bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic Lethality in Ovarian Cancer
Authors: Chandrasekaran Akshaya , Elias Kevin M. 
Published: September 2021

AbstractOvarian cancers include several distinct malignancies which differ with respect to clinicopathologic features and prognosis. High-grade serous cancer is the most common histologic subtype and accounts for most ovarian cancer–related deaths. High-grade serous ovarian cancer (HGSOC) is treated with surgery and platinum-based chemotherapy, but most patients relapse and succumb to chemoresistant disease. The genetic concept of synthetic lethality, in which the synergy of mutations in multiple genes results in cell death, provides a framework to design novel therapeutic approaches to overcome chemoresistance in ovarian cancer. Recent progress in understanding the genomic architecture and hereditary drivers of ovarian cancer has shown potential for synthetic lethality strategies designed around homologous DNA repair. Clinical trials have validated high response rates for PARP inhibitors in patients with BRCA1 or BRCA2 mutations. Here we discuss the biological rationale behind targeting BRCA–PARP synthetic lethality based on genetic context in ovarian cancer and how this approach is being assessed in the clinic. Applying the concept of synthetic lethality to target non–BRCA-mutant cancers is an ongoing challenge, and we discuss novel approaches to target ovarian cancer using synthetic lethality in combination with and beyond PARP inhibitors. This review will also describe obstacles for synthetic lethality in ovarian cancer and new opportunities to develop potent targeted drugs for patients with ovarian cancer.
Outcomes of Endovascular Therapy in Patients With Prestroke Mobility Impairment
Authors: Beekman Rachel , Sun Jie-Lena , Alhanti Brooke , Schwamm Lee H. , Smith Eric E. , Bhatt Deepak L. , Xian Ying , Shah Shreyansh , Lytle Barbara L. , Fonarow Gregg C. , Sheth Kevin N. 
Published: September 2021

Background and Purpose:
Patients with prestroke mobility impairment (PSMI) were excluded from endovascular clinical trials. There are limited data regarding safety and outcomes of endovascular thrombectomy in this population. We used a large, national data set (Get With The Guidelines–Stroke) to evaluate the safety and outcomes of endovascular thrombectomy in patients with PSMI.

Methods:
We included patients who underwent endovascular thrombectomy in the Get With The Guidelines–Stroke registry between 2015 and 2019. PSMI was defined as the inability to ambulate independently. Generalized estimating equations for logistic regression models were used to evaluate the association between PSMI and outcomes.

Results:

Of 56 762 patients treated with endovascular thrombectomy, 2919 (5.14%) had PSMI. PSMI was not associated with symptomatic intracranial hemorrhage (6.0% versus 5.4%;
P
=0.979). In-hospital death or discharge to hospice occurred in 32.3% of patients with PSMI versus 17.5% without PSMI (adjusted odds ratio, 1.45 [1.32–1.58]).

Conclusions:
While procedural adverse outcomes were no higher in patients with PSMI, further study is necessary to determine clinical benefit in this population.
Pathological Level VI Lymph Node Metastasis in Clinical N3b Pyriform Sinus Squamous Cell Carcinoma
Authors: Matsui Hidetoshi , Iwae Shigemichi , Yamamura Yuta , Horichi Yuto 
Published: September 2021

Objective: The frequency of metastasis to level VI lymph nodes in advanced pyriform sinus squamous cell carcinoma (PSSCC) is unknown. We intended to analyze the clinical features and pathological presence or absence of level VI lymph node metastasis in patients with PSSCC. Methods: The data of 270 patients with previously untreated hypopharyngeal squamous cell carcinoma from 2006 to 2016 were obtained. Patients who underwent pharyngolaryngectomy for the pyriform sinus subsite with a curative intent with level VI dissection were included. We retrospectively analyzed the clinical Tumor-Node (TN) status (TNM classification of malignant tumors, eighth edition) and the presence or absence of pathological level VI lymph node metastasis. Results: A total of 34 patients were included. Eight patients (24%) had pathological level VI lymph node metastasis. The rate of pathological level VI lymph node metastasis was directly proportional to the clinical N status ( P = .0002, Chi-square test for trend). In all, 5 patients with cN2b- 3 were classified as cN3b. Ipsilateral pathological level VI lymph node metastasis was observed in 1 patient, and bilateral metastasis was observed in 3 patients. There was no association between clinical T status or pyriform sinus apex invasion and pathological level VI metastasis (both P > .99, Fisher’s exact test). Conclusions: PSSCC with cN3b is prone to bilateral level VI metastasis. We recommend that patients with PSSCC with cN3b should undergo bilateral level VI lymph node dissection.
Safety and utility of modified ultrafiltration in pediatric cardiac surgery
Authors: Palanzo David A , Wise Robert K , Woitas Karl R , Ündar Akif , Clark Joseph B , Myers John L 
Published: September 2021

Introduction: Modified ultrafiltration (MUF) is employed at the termination of cardiopulmonary bypass (CPB) in pediatric and neonatal patients undergoing congenital heart surgery to reduce the accumulation of total body water thus increasing the concentration of red blood cells and the other formed elements in the circulation. Modified ultrafiltration has been reported to remove circulating pro-inflammatory mediators that result in systemic inflammatory response syndrome (SIRS) postoperatively. Methods: Four hundred patients undergoing cardiac surgery requiring cardiopulmonary bypass and weighing less than or equal to 12 kg were retrospectively evaluated for the effectiveness of MUF. After the termination of CPB, blood was withdrawn through the aortic cannula and passed through a hemoconcentrator attached to the blood cardioplegia set and returned to the patient through the venous cannula. The entire CPB circuit volume in addition to the patient’s circulating blood volume were concentrated until the hematocrit value displayed on the CDI cuvette within the MUF circuit reached 45% or there was no more volume to safely remove. At the same time a full unit of FFP can be infused as water is being removed, thus maintaining euvolemia. Results: MUF was performed in all 400 patients with no MUF-related complications. Following the conclusion of MUF, anecdotal observations included improved surgical hemostasis, improved hemodynamic parameters, decreased transfusion requirements, and decreased ventilator times. Conclusions: Complete MUF enables the clinician to safely raise the post-CPB hematocrit to at least 40% while potentially removing mediators that could result in SIRS. In addition a full unit of FFP can be administered while maintaining euvolemia.
Risk factors and treatment of oxygenator high-pressure excursions during cardiopulmonary bypass
Authors: Hjärpe Anders Karl , Jeppsson Anders , Lannemyr Lukas , Lindgren Martin 
Published: September 2021

Introduction: A high-pressure excursion (HPE) is a sudden increase in oxygenator inlet pressure during cardiopulmonary bypass (CPB). The aims of this study were to identify factors associated with HPE, to describe a treatment protocol utilizing epoprostenol in severe cases, and to assess early outcome in HPE patients. Methods: Patients who underwent cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital 2016–2018 were included in a retrospective observational study. Pre- and post-operative data collected from electronic health records, local databases, and registries were compared between HPE and non-HPE patients. Factors associated with HPE were identified with logistic regression models. Results: In total, 2024 patients were analyzed, and 37 (1.8%) developed HPE. Large body surface area (adjusted Odds Ratio (aOR): 1.43 per 0.1 m2; 95% confidence interval (CI): 1.16–1.76, p < 0.001), higher hematocrit during CPB (aOR: 1.20 per 1%; (1.09–1.33), p < 0.001), acute surgery (aOR: 2.98; (1.26–6.62), p = 0.018), and previous stroke (aOR: 2.93; (1.03–7.20), p = 0.027) were independently associated with HPE. HPE was treated with hemodilution ( n = 29, 78.4%), and/or extra heparin ( n = 23, 62.2%), and/or epoprostenol ( n = 12, 32.4%). No oxygenator change-out was necessary. While there was no significant difference in 30-day mortality (2.7% vs 3.2%, p = 1.0), HPE was associated with a higher perioperative stroke rate (8.1% vs 1.8%, aOR 5.09 (1.17–15.57), p = 0.011). Conclusions: Large body surface area, high hematocrit during CPB, previous stroke and acute surgery were independently associated with HPE. A treatment protocol including epoprostenol appears to be a safe option. Perioperative stroke rate was increased in HPE patients.
Fully Intra-articular Lasso-Loop Stitch Technique for Arthroscopic Anterior Talofibular Ligament Repair
Authors: Qin Jiajun , Fu Qiang , Zhou Qing , Wu Helin , Zhi Xiaosong , Xu Feng , Cai Xianhua , Wei Shijun 
Published: September 2021

Background: Arthroscopic techniques have gradually become popular for anterior talofibular ligament (ATFL) repair. However, the reliability of the repair and the risk of nerve injuries are of concern. The aim of this study was to evaluate the fully intra-articular lasso-loop stitch technique for arthroscopic ATFL repair. Methods: From October 2018 to December 2019, 43 cases with chronic lateral ankle instability were treated with this fully intra-articular lasso-loop stitch technique using the Arthro-Pierce instrument. The Karlsson-Peterson score, Cumberland Ankle Instability Tool (CAIT) score, visual analog scale (VAS) score, anterior drawer and talar tilt stress fluoroscopy were evaluated at the preoperative and final follow-up appointments, respectively. All surgical complications were also recorded. Results: A total of 39 cases were followed up for a mean of 28.23 ± 3.64 months (range, 23-34 months). At the final follow-up, the averages of the Karlsson-Peterson, CAIT and VAS scores were 90.26 ± 6.58, 88.56 ± 7.21 and 0.79 ± 1.06, respectively. During surgery, 2 cases were modified with augmentation of the inferior extensor retinaculum. No nerve injuries were encountered. Only 1 female complained about mild knot irritation. A 25-year-old solider required revision surgery due to an accidental injury. Conclusion: We found the fully intra-articular lasso-loop stitch technique for ATFL repair using the Arthro-Pierce instrument to be reliable and safe with a sufficient and good-quality ligament remnant. Level of Evidence: Level IV, retrospective case series.
Ocular dermoids in 13 cats: a multicentre retrospective study
Authors: Cathelin Anaïs , Augsburger Anne-Sandrine , Anne Jennifer , Medan Sylvain , Michel Julien , Isard Pierre-François , Douet Jean-Yves , Dulaurent Thomas 
Published: September 2021

Objectives The aim of this multicentre retrospective study was to review the clinical data, outcomes and histopathological features of cats that had been treated for ocular surface dermoids. Methods Thirteen cats from various private practices in France with a clinical diagnosis of ocular surface dermoid were included in the study. Results The mean age of the study population at the time of diagnosis was 5 months. There were nine males and four females. Three different breeds were domestic shorthair (n = 7), Birman (n = 4) and Havana Brown (n = 2). Two of the four Birmans were related (same sire). The two Havana Browns were also related (same sire). All of the dermoids were unilateral. Five of the dermoids were strictly conjunctival. Four affected both the conjunctiva and the cornea. Three affected both the conjunctiva and the eyelid, and one was strictly corneal. They were located in various positions: temporal (n = 9), inferonasal (n = 1), dorsonasal (n = 1) and dorsotemporal (n = 1). The last dermoid was heterogeneous and involved the nasal, dorsal and temporal quadrants. Concurrent eye diseases were observed in five patients: four cats exhibited associated eyelid agenesis and one cat exhibited persistent iris-to-iris pupillary membranes. Ten dermoids were surgically excised with no recurrences. Surgery was not performed for three cats: one cat died a few days after diagnosis and two cats were lost to follow-up after initial presentation. Conclusions and relevance Ocular surface dermoids are a rare condition in cats that can be treated successfully by surgical excision. Although our study reports only a small number of cases, the observation of ocular surface dermoids in two related cats in two different breeds indicates that genetic transmission is likely.
Examining different outcome measures for reliability in assessing the impact of cataract surgery in quality of health
Authors: Mylona Ioanna , Aletras Vassilis , Ziakas Nikolaos , Tsinopoulos Ioannis 
Published: September 2021

Introduction: The aim of this study was to determine a reliable combination of vision-specific measures and general health measures to assess the improvement on the patient’s QoL following cataract surgery either when patients had first time surgery or had already received successful surgery in the fellow eye for cataract. Methods: Study sample included two waves of data measurement in 150 patients undergoing uncomplicated cataract surgery who were assessed for visual acuity, vision-specific quality of life, and general health. Data were acquired pre-surgery and 2 months post-surgery. About 90 patients haven’t had prior cataract surgery while 60 patients had prior successful cataract surgery in the fellow eye. Results: There was considerable improvement in all outcome measures following cataract surgery. Patients who have had prior surgery presented with modestly higher scores in the vision-specific QoL measures and minimal benefit pre-operatively compared to those who haven’t had any surgery in the general health measure. They also had more gains post-surgery in the vision-specific QoL measures only. Conclusions: There is a possibility that gains in QoL plateau after a certain level of visual acuity improvement. While improvement can be detected with a general health QoL measure, this measure may require additional psychometric validation to the particular population beforehand. Otherwise, a combination of vision-specific outcome measures will provide the most reliable estimate.
Work-retirement transitions and mental health: A longitudinal analysis of the role of social protection generosity in 11 countries
Authors: Sjöberg Ola 
Published: September 2021

Aims: This study aimed to analyse the effect of work-retirement transitions on post-retirement mental health in individuals with different working conditions in late working life. The focus was on transitions that involve the use of social protection schemes to bridge the gap between the exit from work and retirement, and the extent to which the generosity of such schemes is related to mental health after retirement. Methods: Individual-level panel data from the Survey of Health, Ageing and Retirement in Europe for 11 European countries were analysed using structural equation models. A total of 1642 individuals who worked in 2004 or 2007 and who retired in 2013 or 2015 were included in the analyses. The outcome measure was mental health as measured by the EURO-D scale. Results: Respondents with a ‘high strain’ and ‘passive’ work situation have a significantly higher likelihood of using social protection schemes, such as early retirement, sickness, disability and invalidity schemes before retirement. The generosity of such schemes has a significant positive relation to post-retirement mental health. Conclusions: This study shows that the generosity of early exit pathways is important for post-retirement mental health, especially for individuals with adverse working conditions at the end of their working lives.
The effect of a large dose of intravenous immunoglobulin on general paresis of the insane
Authors: Qingqing Chen , Dongliang Liu , Qingqing Sang , Daoqian Sang 
Published: September 2021

General paresis of the insane (GPI) remains the form of neurosyphilis most closely associated with dementia, even after the advent of penicillin. Penicillin remains the top treatment choice for syphilis, but treatment failure is not rare. Although the neurological symptoms of GPI can be alleviated by antibiotic treatment, mental symptoms may continue. A 60-year-old man was admitted to hospital due to rapidly progressive dementia. He was diagnosed as GPI. With the patient’s informed consent, we treated him with a large dose of intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days, as well as penicillin (24 million units daily divided into six doses) for 14 days. A near-immediate improvement in his emotions and orientation occurred on the 17th day in hospital. The patient made an excellent recovery 6 weeks after treatment, his psychotic and mood symptoms improved significantly. Therefore, we hypothesize that patients with GPI treated with IVIG and penicillin G would have better outcomes than those treated with penicillin G alone. IVIG may be introduced as a necessary treatment for GPI.
Increased Comorbidity Burden Among Hip Fracture Patients During the COVID-19 Pandemic in New York City
Authors: LeBrun Drake G. , Konnaris Maxwell A. , Ghahramani Gregory C. , Premkumar Ajay , DeFrancesco Chris J. , Gruskay Jordan A. , Dvorzhinskiy Aleksey , Sandhu Milan S. , Goldwyn Elan M. , Mendias Christopher L , Ricci William M. 
Published: September 2021

Background The coronavirus disease 19 (COVID-19) pandemic had a devastating effect on New York City in the spring of 2020. Several global reports suggested worse early outcomes among COVID-positive patients with hip fractures. However, there is limited data comparing baseline comorbidities among patients treated during the pandemic relative to those treated in non-pandemic conditions. Materials and Methods A multicenter retrospective cohort study was performed at two Level 1 Trauma centers and one orthopedic specialty hospital to assess demographics, comorbidities, and outcomes among 67 hip fracture patients treated (OTA/AO 31, 32.1) during the peak of the COVID-19 pandemic in New York City (March 20, 2020 to April 24, 2020), including 9 who were diagnosed with COVID-19. These patients were compared to a cohort of 76 hip fracture patients treated 1 year prior (March 20, 2019 to April 24, 2019). Baseline demographics, comorbidities, treatment characteristics, and respiratory symptomatology were evaluated. The primary outcome was inpatient mortality. Results Relative to patients treated in 2019, patients with hip fractures during the pandemic had worse Charlson Comorbidity Indices (median 5.0 vs 6.0, P = .03) and American Society of Anesthesiologists (ASA) scores (mean 2.4 vs 2.7, P = .04). Patients during the COVID-19 pandemic were more likely to have decreased ambulatory status ( P<.01) and a smoking history ( P = .04). Patients in 2020 had longer inpatient stays (median 5 vs 7 days, P = .01), and were more likely to be discharged home (61% vs 9%, P<.01). Inpatient mortality was significantly increased during the COVID-19 pandemic (12% vs 0%, P = .002). Conclusions Patients with hip fractures during the COVID-19 pandemic had worse comorbidity profiles and decreased functional status compared to patients treated the year prior. This information may be relevant in negotiations regarding reimbursement for cost of care of hip fracture patients with COVID-19, as these patients may require more expensive care.
How to write a guideline: a proposal for a manuscript template that supports the creation of trustworthy guidelines
Authors: Nieuwlaat Robby , Wiercioch Wojtek , Brozek Jan L. , Santesso Nancy , Kunkle Robert , Alonso-Coello Pablo , Anderson David R. , Bates Shannon M. , Dahm Philipp , Iorio Alfonso , Lim Wendy , Lyman Gary H. , Middeldorp Saskia , Monagle Paul , Mustafa Reem A. , Neumann Ignacio , Ortel Thomas L. , Rochwerg Bram , Vesely Sara K. , Witt Daniel M. , Cuker Adam , Schünemann Holger J. 
Published: September 2021

AbstractTrustworthy health guidelines should provide recommendations, document the development process, and highlight implementation information. Our objective was to develop a guideline manuscript template to help authors write a complete and useful report. The McMaster Grading of Recommendations Assessment, Development and Evaluation Centre collaborated with the American Society of Hematology (ASH) to develop guidelines for the management of venous thromboembolism. A template for reporting the guidelines was developed based on prior approaches and refined using input from other key stakeholders. The proposed guideline manuscript template includes: (1) title for guideline identification, (2) abstract, including a summary of key recommendations, (3) overview of all recommendations (executive summary), and (4) the main text, providing sufficient detail about the entire process, including objectives, background, and methodological decisions from panel selection and conflict-of-interest management to criteria for updating, as well as supporting information, such as links to online (interactive) tables. The template further allows for tailoring to the specific topic, using examples. Initial experience with the ASH guideline manuscript template was positive, and challenges included drafting descriptions of recommendations involving multiple management pathways, tailoring the template for a specific guideline, and choosing key recommendations to highlight. Feedback from a larger group of guideline authors and users will be needed to evaluate its usefulness and refine. The proposed guideline manuscript template is the first detailed template for transparent and complete reporting of guidelines. Consistent application of the template may simplify the preparation of an evidence-based guideline manuscript and facilitate its use.
Methods of induction of labor and women’s experience: a population-based cohort study with mediation analyses
Authors: Blanc-Petitjean Pauline , Dupont Corinne , Carbonne Bruno , Salomé Marina , Goffinet François , Ray Camille Le ,   for the MEDIP study group, Crenn-Hebert Catherine , Gaudineau Adrien , Perrotte Frédérique , Raynal Pierre , Clouqueur Elodie , Beucher Gaël , Deneux-Tharaux Catherine , Ancel Pierre-Yves 
Published: September 2021

AbstractBackgroundNegative childbirth experience may affect mother wellbeing and health. However, it is rarely evaluated in studies comparing methods of induction of labor (IoL).AimTo compare women’s experience of IoL according to the method, considering the mediating role of interventions and complications of delivery.MethodsWe used data from the MEDIP prospective population-based cohort, including all women with IoL during one month in seven French perinatal networks. The experience of IoL, assessed at 2 months postpartum, was first compared between cervical ripening and oxytocin, and secondarily between different cervical ripening methods. Mediation analyses were used to measure the direct and indirect effects of cervical ripening on maternal experience, through delivery with interventions or complications.FindingsThe response rate was 47.8% (n = 1453/3042). Compared with oxytocin (n = 541), cervical ripening (n = 910) was associated less often with feelings that labor went ‘as expected’ (adjusted risk ratio for the direct effect 0.78, 95%CI [0.70–0.88]), length of labor was ‘acceptable’ (0.76[0.71–0.82]), ‘vaginal discomfort’ was absent (0.77[0.69–0.85]) and with lower global satisfaction (0.90[0.84–0.96]). Interventions and complications mediated between 6 and 35% of the total effect of cervical ripening on maternal experience. Compared to the dinoprostone insert, maternal experience was not significantly different with the other prostaglandins. The balloon catheter was associated with less pain.DiscussionCervical ripening was associated with a less positive experience of childbirth, whatever the method, only partly explained by interventions and complications of delivery.ConclusionCounselling and support of women requiring cervical ripening might be enhanced to improve the experience of IoL.