Weak Recommendation Research Articles

Use of Induction Therapy Post Heart Transplantation: A Heart Transplant Rapid Recommendations

<h3>Purpose</h3> Induction therapy provides, when the risk of allograft rejection is the highest, early intense immunosuppression. Whether to use induction therapy, and the choice of optimal regimen remains controversial. Our goal is to develop a clinical practice guideline for the use of induction therapy (IT) in the heart transplant (HT) setting. <h3>Methods</h3> We recruited a worldwide multidisciplinary panel free of financial and intellectual conflicts of interest made up of three patient partners, five cardiologists, two surgeons, one nurse practitioner, one pharmacist, two guideline methodologists, and one systematic reviewer. This panel will use the GRADE framework and follow the standards for trustworthy guideline development, in compliance with Institute of Medicine and the Guideline International Network. Through consideration of balance between benefits and harms, quality of the evidence, and patient's values and preferences, the panel will make strong or weak recommendations for or against the use of the currently available IT agents. The panel has held its first meeting at which it finalized the guideline question as: Which aspects of IT should be used in adult HT recipients in the early post-operative period? The panel determined that to answer this question, knowledge of the impact of IT on the following outcomes is critical: all-cause mortality, re-transplant, rate of treated rejection (cellular and antibody-mediated), graft dysfunction (heart failure symptoms), infections and need for dialysis. The panel assessed the following as further important outcomes: length of hospital stay, post-surgical bleeding, risk of cancer, and quality of life. The panel's assessment of outcome importance was similar whether the time-frame was early (within the first-year) or late post-transplant. The panel will meet two further times during a timeframe of 6 months: once to review the evidence synthesized by the systematic review and a second time to develop recommendations including their direction and strength for or against the use of specific aspects of IT. <h3>Endpoints</h3> Our recommendations will be based on the perspective of patients. We have already begun a systematic review and network meta-analysis on all agents used for IT. The results of this review will inform our panel in making their final recommendations by February 28^th, 2022.

Clinical practice guideline for the prevention and management of hypertensive disorders of pregnancy

RESUMENObjetivos: Proveer recomendaciones clínicas basadas en evidencia para la prevención y el manejo de la enfermedad hipertensiva del embarazo (EHE) en el Seguro Social de Salud (EsSalud) del Perú. Materiales y métodos: se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló ocho preguntas clínicas para ser respondidas por la presente Guía de Práctica Clínica (GPC). Se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando se consideró pertinente, estudios primarios en PubMed y Central durante 2021. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas . En reuniones de trabajo periódicas, el GEG usó la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE) para calificar la evidencia y formular las recomendaciones. Además se resentan los puntos de buenas prácticas clínicas (BPC) y los flujogramas de prevención, manejo y seguimiento. Finalmente, la GPC fue aprobada por Resolución 112-IETSI-ESSALUD-2021.Resultados: En la presente GPC se formularon 11 recomendaciones (6 fuertes y 5 condicionales) que respondieron las preguntas clínicas definidas en el alcance de la GPC, acompañadas de 32 puntos de BPC y 3 flujogramas que abordan temas de prevención, tratamiento y seguimiento de la EHE. Conclusiones: Como recomendaciones centrales de la guía se dan el uso de sulfato de magnesio para el tratamiento de la preeclampsia severa y la eclampsia. La guía deberá ser actualizada en tres años.

Canadian Consensus Statements on the Transition of Adolescents and Young Adults with Inflammatory Bowel Disease from Pediatric to Adult Care: A Collaborative Initiative Between the Canadian IBD Transition Network and Crohn's and Colitis Canada.

ObjectivesWith the increased prevalence of childhood-onset inflammatory bowel disease (IBD), there is a greater need for a planned transition process for adolescents and young adults (AYA). The Canadian IBD Transition Network and Crohn’s and Colitis Canada joined in collaborative efforts to describe a set of care consensus statements to provide a framework for transitioning AYA from pediatric to adult care.MethodsConsensus statements were drafted after focus group meetings and literature reviews. An expert panel consisting of 20 IBD physicians, nurses, surgeon, adolescent medicine physician, as well as patient and caregiver representatives met, discussed and systematically voted. The consensus was reached when greater than 75% of members voted in agreement. When greater than 75% of members rated strong support, the statement was rendered a strong recommendation, suggesting that a clinician should implement the statement for all or most of their clinical practice.ResultsThe Canadian expert panel generated 15 consensus statements (9 strong and 6 weak recommendations). Areas of focus of the statements included: transition program implementation, key stakeholders, areas of potential need and gaps in the research.ConclusionsThese consensus statements provide a framework for the transition process. The quality of evidence for these statements was generally low, highlighting the need for further controlled studies to investigate and better define effective strategies for transition in pediatric to adult IBD care.

Guideline for the diagnosis and treatment of Faecal Incontinence-A UEG/ESCP/ESNM/ESPCG collaboration.

IntroductionThe goal of this project was to create an up‐to‐date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g., general practitioners, surgeons, gastroenterologists, other healthcare workers) and any patients who are interested in information regarding the diagnosis and management of FI.MethodsThese guidelines have been created in cooperation with members from the United European Gastroenterology (UEG), European Society of Coloproctology (ESCP), European Society of Neurogastroenterology and Motility (ESNM) and the European Society for Primary Care Gastroenterology (ESPCG). These members made up the guideline development group (GDG). Additionally, a patient advisory board (PAB) was created to reflect and comment on the draft guidelines from a patient perspective. Relevant review questions were established by the GDG along with a set of outcomes most important for decision making. A systematic literature search was performed using these review questions and outcomes as a framework. For each predefined review question, the study or studies with the highest level of study design were included. If evidence of a higher‐level study design was available, no lower level of evidence was sought or included. Data from the studies were extracted by two reviewers for each predefined important outcome within each review question. Where possible, forest plots were created. After summarising the results for each review question, a systematic quality assessment using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was performed. For each review question, we assessed the quality of evidence for every predetermined important outcome. After evidence review and quality assessment were completed, recommendations could be formulated. The wording used for each recommendation was dependent on the level of quality of evidence. Lower levels of evidence resulted in weaker recommendations and higher levels of evidence resulted in stronger recommendations. Recommendations were discussed within the GDG to reach consensus.ResultsThese guidelines contain 45 recommendations on the classification, diagnosis and management of FI in adult patients.ConclusionThese multidisciplinary European guidelines provide an up‐to‐date comprehensive evidence‐based framework with recommendations on the diagnosis and management of adult patients who suffer from FI.

Clinical Practice Guidelines for diagnosis of organic involvement of amyloidosis: Part 2/3.Year 2020

Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in English and Spanish from July to August 2019. The level of evidence and recommendation are based on the GRADE system (http://www.gradeworkinggroup.org/index.htm). The recommendations are graded according to their direction (for or against) and strength (strong and weak). Finally, it is recommended to use GLIA tools to evaluate the obstacles and facilitators in implementation. A strong suggestion indicates a high degree of trust in support or opposition to the intervention. When defining a strong recommendation, this guide uses the "recommended" language. The weaker recommendations indicate that the outcome of the intervention (favorable or unfavorable) is doubtful. In this case, if a weak recommendation is defined, the "recommendation" language is used. Recommendations must be explained within the scope of special care in validated diagnostic studies conducted by specially trained doctors. Presumably, the attending physician has a high degree of suspicion of amyloidosis. It assumes that diagnostic research is conducted by well-trained doctors using a validated standardized method. This guide is intended for health care professionals and those involved in health care policies to help ensure that the necessary agreements have been reached to provide appropriate care. For patients with suspected amyloidosis, it is recommended: Electrocardiogram be used as a preliminary assessment for all patients with amyloidosis. Doppler echocardiography conventional be used as the initial image of the first choice for cardiac amyloidosis in patients diagnosed with suspected heart involvement due to amyloidosis. Echocardiographic strain diagnosis for patients with amyloidosis prompted by conventional echocardiography or uncertain. Cardiac magnetic resonance imaging (MRI) be used for the diagnosis of cardiac amyloidosis in patients with previous studies suggesting or uncertain amyloidosis. T1 mapping technology for cardiac MRI to diagnose myocardial amyloidosis as an alternative to MRI, for patients with kidney failure or contraindication to other studies Cardiac MRI examination with T1 localization technique for patients who have previously studied amyloidosis, and measure the extracellular volume and quantify the degree of cardiac involvement in order to diagnose and measure the cardiac involvement caused by amyloidosis. Cardiac MRI with T1 mapping technique and extracellular volume measurement for the early diagnosis of amyloidosis in patients with previous studies suggestive of amyloidosis. Measurement of type B-type natriuretic peptide measurement be used for screening and diagnosis of cardiac amyloidosis. Pyrophosphate scintigraphy to make a preliminary diagnosis of patients with suspected cardiac amyloidosis, so as to distinguish ATTR (positive) from other patients.

UEG and EAES rapid guideline: Systematic review, meta-analysis, GRADE assessment and evidence-informed European recommendations on TaTME for rectal cancer

BackgroundEvidence and practice recommendations on the use of transanal total mesorectal excision (TaTME) for rectal cancer are conflicting.ObjectiveWe aimed to summarize best evidence and develop a rapid guideline using transparent, trustworthy, and standardized methodology.MethodsWe developed a rapid guideline in accordance with GRADE, G-I-N, and AGREE II standards. The steering group consisted of general surgeons, members of the EAES Research Committee/Guidelines Subcommittee with expertise and experience in guideline development, advanced medical statistics and evidence synthesis, biostatisticians, and a guideline methodologist. The guideline panel consisted of four general surgeons practicing colorectal surgery, a radiologist with expertise in rectal cancer, a radiation oncologist, a pathologist, and a patient representative. We conducted a systematic review and the results of evidence synthesis by means of meta-analyses were summarized in evidence tables. Recommendations were authored and published through an online authoring and publication platform (MAGICapp), with the guideline panel making use of an evidence-to-decision framework and a Delphi process to arrive at consensus.ResultsThis rapid guideline provides a weak recommendation for the use of TaTME over laparoscopic or robotic TME for low rectal cancer when expertise is available. Furthermore, it details evidence gaps to be addressed by future research and discusses policy considerations. The guideline, with recommendations, evidence summaries, and decision aids in user-friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/4494.ConclusionsThis rapid guideline provides evidence-informed trustworthy recommendations on the use of TaTME for rectal cancer.

Travail bimanuel versus travail unimanuel chez les enfants (0–18 ans) atteints de paralysie cérébrale spastique unilatérale

ObjectiveThe objective of this work is to research, from the literature, whether there is an interest of bimanual training compared unimanual training in improving the upper limb function in children with unilateral spastic cerebral palsy. MethodPubMed and Science Direct databases have been consulted to find articles since 2000 discussing the intensive bimanual therapy and the constraint induced movement therapy in these patients. ResultsFive articles were selected between 2011 and 2017, including two systematic reviews, a multisite clinical trial, a secondary analysis of a randomized controlled trial and a literature review. ConclusionThe literature shows a strong but nonspecific recommendation for one or the other approach in improving the hemiparetic upper limb function. However, constraint induced movement therapy appears to be more effective in improving grip in the injured hand and there is a weak recommendation for intensive bimanual therapy in improving coordination between limbs and for bimanual activities. The conclusion would be to approach these two therapies by making them complementary and to link unimanual training and bimanual training in the rehabilitation of children with unilateral spastic cerebral palsy.

Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis.

BackgroundOral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC).ObjectiveTo evaluate the effect of nicotinamide in prevention of skin cancers.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of nicotinamide. We used Medline, EMBASE, CENTRAL, and Web of Science databases from their inception to October 2020 to search the following concepts: “nicotinamide”; “randomized controlled trial” (validated filters). Two independent reviewers screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. To be eligible, ≥1 outcome had to be covered. We used a standardized collection grid to complete data extraction in duplicate. The primary outcome was skin cancers (all types). Secondary outcomes were basal cell carcinomas (BCCs); cSCCs; actinic keratoses; melanomas; digestive, cutaneous, and biochemical adverse effects (AEs). Subgroup analyses were planned a priori.ResultsWe screened 4730 citations and found 29 trials (3039 patients) meeting inclusion criteria. Nicotinamide was associated with a significant reduction in skin cancers compared to control (rate ratio 0.50 (95% CI, 0.29-0.85; I 2 = 64%; 552 patients; 5 trials); moderate strength of the evidence). Heterogeneity was explained by risk of bias. Nicotinamide was associated with a significant reduction in BCCs and cSCCs, and increased risk of digestive AEs.ConclusionOral nicotinamide should be considered in healthy patients or organ transplant recipients with history of skin cancer (GRADE: weak recommendation; moderate-quality evidence), in particular of BCC and cSCC.

Characteristics and quality of clinical practice guidelines addressing acupuncture interventions: a systematic survey of 133 guidelines and 433 acupuncture recommendations

ObjectiveTo systematically summarise acupuncture-related Clinical Practice Guidelines (CPGs)’s clinical and methodological characteristics and critically appraise their methodology quality.DesignWe summarised the characteristics of the guidelines and recommendations and evaluated their methodological...

Prehabilitation in patients undergoing colorectal surgery fails to confer reduction in overall morbidity: results of a single-center, blinded, randomized controlled trial.

Currently, there are solely weak recommendations in the enhanced recovery after surgery (ERAS) protocol regarding the role of preoperative physical activity and prehabilitation in patients undergoing colorectal surgery. Studies in heterogenous groups showed contradictory results regarding the impact of prehabilitation on the reduction of postoperative complications. The aim of this study was to assess the impact of prehabilitation on postoperative complications in patients undergoing colorectal surgery within an ERAS protocol. Between July 2016 and June 2019, a single-center, blinded, randomized controlled trial designed to test whether physiotherapeutic prehabilitation vs. normal physical activities prior to colorectal surgery may decrease morbidity within a stringent ERAS protocol was carried out. The primary endpoint was postoperative complications assessed by Comprehensive Complications Index (CCI®). Primary and secondary endpoints for both groups were analyzed and compared. A total of 107 patients (54 in the prehabilitation enhanced recovery after colorectal surgery [pERACS] group and 53 in the control group) were included in the study and randomized. Dropout rate was 4.5% (n = 5). Baseline characteristics were comparable between the pERACS and control groups. The percentage of colorectal adenocarcinoma was low in both groups (pERACS 32% vs. control 23%, p = 0.384). Almost all patients underwent minimally invasive surgery in both groups (96% vs. 98%, p = 1.000). There was no between-group difference in the primary outcome, as the mean CCI at 30-day postoperative in the pERACS group was 18 (SD 0-43) compared to 15 (SD 0-49) in the control group (p = 0.059). Secondary outcome as complications assessed according to Clavien-Dindo, length of hospital stay, reoperation rate, and mortality showed no difference between both groups. Routine physiotherapeutic prehabilitation has no additional benefit for patients undergoing colorectal surgery within an ERAS protocol. ClinicalTrial.gov: ID: NCT02746731; Institution Ethical Board Approval: KEK-ZH Nr. 2016-00,229.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Korean guideline of desmopressin for the treatment of nocturia in men.

PurposeNocturia is the most bothersome of lower urinary tract symptoms in men. Desmopressin, a synthetic analog of the human hormone vasopressin, has been used for the treatment of nocturia. However, the guidelines include varying recommendations for the use of desmopressin for the management of nocturia in men. Therefore, the Korean Urological Association (KUA) developed recommendations for desmopressin for the treatment of nocturia in men.Materials and MethodsA rigorous systematic review was performed and Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to rate the certainty of evidence for patient outcomes and to develop the evidence into recommendations. The steering group, guidelines development group, systematic review team, and external review group consisted of members of the Korean Continence Society, Korean Society of Geriatric Urological Care, and KUA, respectively, who were involved in the guidelines development process.ResultsThe guidelines address the benefits, harms, patients’ values and preferences, costs, and resources related to desmopressin by using a single clinical question: What is the effectiveness of desmopressin compared to that of placebo, behavior modification, or other pharmacological therapies?ConclusionsThe guidelines development panel suggests desmopressin for men with nocturia instead of placebo, behavior modification, or alpha-blocker monotherapy (low certainty of evidence, weak recommendation). Additionally, the panel suggests desmopressin combination therapy with alpha-blockers for men with nocturia instead of alpha-blocker monotherapy or alpha-blocker combination therapy with anticholinergic agents (low certainty of evidence, weak recommendation).

Review: Steroid Use in Patients With Acute Spinal Cord Injury and Guideline Update.

Acute spinal cord injury (SCI) is a devastating condition that causes enormous damage to a patient’s physical, mental, and economic situation and requires a multidisciplinary approach to treatment. Research on SCI has been performed for a long time, and the management of SCI has developed dramatically in recent decades as a mechanism of injury and the pathophysiology of SCI have been revealed from the primitive stage in the past. In the treatment of patients with acute SCI, there is a lot of debate regarding surgical treatment strategies and pharmacological management, such as steroid use. In particular, the efficacy of steroid use, such as methylprednisolone sodium succinate, has been increasing and decreasing and is still intensely debated. The practice guidelines reported so far for this are also at the “suggest” stage with weak recommendations. Therefore, this review aims to summarize the effects of steroid use on SCI. This review provides an overview of current practical guidelines and clinical studies on steroid use in patients with SCI.

May 25-31, International thyroid awareness week &amp; May 25, world thyroid day, 2022: Indetermination of indeterminate cytology, aus/flus, fn, susp, in thyroidology?

May 25, World Thyroid Day, WTD, was officially accepted at the Annual General Meeting of the European Thyroid Association (ETA) before the September 2007 Congress in Leipzig, Germany. Although the date also refers to the establishment day of ETA in 1965, the aim is to create awareness about thyroid diseases on this day. After World Thyroid Day was first celebrated by ETA, in 2010, the American Thyroid Association (ATA) declared its support for this day. In addition, on May 25-31, International Thyroid Awareness Week, ITAW, is celebrated worldwide with the mentorship of Thyroid Federation International. The "thyroid gland", commonly used terminology simply "thyroid", is an important endocrine organ localized in front of the neck, extending laterally on both sides. This butterfly-shaped and delicate (1) vital organ is responsible for many metabolic activities that are critical for the organism through the secretion of thyroid hormones. Therefore, "thyroid health" becomes extremely important. As such, thyroid gland disorders continue to affect all age groups globally and possess a wide spectrum of signs and symptoms. Among these, hypothyroidism (abnormally decreased thyroid activity), thyrotoxicosis with or without hyperthyroidism (abnormally increased thyroid activity), goiter (enlargement of the thyroid gland), congenital thyroid diseases, thyroiditis (inflammation of the thyroid gland), retro/substernal goiter (gland growth and extension behind the sternum), follicular nodular thyroid disease with primary and secondary thyroid carcinomas are noteworthy. Family history, genetic and familial predisposition, radiation exposure to the head &amp; neck and thorax region during the first two decades particularly in children and women (0-20 years of age), iodine deficiency, and some drugs such as amiodarone are known as the leading factors to the thyroid gland disorders. Nevertheless, the Public Health Update reported that more than 200 million people worldwide are facing thyroid disorders, and over 50% of them remain undiagnosed. To achieve an accurate diagnosis for disorders and also carcinomas with their metastasis and recurrences before histopathology and during postoperative follow-up of this small, delicate, and papillon vital organ that can affect the whole organism: (i) biochemical essays (fT3, fT4, tT3, tT4, TSH, Tg, antiTg, antiTPO, calcitonin, TSI/TRAb, US-guided-Tg/calcitonin washout); (ii) imaging modalities (sonography, strain, and shear wave elastography, SWE, scintigraphy and CT, MRI, 18-FDG PET/CT, and 131I-WBS, when necessary) and (iii) cytopathologic examinations have been utilized. However, thyroid and neck US and cytopathological examination, in particular, still maintain their importance today. Indeterminate cytology (Category III, IV, V, The Bethesda System for Reporting Thyroid Cytopathology, TBSRTC, 1st and 2nd ed.s) (2,3) in cytopathology and follicular nodular thyroid disease, in general, is one of the controversial topics which remains to be a significant topic in Thyroidology (4,5). The latest ATA guidelines, 2015 ATA Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (6), recommended repeat FNA cytology, molecular tests with further surveillance or diagnostic surgery, considering worrisome sonographic and clinical features with patient preference, as novel approaches in Endocrine Surgery, Endocrine Pathology, and Thyroidology to resolve the challenging issue, Category III, TBSRTC (AUS/FLUS, atypia of undetermined/follicular lesion of undetermined significance), which is at the center of the aforementioned controversion (Recommendation 15A, Weak recommendation, Moderate-quality evidence; 15B, Strong recommendation, Low-quality evidence). Of note, some authors and authorities have advocated the potential need for separation in TBSRTC in terms of Category III, AUS/FLUS (7,8,9). We very recently also postulated the so-called subdivision concept in Category III, TBSRTC, id est, (i) Category IIIA: AUS/FLUS without nuclear atypia (AUS/FLUS wo NA), and (ii) Category IIIB: AUS/FLUS with nuclear atypia (AUS/FLUS w NA) within the possible forthcoming 3rd ed., the 202X TBSRTC (10,11). Mater artium necessitas. Therefore, a novel risk of malignancy, ROM, for each diagnostic category of possible forthcoming TBSRTC would selectively enrich the different management proposals in Thyroidology. As a matter of fact that this issue merits further investigation. Bene diagnoscitur bene curatur.. Dum vivimus servimus..

Cost-Effectiveness and Guidelines for Opioid Substitution Treatment

&#x0D; There was evidence indicating that in the treatment of opioid use disorder, injectable hydromorphone, or injectable methadone provided more benefit at less cost compared with injectable diacetylmorphine over a 6-month time horizon.&#x0D; Evidence suggests that in the treatment of opioid use disorder, both injectable hydromorphone and injectable diacetylmorphine are likely to provide more benefit at less cost than methadone maintenance treatment. Treatment with injectable hydromorphone was more cost-effective than injectable diacetylmorphine in opioid use disorder patients who do not respond to or relapse from drug treatments.&#x0D; The evidence is limited because observed data were collected during a short-term follow-up, and long-term cost-effectiveness outcomes were based on extrapolations beyond data from the actual studies.&#x0D; One guideline provided a weak recommendation, supported by low-quality evidence, for using slow-release oral morphine in older adults with adequate renal function in whom buprenorphine and methadone maintenance have been ineffective to treat opioid use disorder or could not be tolerated. Another guideline recommends using injectable hydromorphone or injectable diacetylmorphine for individuals with severe opioid use disorders who relapsed previous treatments failed.&#x0D; No relevant cost-effectiveness evidence or guidelines with recommendations regarding the use of oral hydromorphone, fentanyl patches, or fentanyl buccal tablets for opioid use disorder treatment were identified; therefore, no summary can be provided.&#x0D;

2021 Updated European Association of Urology Guidelines on the Use of Adjuvant Pembrolizumab for Renal Cell Carcinoma

Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. Patient summaryNew data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness in the United States.

The Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the prevention and management of tick-borne illness (TBI). Recommendations are graded based on quality of supporting evidence according to criteria put forth by the American College of Chest Physicians. The guidelines include a brief review of the clinical presentation, epidemiology, prevention, and management of TBI in the United States, with a primary focus on interventions that are appropriate for resource-limited settings. Strong recommendations are provided for the use of DEET, picaridin, and permethrin; tick checks; washing and drying clothing at high temperatures; mechanical tick removal within 36 h of attachment; single-dose doxycycline for high-risk Lyme disease exposures versus "watchful waiting;" evacuation from backcountry settings for symptomatic tick exposures; and TBI education programs. Weak recommendations are provided for the use of light-colored clothing; insect repellents other than DEET, picaridin, and permethrin; and showering after exposure to tick habitat. Weak recommendations are also provided against passive methods of tick removal, including the use of systemic and local treatments. There was insufficient evidence to support the use of long-sleeved clothing and the avoidance of tick habitat such as long grasses and leaf litter. Although there was sound evidence supporting Lyme disease vaccination, a grade was not offered as the vaccine is not currently available for use in the United States.

Extracorporeal Treatment for Gabapentin and Pregabalin Poisoning: Systematic Review and Recommendations From the EXTRIP Workgroup

Toxicity from gabapentin and pregabalin overdose is commonly encountered. Treatment is supportive, and the use of extracorporeal treatments (ECTRs) is controversial. The EXTRIP workgroup conducted systematic reviews of the literature and summarized findings following published methods. Thirty-three articles (30 patient reports and 3 pharmacokinetic studies) met the inclusion criteria. High gabapentinoid extracorporeal clearance (>150mL/min) and short elimination half-life (<5 hours) were reported with hemodialysis. The workgroup assessed gabapentin and pregabalin as "dialyzable" for patients with decreased kidney function (quality of the evidence grade as A and B, respectively). Limited clinical data were available (24 patients with gabapentin toxicity and 7 with pregabalin toxicity received ECTR). Severe toxicity, mortality, and sequelae were rare in cases receiving ECTR and in historical controls receiving standard care alone. No clear clinical benefit from ECTR could be identified although major knowledge gaps were acknowledged, as well as costs and harms of ECTR. The EXTRIP workgroup suggests against performing ECTR in addition to standard care rather than standard care alone (weak recommendation, very low quality of evidence) for gabapentinoid poisoning in patients with normal kidney function. If decreased kidney function and coma requiring mechanical ventilation are present, the workgroup suggests performing ECTR in addition to standard care (weak recommendation, very low quality of evidence).

Efficacy of Penile Low-Intensity Shockwave Therapy and Determinants of Treatment Response in Taiwanese Patients with Erectile Dysfunction.

Background: Erectile dysfunction (ED) remains an emotional wrench to patients and a therapeutic challenge to urologists in andrology clinics worldwide. This is, in part, related to refraction to, or transient effect of phosphodiesterase 5 inhibitors (PDE5i), coupled with patients’ dissatisfaction with this treatment modality. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is an evolving treatment option, with promising curative potential. Current international guidelines are inconclusive, bear weak recommendation strength, and lack ethnogeographic consensus. Objectives: This study evaluated the safety, efficacy, and effect duration of Li-ESWT, as well as exploring disease-associated determinants of treatment success in Taiwanese males with ED. Methods: A cohort of 69 eligible cases treated with 12 sessions of Li-ESWT and followed up for at least 12 months after treatment, between January 2018 and December 2019 at our medical facility, was used. The present single-center, retrospective, non-randomized, single-arm study employed standardized erectile function evaluation indices, namely, the five-item International Index of Erectile Function (IIEF-5) and Erection Hardness Score (EHS). Clinicopathological analyses of selected variables and comparative analyses of time-phased changes in the EF indices relative to baseline values were performed. Evaluation of treatment success was based on minimal clinically important difference (MCID), using a binomial logistic regression model. Results: The median age and duration of ED for our Taiwanese cohort were 55 years and 12 months, respectively, and an average of 31.3% presented with co-morbidities. The mean improvement in IIEF-5, EHS, and quality of life (QoL) domain scores relative to the baseline values was statistically very significant (p < 0.001) at all indicated follow-up time-points. When stratified, Taiwanese patients with severe and moderate ED benefited more from Li-ESWT, compared with those in the mild or mild-to-moderate group. Patients’ pre-Li-ESWT PDE5i response status was not found to significantly influence Li-ESWT response. Univariate analysis showed that age > 45 years (p = 0.04), uncontrolled diabetes mellitus (p = 0.04), and uncontrolled hyperlipidemia (p = 0.01) were strongly associated with Li-ESWT efficacy; however, only age > 45 years (p = 0.04) and uncontrolled hyperlipidemia (p = 0.03) were found to be independent negative predictors of Li-ESWT success by the multivariate logistic model. Follow-up was uneventful, with no treatment-related adverse events or side effects reported. Of the treated patients, 86.1% indicated satisfaction with the treatment regimen, and over 90% indicated they would recommend the same therapy to others. Conclusions: Li-ESWT is a safe and efficacious therapeutic modality for Taiwanese patients with ED. Uncontrolled hyperlipidemia and age > 45 years are independent negative predictors of treatment success for this cohort.

Assessment of Cardiac Sympathetic Activity by Nuclear Medicine: Many Clinical Benefits but Weak Recommendation

The autonomous nervous system (ANS) regulates important cardiac functions, including heart rate, ventricular contractility, QT interval and systemic vascular resistance. ANS dysfunction, known as dysautonomia, can lead to many clinical manifestations, some of them severe and debilitating. Dysautonomia is often underdiagnosed and detected at late stages, due to its wide phenotypic variability and the poor familiarity of the physicians with the disease, leading to higher cardiovascular mortality and morbidity. The diagnostic and prognostic potential of nuclear cardiology in the assessment [...]