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Restricted sub-tree learning to estimate an optimal dynamic treatment regime using observational data.

Kelly Speth Lu Wang

Stat Med 2021 Aug 2. Epub 2021 Aug 2.

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

Dynamic treatment regimes (DTRs), consisting of a sequence of tailored treatment decision rules that span multiple stages of care, present a unique opportunity in our drive toward personalized medicine. Given that estimation of optimal DTRs is often exploratory and communication with clinicians is vital, robust and flexible methods that yield interpretable results are needed. Tree-based methods utilizing a purity measure defined on the full set of covariates have enjoyed much success in meeting this goal. Read More

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A global review of seed enhancement technology use to inform improved applications in restoration.

Sci Total Environ 2021 Jul 16;798:149096. Epub 2021 Jul 16.

School of Biological Sciences, The University of Western Australia, 35 Stirling Hwy, Crawley, Western Australia 6009, Australia; Kings Park Science, Department of Biodiversity Conservation and Attractions, 2 Kattidj Close, Kings Park, Western Australia, 6005, Australia.

Seed-based restoration often experiences poor success due to a range of edaphic and biotic issues. Seed enhancement technologies (SETs) are a novel approach that can alleviate these pressures and improve restoration success. Broadly, SETs have been reviewed for agricultural and horticultural purposes, for specific types of SETs such as coating or priming, or for focal ecosystems. Read More

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Conjugation of oxaliplatin with PEGylated-nanobody for enhancing tumor targeting and prolonging circulation.

J Inorg Biochem 2021 Jul 24;223:111553. Epub 2021 Jul 24.

CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China; Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine; University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address:

Oxaliplatin is a platinum-based drug used in clinic for cancer chemotherapy. Despite of its success, the non-selective effect on normal cells causes severe side-effects and hampers its applications. Targeted delivery of oxaliplatin to cancer cells is an effective approach to enhance drug efficacy and reduce adverse effect. Read More

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Design, synthesis and evaluation of side-chain hydroxylated derivatives of lithocholic acid as potent agonists of the vitamin D receptor (VDR).

Bioorg Chem 2021 Jul 22;115:105202. Epub 2021 Jul 22.

Departamento de Química Orgánica, Laboratorio de Investigación Ignacio Ribas, Universidad de Santiago de Compostela, Avda das Ciencias s/n, 15782 Santiago de Compostela, Spain. Electronic address:

A high number of biologically active and low-calcemic secosteroidal ligands of the vitamin D receptor (VDR) have been developed, some of which are already used clinically although with limited success in the treatment of hyperproliferative diseases because the required pharmaceutical dosages induce toxicity. We describe here the in silico design, synthesis, structural analysis and biological evaluation of two novel active lithocholic acid derivatives hydroxylated at the side chain as highly potent inhibitors of atopic dermatitis-relevant keratinocyte inflammation of potential therapeutic interest. Read More

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Advances in cell death - related signaling pathways in acute-on-chronic liver failure.

Clin Res Hepatol Gastroenterol 2021 Jul 30:101783. Epub 2021 Jul 30.

Guangdong Key Laboratory for Research and Development of Natural Drugs, Key Laboratory of Research and Development of New Medical Materials of Guangdong Medical University, School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China. Electronic address:

Acute-on-chronic liver failure (ACLF) has been a hot spot in the field of liver disease research in recent years, with high morbidity, rapid course change and high mortality. Currently, there is the absence of specific treatment in clinical practice. Liver transplantation has the best therapeutic effect, but it is prone to have internal environment disorder and liver cell death after transplantation, which leads to the failure of transplantation. Read More

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Sinus Node Sparing Hybrid Thoracoscopic Ablation Outcomes in Patients with Inappropriate Sinus Tachycardia (SUSRUTA-IST Registry).

Heart Rhythm 2021 Jul 21. Epub 2021 Jul 21.

Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, KS.

Background: Medical treatment for inappropriate sinus tachycardia (IST) remains suboptimal. Radiofrequency sinus node (RF-SN) ablation has poor success and higher complication rates.

Objective: We aimed to compare clinical outcomes of novel SN sparing hybrid ablation technique versus RF-SN modification for IST management. Read More

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Non-carbapenem beta-lactam/beta-lactamase inhibitors versus carbapenems for urinary tract infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a systematic review.

Int J Antimicrob Agents 2021 Jul 30:106410. Epub 2021 Jul 30.

Centre of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, Beijing 100853, China. Electronic address:

Objective: The systematic review was conducted to compare the efficacy of non-carbapenem beta-lactam/beta-lactamase inhibitors (BLBLIs) versus carbapenems for the treatment of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) induced urinary tract infections (UTIs).

Methods: A comprehensive search of the Cochrane Library, PubMed and Embase was conducted from January 1979 to December 2020. Clinical success, microbiologic success, clinical and microbiologic success, and mortality were assessed as efficacy outcomes. Read More

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Computation of the conditions for anti-angiogenesis and gene therapy synergistic effects: sensitivity analysis and robustness of target solutions.

J Theor Biol 2021 Jul 30:110850. Epub 2021 Jul 30.

Universite de Lorraine - CNRS UMR 7360 Laboratoire Interdisciplinaire des Environnements Continentaux Campus Bridoux - 8 Rue du General Delestraint, Metz 57070, France. Electronic address:

Both anti-angiogenesis and gene therapy involve complex processes depending on non-point parameters belonging to a space of values. To successfully overcome the challenges involved in their therapeutic approaches, there is a need to analyze the sensitivity of these parameters. In this paper, a new mathematical model that combines immune system stimulations, inflammatory processes associated with tumor development, and gene therapy aimed at enhancing the efficacy of both treatments are explored. Read More

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Optimal Noninvasive Medicare Access Promotion: Patients with Obstructive Sleep Apnea A Technical Expert Panel Report from the American College of Chest Physicians, the American Association for Respiratory Care, the American Academy of Sleep Medicine, and the American Thoracic Society.

Chest 2021 Jul 28. Epub 2021 Jul 28.

Ascension Medical Group, Carmel, IN.

This document summarizes the work of the CPAP and Bilevel PAP Therapy for Obstructive Sleep Apnea (OSA) Technical Expert Panel working group. For PAP therapy, the most pressing current coverage barriers identified were: an insufficient symptom list describing all potential symptoms in patients with mild OSA; the 4 hours/night of PAP usage requirement to keep the device; the additional sleep studies requirement to re-qualify for PAP or supplemental oxygen; the inability to use telehealth visits for followup visits. Critical evidence support changes to current policies and include: symptom list inadequate to cover all scenarios based on updated clinical practice guidelines; published evidence that 2 hours/night of PAP use can result in benefit to quality of life and other metrics; the costs of another sleep study not justified for all non-adherent patients or for supplemental oxygen due to other types of assessment currently available; and the remarkable success and acceptance of telehealth visits. Read More

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Safety and efficacy of a novel electrocautery-enhanced lumen-apposing metal stent in interventional EUS procedures (with video).

Gastrointest Endosc 2021 Jul 30. Epub 2021 Jul 30.

Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy; Humanitas Clinical and Research Center - IRCCS, Rozzano (MI), Italy.

Background And Aims: Electrocautery-tip lumen-apposing metal stents (EC-LAMSs) have extended the indications of therapeutic EUS. We aimed to retrospectively evaluate safety, technical and clinical success of a newly developed EC-LAMS for various EUS-guided procedures.

Methods: We included and retrospectively analyzed consecutive patients at 8 tertiary care referral centers who had undergone EUS interventional procedures using the Hot-Spaxus (Taewoong Medical Co, Gimpo, Korea) between October 2018 and February 2021. Read More

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Meaningfulness among frail older adults receiving home-based care in Finland.

Health Promot Int 2021 Aug 2. Epub 2021 Aug 2.

Faculty of Education and Welfare Studies, Social Policy Unit, Åbo Akademi University, PB 311, 65101 Vaasa, Finland.

Meaningfulness is a fundamental aspect in the promotion of frail older adults' health and well-being. From a salutogenic point of view, meaningfulness is a vital component of a sense of coherence (SOC), since having a strong SOC aids toward assembling the resources needed to cope with stressors and manage tensions with success. In order to respond to the challenges of population aging and the need to enable frail older adults to live at home for as long as possible, it is important to explore their meaningfulness in the context of home-based care. Read More

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Integrated care pathways in neurosurgery: A systematic review.

PLoS One 2021 2;16(8):e0255628. Epub 2021 Aug 2.

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Introduction: Integrated care pathways (ICPs) are a pre-defined framework of evidence based, multidisciplinary practice for specific patients. They have the potential to enhance continuity of care, patient safety, patient satisfaction, efficiency gains, teamwork and staff education. In order to inform the development of neurosurgical ICPs in the future, we performed a systematic review to aggregate examples of neurosurgical ICP, to consider their impact and design features that may be associated with their success. Read More

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Wastewater-Based Epidemiology of Enteric Viruses and Surveillance of Acute Gastrointestinal Illness Outbreaks in a Resource-Limited Region.

Am J Trop Med Hyg 2021 Aug 2. Epub 2021 Aug 2.

Instituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, San José, Costa Rica.

Acute gastrointestinal illness (AGI) continues to be an important cause of morbidity and mortality among all ages. This study applied the principles of wastewater-based epidemiology for the preventive identification of potential outbreaks of acute viral gastroenteritis and hepatitis A by analyzing the presence of human enteric viruses in influents of small municipal wastewater treatment plants (WWTPs) handling domestic sewage, together with public health reports of acute diarrheal and hepatitis A disease in Costa Rica during 2013. Raw wastewater samples were collected during four seasonal periods with different rainfall levels. Read More

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Barriers To US Biosimilar Market Growth: Lessons From Biosimilar Patent Litigation.

Health Aff (Millwood) 2021 Aug;40(8):1198-1205

Ameet Sarpatwari is an assistant professor of medicine and the assistant director of the Program on Regulation, Therapeutics, and Law in the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School.

High biologic drug prices have placed substantial strain on the US health care system. The Biologics Price Competition and Innovation Act (BPCIA), passed in 2010 as part of the Affordable Care Act, created an abbreviated approval pathway for biosimilars-versions of "originator" biologic drugs made by different manufacturers-to help address this issue. However, a decade after its passage, the BPCIA has spurred only limited competition. Read More

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Dendronized Arm Snowflake Polymer as a Highly Branched Scaffold for Cellular Imaging and Delivery.

Biomacromolecules 2021 Aug 2. Epub 2021 Aug 2.

State Key Laboratory of Chem-/Bio-Sensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China.

Incorporation of branched structures is a major pathway to build macromolecules with desired three-dimensional (3D) structures, which are of high importance in the rational design of functional polymeric scaffolds. Dendrimers and hyperbranched polymers have been extensively studied for this purpose, but proper gain-of-function for these structures usually requires large enough molecular weights and a highly branched interior so that a spherical 3D core-shell architecture can be obtained, yet it is generally challenging to achieve precise control over the structure, high molecular weight, and high degree of branching (DoB) simultaneously. In this article, we present a set of snowflake-shaped star polymers with functional cores and dendronized arms, which ensure a high DoB and an overall globular conformation, thus facilitating the introduction of functional moieties onto the easily achieved scaffold without the need for high-generation dendrons. Read More

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Salicylanilides Reduce SARS-CoV-2 Replication and Suppress Induction of Inflammatory Cytokines in a Rodent Model.

ACS Infect Dis 2021 Aug 2. Epub 2021 Aug 2.

Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

SARS-CoV-2 virus has recently given rise to the current COVID-19 pandemic where infected individuals can range from being asymptomatic, yet highly contagious, to dying from acute respiratory distress syndrome. Although the world has mobilized to create antiviral vaccines and therapeutics to combat the scourge, their long-term efficacy remains in question especially with the emergence of new variants. In this work, we exploit a class of compounds that has previously shown success against various viruses. Read More

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Nanotechnology for Boosting Cancer Immunotherapy and Remodeling Tumor Microenvironment: The Horizons in Cancer Treatment.

ACS Nano 2021 Aug 2. Epub 2021 Aug 2.

Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, 44 WenhuaXilu, Jinan 250012, China.

Immunotherapy that harnesses the human immune system to fight cancer has received widespread attention and become a mainstream strategy for cancer treatment. Cancer immunotherapy not only eliminates primary tumors but also treats metastasis and recurrence, representing a major advantage over traditional cancer treatments. Recently with the development of nanotechnology, there exists much work applying nanomaterials to cancer immunotherapy on the basis of their excellent physiochemical properties, such as efficient tissue-specific delivery function, huge specific surface area, and controllable surface chemistry. Read More

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S100A8 may govern hyper-inflammation in severe COVID-19.

FASEB J 2021 Sep;35(9):e21798

Department of Pharmacology, Tokyo Women's Medical University, Tokyo, Japan.

The coronavirus disease 2019 (COVID-19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID-19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. Read More

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September 2021

A First Wide-Open LDH Structure Hosting InP/ZnS QDs: A New Route Toward Efficient and Photostable Red-Emitting Phosphor.

Adv Mater 2021 Aug 2:e2103411. Epub 2021 Aug 2.

Université Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, Clermont-Ferrand, F-63000, France.

The architecture of Zn-Al layered double hydroxides (LDHs), organo-modified with bola-amphiphiles molecules, is matching its interlayer space to the size of narrow-band red-emitting InP/ZnS core-shell quantum dots (QDs) to form original high-performance functional organic-inorganic QD-bola-LDH hybrids. The success of size-matching interlayer space (SMIS) approach is confirmed by X-ray diffraction, small angle X-ray scattering (SAXS), TEM, STEM-HAADF, and photoluminescence investigations. The QD-Bola-LDH hybrid exhibits a photoluminescence quantum yield three times higher than that of pristine InP/ZnS QDs and provides an easy dispersion into silicone-based resins, what makes the SMIS approach a change of paradigm compared to intercalation chemistry using common host structures. Read More

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One-year outcomes of microhook trabeculotomy versus suture trabeculotomy ab interno.

Graefes Arch Clin Exp Ophthalmol 2021 Aug 2. Epub 2021 Aug 2.

Department of Ophthalmology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.

Purpose: To compare clinical success rates and reductions in intraocular pressure (IOP) and IOP-lowering medication use following suture trabeculotomy ab interno (S group) or microhook trabeculotomy (μ group).

Methods: This retrospective review collected data from S (n = 104, 122 eyes) and μ (n = 42, 47 eyes) groups who underwent treatment between June 1, 2016, and October 31, 2019, and had 12-month follow-up data including IOP, glaucoma medications, complications, and additional IOP-lowering procedures. The Kaplan-Meier survival analysis was used to evaluate treatment success rates defined as normal IOP (> 5 to ≤ 18 mm Hg), ≥ 20% reduction of IOP from baseline at two consecutive visits, and no further glaucoma surgery. Read More

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Long-term outcomes of Altis® single-incision sling procedure for stress urinary incontinence.

Int Urogynecol J 2021 Aug 2. Epub 2021 Aug 2.

Urology Department, Centro Hospitalar Vila Nova de Gaia/Espinho EPE, Vila Nova de Gaia, Portugal.

Introduction And Hypothesis: In women with predominant stress urinary incontinence (SUI), recent data are still controversial regarding the short-term outcomes of mini-slings and there is a lack of evidence about the outcomes in the long term. Our aim was to evaluate the long-term effectiveness and complication rates of Altis® (Coloplast).

Methods: A total of 145 women with clinical SUI were implanted with an Altis® sling between April 2012 and December 2015. Read More

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Electronic consultations and economies of scale: a qualitative study of clinician perspectives on scaling up e-consult delivery.

J Am Med Inform Assoc 2021 Aug 2. Epub 2021 Aug 2.

Center for Healthcare Organization and Implementation Research, VA Bedford Healthcare System, Bedford, Massachusetts, USA.

Objective: To explore Veterans Health Administration clinicians' perspectives on the idea of redesigning electronic consultation (e-consult) delivery in line with a hub-and-spoke (centralized) model.

Materials And Methods: We conducted a qualitative study in VA New England Healthcare System (VISN 1). Semi-structured phone interviews were conducted with 35 primary care providers and 38 specialty care providers, including 13 clinical leaders, at 6 VISN 1 sites varying in size, specialist availability, and e-consult volume. Read More

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Effect of surface treatment on the mechanical stability of orthodontic miniscrews.

Angle Orthod 2021 Aug 2. Epub 2021 Aug 2.

Objectives: To provide collective quantitative evidence about the effect of surface treatments on the mechanical stability of orthodontic miniscrews (MSs).

Materials And Methods: The study was registered in PROSPERO (No. CRD42020209652). Read More

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Balloon Pulmonary Angioplasty in Chronic Totally Occluded Pulmonary Arteries: Applying Lessons Learned From the Treatment of Coronary Artery Chronic Total Occlusions.

J Invasive Cardiol 2021 Aug;33(8):E632-E639

University of Washington Medical Center, Box 356422, Seattle, WA 98195 USA.

Objectives: This study aims to describe the safety and efficacy of revascularizing chronic total occlusions (CTOs) of the pulmonary arteries with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Background: BPA has emerged as an effective treatment for CTEPH patients when surgical treatment is not possible. Experience to date has suggested treating CTOs may be associated with excess risk and less procedural success relative to other lesion types. Read More

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Preferences and experiences regarding the treatment of obstructive sleep apnea with mandibular advancement splints - a cross-sectional pilot survey.

Cranio 2021 Aug 2:1-7. Epub 2021 Aug 2.

Department of Oral and Maxillofacial Surgery, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Objective: To obtain a current overview of the use of mandibular advancement splints (MAS) as a therapeutic option for obstructive sleep apnea (OSA) in the dental profession in Northern Germany.

Methods: A questionnaire was mailed to 2431 dental professionals, and 8.3% responded. Read More

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Cancer Cytomembrane-Cloaked Prussian Blue Nanoparticles Enhance the Efficacy of Mild-Temperature Photothermal Therapy by Disrupting Mitochondrial Functions of Cancer Cells.

ACS Appl Mater Interfaces 2021 Aug 2. Epub 2021 Aug 2.

Fujian Provincial Key Laboratory of Biochemical Technology, Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, P. R. China.

Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). Read More

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Evaluation of physician-modified endografts for the treatment of thoraco-abdominal and pararenal aortic pathologies at a single institution.

J Cardiovasc Surg (Torino) 2021 Aug 2. Epub 2021 Aug 2.

Department of Vascular Surgery, Drum Tower Hospital, Affiliated to School of Medicine, Nanjing University, Nanjing, Jiangsu, China -

Background: This study aimed to describe the outcomes of high-risk patients with symptomatic or impending ruptured pararenal aneurysm and thoraco-abdominal aortic aneurysm with comorbidities unsuitable for conventional open surgery, using physician-modified endografts (PMEGs).

Methods: A single-center retrospective analysis was conducted on 59 patients (mean age: 75 years; 47 males) treated with PMEGs between 2017 and 2020. Data on baseline characteristics, procedures, and clinical follow up were collected to retrospectively analyze early (technical success, perioperative mortality, and major adverse events) and late (patency, endoleak, intervention, aneurysm thrombosis, and survival) outcomes. Read More

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Relevance of pneumoperitoneum in the conservative approach to complicated acute diverticulitis. A retrospective study identifying risk factors associated with treatment failure.

Minerva Surg 2021 Aug 2. Epub 2021 Aug 2.

Colorectal Unit, Department of General and G.I. Surgery, University General Hospital Gregorio Marañón, Madrid, Spain.

Background: The aim was to evaluate the relevance of pneumoperitoneum on the success rate of non-operative management (NOM) of patients with complicated acute diverticulitis (AD), and the risk factors associated with failure.

Methods: Observational retrospective cohort study of patients attended at the emergency department for AD from January 2015-August 2019. Patient demographics, blood tests, radiological data and initial treatment strategies were registered. Read More

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Pudendal nerve block (PNB): a safe, simple and effective approach in surgical proctological patients.

Minerva Surg 2021 Aug 2. Epub 2021 Aug 2.

General Surgery Division, Maria Vittoria Hospital, Turin, Italy.

Background: Pudendal nerve block (PNB) is commonly used in pudendal neuralgia (PN) and as an anaesthesiological technique in obstetrical and urological procedures. The purpose of this retrospective study was to compare the efficacy of PNB with other anaesthesiolocal techniques in proctological surgery.

Methods: A total of 362 patients were seen from a 22 months time interval. Read More

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Slide Tracheoplasty for Repair of Complex Tracheoesophageal Fistulas.

Laryngoscope 2021 Aug 2. Epub 2021 Aug 2.

Division of Pediatric Otolaryngology-Head and Neck Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A.

Objectives/hypothesis: Repair of large, recurrent, and complex tracheoesophageal fistulas (TEFs) is challenging and numerous different surgical approaches exist. These various techniques each carry a set of risks and possible complications such as fistula recurrence, tracheal stenosis or pouches, esophageal stenosis, and recurrent laryngeal nerve injury. Slide tracheoplasty is a reconstructive technique successfully used in many different airway pathologies, including TEF repair. Read More

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