 0.005) as well as 12 months postoperatively (20.27 ± 18.6 vs. 17.34 ± 17.79, P = 0.001) compared with preoperatively, although 12 and 24 months postoperatively they were subjectively less satisfied with the outcome ( P < 0.001) and had a higher reintervention rate at 24 months (0.17 ± 0.38 vs. 0.12 ± 0.33, P = 0.008). In summary, the present work shows specific gender differences in terms of patient characteristics, defect etiology, defect localization, concomitant therapy, and the choice of cartilage repair procedure. Unexpectedly, contrary to the established scientific opinion, it could be demonstrated that women show relatively better postoperative KOOS increases, despite a higher revision rate and higher subjective dissatisfaction.
Urethral injury in children: Experience in a teaching hospital in Enugu, Nigeria
Authors: Chukwubuike Kevin Emeka , Enebe Joseph Tochukwu , Nduagubam Obinna Chukwuebuka
Published: June 2020

Background:

Urethral injury in children is uncommon, and its treatment is challenging. This study evaluated our experience in the management of urethral injuries in children who presented at the paediatric surgical unit of a teaching hospital in Enugu, Nigeria.

Methods:

The medical records of patients younger than 15 years old admitted to our centre with urethral injury from January 2008 and December 2017 were reviewed retrospectively.

Results:

During the period of the study, 11 cases (all male) were managed. The mean age of the patients at presentation was 11 years. Road traffic accident was the most common mechanism of injury, and the bulbar urethra was the most injured part of the urethra. All the patients had urethroplasty through the perineal approach. There was 90% success at first instance. One patient required redo urethroplasty.

Conclusion:

Urethral trauma is associated with considerable morbidity. Road traffic accident was the most common mechanism of injury, and the bulbar urethra was the part of the urethra most affected. Transperineal urethroplasty was an effective modality of treatment.
Chronic myeloid leukaemia with pulmonary leucostasis in a young Down syndrome patient
Authors: Che Rahim Mohd Jazman bin , Wan Hanafi Hany Haqimi bin , Kamaruddin Muhammad Imran bin , Husin Azlan bin
Published: June 2020

We reported a rare case of chronic myeloid leukaemia (CML) complicated with pulmonary leucostasis in an 11-year-old Down syndrome (DS) patient who presented with respiratory distress. His peripheral blood investigation showed features of CML with 17% circulating blast, with immunophenotyping showing positivity towards myeloid markers. Peripheral blood polymerase chain reaction for BCR–ABL fusion transcripts was positive, and cytogenetic studies showed Ph chromosome with trisomy 21. Despite cytoreduction therapy with hydroxyurea and leukapheresis, the patient succumbed due to shock, with multiple organ failure. Our case highlights the need for early detection and rapid referral for aggressive treatment in DS patients with CML, as the combination is associated with a poor outcome.
Insights into the role of the JAK/STAT signaling pathway in graft-versus-host disease
Authors: Abboud Ramzi , Choi Jaebok , Ruminski Peter , Schroeder Mark A. , Kim Sena , Abboud Camille N. , DiPersio John F.
Published: June 2020

Allogeneic hematopoietic transplantation (allo-HCT) is a curative therapy for a variety of hematologic malignancies, primarily through immune-mediated clearance of malignant cells. This graft- versus-leukemia (GvL) effect is mediated by alloreactive donor T-cells against recipient malignant cells. Unfortunately, graft versus host disease is a potentially lethal complication of this procedure, also mediated by alloreactive donor T-cells against recipient normal tissues. Graft- versus-host disease (GVHD) remains a key contributor to nonrelapse mortality and long-term morbidity in patients undergoing allo-HCT. Reducing GVHD without interfering with – or ideally while enhancing – GvL, would improve outcomes and increase patient eligibility for allo-HCT. The JAK/STAT signaling pathway acts downstream of over 50 cytokines and is central to a wide variety of inflammatory pathways. These pathways play a role in the development and maintenance of GVHD throughout the disease process and within T-cells, B-cells, macrophages, neutrophils, and natural killer cells. Agents targeting JAK/STAT signaling pathways have shown clinical efficacy and gained US Food and Drug Administration approval for numerous diseases. Here, we review the preclinical and clinical evidence for the role of JAK/STAT signaling in the development and maintenance of GVHD and the utility of blocking agents at preventing and treating GVHD.
Urothelial carcinoma with sarcomatoid/osteosarcoma variant of the bladder: A case report
Authors: Murata Masaki , Hasegawa Go , Inui Kohei , Ikeda Yohei , Hasegawa Moto , Hara Noboru , Nakagawa Yuki , Nishiyama Tsutomu
Published: June 2020

A 67-year-old man was diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection of the lesions in August 2017. The pathological findings revealed high-grade urothelial carcinoma. The tumor relapsed as urothelial carcinoma with sarcomatoid/osteosarcoma variant with vascular invasion, and transurethral resection was performed in December 2017. He underwent laparoscopic radical cystoprostatectomy and orthotopic neobladder reconstruction using ileum in March 2018. The patient developed lung metastasis in July 2018. He underwent four courses of chemotherapy with doxorubicin and thoracoscopic left lower lobectomy of the lung in October 2018.
Assessing the current state of quality improvement training in urology in the UK: Findings from the General Medical Council 2018 trainee survey
Authors: Pallari Elena , Hughes-Hallett Archie , Vitoratou Silia , Khadjesari Zarnie , Cornford Phil , Morley Roland , Sevdalis Nick , Green James S. A.
Published: June 2020

Objective:

The General Medical Council (GMC) of the UK has identified the need to support doctors through education in safety and quality improvement (QI) methods. This study reports findings from the GMC annual survey of 2018 from urology trainees regarding the state of QI training and their training needs.

Material and methods:

We designed a set of four questions to assess how QI methods are being taught nationally, and inserted them in the 2018 annual GMC trainee survey for urology. This is a cross-sectional study assessing the current state of QI training and mentoring received by trainees, and their self-assessed ability and confidence in completing a QI project as part of training requirements. Data were statistically analysed in Stata 15 stratified by Local Education Training Boards (LETBs)/Deanery and by specialty trainee level (ST3–7).

Results:

In total, 270 responses were received from urology trainees. Data showed significant variation across the country. Responses from ST3–7 trainees ranged from 5–20% on completing more than three QI projects, while 7–58% replied that they had done none. Across all ST grades, 40% of trainees stated they had not undertaken QI, whereas 0–27% reported they had not received any mentoring on QI to date. There was significant variation across training regions too: 11–74% of trainees answered that they have received training in QI methods, and 58–100% responded that they were confident in undertaking QI projects. Across all LETBs, 1–3% responded that they uploaded projects on national websites for dissemination; finally, a range of 0–18% stated they had completed more than three projects.

Conclusion:

This is the first national snapshot of QI training for the entire urology specialty in the UK. The study demonstrates wide variation in QI training and activity undertaken by trainees, and shows a lack of systematic implementation of QI education across training regions.

Level of evidence:

2c
Suspected pancreatic carcinoma needle tract seeding in a cat
Authors: Jegatheeson Selvi , Dandrieux Julien RS , Cannon Claire M
Published: June 2020

Case summary

A 15-year-old male neutered domestic longhair cat was referred for investigation of a pancreatic nodule. Fine-needle aspiration of the nodule was performed on two occasions, 2 weeks apart, and cytology revealed pyogranulomatous inflammation and moderately dysplastic exocrine pancreatic epithelium, suspicious for neoplasia. Thoracic radiographs were unremarkable and a partial pancreatectomy was performed. On histopathology, the nodule was diagnosed as a moderately differentiated pancreatic adenocarcinoma. Two weeks after surgery, a firm subcutaneous nodule was detected on the left ventrolateral abdomen. Cytology of the nodule was suggestive of pancreatic carcinoma and needle tract seeding was suspected. With palliative treatment, the cat lived a further 136 days.

Relevance and novel information

To our knowledge, this represents the first report of suspected transabdominal needle tract seeding of pancreatic carcinoma following fine-needle aspiration in veterinary medicine. Veterinarians should consider this when discussing risks of pancreatic fine-needle aspiration with owners and should attempt to minimise the number of needle aspirations where possible.
Utilization of an Orthopedic Hood as Personal Protective Equipment for Intubation of Coronavirus Patients: a Brief Technical Report
Authors: Wills Timothy T. , Zuelzer Wilhelm A. , Tran Bryant W.
Published: June 2020

Background:

The novel coronavirus disease (COVID-19) has afflicted millions of people worldwide since its first case was reported in December 2019. Personal protective equipment (PPE) has been tailored accordingly, but as of April 2020, close to 10 000 health care workers in the United States have contracted COVID-19 despite wearing recommended PPE. As such, standard guidelines for PPE may be inadequate for the health care worker performing high-risk aerosolizing procedures such as endotracheal intubation. In this brief technical report, we describe the integration of an orthopedic hood cover as an item for full barrier protection against COVID-19 transmission.

Technical Description:

The Coronavirus Airway Task Force at Virginia Commonwealth University Medical Center approved this initiative and went live with the full barrier suit during the last week of March 2020. The PPE described in this report includes a Stryker T4 Hood, normally used in conjunction with the Stryker Steri-Shield T4 Helmet. Instead of the helmet, the hood is secured to the head via a baseball cap and binder clip. This head covering apparatus is to be used as an accessory to other PPE items that include an N95 mask, waterproof gown, and disposable gloves. The motor ventilation system is not used in order to prevent airborne viral entry into the hood.

Discussion:

An advantage of the full barrier suit is an additional layer of droplet protection during intubation. The most notable disadvantage is the absence of a ventilation system within the hood covering.

Conclusion:

Modification of existing PPE may provide protection for health care workers during high-risk aerosolizing procedures such as endotracheal intubation. Although the integration of this medical equipment meets the immediate needs of an escalating crisis, further innovation is on the horizon. More research is needed to confirm the safety of modified PPE.
Specific Antibody Immunodeficiency Presenting With Streptococcal pneumonia-Induced Spontaneous Bacterial Peritonitis
Authors: Jeskey Jack , Parida Akash , Graven Kelsey , Hostoffer Robert
Published: June 2020

Specific antibody immunodeficiency (SAD) is a primary immunodeficiency disorder characterized by normal levels of serum immunoglobulins (IgG, IgA, and IgM) associated with a dysfunctional immune response. SAD is associated with recurrent infections in the setting of an insufficient response to polysaccharide vaccinations. Streptococcus pneumoniae is a well-established cause of respiratory infections in SAD. However, there has been a paucity of evidence of pneumococcal peritonitis in SAD patients, being reported as spontaneous in acquired immunodeficiency such as AIDS. We report the first case of S. pneumoniae-induced peritonitis as the presenting sign for SAD.
Ultrasound-guided total dorsal ramus block for the treatment of chronic low back pain
Authors: Kimura Ryota , Miyakoshi Naohisa , Yuasa Yusuke , Shimada Yoichi
Published: June 2020

Background:

To reduce the risk of radiation exposure, we explored whether the total dorsal ramus block can be performed under ultrasound guidance. We evaluated the accuracy and effect of ultrasound-guided total dorsal ramus block for chronic low back pain.

Methods:

Accuracy of ultrasound guidance after total dorsal ramus block to the L4–L5 level was evaluated using fluoroscopy ( n = 5). A second group was assigned into two groups: ultrasound-guided group ( n = 19) or fluoroscopy-guided group ( n = 18). The effects and adverse events were compared.

Results:

In all cases, the fluoroscopic findings revealed an accurate injection at the L5 level. Significant alleviation of pain was observed after ultrasound-guided total dorsal ramus block, and comparable effectiveness was observed with both ultrasound guidance and fluoroscopic guidance. There were no complications.

Conclusions:

The ultrasound-guided total dorsal ramus block may sufficiently block all three branches of the lumbar dorsal ramus at the targeted level resulting in significant pain reduction.
Multimodal thromboprophylaxis in low-risk patients undergoing lower limb arthroplasty: A retrospective observational cohort analysis of 1400 patients with ultrasound screening
Authors: Harrison-Brown Meredith , Scholes Corey , Douglas Stephen L , Farah Sami B , Kerr Dennis , Kohan Lawrence
Published: June 2020

Purpose:

This study reports the results of a multimodal thromboprophylaxis protocol for lower limb arthroplasty involving risk stratification, intraoperative calf compression, aspirin prophylaxis and early (within 4 h) post-operative mobilisation facilitated by the use of local infiltration analgesia. The study also aimed to identify risk factors for venous thromboembolism (VTE) within a 3-month period following surgery for patients deemed not at elevated risk.

Methods:

Patients undergoing knee/hip arthroplasty or hip resurfacing were preoperatively screened for VTE risk factors, and those at standard risk were placed on a thromboprophylaxis protocol consisting of intraoperative intermittent calf compression during surgery, 300 mg/day aspirin for 6 weeks from surgery and early mobilisation. Patients were screened bilaterally for deep vein thrombosis (DVT) on post-operative days 10–14. If proximal DVT was detected, patients were anticoagulated and outcomes were recorded. Symptomatic VTE within 3 months of surgery were recorded separately. Patient notes were retrospectively collated and cross-validated against ultrasound reports.

Results:

At initial screening, the rate of proximal DVT was 0.54% (1.1% for knee and 0.27% for hip), and distal DVT was 6.63% (20.11% for knee and 2.31% for hip). One small, nonfatal pulmonary embolism (PE) was detected within 3 months of surgery (0.28% of total knee arthroplasty patients or 0.07% of total). All proximal DVTs were treated successfully with anticoagulants; however, one patient suffered a minor PE approximately 10 months post-operatively. Regression analysis identified knee implant and advanced age as independent risk factors for VTE in this cohort.

Conclusion:

Although knee arthroplasty patients remained at higher risk than hip replacement/resurfacing patients, the incidence and outcomes of VTE remained positive compared with protocols involving extended immobilisation, and episodes of PE were extremely rare. Thus, we conclude that patients at standard preoperative risk of VTE may safely be taken through the post-operative recovery process with a combination of intraoperative mechanical prophylaxis, early mobilisation and post-operative aspirin, with closer attention required for older patients and those undergoing knee surgery.
Long-term Prognosis After Successful Nonoperative Treatment of Osteochondral Lesions of the Talus: An Observational 14-Year Follow-up Study
Authors: Weigelt Lizzy , Laux Christoph J. , Urbanschitz Lukas , Espinosa Norman , Klammer Georg , Götschi Tobias , Wirth Stephan H.
Published: June 2020

Background:

Little is known about the long-term prognosis of osteochondral lesions of the talus (OLTs) after nonoperative treatment.

Purpose:

To evaluate the clinical and radiological long-term results of initially successfully treated OLTs after a minimum follow-up of 10 years.

Study Design:

Case series; Level of evidence, 4.

Methods:

Between 1998 and 2006, 48 patients (50 ankles) with OLTs were successfully treated nonoperatively. These patients were enrolled in a retrospective long-term follow-up, for which 24 patients could not be reached or were available only by telephone. A further 2 OLTs (6%) that had been treated surgically were excluded from the analysis and documented as failures of nonoperative treatment. The final study group of 22 patients (mean age at injury, 42 years; range, 10-69 years) with 24 OLTs (mean size, 1.4 cm2; range, 0.2-3.8 cm2) underwent clinical and radiological evaluation after a mean follow-up of 14 years (range, 11-20 years). Ankle pain was evaluated with a visual analog scale (VAS), ankle function with the American Orthopaedic Foot and Ankle Society (AOFAS) score, and sports activity with the Tegner score. Progression of ankle osteoarthritis was analyzed based on plain ankle radiographs at the initial presentation and the final follow-up according to the Van Dijk classification.

Results:

At final follow-up, the 24 cases (ie, ankles) showed a median VAS score of 0 (IQR, 0.0-2.25) and a median AOFAS score of 94.0 (IQR, 85.0-100). Pain had improved in 18 cases (75%), was unchanged in 3 cases (13%), and had increased in 3 cases (13%). The median Tegner score was 4.0 (IQR, 3.0-5.0). Persistent ankle pain had led to a decrease in sports activity in 38% of cases. At the final follow-up, 11 cases (73%) showed no progression of ankle osteoarthritis and 4 cases (27%) showed progression by 1 grade.

Conclusion:

Osteochondral lesions of the talus that successfully undergo an initial nonoperative treatment period have minimal symptoms in the long term, a low failure rate, and no relevant ankle osteoarthritis progression. However, a decrease in sports activity due to sports-related ankle pain was observed in more than one-third of patients.
Assessing Medical Student Interest in Training About Medications for Opioid Use Disorder: A Pilot Intervention
Authors: Thomas Jennifer , Slat Stephanie , Woods Gregory , Cross Kristen , Macleod Colin , Lagisetty Pooja
Published: June 2020

Objective:

Educating medical students about buprenorphine may lessen barriers to providing treatment for opioid use disorder (OUD) by addressing stigma, removing the need to complete training while practicing, and normalizing it as a pharmacological option. We conducted a needs assessment to measure student interest in buprenorphine waiver training and pilot tested an online course with an in-person discussion for feasibility and acceptability.

Methods:

All 2019 graduating students were surveyed to assess interest in completing buprenorphine waiver training and understand in which format they preferred to receive the training. Interested students received information about a free online buprenorphine waiver course and an optional in-person case discussion with a faculty member. Baseline and follow-up surveys were used to assess the intervention.

Results:

Out of 228 students contacted, 173 (75.9%) responded to at least 1 survey. Of the 228, 62 (27.2%) responded to the initial survey asking students about receiving buprenorphine waiver training. The 166 non-responding students were sent a second survey, and 111 (66.9%) students responded. Of those 111, 29 (26.1%) indicated they forgot to respond to the first survey, and 24 (21.6%) did not see the survey. Of the 62 interested students, 41 students (66.1%) wanted a combination of online and in-person training. Of the 62, 30 (48.4%) interested students completed the online course and 10 (16.1%) attended the case discussion. While not significantly different, a higher proportion of students (88.9%) indicated being likely to prescribe buprenorphine after attending the case discussion than after completing the online course only (69.2%).

Conclusions:

This assessment suggested that most of the medical students are willing to complete a buprenorphine waiver course. Feedback indicated an in-person component could increase future prescribing more than an online-only curriculum, and additional advertising could result in higher participation.
A minority of T cells recognizing tumor-associated antigens presented in self-HLA can provoke antitumor reactivity
Authors: Roex Marthe C. J. , Hageman Lois , Veld Sabrina A. J. , van Egmond Esther , Hoogstraten Conny , Stemberger Christian , Germeroth Lothar , Einsele Hermann , Falkenburg J. H. Frederik , Jedema Inge
Published: June 2020

Tumor-associated antigens (TAAs) are monomorphic self-antigens that are proposed as targets for immunotherapeutic approaches to treat malignancies. We investigated whether T cells with sufficient avidity to recognize naturally overexpressed self-antigens in the context of self-HLA can be found in the T-cell repertoire of healthy donors. Minor histocompatibility antigen (MiHA)-specific T cells were used as a model, as the influence of thymic selection on the T-cell repertoire directed against MiHA can be studied in both self (MiHApos donors) and non-self (MiHAneg donors) backgrounds. T-cell clones directed against the HLA*02:01-restricted MiHA HA-1H were isolated from HA-1Hneg/HLA-A*02:01pos and HA-1Hpos/HLA-A*02:01pos donors. Of the 16 unique HA-1H–specific T-cell clones, five T-cell clones derived from HA-1Hneg/HLA-A*02:01pos donors and one T-cell clone derived from an HA-1Hpos/HLA-A*02:01pos donor showed reactivity against HA-1Hpos target cells. In addition, in total, 663 T-cell clones (containing at least 91 unique clones expressing different T-cell receptors) directed against HLA*02:01-restricted peptides of TAA WT1-RMF, RHAMM-ILS, proteinase-3-VLQ, PRAME-VLD, and NY-eso-1-SLL were isolated from HLA-A*02:01pos donors. Only 3 PRAME-VLD–specific and one NY-eso-1-SLL–specific T-cell clone provoked interferon-γ production and/or cytolysis upon stimulation with HLA-A*02:01pos malignant cell lines (but not primary malignant samples) naturally overexpressing the TAA. These results show that self-HLA–restricted T cells specific for self-antigens such as MiHA in MiHApos donors and TAAs are present in peripheral blood of healthy individuals. However, clinical efficacy would require highly effective in vivo priming by peptide vaccination in the presence of proper adjuvants or in vitro expansion of the low numbers of self-antigen–specific T cells of sufficient avidity to recognize endogenously processed antigen.
Isolation and characterization of bacteriophages against virulent Aeromonas hydrophila
Authors: Liu Jin , Gao Shanshan , Dong Yuhao , Lu Chengping , Liu Yongjie
Published: June 2020

Background

Aeromonas hydrophilais an important water-borne pathogen that leads to a great economic loss in aquaculture. Along with the abuse of antibiotics, drug-resistant strains rise rapidly. In addition, the biofilms formed by this bacterium limited the antibacterial effect of antibiotics. Bacteriophages have been attracting increasing attention as a potential alternative to antibiotics against bacterial infections.

Results

Five phages against pathogenicA. hydrophila, named N21, W3, G65, Y71 and Y81, were isolated. Morphological analysis by transmission electron microscopy revealed that phages N21, W3 and G65 belong to the familyMyoviridae, while Y71 and Y81 belong to thePodoviridae. These phages were found to have broad host spectra, short latent periods and normal burst sizes. They were sensitive to high temperature but had a wide adaptability to the pH. In addition, the phages G65 and Y81 showed considerable bacterial killing effect and potential in preventing formation ofA. hydrophilabiofilm; and the phages G65, W3 and N21 were able to scavenge mature biofilm effectively. Phage treatments applied to the pathogenicA. hydrophilain mice model resulted in a significantly decreased bacterial loads in tissues.

Conclusions

FiveA. hydrophilaphages were isolated with broad host ranges, low latent periods, and wide pH and thermal tolerance. And the phages exhibited varying abilities in controllingA. hydrophilainfection. This work presents promising data supporting the future use of phage therapy.
Association mapping for yield traits in Paeonia rockii based on SSR markers within transcription factors of comparative transcriptome
Authors: Liu Na , Cheng Fangyun
Published: June 2020

Background

Allelic variation underlying the quantitative traits in plants is caused by the extremely complex regulation process. Tree peony originated in China is a peculiar ornamental, medicinal and oil woody plant.Paeonia rockii, one of tree peony species, is a precious emerging woody oil crop. However, in this valuable plant, the study of functional loci associated with yield traits has rarely been identified. Therefore, to explore the genetic architecture of 24 yield quantitative traits, the association mapping was first reported in 420 unrelated cultivatedP. rockiiindividuals based on the next-generation sequencing (NGS) and single-molecule long-read sequencing (SMLRS).

Results

The developed 58 pairs of polymorphic expressed sequence tag-simple sequence repeat (EST-SSR) markers from 959 candidate transcription factors (TFs) associated with yield were used for genotyping the 420P. rockiiaccessions. We observed a high level of genetic diversity (polymorphic information content, PIC = 0.514) and low linkage disequilibrium (LD) between EST-SSRs. Moreover, four subpopulations in the association population were revealed by STRUCTURE analyses. Further, single-marker association analysis identified 141 significant associations, involving 17 quantitative traits and 41 EST-SSRs. These loci were mainly from AP2, TCP, MYB, HSF, bHLH, GATA, and B3 gene families and showed a small proportion of the phenotypic variance (3.79 to 37.45%).

Conclusions

Our results summarize a valuable collection of functional loci associated with yield traits inP. rockii, and provide a precious resource that reveals allelic variation underlying quantitative traits inPaeoniaand other woody oil crops.
Anesthesia management in neonatal congenital bronchobiliary fistula: case report and literature review
Authors: Yin Hong , Zhao Guangyi , Du Yingjie , Zhao Ping
Published: June 2020

Background

There is very little published literature and none that discussed care in a neonate regarding anesthetic risk and management of neonate with congenital bronchobiliary fistula during thoracoscopy and thoracotomy. This article analyzes related risk factors and literature review from perioperative ventilation, circulation and other aspects of management.

Case presentation

A neonate diagnosed as congenital bronchobiliary fistula combined with severe chemical pneumonia, consolidation of the lungs, and infection was facing the risk of anaesthesia under thoracoscopy exploration surgery, who experiened more than 20 days diagnostic period before operation. Many risk factors have led to conversion from minimally invasive surgery to thoracotomy, including persistent hypoxemia, hypercapnia, difficult surgical exposure and extremly difficulty of intraoperative ventilation management. Anesthesia maintenance after conversion to open access remained problematic. Fortunately the patient showed no sign of any adverse CNS effects after 4 months of follow-up.

Conclusions

The most prominent anesthesia challenges are hypoxemia, increased airway resistance, impaired ventilation, and the risk of metabolic acidosis. Close cooperation among the entire neonatal medical team is the key factors in successful management of this rare case.
In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis
Authors: Gallone Guglielmo , Landra Federico , D’Ascenzo Fabrizio , Conrotto Federico , Casoni Roberta , Bruno Francesco , Omedè Pierluigi , Alunni Gianluca , Andreis Alessandro , Vairo Alessandro , Giorgi Mauro , Fava Antonella , De Ferrari Gaetano Maria
Published: June 2020

Background

One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients.

Clinical case

We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient’s severe AS conservatively.

Conclusion

In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient’ prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.
Database combinations to retrieve systematic reviews in overviews of reviews: a methodological study
Authors: Goossen Käthe , Hess Simone , Lunny Carole , Pieper Dawid
Published: June 2020

Background

When conducting an Overviews of Reviews on health-related topics, it is unclear which combination of bibliographic databases authors should use for searching for SRs. Our goal was to determine which databases included the most systematic reviews and identify an optimal database combination for searching systematic reviews.

Methods

A set of 86 Overviews of Reviews with 1219 included systematic reviews was extracted from a previous study. Inclusion of the systematic reviews was assessed in MEDLINE, CINAHL, Embase, Epistemonikos, PsycINFO, and TRIP. The mean inclusion rate (% of included systematic reviews) and corresponding 95% confidence interval were calculated for each database individually, as well as for combinations of MEDLINE with each other database and reference checking.

Results

Inclusion of systematic reviews was higher in MEDLINE than in any other single database (mean inclusion rate 89.7%; 95% confidence interval [89.0–90.3%]). Combined with reference checking, this value increased to 93.7% [93.2–94.2%]. The best combination of two databases plus reference checking consisted of MEDLINE and Epistemonikos (99.2% [99.0–99.3%]). Stratification by Health Technology Assessment reports (97.7% [96.5–98.9%]) vs. Cochrane Overviews (100.0%) vs. non-Cochrane Overviews (99.3% [99.1–99.4%]) showed that inclusion was only slightly lower for Health Technology Assessment reports. However, MEDLINE, Epistemonikos, and reference checking remained the best combination. Among the 10/1219 systematic reviews not identified by this combination, five were published as websites rather than journals, two were included in CINAHL and Embase, and one was included in the database ERIC.

Conclusions

MEDLINE and Epistemonikos, complemented by reference checking of included studies, is the best database combination to identify systematic reviews on health-related topics.
A novel mutation in TRIOBP gene leading to congenital deafness in a Chinese family
Authors: Zhou Bingxin , Yu Lili , Wang Yan , Shang Wenjing , Xie Yi , Wang Xiong , Han Fengchan
Published: June 2020

Background

The autosomal recessive non-syndromic deafness DFNB28 is characterized by prelingual sensorineural hearing loss. The disease is related with mutations in TRIOBP (Trio- and F-actin-Binding Protein) gene, which has three transcripts referred to as TRIOBP-5, TRIOBP − 4 and TRIOBP-1. Among them, TRIOBP-5/− 4 are expressed in the inner ears and crucial for maintaining the structure and function of the stereocilia.

Methods

The proband is a 26-year-old Chinese female. She and her younger brother have being suffered from severe deafness since birth, whereas her parents, who are cousins, have normal communication ability. Hearing impairment of the two siblings was determined by pure tone audiometry. Whole Exome Sequencing (WES) was performed on the genomic DNA of the proband and Sanger sequencing was conducted on the DNA samples of the four family members.

Results

Tests of pure tone hearing thresholds showed a severe to profound symmetric hearing loss for the proband and her younger brother. Moreover, a novel TRIOBP c.1342C > T (p.Arg448*) variant was identified by WES in the DNA sample of the proband and confirmed by Sanger sequencing in DNA of the family members.

Conclusions

The TRIOBP c.1342C > T (p.Arg448*) variant is predicted to disrupt TRIOBP-5 and TRIOBP-4, which may lead to the congenital deafness. The results will broaden the spectrum of pathogenic variants in TRIOBP gene. The characteristics of deafness in the family imply that marriage between close relatives should be avoided.
Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease
Authors: Li Xiaoli , Zhang Dingwei , Ding Jiahui , Li Li , Wang Zhenghui
Published: June 2020

Background

Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKII proteins in the skin lesions of HHD patients.

Methods

Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined.

Results

One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKII levels.

Conclusion

In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKII levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.
Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies
Authors: Nie Daijing , Zhang Jing , Wang Fang , Zhang Wei , Liu Lili , Chen Xue , Zhang Yang , Cao Panxiang , Xiong Min , Wang Tong , Wu Ping , Ma Xiaoli , Tian Wenjun , Wang Mangju , Chen Kylan N. , Liu Hongxing
Published: June 2020

Background

Fanconi anemia (FA) is the most common inherited bone marrow failure (BMF) syndrome with 22 related genes identified. The ALDH2 rs671variant has been proved related to accelerate the progression of BMF in FA patients. The phenotype and genetic basis of Chinese FA patients have not been investigated yet.

Methods

We analyzed the 22 FA-related genes of 63 BMF patients suspected to be FA. Clinical manifestations, morphological and cytogenetic feathers, ALDH2 genotypes, treatment, and outcomes of the definite cases were retrospectively studied.

Results

A total of 21 patients were confirmed the diagnosis of FA with the median age of BMF onset was 4-year-old. The number of patients manifested as congenital malformations and growth retardation were 20/21 and 14/21, respectively. BM dysplasia and cytogenetic abnormalities were found in 13/20 and 8/19 patients. All the patients with abnormal karyotypes also manifested as BM dysplasia or had evident blasts. Thirty-five different mutations were identified involving six genes and including twenty novel mutations. FANCA mutations contributed to 66.67% of cases. Eight patients harboring ALDH2-G/A genotype have a significantly younger age of BMF onset (p = 0.025). Within the 19 patients adhering to continuous follow-up, 15 patients underwent hematopoietic stem cell transplantations (HSCTs). During the 29 months of follow-up, 8/19 patients died, seven of which were HSCT-related, and one patient who did not receive HSCT died from severe infection.

Conclusions

The phenotypic and genetic spectrum of Chinese FA patients is broad. Bone marrow dysplasia and cytogenetic abnormalities are prevalent and highly consistent. The overall outcome of HSCTs is disappointing. Nationwide multicenter studies are needed for the rarity and adverse outcome of this disease.
Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study
Authors: Katsuyama Eri , Miyawaki Yoshia , Sada Ken-ei , Asano Yosuke , Hayashi Keigo , Yamamura Yuriko , Hiramatsu-Asano Sumie , Morishita Michiko , Ohashi Keiji , Watanabe Haruki , Katsuyama Takayuki , Narazaki Mariko , Matsumoto Yoshinori , Wada Jun
Published: June 2020

Background

The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN).

Methods

In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels.

Results

The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74).

Conclusion

As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.
Ipilimumab or FOLFOX with Nivolumab and Trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric Adenocarcinoma - the randomized phase 2 INTEGA trial (AIO STO 0217)
Authors: Tintelnot Joseph , Goekkurt Eray , Binder Mascha , Thuss-Patience Peter , Lorenzen Sylvie , Knorrenschild Jorge Riera , Kretzschmar Albrecht , Ettrich Thomas , Lindig Udo , Jacobasch Lutz , Pink Daniel , Al-Batran Salah-Eddin , Hinke Axel , Hegewisch-Becker Susanna , Nilsson Sven , Bokemeyer Carsten , Stein Alexander
Published: June 2020

Background

Esophagogastric adenocarcinoma (EGA) currently represents a main cause of cancer related death. Despite an intensified treatment for locally advanced or metastatic EGA with a doublet chemotherapy consisting of a platinum compound and a fluoropyrimidine in combination with trastuzumab for HER2-positive disease or in selected cases with docetaxel, survival remains poor. Recently, immune-oncology based strategies relevantly improved the treatment of different solid tumors and showed some promise in late or later stage trials in EGA. Notably, the combination of immunotherapy with trastuzumab to enhance anti-tumor immunity through activation of innate and adaptive immunity was beneficial in preclinical studies or clinical studies in breast cancer.

Methods

The INTEGA study is an open-label, randomized, multicenter, exploratory phase II trial designed to assess clinical performance, safety and tolerability of ipilimumab or 5-FU/folinic acid and oxaliplatin (FOLFOX) in combination with nivolumab and trastuzumab in patients with previously untreated HER2-positive, locally advanced or metastatic EGA. The primary objective is to determine the clinical performance of ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in terms of overall survival. Secondary objectives are safety and tolerability, efficacy in terms of progression-free survival and objective response rate and blood-based signatures (e.g. immune response or suppression of anti-HER2 resistance) that may correlate with treatment response.

Discussion

Recent evidence from the phase II NCT02954536 study (oxaliplatin, capecitabine, trastuzumab and pembrolizumab) suggests the clinical feasibility of combining chemotherapy, trastuzumab and checkpoint inhibition in EGA. However, evidence for a chemotherapy-free regimen is also mounting in HER2-positive disease (NCT02689284) i.e. margetuximab and Pembrolizumab. Both studies excelled with high overall response rates and manageable toxicities. The INTEGA study aims to comparatively assess these results and select a promising new 1st line regimen which then needs to be confirmed in a randomized phase III trial. Further, the translational part of the study might help to better stratify patients and tailor treatment of either arm.

Trial registration

NCT03409848 24.01.2018.
MassARRAY analysis of twelve cancer related SNPs in esophageal squamous cell carcinoma in J&K, India
Authors: Shah Ruchi , Sharma Varun , Bhat Amrita , Singh Hemender , Sharma Indu , Verma Sonali , Bhat Gh. Rasool , Sharma Bhanu , Bakshi Divya , Kumar Rakesh , Dar Nazir Ahmed
Published: June 2020

Background

MassARRAY (Agena Bioscience™) combines competitive PCR with MALDI-TOF mass spectrometry (MS) analysis that gives highly accurate, sensitive, and high-throughput methods for the quantitative analysis of variation of gene expression in multiple samples. SNPs (Single Nucleotide Polymorphisms) have a very high potential of discovering disease-gene relationships. SNP-genotyping through MassARRAY is not only a cost-effective genotyping method but also provides a platform to validate variants observed through a high-throughput Next-generation sequencing (NGS).

Methods

In the present study, we have incorporated the use of matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) as a tool for differentiating genotypes based on the mass of variant. We have performed multiplex PCR and genotyped 12 SNPs in 758 samples (166 cases and 592 controls). The 12 studied SNPs were chosen with a rationale for their association with multiple cancers in literature.

Results

This is the first study to explore these SNPs with esophageal cancer within the J&K population. Out of 12 SNPs, two SNPs rs12190287 of TCF21 and rs10046 of CYP19A1 were significantly associated with esophageal cancer with Odds Ratio (OR) 1.412 (1.09–1.8 at 95% CI, p = 0.008) and 1.54 (1.21–2.072 at 95% CI, p = 0.0007) within the population of Jammu and Kashmir.

Conclusion

We explored 12 SNPs that were found to be associated with multiple cancers in literature with esophageal cancer within the population of J&K. This is the first study to find the relation of these SNPs with ESCC within the studied population. This study explores the relation of genetic and environmental factors with the ESCC susceptibility.