The SCARE Statement: Consensus-based surgical case report guidelines

A protocol for the development of reporting criteria for surgical case reports: The SCARE statement

Preferred reporting of case series in surgery; the PROCESS guidelines

INTRODUCTION Artificial intelligence (AI) is rapidly transforming healthcare and scientific publishing. Reporting guidelines need to be updated to consider this advance.The SCARE Guideline 2025 update introduces a new AI-focused domain to promote transparency, reproducibility, and ethical integrity in surgical case reports (SCAREs) involving AI. METHODS A Delphi consensus exercise was conducted to update the SCARE guidelines. A panel of 49 surgical and scientific experts was invited to rate proposed new items. In round 1, participants scored each item on a nine-point Likert scale and provided feedback. Items not meeting consensus were revised or discarded. RESULTS A 94% response rate occurred amongst participants (46/49) in the first round. Ratings were analyzed for agreement levels, and consensus was reached on all six proposed AI-related items. A revised SCARE checklist is presented, which incorporates these new AI-related items. Authors are now expected to disclose AI involvement in patient care and manuscript preparation, as exemplified by this article. CONCLUSION The SCARE 2025 guideline provides an up-to-date framework for SCAREs in the era of AI. Through a robust consensus process, we have added specific reporting criteria for AI to ensure that any use of AI in a case report is documented, explained, and discussed concerning bias and ethics. This update will help maintain the quality, transparency, and clinical relevance of case reports, ultimately improving their educational value and trustworthiness for the surgical community.

Lack of Uniformity in Levels of Evidence and Recommendation Grades in Surgical Oncology Guidelines

"Closing the chasm" - guidelines bridge the gap from evidence to implementation.

Methods and Results Report - Evidence and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis -International League of Dermatological Societies in cooperation with the European Dermatology Forum.

The purpose of this study was to assess the quality of the case reports in the Journal of Acupuncture Research (JAR). All case reports were retrieved from November 2017 to June 2020. There were 19 case reports included in this assessment based on the case report (CARE) guidelines and case report and standards for reporting interventions in clinical trials of acupuncture (STRICTA) guidelines. The overall quality of reporting was relatively high (83.08% on Case Report guidelines and 77.78% on Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines), but several crucial items remained substantially underreported, such as identifying as a case report (keywords), patient information and perspective, clinical findings, diagnostic assessment, and intervention information. In 18 out of 19 included case reports of acupuncturerelated interventions, several items remained considerably underreported such as acupuncture regimen variation, depth of needle insertion, response sought, and experience of acupuncturists. In the classification by disease, condition, or syndrome, 13 out of 19 included case reports were for musculoskeletal disorders (68.4%), which is the main clinical medical field of Korean medicine services. The results of this study may help develop more appropriate reporting guidelines for case reports published in JAR.

It gives us great pleasure to announce the launch of our new journal, Surgical Case Reports: an international peer-reviewed open-access journal, published online by the Japan Surgical Society, in partnership with Springer. This new journal is devoted to original case reports and letters to the editor. Surgical techniques and perioperative management have advanced rapidly and become more specialized. For example, the archive of robotic surgery is representative of the progress of this exciting breakthrough, which has gained widespread popularity over the last decade. In addition, translational research has come to be a critical and core component of full-spectrum biomedical research and is becoming more important in all medical fields. Large studies on these aspects of surgery, as well as randomized control trials (RCTs) and meta-analyses have provided critical evidence. The guidelines and general rules for the diagnosis and management of various diseases such as malignancy are generally established based on this evidence. However, surgeons are encouraged to report very rare cases, unanticipated surgical complications, or adverse events and explain how they used their resources to resolve them. Surgeons also often report on innovative new ideas to improve procedures in their specialty. Thus, an excellent case report can provide important detailed information about an individual case, which would be lost in an RCT or large study [1]. From case reports, readers can acquire early warning of the adverse effects of new medications or the rare presentations of new and emerging diseases. Whereas much medical and surgical literature includes case reports, these articles are underrepresented in those journals and journals that do publish valuable case reports specifically are very limited. Surgical Case Reports fills this void. This exciting new journal is dedicated to the publication of high-quality case reports and aims to expand current knowledge in all surgical fields. Since 1992, the Japan Surgical Society has been publishing Surgery Today as its official journal. Surgery Today is a monthly journal, with an archive of 44 volumes to date. Because Surgery Today is published in English and documents the latest progress in all surgical fields, articles in this journal have been widely indexed. The number of submissions to Surgery Today has increased steadily to more than 1,200 per year; however, as the number of pages is limited, so is the number of papers that can be published after careful peer review. Until now, Surgery Today has included original articles, review articles, short communications, ‘how-to-do-it’ papers, letters to the editor, and case reports. It has been decided that the focus of Surgery Today will be original articles, so that more papers documenting recent surgical progress can be communicated to the world in a timely manner. Hence, we decided to establish a new journal: Surgical Case Reports [2]. The purpose of this journal is to contribute to the progress of surgery by providing clinicians and researchers with an educational forum. This journal will disseminate each contributor's personal experience and novel treatments to a wide readership and share interesting rare cases encountered by colleagues all over the world. Surgical Case Reports welcomes well-described reports of cases, which include the following: ✓ New associations or variations in disease processes. ✓ Presentations, diagnoses, and/or management of new and emerging diseases. ✓ Unreported or unusual side effects or adverse interactions involving medications. ✓ Unexpected or unusual presentations of a disease. ✓ An unexpected association between diseases or symptoms. ✓ An unexpected event in the course of observing or treating a patient. ✓ Findings that shed new light on the possible pathogenesis of a disease or an adverse effect. ✓ Movies of the author's surgical teaching or technical development. Surgical Case Reports also invites letters to the editor, which generally take one of the following forms: ✓ A substantial re-analysis of a previously published article in Surgical Case Reports or another journal. ✓ An article that may not cover ‘standard research,’ but is of general interest to the broad readership of Surgical Case Reports. ✓ A brief report of research findings adequate for the journal's scope and of particular interest to the community. All manuscripts submitted to Surgical Case Reports will be subject to immediate screening by the in-house editorial team and selected manuscripts will be sent for peer review. Accepted articles will be published online and indexed in PubMed. Open-access is a modern system of publication, which provides a valuable opportunity for both readers and authors to expose and share the publications. Based on this new form of publication, we anticipate that Surgical Case Reports will become a useful interdisciplinary journal. We hope that we have aroused your interest and that you will support this exciting new journal by submitting your next case report to Surgical Case Reports.

ObjectiveTo systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).DesignUmbrella review.Data sourcesPubMed, PsychInfo, Embase,...

Recent changes to the commissioned regimens and the COVID-19 pandemic necessitate an update of the 2018 British Society of Haematology guidance on chronic lymphocytic leukaemia (CLL).1 Here we discuss: (1) considerations prior to treatment; (2) front-line treatment recommendations; (3) management of relapsed or refractory disease; (4) management of intolerance to Bruton tyrosine kinase inhibitors (BTKi); and (5) guidance for vaccinations and prophylaxis. We focus particularly on therapies approved for use in the UK at the time of writing. Guidance on initial approach to patient management, indications for treatment, molecular assessment prior to treatment, assessment of response to treatment, supportive care, and autoimmune cytopenia remain unchanged. In addition to this CLL treatment update, we have published recent guidance on management of cardiovascular complications secondary to treatment with BTKi2 and Good Practice Guidance on the management of Richter transformation (RT) of CLL.3 These guidelines were compiled according to the BSH process (https://b-s-h.org.uk/media/16732/bsh-guidance-development-process-dec-5-18.pdf). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. Recommendations are based on a review of the literature using Medline/Pubmed. Search terms included; CLL treatment, randomised, clinical trial, FCR, TP53 disruption, Bruton tyrosine kinase inhibitor, BCL2 inhibitor, rituximab, obinutuzumab, vaccination, Covid19. The search was limited to English-language publications and conference abstracts from the date of publication of the previous CLL guideline in 2018 to July 2021. Titles/abstracts obtained were curated and manually reviewed by the writing group who conducted additional searches, using subsection heading terms. Review of the manuscript was performed by the BSH Guidelines Committee Haemato-Oncology Task Force, the BSH Guidelines Committee and the Haemato-Oncology sounding board of the BSH. It was also posted on the members section of the BSH website for comment. This guideline has also been reviewed by patient representatives from the UK CLL Support Association (https://www.cllsupport.org.uk) and Leukaemia Care (https://www.leukaemiacare.org.uk). Choosing the optimal therapy for a patient with CLL requires consideration of both patient-related factors (such as comorbidities, concomitant medication, patient preference) and disease-related factors (prognostic and predictive). In addition, previous responses and toxicities from prior therapies and the impact of treatment on cellular and humoral immunity will also influence therapy choices. The availability of targeted agents provides effective therapy for older patients for whom palliative chemoimmunotherapy was previously the only option. However, differences in the side effect profiles of first- and second-generation BTKi and B-cell lymphoma-2 inhibitors (BCL2i), phosphoinositide 3-kinase inhibitors (PI3Ki), and the option of fixed-duration venetoclax-including regimens versus continuous BTKi therapy all impact on the choice of therapy for individual patients. Screening for TP53 disruption (i.e. del 17p13.1 and/or TP53 mutation) prior to each line of treatment is recommended as patients with these genetic abnormalities remain a high-risk group, even in the era of targeted therapy. IGHV gene mutation analysis should be performed to identify a subgroup of patients who often fare particularly well and may be functionally cured with fludarabine, cyclophosphamide and rituximab (FCR) (fit, younger patients) and have excellent, durable responses with 12 months' fixed-duration venetoclax–obinutuzumab (VenO) (older patients). Since the last BSH CLL guidelines were published in 2018, targeted pathway inhibitors have challenged the role of chemoimmunotherapy (CIT) and represent a paradigm shift in front-line treatment. Criteria for initiating treatment remain as defined by the iwCLL.4 Given the natural CLL age distribution, the majority of patients fall into the category of 'less fit', with almost 90% having comorbidities.5 Prior to the approval of targeted agents, the German CLL Study Group (DCLLSG) CLL11 trial established chlorambucil with obinutuzumab (CO) as an international standard of care for this patient cohort.6 Three major randomised clinical trials in unfit patients7-9 have since shown an improved progression-free survival (PFS) with targeted inhibitors using either a BTKi or BCL2i in combination with obinutuzumab, compared to CO (Table 1), but no overall survival benefit to date. Ibrutinib Chlorambucil 73 72 136 133 92/30 37 NR (78% 6.5 years) NR (68% 5 years) – – Ibrutinib: Hypertension (26%) AF (16%) Major haemorrhage (11%) Ibrutinib Ibrutinib-Rituximab Bendamustine-Rituximab 71 71 70 182 183 183 93 94 81 NR (87% 2 years) NR (88% 2 years) NR (74% 2 years) 0.38 (0.250–0.59) IR vs BR 1.00 (0.62–1.62) I vs IR NR (90% 2 years) NR (94% 2 years) NR (95% 2 years) – – – 1 4 8 ≥G3 neutropenia-I (15%), IR (21%), BR (40%) AF-I (9%), IR (6%), BR (3%) Hypertension >G3-I (29%), IR (34%), BR (15%) Ibrutinib-obinutuzumab Chlorambucil-obinutuzumab 70 72 113 116 88 73 NR (76% 36 m) 22 m 0.251 (0.160–0.395) NR (86% 40 m) NR (85% 30 m) – – 35 25 Acalabrutinib Acalabrutinib-obinutuzumab Chlorambucil-obinutuzumab 70 70 71 179 179 177 86 94 79 NR (78% 4 years) NR (87% 4 years) 27.8 m – – – NR (88% 4 years) NR (93% 4 years) NR (88% 4 years) – – – – – – AF-A (4%), AO (3%), CO (1%) Hypertension ≥G3 A (2%), AO (3%), CO (3%) Bleeding >G3 A & AO (2%) Venetoclax-obinutuzumab Chlorambucil-obinutuzumab 72 72 216 216 85 71 NR (74% 4 years) 36.4 m NR (85.3% 4 years) NR (83.1% 4 years) 76 35 ECOG-ACRIN E1912 Ibrutinib-rituximab FCR 56.7 56.7 354 175 96 81 NR (89% 3 years) NR (73% 3 years) NR (99% 3 years) NR (92% 3 years) 8 59 Neutropenia ≥G3 IR (25.6), FCR (44.9%) AF-IR (7.4%), FCR (3.2%) Ibrutinib was the first-in-class BTKi to be licensed in CLL. The phase 3 RESONATE-2 study compared indefinite ibrutinib with ≤12 cycles of chlorambucil in untreated patients over 65 years old without del17p13.1.10 After seven years of follow-up, the ibrutinib arm displayed superior survival: PFS 61% vs 9%, and overall survival (OS) at five years of 83% vs 68% (78% of ibrutinib-treated patients were estimated to be alive at 6.5 years). Ibrutinib was well tolerated in this older population with 47% of patients remaining on treatment at this timepoint. Continued ibrutinib also improved depth of response with complete remission/complete remission with incomplete count recovery (CR/CRi) increasing from 11% at 18 months to 34% after a median follow-up of seven years.11, 12 The ALLIANCE A041707 study demonstrated an improved two-year PFS for ibrutinib with or without rituximab, compared to bendamustine–rituximab (87% vs 88% vs 74%, hazard ratio [HR] 0.38; 95% confidence interval [CI] 0.25–0.59).13 Notably, there was no additional benefit in adding rituximab to ibrutinib. Most common/clinically relevant adverse events (AEs) are included in Table 1. In the ELEVATE-TN study, acalabrutinib, the second-generation BTKi, in combination with obinutuzumab or as monotherapy improved the four-year PFS compared to chlorambucil–obinutuzumab (87% vs 78% vs 25%). An ad hoc analysis showed the addition of obinutuzumab to acalabrutinib improved PFS, but at the expense of an increased rate of ≥grade 3 infection (23.6% vs 16.2%, compared with 8.3% with chlorambucil–obinutuzumab), neutropenia rate (30.9% vs 11.2% vs 41.4%), and infusion-related reactions (2.8% vs 0 vs 5.9%)14 (see Table 1 for more information on AEs). The DCLLSG CLL14 study, which compared venetoclax in combination with obinutuzumab (VenO) to CO, showed improved four-year PFS (74% vs 35%).15 The improved PFS of CO, compared to that in the CLL11 study,6 is possibly explained by longer chlorambucil treatment (12 vs 6 cycles). VenO has some potential advantages over BTKi combinations, offering a fixed-duration treatment of one year, and high rates of minimal residual disease (MRD)-negative (<10−4) response (75.5% MRD-negative in peripheral blood and 56.9% in bone marrow). Additionally, there was a significantly lower incidence of subsequent clonal evolution than in the CO arm. Specific mutations associated with venetoclax resistance were not detected, such as mutations in BCL2, BIM, BAX, BCL-XL and MCL1). Grade ≥3 neutropenia occurred in 52.8% of VenO-treated patients, but precautions (use of adequate prophylaxis, initial debulking with obinutuzumab, and the well-established weekly venetoclax ramp-up dosing schedule) resulted in significant reduction of tumour lysis syndrome (TLS). FCR was previously the standard of care for front-line treatment of fit patients with CLL and intact TP53. The phase 3 ECOG-ACRIN 1912 trial randomised patients to receive either ibrutinib and rituximab (IR) for six cycles, followed by ibrutinib until disease progression or unacceptable toxicity, or six cycles of FCR.16 The IR cohort had a superior survival compared to FCR (three-year PFS 89.4% vs 72.9%, HR 0.35; 95% CI 0.22–0.56, with three-year OS 98.8% vs 91.5% HR 0.17; 95% CI 0.05–0.54). A subgroup analysis of patients with unmutated IGHV showed a PFS of 90.7% vs 62.5% at three years in favour of IR; whereas among those with mutated IGHV, PFS was comparable (87.7% vs 88.0%). The overall incidence of grade ≥3 AEs was similar; however, grade ≥3 infections were less common (10.5% vs 20.3%) in the IR group. Acalabrutinib Investigator's choice (BR/IdelaR) 68 67 155 155 81/0 76/2 NR (88% 1 year) 16.5 (68% 1 year) NR (90% 1 year) NR (88% 1 year) N/A N/A MURANO (Seymour et al.35) (Kater et al.37) VenR BR 64 66 194 195 92.3/26.8a 72.3/8.2a 53.6 17 NR (82% 5 years) NR (62% 5 years) X°62.4 13.3 Ibrutinib Ofatumumab 67 71 195 196 44.1 8.1 67.7 65.2 N/A N/A GS-US-312-0116 (Furman et al.31) (Sharman et al.82) IdelaR Rituximab 71 71 110 110 85.5/0 17/0 19.4 6.5 40.6 34.6 N/A N/A Among patients with mutated IGHV who receive front-line FCR and obtain a MRD-negative remission, extremely durable responses can be achieved leading to 'functional cure' in about 50% of patients with mutated IGHV,17 while the very long-term durability of responses to targeted inhibitors is as yet unknown. FCR therefore remains a viable option for fit, younger patients with mutated IGHV and intact TP53. However, this indication for FCR may change once longer-term follow-up data exist for the targeted inhibitors. Currently, front-line BTKi with ibrutinib or acalabrutinib does not have NICE approval for use in fit, younger patients without TP53 disruption, although the E1912 study showed an OS advantage of ibrutinib compared to FCR in this patient group. Prospective data from a phase 1b study of 32 patients indicates that VenO may be equally effective in fit patients.18 NICE TA633 permits use, via the Cancer Drugs Fund (CDF) in England and Northern Ireland, and through a different funding stream in Wales, of up-front VenO for fit patients lacking TP53 disruption, while more data are collected in this group. NICE-approved front-line treatment options for all patients with CLL and TP53 disruption include VenO, ibrutinib, acalabrutinib and venetoclax monotherapy where BTKi is contra-indicated (Figure 1). A growing body of evidence suggests that BTKi and BCL2i with or without anti-CD20 antibodies are highly effective front-line combination treatment. The phase 2 CAPTIVATE19 trial of venetoclax combined with ibrutinib (VI) in previously untreated CLL, included patients who were fit, under 65 years, but had at least one of: del(17p), TP53 mutation, del(11q) or unmutated IGHV. After 12 cycles of combined treatment, 88% of patients had CR/CRi, and 61% were MRD-negative in bone marrow, leading to FDA approval. The most common grade 3/4 AE across cohorts was neutropenia.20 In the less fit populations (over 65 years old or younger patients with a cumulative illness rating scale (CIRS) score of >6 or creatinine clearance <70 ml/min) efficacy and safety of fixed-duration VI is being evaluated in a phase 3 trial, GLOW. Improved PFS with VI (76% at 27.7 months) compared with CO (29%) (HR for progression or death 0.216; 95% CI 0.131–0.357) was consistent across predefined subgroups, including patients with unmutated IGHV. High-risk patients with known TP53 disruption were excluded. Undetectable bone-marrow (BM) MRD rates by next-generation sequencing (NGS) were significantly higher for VI at three months after the end of treatment compared with CO (51.9% vs 17.1% respectively, p = 0.0259). The most common grade 3/4 AE in both treatment groups was neutropenia (VI 34.9% vs CO 49.5%), infections (17% vs 11.4%), and diarrhoea (10.4% vs 1%); 22.6% participants discontinued VI.21 The relatively high incidence of early treatment-related mortality in VI patients compared with the control arm and VI patients in the CAPTIVATE trial suggests this combination should be used with caution in older/more comorbid patients and should be limited to fit patients with high-risk CLL. The pivotal studies described above have demonstrated superior long-term efficacy and tolerability of targeted therapy over CIT in the front-line setting for patients over 65 or with CIRS scores of >6. As result, both continuous therapy with acalabrutinib monotherapy and 12 months' fixed-duration VenO are now NICE-approved in the UK. The decision on which regimen to choose has to be based on a number of different factors including CLL-specific risk factors, past medical history, concomitant medication and patients' choice. Front-line ibrutinib monotherapy is NICE-approved and funded in the UK for patients with TP53 disruption but not routinely for all other front-line patients at the time of writing. There is no evidence directly comparing targeted agents in TP53 aberrant to recommend one over the other. Long-term follow-up of CLL14 shows that the small proportion of patients with TP53 disruption have a shorter PFS compared to those with wild-type (WT) TP53 following fixed-duration VenO. A similar patient population receiving continuous ibrutinib plus obinutuzumab in the Illuminate trial had a PFS of 72% at 36 months (HR 0.162; 95% CI 0.096–0.275).22 There is long-term benefit with ibrutinib monotherapy despite lack of undetectable MRD: Ahn et al. reported a six-year PFS in CLL patients with TP53 aberrations of 61% (95% CI 46–80) and an OS of 79% (95% CI 67–94).23 Zanubrutinib, a selective, second-generation covalent BTK inhibitor, had been tested in 109 TP53-deleted naïve patients with overall response rates of 94.5%, 18-months PFS of 88.6% (95% CI, 79.0–94.0) and an OS of 95.1% (95% CI, 88.4–98).24 With respect to IGHV mutational status, ibrutinib and acalabrutinib with or without anti-CD20 showed broadly equal responses for IGHV-mutated and unmutated patients,7, 13, 16 whereas IGHV-unmutated patients have an inferior PFS compared to those with mutated IGHV following VenO in CLL14.9 Whether IGHV status should be used to determine use of BTKi- or BCL2i-based treatment remains unclear. Longer-term sequencing studies may provide further guidance in this area in the future. Impact of past medical history such as cardiovascular comorbidities, use of anticoagulation, and bleeding risk on choice of front-line therapy is covered by related guidance.2 Here, the use of a more selective BTKi, such as acalabrutinib, with fewer cardiovascular side effects may be preferable.25 Alternatively, a combination is a for this patient group. with a history of disease should be obinutuzumab also treatment with BCL2 inhibitors requires adequate and patients with clearance and ml/min) should only be for venetoclax benefit with for the increased risk of for patients with high tumour and/or chronic BTKi may be a option. on the of treatment, medication should be with to or inhibitors which should be or by other of for all targeted inhibitors is are with and inhibitors. to the of for guidance on management of therapy to the BSH on management of cardiovascular complications of Bruton tyrosine kinase A of the and of fixed-duration therapy and continuous therapy should patient age patients, fixed-duration treatment may be and the effect of treatment on of should be In addition, the long-term of secondary should be with younger patients with mutated IGHV, CLL where FCR is being and side effects is treatment but is particularly relevant in the months following of a data demonstrated a rate of ibrutinib with subsequent also a rate of at 17 Acalabrutinib rates were for acalabrutinib with obinutuzumab and for acalabrutinib Most side effects with time with the of and The licensed therapies in relapsed CLL are BTKi and BCL2i monotherapy or in combination with and phosphoinositide 3-kinase inhibitors and After one or cycles of and BCL2 or in combination with anti-CD20 standard treatment options for relapsed CLL, of or of TP53 randomised evidence has compared BTKi versus in CLL after are into patient and There are also data on the sequencing patients following targeted agents (Table a patient is on a targeted treatment should be for as as the patient clinical benefit until the subsequent targeted therapy is as there is a risk of progression once therapy is Acalabrutinib monotherapy demonstrated benefit in relapsed CLL over choice or in the With a median follow-up of patients with acalabrutinib showed an overall response rate of and a PFS of 88% compared to 68% on the choice. Acalabrutinib also improved PFS in and unmutated IGHV There were no safety for acalabrutinib and the rate of to AEs was fixed-duration venetoclax and rituximab for CLL demonstrated PFS and OS benefit compared to BR in MURANO with a four-year PFS of and (HR 95% CI A proportion of patients peripheral blood MRD at the end of treatment vs 37 patients had previously been to VenR was in unmutated IGHV patients and in those with TP53 Ibrutinib showed superior efficacy in CLL compared to in follow-up demonstrated an of and a rate of of therapy was months with on ibrutinib at study PFS was 44.1 months for the ibrutinib arm and 8.1 months for the arm. and were in and In a phase 3 trial of patients unfit for standard IdelaR demonstrated an of a PFS of 19.4 months and an OS of 40.6 months compared to rituximab The IdelaR subgroup of showed a similar median PFS of However, IdelaR remains a less used treatment option to and data exist to the sequencing of targeted with pivotal randomised trials performed in targeted patients after A phase 2 35 of venetoclax monotherapy in patients an of and a progression-free survival of patients who prior showed an of and a estimated PFS of patients demonstrated an of 50% and a of monotherapy is further by studies provide evidence for sequencing with Recent evidence suggests that BTKi provide high in patients including those previously to and more than in this monotherapy is licensed for relapsed CLL patients who have or are for monotherapy remains a option for following venetoclax evidence for this approach remains 1). The BTKi has efficacy in patients to both covalent BTKi and but is not yet approved in The majority of data on BTKi intolerance from of with ibrutinib and small clinical demonstrated that acalabrutinib is effective in patients ibrutinib to A phase 2 trial of found an of and a two-year PFS of AEs were diarrhoea and Prospective trial data that long-term are for patients who a BTKi for intolerance than but there are no data on responses to subsequent In subgroup 95% CI of 30 patients who had discontinued ibrutinib therapy of AEs had an overall response with compared with 95% CI of patients who had discontinued ibrutinib of disease of acalabrutinib and ibrutinib showed that acalabrutinib is tolerated with similar efficacy to ibrutinib in previously patients, but has lower of common AEs and treatment In cardiovascular events were less A phase 2 trial has demonstrated that the selective is and effective in BTKi and British Society of and and indications for in CLL remain as defined in This therapy to be an option for patients with high-risk such as TP53 disruption and treatment The decision to patients with high-risk disease should be based on remission status, patient status, and patient status and availability of Given the evolution of targeted treatment options the of treatment that indicates remains unclear. the time of patients who are refractory to CIT and/or TP53 disruption, and following at least one targeted should be targeted inhibitors not to impact the safety of and survival are similar of number of agents prior chemoimmunotherapy or targeted inhibitors prior to therapies to are including therapy which has been evaluated in clinical trials the last years following initial reported in A of and with ibrutinib have been or are in phase 1 and 2 response rates of to 95% of patients have been with rates of to in patients. These may be to of has also limited the use of to the of patients with CLL who not have Long-term follow-up data are lacking and such treatment remains an option only through clinical It is of that a number of trials of cellular licensed for other B-cell have either been using or are not using remains a very of CLL for which therapy may have a the management of to the recent BSH is a treatment option for patients with high-risk CLL defined by A of CLL is by responses to vaccination, including and We patients to a (see the is followed at least months by the response to should be in those with a history of or The is and should not be should with who have the for seven The is for patients with and is in the UK for those years of age should be for all patients with a history of or Most patients with disease from secondary patients BTKi is recommended either therapy or for at least the 12 months the risk of infection to be patients on fixed-duration regimen may be for at least six months after the end of treatment or until from the and on in patients with BTKi in a front-line setting and use of is We recommend for the of BTKi therapy in those on combination therapy or for patients with significant and a history of or of infection are and limited to those with is not routinely recommended with BTKi or BCL2i to potential There are of infections on patients receiving BTKi and the and of with targeted therapy should be each other on the individual risk is a common in patients with therapy is for patients (1) or infections despite six months of continuous (2) have a and (3) have to to of therapy that can be may be more for patients and can be used as an to A of is recommended with according to the In a small the resulted in higher levels and patient of improved in to In addition, a reduction in the number of AEs were with This information on to for the information found The COVID-19 pandemic has for patients with CLL and It is that the secondary associated with CLL a higher risk of COVID-19 disease but no data exist to the risk compared with An early the of COVID-19 in patients with CLL was similar to that in the population but associated with a high mortality rate in those with infection to be and rates were similar patients and those on including those on In a where CLL patients were for COVID-19 infection the mortality was lower but this included a number of who have from COVID-19 infection have lower rates in without and this is most in those with The of to patients with CLL by the COVID-19 is lower than that of An initial study from found responses to the COVID-19 of compared with for The response rate for untreated patients was compared with in those on BTKi therapy. patient 12 months of anti-CD20 therapy a response to The UK study patients who had either the and vaccination, with an interval the Here, an response rate of was compared to in This increased to 79% those on and response rates were in those on BTKi therapy or with Notably, the which was in the UK at the time of study, were compared to a further in those with The of from COVID-19 disease with levels remains unknown. response to COVID-19 is and cellular which are to in However, recent that cellular responses to are also in CLL compared to and compared to rates and to with subsequent of should be recommended to all patients and particularly for those to the inferior response rates patients with CLL, a followed at least three months by a is now patients who COVID-19 treatment options have been and are now for patients with CLL in the has been shown to the risk of and death in high-risk patients by to is to patients who for infection and have the last five are for use as a treatment option. an is associated with a reduction in the risk of or and is with the criteria and where of therapy is not or contra-indicated CLL Support Association Leukaemia Care and other groups provide to CLL patients. After of and initial we recommend that patients are to these and also of the where can receive on a treatment patients should be using the or to the writing of the The to members of the UK CLL for and review of the to to Richter and who reviewed the and to the members of the BSH The BSH the the writing of this have a of to the BSH and Task which may be on The is not for the or of information by the than should be to the for the

Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged length of hospital stay and increased healthcare costs in critically ill patients. Guidelines recommend a semi-recumbent position (30º to 45º) for preventing VAP among patients requiring mechanical ventilation. However, due to methodological limitations in existing systematic reviews, uncertainty remains regarding the benefits and harms of the semi-recumbent position for preventing VAP. To assess the effectiveness and safety of semi-recumbent positioning versus supine positioning to prevent ventilator-associated pneumonia (VAP) in adults requiring mechanical ventilation. We searched CENTRAL (2015, Issue 10), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and the Chinese Biomedical Literature Database (CBM) (1978 to October 2015). We included randomised controlled trials (RCTs) comparing semi-recumbent versus supine positioning (0º to 10º), or RCTs comparing alternative degrees of positioning in mechanically ventilated patients. Our outcomes included clinically suspected VAP, microbiologically confirmed VAP, intensive care unit (ICU) mortality, hospital mortality, length of ICU stay, length of hospital stay, duration of ventilation, antibiotic use and any adverse events. Two review authors independently and in duplicate screened titles, abstracts and full texts, assessed risk of bias and extracted data using standardised forms. We calculated the mean difference (MD) and 95% confidence interval (95% CI) for continuous data and the risk ratio (RR) and 95% CI for binary data. We performed meta-analysis using the random-effects model. We used the grading of recommendations, assessment, development and evaluation (GRADE) approach to grade the quality of evidence. We included 10 trials involving 878 participants, among which 28 participants in two trials did not provide complete data due to loss to follow-up. We judged all trials to be at high risk of bias. Semi-recumbent position (30º to 60º) versus supine position (0° to 10°) A semi-recumbent position (30º to 60º) significantly reduced the risk of clinically suspected VAP compared to a 0º to 10º supine position (eight trials, 759 participants, 14.3% versus 40.2%, RR 0.36; 95% CI 0.25 to 0.50; risk difference (RD) 25.7%; 95% CI 20.1% to 30.1%; GRADE: moderate quality evidence).There was no significant difference between the two positions in the following outcomes: microbiologically confirmed VAP (three trials, 419 participants, 12.6% versus 31.6%, RR 0.44; 95% CI 0.11 to 1.77; GRADE: very low quality evidence), ICU mortality (two trials, 307 participants, 29.8% versus 34.3%, RR 0.87; 95% CI 0.59 to 1.27; GRADE: low quality evidence), hospital mortality (three trials, 346 participants, 23.8% versus 27.6%, RR 0.84; 95% CI 0.59 to 1.20; GRADE: low quality evidence), length of ICU stay (three trials, 346 participants, MD -1.64 days; 95% CI -4.41 to 1.14 days; GRADE moderate quality evidence), length of hospital stay (two trials, 260 participants, MD -9.47 days; 95% CI -34.21 to 15.27 days; GRADE: very low quality evidence), duration of ventilation (four trials, 458 participants, MD -3.35 days; 95% CI -7.80 to 1.09 days), antibiotic use (three trials, 284 participants, 84.8% versus 84.2%, RR 1.00; 95% CI 0.97 to 1.03) and pressure ulcers (one trial, 221 participants, 28% versus 30%, RR 0.91; 95% CI 0.60 to 1.38; GRADE: low quality evidence). No other adverse events were reported. Semi-recumbent position (45°) versus 25° to 30° We found no statistically significant differences in the following prespecified outcomes: clinically suspected VAP (two trials, 91 participants, RR 0.74; 95% CI 0.35 to 1.56; GRADE: very low quality evidence), microbiologically confirmed VAP (one trial, 30 participants, RR 0.61; 95% CI 0.20 to 1.84: GRADE: very low quality evidence), ICU mortality (one trial, 30 participants, RR 0.57; 95% CI 0.15 to 2.13; GRADE: very low quality evidence), hospital mortality (two trials, 91 participants, RR 1.00; 95% CI 0.38 to 2.65; GRADE: very low quality evidence), length of ICU stay (one trial, 30 participants, MD 1.6 days; 95% CI -0.88 to 4.08 days; GRADE: very low quality evidence) and antibiotic use (two trials, 91 participants, RR 1.11; 95% CI 0.84 to 1.47). No adverse events were reported. A semi-recumbent position (≧ 30º) may reduce clinically suspected VAP compared to a 0° to 10° supine position. However, the evidence is seriously limited with a high risk of bias. No adequate evidence is available to draw any definitive conclusion on other outcomes and the comparison of alternative semi-recumbent positions. Adverse events, particularly venous thromboembolism, were under-reported.

The SCARE 2018 statement: Updating consensus Surgical CAse REport (SCARE) guidelines

GRADE (Grading of Recommendations, Assessment, Development and Evaluation) is awidely used approach in the fields of medicine and public health to assess the outcome-specific certainty of the evidence in systematic reviews. To make the GRADE approach comprehensible in order to facilitate the reading, understanding and interpretation of GRADE assessments in systematic reviews. Presentation of the procedure of the GRADE approach using the example of aCochrane review on selenium supplements in the prevention of prostate cancer. GRADE provides criteria for rating the certainty of evidence. GRADE's approach to rating the certainty of the evidence is based on afour-level system (high, moderate, low, very low). The GRADE approach classifies bodies of randomized controlled trials as initially starting at high certainty and bodies of observational studies at initially starting at low certainty. By assessing the five domains (risk for bias, inconsistency, indirectness, insufficient precision and publication bias), certainty can be rated down or, in the case of large effects, existing dose-response relationships or plausible confounders, rated up. GRADE is aconsistent and transparent approach for rating the certainty of abody of evidence by offering explicit key questions.

Experiences and challenges faced by systematic review authors in using the GRADE approach: a qualitative study.

BackgroundZheng Qing Feng Tong Ning (ZQFTN) is a sinomenine (SIN) preparation that has been used in clinical practice. Our study aimed to assess the methodological and reporting quality of meta-analyses on the Chinese herbal formula ZQFTN for the treatment of rheumatoid arthritis (RA).MethodsSystematic searches were carried out with the 5 following electronic databases from inception to July 2019: China National Knowledge Infrastructure (CNKI), Wanfang, VIP database for Chinese technical periodicals (VIP), Cochrane Library and PubMed. The quality of the methodology and reporting was measured with the assessment of multiple systematic reviews 2 (AMSTAR 2) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).ResultsEight studies were identified. Among the 16 items of the AMSTAR 2 scale, four items were optimally reported (“Y” =100% of the items), and another four items were poorly reported (“Y” =0% of the items). Only 2 studies received a good overall score (“Y” ≥50% of the items). Regarding the PRISMA statement, the scores of 5 studies were lower than the average score (17.69), indicating that the quality of the reports was very low. In terms of the GRADE, none of the 61 results were of high quality (0.0%). Fifteen results were of medium quality (25%), 34 were of low quality (55%), and 12 were of very low quality (20%). Among the five downgrading factors, deviation risk (n = 61, 100%) was the most common downgrading factor, followed by inconsistency (n = 30, 50%), publication bias (n = 17, 28%), inaccuracy (n = 11, 18%) and indirectness (n = 0, 0%).ConclusionsThe methodological and reporting quality of the meta-analyses and systematic reviews in the included studies are less than optimal, and researchers should undergo additional training and follow the AMSTAR 2 scale, PRISMA statement and GRADE to design high-quality studies in the future.