Guidelines Committee Research Articles

Fabry Disease practice resource: Focused revision

Fabry Disease practice resource: Focused revision

Editorial introductions

Editorial introductions

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

Consensus Guidelines for Pediatric Intensive Care Units in India, 2020

BackgroundConsensus Guidelines for Pediatric Intensive Care Units (PICUs) were published in Indian Pediatrics in 2002.ObjectiveThe current document represents a recent update in the Indian context, regarding unit design, equipment, organization, staffing as well as admission and discharge criteria for different levels of Pediatric Intensive Care and teaching units with PICU training programs, as well as nonteaching units.ProcessThe Pediatric Intensive Care College Council (PICC), an academic wing of the Indian Academy of Pediatrics (IAP) Intensive Care Chapter took the initiative to update the guidelines with members of the PICU guidelines Committee writing group. After a great deal of discussion at conferences and through mailing and feedback with listed members, as well as with the guidance and feedback of senior PICU guidelines advisory committee members, The consensus is now updated. These guidelines are intended to serve as a reference for health Care institutions wishing to establish a new PICU or to modify an existing PICU. As a resource, experience of those members who have worked extensively in western PICUs was also taken into consideration, in addition to published guidelines in the medical literature. PICUs with teaching programs run by the IAP Intensive Care Chapter must follow these criteria for unit accreditation and teaching curricula as applicable.RecommendationsUnit design, equipment, organization, staffing as well as admission and discharge criteria for different levels of pediatric intensive care are updated.

University of Alberta Faculty of Medicine and Dentistry.

University of Alberta Faculty of Medicine and Dentistry.

Are urologists in trouble with SARS-CoV-2? Reflections and recommendations for specific interventions.

ObjectiveTo assess the risk of viral infection during urological surgeries due to the possible hazards in tissue, blood, urine and aerosolised particles generated during surgery, and thus to understand the risks and make recommendations for clinical practice.Patients and MethodsWe reviewed the available literature on urological and other surgical procedures in patients with virus infections, such as human papillomavirus, human immunodeficiency virus and hepatitis B, and current publications on coronavirus disease 2019 (COVID‐19).ResultsSeveral possible pathways for viral transmission appear in the literature. Recently, groups have detected severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) in the urine and faeces, even after negative pharyngeal swabs. In addition, viral RNA can be detected in the blood and several tissues. During surgery, viral particles are released, aerosol‐borne and present a certain risk of transmission and infection. However, there is currently no evidence on the exact risk of infection from the agents mentioned above. It remains unclear whether or not viral particles in the urine, blood or faeces are infectious.ConclusionsWhether SARS‐CoV‐2 can be transmitted by aerosols remains controversial. Irrespective of this, standard surgical masks offer inadequate protection from SARS‐CoV‐2. Full personal protective equipment, including at least filtering facepiece‐2 masks and safety goggles should be used. Aerosolised particles might remain for a long time in the operating theatre and contaminate other surfaces, e.g. floors or computer input devices. Therefore, scrupulous hygiene and disinfection of surfaces must be carried out. To prevent aerosolisation during laparoscopic interventions, the pneumoperitoneum should be evacuated with suction devices. The use of virus‐proof high‐efficiency particulate air filters is recommended. Local separation of anaesthesia/intubation and the operating theatre can reduce the danger of viral transmission. Lumbar anaesthesia should be considered especially in endourology. Based on current knowledge, COVID‐19 is not a contraindication for acute urological surgery. However, if possible, as European guideline committees recommend, non‐emergency urological interventions should be postponed until negative SARS‐CoV‐2 tests become available.

Abstract 608: The MPS1 inhibitor S81694 is active in acute myeloid leukemia (AML)

Abstract Background: AML is a genetically heterogenous disease with poor prognosis and new treatments are needed. MPS1 is the main kinase of the spindle assembly checkpoint (SAC), critical for segregation of chromatids during mitosis. A hallmark of cancer cells is chromosomal instability caused by deregulated cell cycle checkpoints and SAC dysfunction. MPS1 inhibition has been investigated in several solid tumors but not yet in AML. Here, we demonstrate the efficacy of the small molecule MPS1 inhibitor (MPS1i) S81694 in AML cell lines, primary cells and mouse models. Materials and Methods: Cell viability, cell stress and apoptosis were assessed by MTS assays, DiOC2(3) or annexin-V modifications and PI incorporation after exposure to S81694. Cell-cycle and polyploidy were determined by cytofluorometry and FISH. Phosphorylation of MPS1 was detected in synchronized cells by immunofluorescence detecting phosphorylated Thr33/Ser37 residues. Protein modifications were studied by WB. Time-lapse microscopy was used to determine mitosis duration using cells stained with the SiR-DNA live cell probe. Bone marrow cells from patients were obtained after informed consent and incubated on a MSC feeder or in methylcellulose for colony formation assays. All animal studies were performed in accordance with the animal ethics committee's guidelines. NSG mice were sub-lethally-irradiated and injected with AML-NS8 or AML-PS patient derived xenografts. Mice were treated intravenously with S81694 or with vehicle. Results: IC50 for viability after S81694 exposure alone was <1000nM in a panel of 8 AML cell lines. Three cell lines had IC50 >1000nM: the NPM1cmut cell line OCI-AML3, OCI-AML3-TP53mut and K562. In the most sensitive cell lines, including OCI-AML2, S81694 led to inhibition of MPS1 auto-phosphorylation, induced significant cell stress and apoptosis as detected by mitochondrial membrane potential loss, phosphatidylserine exposure and PI incorporation. In these cell lines, the cell cycle was strongly affected by treatment with S81694 showing aberrant 2n/4n ploidy distribution due to SAC abrogation as well as polyploidy (8n and 16n). S81694 exposure triggered mitotic exit as shown by cyclin B1 downregulation and significantly accelerated mitosis. For treated OCI-AML2 and OCI-AML3 cells we observed induction of gamma-H2AX (ser139), p53 upregulation and downstream caspase-3 and PARP cleavage indicating that S81694 induces p53 dependent apoptosis. Furthermore, MPS1i induced downregulation of anti-apoptotic proteins MCL-1 and BCLXL. Finally, for AML patient derived blast cells cells we observed apoptosis after exposure to S81694 and significant reduction of colony number. In two AML PDX models, intravenous administration of S81694 was shown to improve significantly median survival time, as compared to control, by 28 to 41 days and by 33 to 46 days respectively. Conclusion: The MPS1i S81694 shows significant preclinical activity in vitro and in vivo in AML. Combinations with different drugs active in AML are ongoing. Citation Format: Anna Kaci, Emilie Adicéam, Etienne De Braekeleer, Marine Garrido, Jeannig Berrou, Mélanie Dupont, Hanane Djamai, Virginie Eclache, Baruchel André, Claude Gardin, Hervé Dombret, Mike Burbridge, Thorsten Braun. The MPS1 inhibitor S81694 is active in acute myeloid leukemia (AML) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 608.

Abstract 4251: A performance characterization of microsatellite instability and mismatch repair testing methods in endometrial samples

Abstract Microsatellite instability (MSI), a functional measure of mismatch repair (MMR) deficiency, and immunohistochemistry testing for MMR proteins are well established technologies traditionally used for Lynch Syndrome screening in colorectal cancer. Recently testing for MMR deficiency, by MSI analysis or MMR protein expression, has expanded from hereditary cancer risk testing to a new role predicting immunotherapeutic response in all solid tumors. With this increase in utility and awareness, mismatch repair deficiency is now relevant in a variety of other cancer tissue types. However, little data is available for the performance of these testing techniques in non-colorectal cancer samples. In this study, we examine performance of methods for detecting MSI and MMR protein expression in endometrial cancer samples. 200 endometrial cancer samples were obtained for testing with MSI by PCR followed by capillary electrophoresis, and immunohistochemistry for MMR protein expression. Instability at 2/5 microsatellite loci was used as criteria for MSI-H designation and loss of immunostaining for one or more MMR protein was considered dMMR. Performance of these analysis methods for identification of MMR protein mutations was measured by comparing results to sequencing of MMR proteins using NGS. MSI by PCR followed by capillary electrophoresis and immunohistochemistry for all four major MMR proteins was successfully performed on all (200/200) samples. 140/200 samples had matched adjacent tissue for reference when performing MSI analysis. MSI and MMR did not exhibit 100% concordance, as expected due to their measurement of different biological effects associated with MMR deficiency. We also describe instances of microsatellite loci exhibiting more subtle shifts than those commonly observed in colorectal cancer, especially at shorter nucleotide repeats, an important consideration for future studies with pan-tumor MSI testing. With the increasing utility of identifying mismatch repair defects in hereditary and immuno-oncology for pan-tumor applications, choosing a testing approach that has the highest sensitivity is key. Our findings suggest that for maximal identification of mismatch repair deficiency, MMR by IHC and MSI by PCR are complementary technologies and should not be considered interchangeable. Consistent with these findings, a number of guideline committees globally have begun recommending co-testing for MMR and MSI. These two cost effective tools can be used together for both a functional and informative approach prior to more costly downstream testing. Citation Format: Samantha R. Lewis, Kathryn Oostdik, Shaun Peterson, Heather Tomlinson. A performance characterization of microsatellite instability and mismatch repair testing methods in endometrial samples [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4251.

Cardiac Surgery-Enhanced Recovery Programs Modified for COVID-19: Key Steps to Preserve Resources, Manage Caseload Backlog, and Improve Patient Outcomes

Abstract The COVID-19 pandemic has magnified the importance of delivering high-quality healthcare while preserving limited or depleted resources. This is particularly true in cardiac surgery, which depends on the same equipment, hospital capacity, and personnel that have been re-directed to COVID-19 care. Enhanced recovery programs promote standardized, consistent perioperative care, with an emphasis on incorporating evidence-based measures to optimize the patient experience, improve outcomes and utilize resources efficiently. Developing and implementing a program in the current COVID-19 environment is a daunting task. The Society for Enhanced Recovery After Cardiac Surgery (ERAS® Cardiac), representing an international, multi-disciplinary group of experts, provides the rationale, supportive evidence, and a proposed outline for a sustainable modified program within the constraints of the COVID-19 pandemic. It is feasible to launch in the current healthcare climate and is designed to preserve resources, reduce case backlog, and protect patient and provider safety while improving patient care and preserving institutional quality metrics. The program can also create the foundation for future growth.

ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee.

The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5-7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

Evaluation of a National Competency-Based Assessment System in Emergency Medicine: A CanDREAM Study

In 2018, Canadian postgraduate emergency medicine (EM) programs began implementing a competency-based medical education (CBME) assessment program. Studies evaluating these programs have focused on broad outcomes using data from national bodies and lack data to support program-specific improvement. We evaluated the implementation of a CBME assessment program within and across programs to identify successes and opportunities for improvement at the local and national levels. Program-level data from the 2018 resident cohort were amalgamated and analyzed. The number of entrustable professional activity (EPA) assessments (overall and for each EPA) and the timing of resident promotion through program stages were compared between programs and to the guidelines provided by the national EM specialty committee. Total EPA observations from each program were correlated with the number of EM and pediatric EM rotations. Data from 15 of 17 (88%) programs containing 9842 EPA observations from 68 of 77 (88%) EM residents in the 2018 cohort were analyzed. Average numbers of EPAs observed per resident in each program varied from 92.5 to 229.6, correlating with the number of blocks spent on EM and pediatric EM (r = 0.83, P < .001). Relative to the specialty committee's guidelines, residents were promoted later than expected (eg, one-third of residents had a 2-month delay to promotion from the first to second stage) and with fewer EPA observations than suggested. There was demonstrable variation in EPA-based assessment numbers and promotion timelines between programs and with national guidelines.

Endovascular Aneurysm Sealing Therapy with the Nellix System in Patients Not Suitable for Conventional EVAR – A Single Centre Experience

Objective: Endovascular aneurysm sealing (EVAS) therapy with the Nellix system was introduced in 2013. In January 2019, the Medicines and Healthcare Regulatory Authority issued a Field Safety Notice to desist use. The aim was to review experience in the use of the Nellix device in a specific cohort of patients. Methods: A prospective study of 27 patients who underwent EVAS with the Nellix system in the Belfast Trust between December 2013 and January 2016. Use of the Nellix system was approved by the Trust Standards and Guidelines Committee. All cases were deemed not suitable for conventional endovascular aneurysm repair and judged suitable for EVAS by the product specialists as per the 2013 instructions for use criteria. Results: Up to April 2019, 17/27 patients had died. Three with confirmed ruptured AAA within an average of 1.8 years. The others were non-AAA related deaths. Four of 27 (14.8%) patients had a type I endoleak on first surveillance imaging, increasing to 10/27(37%) patients on follow up imaging. One out of 27 (3.7%) developed sac expansion. Of the 10 surviving patients, seven have an aneurysm related complication (six endoleaks and one sac expansion). One patient went on to rupture with successful conversion to open repair. Three patients were deemed not suitable or declined further intervention. The remainder of surviving patients will continue on yearly surveillance or await clinical review. Conclusion: The Nellix system is associated with unacceptably high morbidity and mortality rates in this specific cohort. While new technology is essential to progressing healthcare, specialised consent and stringent surveillance strategies are required when adopting new techniques.

Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

&lt;p&gt;Awareness of Physicians in Yemen Toward High Blood Pressure Management According to the Eighth Joint National Committee (JNC 8) Guideline&lt;/p&gt;

BackgroundHypertension is a common public health problem that impacts more than one-third of the world population. Awareness of physicians towards the guidelines of high blood pressure management is an essential step to reduce the consequences of high blood pressure.ObjectiveThis study was aimed to assess the awareness of physicians towards high blood pressure treatment according to the recent report of the Joint National Committee (JNC8) guideline.MethodsA self-administered questionnaire was distributed to 400 physicians during the period from February to April 2017. Physicians were recruited from public and private hospitals as well as clinics. A validated questionnaire that incorporated the changes seen in JNC 8, as well as the specific modality of hypertension management based on other guidelines, was administered to the participating physicians.ResultsThree hundred and eighty-nine physicians completed the questionnaire; with all the interviewed physicians have ever heard about JNC 8. The practice of general practitioners (GPs) was significantly deviated from the recommended guideline of blood pressure management as compared to consultants, specialists, and residents. Additionally, certain variations were found among consultants, specialists, and residents with slight superiority of consultants towards most aspects.ConclusionThe finding of this study highlights an inadequate knowledge of GPs in Yemen towards high blood pressure management guidelines. The findings of this study emphasize the necessity for continuous medical education programs that are specially designed to target GPs. Continued update of medical curricula in Yemeni universities is also needed.

Guidelines for human gene nomenclature.

Standardized gene naming is crucial for effective communication about genes, and as genomics becomes increasingly important in healthcare, the need for a consistent language for human genes becomes ever more vital. Here we present the current HUGO Gene Nomenclature Committee (HGNC) guidelines for naming not only protein-coding but also RNA genes and pseudogenes, and outline the changes in approach and ethos that have resulted from the discoveries of the last few decades.

Editorial introductions

Editorial introductions

AGA Institute Rapid Review and Recommendations on the Role of Pre-Procedure SARS-CoV-2 Testing and Endoscopy

AGA Institute Rapid Review and Recommendations on the Role of Pre-Procedure SARS-CoV-2 Testing and Endoscopy

Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima Prefecture: the Fukushima Health Management Survey

AimAfter the Great East Japan Earthquake, over 160,000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima.MethodsWe conducted a cohort study of residents aged 40–90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption.ResultsIncidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03–1.86).ConclusionThis is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia.

Effectiveness of doxorubicin-based and liposomal doxorubicin chemotherapies for patients with extra-abdominal desmoid-type fibromatosis: a systematic review.

The treatment modality for desmoid-type fibromatosis has shifted from surgery to conservative treatment. The guideline committee for clinical care of extra-abdominal desmoid-type fibromatosis in Japan conducted a systematic review of treatment with doxorubicin-based chemotherapy for desmoid-type fibromatosis. We searched the pertinent literature. Two reviewers evaluated and screened it independently for eligibility and extracted data. They rated each report according to the grading of recommendations development and evaluation methodology. Based on the 'body of evidence', which the reviewers created, the clinical guideline committee decided a recommendation for the clinical question, 'Is doxorubicin-based chemotherapy effective for patients with extra-abdominal desmoid-type fibromatosis?' Fifty-three articles were extracted by the literature search, and one from hand search. After the first and second screenings, five articles were subjected to the final evaluation. There were no randomized controlled trials. According to response evaluation criteria in solid tumors criteria, the response rates of doxorubicin-based regimens and liposomal doxorubicin were 44% (28.6-54) and 33.3% (0-75) on average, respectively. In two reports, the response rates of doxorubicin-based regimens were higher than those of non-doxorubicin-based ones; 54% vs 12%, 40% vs 11%, respectively. The rates of G3 or G4 complications according to common terminology criteria for adverse events were 28% and 13% with doxorubicin-based and liposomal doxorubicin chemotherapy, respectively, including neutropenia or cardiac dysfunction. None of the reports addressed the issue of QOL. Although the evidence level was low in the evaluated studies, doxorubicin-based and liposomal doxorubicin chemotherapy was observed to be effective. However, doxorubicin-based chemotherapy is associated with non-ignorable adverse events, and is not covered by insurance in Japan. We weakly recommend doxorubicin-based chemotherapy for patients with extra-abdominal desmoid-type fibromatosis in cases resistant to other treatments.