Rising to the Challenge: An ID Provider-Led Initiative to Address Penicillin Allergy Labels at a Large Veterans Affairs Medical Center.

Background: Given the negative consequences associated with a penicillin allergy label, broader penicillin allergy delabeling initiatives are highly desirable but hindered by the shortage of allergists in the United States. To address this problem at our facility, the infectious diseases section introduced a quality improvement initiative to evaluate and remove allergy labels among inpatient veterans. Methods: Between 15 November 2022 and 15 December 2023, we identified inpatients with a penicillin allergy label. We subsequently interviewed eligible candidates to stratify penicillin allergy risk and attempt to remove the allergy label directly via chart review, following inpatient oral amoxicillin challenge or outpatient community care allergy referral. Delabeling outcomes, subsequent penicillin-class prescriptions, and relabeling were tracked after successful allergy label removal. Results: We screened 272 veterans, of whom 154 were interviewed for this intervention. A total of 53 patients were delabeled: 26 directly, 23 following oral amoxicillin challenge, and 4 following outpatient allergy referrals. Of the patients who were delabeled, 25 received subsequent penicillin-class prescriptions. No adverse reactions occurred following inpatient oral amoxicillin challenges. Patients with a low-risk penicillin allergy history were more likely to undergo a challenge if admitted with an infectious diseases-related condition. Only 1 inappropriate relabeling event occurred during the study period, which was subsequently corrected. Conclusions: An infectious diseases provider-led initiative resulted in penicillin allergy label removal in more than one third of inpatients evaluated using direct removal or oral amoxicillin challenge. Efforts focused on patients who had been admitted for infections were particularly successful.

Minimally Invasive Treatment of Abdominal Pregnancy Implanted on the Ileocecal Junction.

We report a case of a 32-year-old gravida 1 para 0 with a copper intrauterine device in place and a newly diagnosed pregnancy at 5 weeks gestation. Serum human chorionic gonadotropin (hCG) was 23,940 mIU/mL and transvaginal ultrasound demonstrated a presumed right adnexal ectopic pregnancy with fetal cardiac activity. Upon laparoscopic entry, a 3 cm vascular mass consistent with ectopic pregnancy was noted densely adherent to the cecum, adjacent to the ileocecal junction. Given difficult tissue plane dissection and bleeding, a 4 cm mini-laparotomy was made and the mass was bluntly dissected away from the bowel implantation site. The bowel was oversewn. The patient's postoperative course was uncomplicated.

Traffic Jam activates the Flamenco piRNA cluster locus and the Piwi pathway to ensure transposon silencing and Drosophila fertility.

Flamenco (Flam) is the most prominent piRNA cluster locus expressed in Drosophila ovarian follicle cells, and it is required for female fertility to silence gypsy/mdg4 transposons. To determine how Flam is regulated, we used promoter-bashing reporter assays in OSS cells to uncover novel enhancer sequences within the first exons of Flam . We confirmed the enhancer sequence relevance in vivo with new Drosophila Flam deletion mutants of these regions that compromised Flam piRNA expression and lowered female fertility from activated transposons. Our proteomic analysis of proteins associated with these enhancer sequences discovered the transcription factor Traffic Jam (TJ). Tj knockdowns in OSS cells caused a decrease in Flam transcripts, Flam piRNAs, and multiple Piwi pathway genes. A TJ ChIP-seq analysis from whole flies and OSS cells confirmed TJ binding exactly at the enhancer that was deleted in the new Flam mutant as well as at multiple Piwi pathway gene enhancers. Interestingly, TJ also bound the Long Terminal Repeats of transposons that had decreased expression after Tj knockdowns in OSS cells. Our study reveals the integral role TJ plays in the on-going arms race between selfish transposons and their suppression by the host Piwi pathway and the Flam piRNA cluster locus.

Hysterectomy Techniques and Outcomes for Benign Large Uteri: A Systematic Review.

OBJECTIVE: To identify the optimal hysterectomy approach for large uteri in gynecologic surgery for benign indications from a perioperative morbidity standpoint. DATA SOURCES: PubMed and Embase databases were searched from inception through September 19, 2022. Meta-analyses were conducted as feasible. METHODS OF STUDY SELECTION: This review included studies that compared routes of hysterectomy with or without bilateral salpingo-oophorectomy for large uteri (12 weeks or more or 250 g or more) and excluded studies with any concurrent surgery for pelvic organ prolapse, incontinence, gynecologic malignancy, or any obstetric indication for hysterectomy. TABULATION, INTEGRATION, AND RESULTS: The review included 25 studies comprising nine randomized trials, two prospective, and 14 retrospective nonrandomized comparative studies. Studies were at high risk of bias. There was lower operative time for total vaginal hysterectomy compared with laparoscopically assisted vaginal hysterectomy (LAVH) (mean difference 39 minutes, 95% CI, 18-60) and total vaginal hysterectomy compared with total laparoscopic hysterectomy (mean difference 50 minutes, 95% CI, 29-70). Total laparoscopic hysterectomy was associated with much greater risk of ureteral injury compared with total vaginal hysterectomy (odds ratio 7.54, 95% CI, 2.52-22.58). There were no significant differences in bowel injury rates between groups. There were no differences in length of stay among the laparoscopic approaches. For LAVH compared with total vaginal hysterectomy, randomized controlled trials favored total vaginal hysterectomy for length of stay. When rates of blood transfusion were compared between these abdominal hysterectomy and robotic-assisted total hysterectomy routes, abdominal hysterectomy was associated with a sixfold greater risk of transfusion than robotic-assisted total hysterectomy (6.31, 95% CI, 1.07-37.32). Similarly, single studies comparing robotic-assisted total hysterectomy with LAVH, total laparoscopic hysterectomy, or total vaginal hysterectomy all favored robotic-assisted total hysterectomy for reduced blood loss. CONCLUSION: Minimally invasive routes are safe and effective and have few complications. Minimally invasive approach (vaginal, laparoscopic, or robotic) results in lower blood loss and shorter length of stay, whereas the abdominal route has a shorter operative time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021233300.

Energy Device Preferences Among Gynecologic Surgeons.

Background and Objectives: Multiple vessel-sealing devices are available for use during laparoscopy. The objective of this study is to determine what surgeon-level and device characteristics influence the choice of advanced energy device during gynecologic laparoscopy. Methods: This is a national cross-sectional study of gynecologic surgeons conducted via social media, utilizing an online, publicly-available, anonymous survey. Gynecologic surgeons who had completed residency training were approached for participation in the survey. Survey completion was voluntary and involved no further follow-ups. The web-based survey consisted of six questions with the option to answer three additional questions if time permitted. The institutional review board determined that this study qualified for exemption. Results: There were 92 respondents who participated in the survey. Of these, 81 completed the survey and were included in the analysis. Female respondents were younger and more frequently reported a glove size of 6.5 or less. Surgeon-level characteristics, including gender, age, glove size, case volume, region, and practice setting, were not significantly associated with preferred energy devices. Device availability in the operating room was the only characteristic associated with preferred energy devices (P-value = .0076). Other device-level characteristics such as optimal thermal spread, reduced plume, ease of use, device reliability, and teachability had no statistically significant association with preferred energy devices. Conclusion: Multiple advanced energy devices are available for use during gynecologic laparoscopy. These devices have varying energy profiles, thermal spread, and device size. Despite this diversity, only device availability in the operating room influenced the surgeon's preferred device selection.

Challenges and opportunities related to penicillin allergy in the Veterans Health Administration: a narrative review.

The presence of a penicillin allergy label in a patient's medical chart is associated with negative clinical and economic outcomes. Given that less than 10% of reported reactions are truly immunoglobulin E-mediated, removal of unverified penicillin allergy labels is a public health priority and an area of ongoing implementation research. The Veterans Health Administration (VHA) is the largest integrated healthcare system in the United States, with almost 9 million veterans currently enrolled. However, studies analyzing the impact of the penicillin allergy label in this population are limited to single facilities and largely focus on short-term outcomes of allergy documentation correction, usage of ß-lactams, and avoidance of antibiotic-related side effects. Broader, national VHA studies focusing on health outcomes and costs are lacking. As with non-VHA facilities, penicillin allergy evaluations are limited owing to the absence of formal allergy/immunology services at most VHA facilities. Pharmacy-driven screening and referral for clinic-based penicillin skin testing is a promising and frequently discussed modality in the literature, but its scalability within the VHA is not yet proven. Broader, evidence-based strategies that can be adapted to the available resources of individual VHA facilities, including those without on-site access to allergy providers, are needed.

Leiomyoma Fistulization After Uterine Artery Embolization.

BACKGROUND: Uterine artery embolization (UAE) has been used to treat symptomatic uterine leiomyomas since 1995. This case report describes a rare complication of UAE, with delayed recognition, ultimately requiring definitive hysterectomy. CASE: A 53-year-old women with symptomatic leiomyomas underwent imaging demonstrating an enlarged (16.9×11.3×11.5 cm) uterus with multiple leiomyomas. She underwent UAE and, over the subsequent 3 months, and had five emergency department visits for abdominal pain and dysuria. Pelvic magnetic resonance imaging (MRI) 4 months postprocedure showed nodular mural enhancement of the right anterior bladder dome, and cystoscopy demonstrated irregular tissue on the right dome of the bladder. The patient ultimately underwent total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, partial cystectomy with reconstruction, and omental flap for bladder necrosis and leiomyoma fistulization. CONCLUSION: Bladder necrosis and leiomyoma fistulization are rare complications of UAE that can present with pelvic pain, hematuria, and recurrent bladder stones. Computed tomography and MRI can be useful tools in evaluating for complications, but clinicians should have a low threshold to use cystoscopy to directly visualize potential abnormalities identified on imaging. Patients with complex cases with suspected post-UAE complications warrant referral to tertiary care centers for a multidisciplinary approach.

Corrected and republished from: "VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection".

IMPORTANCE: Rotavirus is a leading cause of severe diarrhea in young children. Like other fecal-oral pathogens, rotaviruses encounter abundant, constitutively expressed defensins in the small intestine. These peptides are a vital part of the vertebrate innate immune system. By investigating the impact that defensins from multiple species have on the infectivity of different strains of rotavirus, we show that some rotaviral infections can be inhibited by defensins. We also found that rotaviruses may have evolved resistance to defensins in the intestine of their host species, and some even appropriate defensins to increase their infectivity. Because rotaviruses infect a broad range of animals and rotaviral infections are highly prevalent in children, identifying immune defenses against infection and how they vary across species and among viral genotypes is important for our understanding of the evolution, transmission, and zoonotic potential of these viruses as well as the improvement of vaccines.

Changes in Pelvic Floor Symptoms After Procedural Interventions for Uterine Leiomyomas: A Systematic Review.

OBJECTIVE: To conduct a systematic review to evaluate the effect of procedural interventions for leiomyomas on pelvic floor symptoms. DATA SOURCES: PubMed, EMBASE, and ClinicalTrials.gov were searched from inception to January 12, 2023, searching for leiomyoma procedures and pelvic floor disorders and symptoms, restricted to primary study designs in humans. METHODS OF STUDY SELECTION: Double independent screening for studies of any study design in all languages that reported pelvic floor symptoms before and after surgical (hysterectomy, myomectomy, radiofrequency volumetric thermal ablation) or radiologic (uterine artery embolization, magnetic resonance-guided focused ultrasonography, high-intensity focused ultrasonography) procedures for management of uterine leiomyomas. Data were extracted, with risk-of-bias assessment and review by a second researcher. Random effects model meta-analyses were conducted, as feasible. TABULATION, INTEGRATION, AND RESULTS: Six randomized controlled trials, one nonrandomized comparative study, and 25 single-group studies met criteria. The overall quality of the studies was moderate. Only six studies, reporting various outcomes, directly compared two procedures for leiomyomas. Across studies, leiomyoma procedures were associated with decreased symptom distress per the UDI-6 (Urinary Distress Inventory, Short Form) (summary mean change -18.7, 95% CI -25.9 to -11.5; six studies) and improved quality of life per the IIQ-7 (Incontinence Impact Questionnaire, Short Form) (summary mean change -10.7, 95% CI -15.8 to -5.6; six studies). There was a wide range of resolution of urinary symptoms after procedural interventions (7.6-100%), and this varied over time. Urinary symptoms improved in 19.0-87.5% of patients, and the definitions for improvement varied between studies. Bowel symptoms were inconsistently reported in the literature. CONCLUSION: Urinary symptoms improved after procedural interventions for uterine leiomyomas, although there is high heterogeneity among studies and few data on long-term outcomes or comparing different procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021272678.

Apolipoprotein E in lipid metabolism and neurodegenerative disease.

Dysregulation of lipid metabolism has emerged as a central component of many neurodegenerative diseases. Variants of the lipid transport protein, apolipoprotein E (APOE), modulate risk and resilience in several neurodegenerative diseases including late-onset Alzheimer's disease (LOAD). Allelic variants of the gene, APOE, alter the lipid metabolism of cells and tissues and have been broadly associated with several other cellular and systemic phenotypes. Targeting APOE-associated metabolic pathways may offer opportunities to alter disease-related phenotypes and consequently, attenuate disease risk and impart resilience to multiple neurodegenerative diseases. We review the molecular, cellular, and tissue-level alterations to lipid metabolism that arise from different APOE isoforms. These changes in lipid metabolism could help to elucidate disease mechanisms and tune neurodegenerative disease risk and resilience.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal PCR to streamline antimicrobial use in treatment of diabetic foot infection with or without osteomyelitis.

BACKGROUND: Diabetic Foot Infection (DFI) guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA)-targeted therapy in settings where there is high prevalence of MRSA infections or in cases of severe infection; however, they do not provide recommendations for de-escalation. This approach has the potential to increase unnecessary use of broad-spectrum antibiotics; therefore, additional strategies are needed to optimize appropriate antibiotic use. This study evaluates the effect of MRSA nasal PCR testing on MRSA-targeted antibiotic use and clinical outcomes in patients with DFI. METHODS: This was a retrospective quasi-experimental study of patients admitted to South Texas Veterans Health Care System for DFI, with or without osteomyelitis (OM), who had an MRSA nasal PCR and culture data. Eligible patients were identified from the Corporate Data Warehouse and reviewed via electronic health record. Patients were allocated into two groups: PRE (5/1/2019-4/30/2020) and POST (12/1/2020-11/30/2021) protocol implementation for de-escalation or avoidance of MRSA-targeted antibiotics. The primary outcome was median (interquartile range [IQR]) hours of empiric inpatient MRSA-targeted antibiotic therapy. A Wilcoxon Rank Sum test was used to assess the difference between the groups for the primary outcome. Secondary outcomes included the proportion of patients needing MRSA coverage added back for MRSA after de-escalation, hospital readmission, length of hospital stay (LOS), patient mortality, and acute kidney injury. RESULTS: A total of 151 patients were included (83 PRE; 68 POST). Most patients were male (98% PRE; 97% POST) with a median age of 64 (IQR, 56-72) years. Incidence of MRSA in DFI in the cohort was 14.7% overall (12% PRE and 17.6% POST). MRSA was detected via nasal PCR in 12% of patients 15.7% PRE and 7.4% POST). After protocol implementation, there was a significant decrease in empiric MRSA-targeted antibiotic therapy use, from a median of 72 (IQR, 27-120) hours in the PRE group, to 24 (IQR, 12-72) hours in the POST group (p < 0.01). No significant differences were found for other secondary outcomes. CONCLUSION: This study of patients presenting to a Veterans Affairs (VA) hospital with DFI identified a statistically significant decrease in median duration of MRSA-targeted antibiotic use post-protocol implementation. This suggests a favorable effect of MRSA nasal PCR for de-escalation or avoidance of MRSA-targeted antibiotics in DFI.

Comparative-Effectiveness of Oral Beta-Lactams and Fluoroquinolones for Stepdown Therapy in Patients with Enterobacterales Bloodstream Infections: A Retrospective Cohort Study.

Background: This study compares treatment failure for patients who received oral beta-lactams (BLs) and fluoroquinolones (FQs) for stepdown treatment of Enterobacterales bloodstream infections (BSIs). Methods: We conducted a single-center, retrospective, age- and sex-matched, cohort study, at a Veterans Affairs (VA) hospital in South Texas. Eligible patients were at least 18 years of age with a monomicrobial BSI treated with a single oral BL or FQ antibiotic. Treatment failure was defined as recurrence or all-cause mortality within 90 days of documented BSI. Bivariate (chi-square, Fisher's Exact, and Wilcoxon Rank Sum) and multivariate (logistic regression) statistical tests were used to compare groups. Results: A total of 130 patients were included in this study, with 65 patients per group. Groups were well balanced with respect to exact age, sex assigned at birth, Caucasian race, source control, intensive care unit admission, and Charlson Comorbidity Index. Importantly, 60% of patients in the BL group had cultures that were resistant to FQs and 71% were prescribed cefpodoxime. Patients in the BL group had higher median (interquartile range [IQR]) Pitt bacteremia scores than those in the FQ group: 2 (1-4) vs. 1 (1-2), p=0.04. Patients in the BL group also had a higher median (IQR) duration of intravenous (IV) antibiotics than those in the FQ group: 5 (3-7) vs. 4 (3-5), p=0.02. Treatment failure was statistically comparable for patients in the BL and FQ groups: 15% vs. 12%, p=0.61. This finding was consistent in a multivariate logistic regression model with group (BL vs. FQ) as the independent variable, treatment failure as the dependent variable, and Pitt bacteremia score and duration of IV antibiotics as covariates (OR: 0.76, 95% CI: 0.27-2.18). One patient in the FQ group experienced Clostridioides difficile infection. Conclusion: This study suggests that BLs may be as effective as FQs for oral stepdown treatment of Enterobacterales BSI without the potential associated risks. Furthermore, in the setting of FQ-resistant Enterobacterales BSI secondary to urinary source, third generation oral cephalosporins (i.e., cefpodoxime) may be reasonable alternatives.

Endometriosis and adenomyosis: shared pathophysiology.

Endometriosis and adenomyosis are closely related disorders. Their pathophysiologies are extremely similar. Both tissues originate from the eutopically located intracavitary endometrium. Oligoclones of endometrial glandular epithelial cells with somatic mutations and attached stromal cells may give rise to endometriosis if they travel to peritoneal surfaces or the ovary via retrograde menstruation and/or may be entrapped in the myometrium to give rise to adenomyosis. In both instances, the endometrial cell populations possess survival and growth capabilities conferred by somatic epithelial mutations and epigenetic abnormalities in stromal cells. Activating mutations of KRAS are the most commonly found genetic variant in endometriotic epithelial cells, whereas the adenomyotic epithelial cells almost exclusively bear KRAS mutations. Epigenetic abnormalities in the stromal cells of endometriosis and adenomyosis are very similar and involve an abnormal expression pattern of nuclear receptors, including the steroid receptors. These epigenetic defects give rise to excessive local estrogen biosynthesis by aromatase and abnormal estrogen action via estrogen receptor-ß. Deficient progesterone receptor expression results in progesterone resistance in both endometriosis and adenomyosis.

Direct percutaneous endoscopic gastrostomy for nutritional support in patients with aerodigestive tract cancers.

BACKGROUND: Conventional pull-through percutaneous endoscopic gastrostomy (PEG) risks infection and tumour implantation in head and neck cancers. Endoscopically inserted direct gastrostomy has lower rates of complications but is underutilised. AIMS: To describe the endoscopic steps for direct gastrostomy insertion and review our single-centre experience to assess the technical feasibility and safety. METHODS: Patients who underwent endoscopic direct gastrostomy insertion between December 2016 and June 2021 were included. A 24Fr introducer kit for gastrostomy feeding tube (Avanos Healthcare, Australia) was used. Patient and tumour characteristics, procedural data and 30-day outcomes were recorded. RESULTS: Thirty patients underwent direct PEG insertion (mean age 64 years and 24 male). All were planned for or currently undergoing radiotherapy. Twenty-six (87%) of 30 cases were performed under conscious sedation over a median procedure time of 21 min (interquartile range 11 min). No tumour seeding was seen, and one case of PEG-site infection was observed. CONCLUSIONS: Direct PEG is safe and effective and should be considered for patients with aerodigestive tract cancer in need of nutritional support.

TLT: Recurrent fine-tuning transfer learning for water quality long-term prediction.

The water quality long-term prediction is essential to water environment management decisions. In recent years, although water quality prediction methods based on deep learning have achieved excellent performance in short-term prediction, these methods are unsuitable for long-term prediction because the accumulation use of short-term prediction will easily introduce noise. Furthermore, The long-term prediction task requires a large amount of data to train the model to obtain accurate prediction results. For some monitoring stations with limited historical data, it is challenging to fully exploit the performance of deep learning models. To this end, we introduce a transfer learning framework into water quality prediction to improve the prediction performance in data-constrained scenarios. We propose a deep Transfer Learning based on Transformer (TLT) model to enable time dependency perception and facilitate long-term water quality prediction. In TLT, we innovatively introduce a recurrent fine-tuning transfer learning method, which can transfer the knowledge learned from source monitoring stations to the target station, while preventing the deep learning model from overfitting the source data during the pre-training phase. So, TLT can fully exert the performance of deep learning models with limited samples. We conduct experiments on data from 120 monitoring stations in major rivers and lakes in China to verify the effectiveness of TLT. The results show that TLT can effectively improve the long-term prediction accuracy of four water quality indicators (pH, DO, NH3-N, and CODMn) from monitoring stations with limited samples.

Treatment of HR+/HER2- breast cancer in urban mainland China: results from the CancerMPact Survey 2019.

PURPOSE: To report the treatment utilization patterns for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer in urban mainland China (CancerMPact®). METHODS: The results presented are from an online survey conducted in September 2019 with 45 physicians treating breast cancer patients from 11 cities in mainland China. RESULTS: Surveyed physicians reported that Stage I HR+/HER2(-) breast cancer patients are often treated with surgery alone (42%), whereas the use of surgery in combination with systemic therapy with or without radiotherapy increases in later stages (Stage II 67%, Stage III 77%). Doxorubicin-cyclophosphamide (AC)-based regimens were the most common in both the neoadjuvant and adjuvant settings in HR+/HER2(-) breast cancer patients, across all stages. In metastatic patients, use of surgery and radiotherapy decreases in favor of utilization of systemic therapy alone. Pre- and post-menopausal metastatic patients were frequently treated with hormone therapy or AC-based regimens in first line. Regardless of the first-line therapy administered, capecitabine-based regimens were commonly used in second line. In third line, chemotherapy regimens containing capecitabine or gemcitabine were given to nearly 40% of HR+/HER2(-) breast cancer patients. There were no standard of care regimens established for fourth or greater lines of treatment. In metastatic HR+/HER2(-) breast cancer, physicians reported 50% objective response rates in first-line settings with a progression-free survival of 16 months. CONCLUSION: HR+/HER2(-) breast cancer patients in urban mainland China were prescribed chemotherapy regimens more frequently than CDK4/6 inhibitors. Treatment practices varied, with physicians reporting the use of multiple modalities and treatment regimens for their patients.

Quality of Life in Chronic Limb Threatening Ischaemia: Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the comparative effectiveness and temporal changes in quality of life (QoL) outcomes after revascularisation, major lower extremity amputation (MLEA), and conservative management (CM) in chronic limb threatening ischaemia (CLTI). DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science. REVIEW METHODS: A systematic review and meta-analysis were performed on QoL measured by any QoL instrument in adult patients with CLTI after open surgery (OS), endovascular intervention (EVI), MLEA, or CM. Randomised controlled trials and prospective observational studies published in any language between 1 January 1990 and 21 May 2021 were included. There was a pre-specified measurement time point of six months. Random effects meta-analysis was conducted on total scores for each QoL instrument. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach (PROSPERO registration: CRD42021253953). RESULTS: Fifty-five studies with 8 909 patients were included. There was significant heterogeneity in the methods used to measure QoL, and the study characteristics. In particular, 14 different QoL instruments were used with various combinations of disease specific and generic instruments within each study. A narrative summary is therefore presented. Comparative effectiveness data showed there was reasonable certainty that QoL was similar between OS and EVI at six months. Temporal outcomes suggested small to moderate improvements in QOL six months after OS and EVI compared with baseline. Limited data indicated that QoL can be maintained or slightly improved after MLEA or CM. Treatment effects were overestimated owing to small study effects, selective non-reporting, attrition, and survivorship bias. CONCLUSION: QoL after OS and EVI appears to be similar. Revascularisation may provide modest QoL benefits, while MLEA or CM can maintain QoL. However, certainty of evidence is generally low or very low, and interpretation is hampered by significant heterogeneity. There is a need for a CLTI specific QoL instrument and methodological standardisation in QoL studies.