Fungal infections in liver cirrhosis.

Liver cirrhosis is a chronic condition that is associated with a variety of complications across organ systems. Patients with cirrhosis also suffer from immune dysfunction, which may predispose them to catastrophic bacterial and fungal infections. Bacterial infections in liver cirrhosis have been well-documented, however, data remains scarce regarding fungal infections. Candida and Aspergillus have been reported as the most common pathogens among patients with cirrhosis, causing both invasive and non-invasive infections. However, other pathogens such as Coccidioides, Pneumocystis, Cryptococcus, and Rhizopus have been increasing in incidence. Diagnosis of fungal infection is often difficult, particularly in regards to distinguishing colonization from invasive infection. Serum markers such as beta-D-glucan (BDG) and galactomannan are beneficial diagnostic tools in conjunction with fungal cultures and imaging modalities. Bronchoscopy with bronchoalveolar lavage (BAL) or lung biopsy can be useful adjuncts as well. Liver transplantation is another important consideration as invasive fungal infection (IFI) is a contraindication to transplant surgery. Additionally, patients are at increased risk for infection due to immunosuppression in the post-transplant period. We aim to discuss the mechanisms responsible for immune dysfunction in advanced liver disease, the epidemiology of fungal infections in this population, as well as presentations and management considerations pertaining to specific pathogens and antifungal regimens.

Repetitive transcranial magnetic stimulation for post-traumatic stress disorder in adults.

BACKGROUND: The estimated lifetime prevalence of post-traumatic stress disorder (PTSD) in adults worldwide has been estimated at 3.9%. PTSD appears to contribute to alterations in neuronal network connectivity patterns. Current pharmacological and psychotherapeutic treatments for PTSD are associated with inadequate symptom improvement and high dropout rates. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive therapy involving induction of electrical currents in cortical brain tissue, may be an important treatment option for PTSD to improve remission rates and for people who cannot tolerate existing treatments. OBJECTIVES: To assess the effects of repetitive transcranial magnetic stimulation (rTMS) on post-traumatic stress disorder (PTSD) in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two clinical trials registers. We checked reference lists of relevant articles. The most recent search was January 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) assessing the efficacy and safety of rTMS versus sham rTMS for PTSD in adults from any treatment setting, including veterans. Eligible trials employed at least five rTMS treatment sessions with both active and sham conditions. We included trials with combination interventions, where a pharmacological agent or psychotherapy was combined with rTMS for both intervention and control groups. We included studies meeting the above criteria regardless of whether they reported any of our outcomes of interest. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in accordance with Cochrane standards. Primary outcomes were PTSD severity immediately after treatment and serious adverse events during active treatment. Secondary outcomes were PTSD remission, PTSD response, PTSD severity at two follow-up time points after treatment, dropouts, and depression and anxiety severity immediately after treatment. MAIN RESULTS: We included 13 RCTs in the review (12 published; 1 unpublished dissertation), with 577 participants. Eight studies included stand-alone rTMS treatment, four combined rTMS with an evidence-based psychotherapeutic treatment, and one investigated rTMS as an adjunctive to treatment-as-usual. Five studies were conducted in the USA, and some predominantly included white, male veterans. Active rTMS probably makes little to no difference to PTSD severity immediately following treatment (standardized mean difference (SMD) -0.14, 95% confidence interval (CI) -0.54 to 0.27; 3 studies, 99 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision (sample size insufficient to detect a difference of medium effect size). We deemed one study as having a low risk of bias and the remaining two as having 'some concerns' for risk of bias. A sensitivity analysis of change-from-baseline scores enabled inclusion of a greater number of studies (6 studies, 252 participants). This analysis yielded a similar outcome to our main analysis but also indicated significant heterogeneity in efficacy across studies, including two studies with a high risk of bias. Reported rates of serious adverse events were low, with seven reported (active rTMS: 6; sham rTMS: 1). The evidence is very uncertain about the effect of active rTMS on serious adverse events (odds ratio (OR) 5.26, 95% CI 0.26 to 107.81; 5 studies, 251 participants; very low-certainty evidence [Active rTMS: 23/1000, sham rTMS: 4/1000]). We downgraded the evidence by one level for risk of bias and two levels for imprecision. We rated four of five studies as having a high risk of bias, and the fifth as 'some concerns' for bias. We were unable to assess PTSD remission immediately after treatment as none of the included studies reported this outcome. AUTHORS' CONCLUSIONS: Based on moderate-certainty evidence, our review suggests that active rTMS probably makes little to no difference to PTSD severity immediately following treatment compared to sham stimulation. However, significant heterogeneity in efficacy was detected when we included a larger number of studies in sensitivity analysis. We observed considerable variety in participant and protocol characteristics across studies included in this review. For example, studies tended to be weighted towards inclusion of either male veterans or female civilians. Studies varied greatly in terms of the proportion of the sample with comorbid depression. Study protocols differed in treatment design and stimulation parameters (e.g. session number/duration, treatment course length, stimulation intensity/frequency, location of stimulation). These differences may affect efficacy, particularly when considering interactions with participant factors. Reported rates of serious adverse events were very low (< 1%) across active and sham conditions. It is uncertain whether rTMS increases the risk of serious adverse event occurrence, as our certainty of evidence was very low. Studies frequently lacked clear definitions for serious adverse events, as well as detail on tracking/assessment of data and information on the safety population. Increased reporting on these elements would likely aid the advancement of both research and clinical recommendations of rTMS for PTSD. Currently, there is insufficient evidence to meta-analyze PTSD remission, PTSD treatment response, and PTSD severity at different periods post-treatment. Further research into these outcomes could inform the clinical use of rTMS. Additionally, the relatively large contribution of data from trials that focused on white male veterans may limit the generalizability of our conclusions. This could be addressed by prioritizing recruitment of more diverse participant samples.

Correction: Effects of structured exercise programmes on physiological and psychological outcomes in adults with inflammatory bowel disease (IBD): A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0278480.].

Bilateral renal agenesis: fetal intervention and outcomes.

Bilateral renal agenesis (BRA) is a fetal anomaly which leads to anhydramnios and resultant pulmonary hypoplasia. Historically, this anomaly was universally fatal early in the neonatal period due to the severity of the associated lung disease. Over the last 30 years, innovations in fetal therapies-specifically, serial amnioinfusions-have led to instances of infant pulmonary survival and initiation of postnatal dialysis, raising the possibility that early neonatal death may not be inevitable. Amnioinfusions are not without risk, and maternal complications can include prelabor rupture of membranes, preterm labor, infection, and bleeding. The data detailing neonatal outcomes are still limited and actively being collected. Two case series and one non-randomized clinical trial have supplied most of the known outcome data for infants with BRA after prenatal amnioinfusion. Although there are survivors reported in the literature, mortality remains high, with many deaths in infancy due to dialysis-associated sepsis. In addition, previously unknown morbidities have been documented in these infants, including neurologic injury. These challenges, in addition to the mechanical difficulties of providing dialysis to extremely small infants, can result in significant burdens for patients and their caregivers and moral distress for the health care team. The present review aims to explain the pathophysiology of BRA, detail the historical context and rationale for serial amnioinfusions to treat the pulmonary insufficiency associated with BRA, describe the available data regarding outcomes of infants born following prenatal amnioinfusions, discuss ethical issues surrounding this fetal intervention, and describe critical aspects of prenatal counseling for patients considering the intervention.

A survey of the treatment and management of ingrown toenails by UK podiatrists: A cross-sectional survey.

BACKGROUND: Ingrown toenails are a common pathology. Although a range of conservative and surgical measures are widely used for this condition, little is known about their use in practice. This study explored current practice relating to the treatment or management of ingrown toenails by podiatrists in the UK. METHODS: A cross-sectional online survey (Qualtrics, Provo, UT, USA) conducted between March to June 2020 was distributed to practicing podiatrists treating or managing ingrown toenails in the UK. RESULTS: A total of 396 practicing podiatrists responded (60.1% based in the private sector). The majority (88.6%) performed nail surgery most commonly (54.3%) less than five a month. Nearly all (95%) only performed nail avulsion with or without chemical matrixectomy, universally using phenol (97.2%). Application time and number of applications varied but was most commonly applied three times (61.5%) for a total of 3 minutes (75%). Aftercare varied considerably between public and private sectors, with public sectors offering fewer follow-up appointments. CONCLUSIONS: Although there is a variation in clinical practice throughout the treatment pathway, almost all respondents offered nail avulsion with phenol matrixectomy, whereas very few provided incisional nail surgery. This data provides the most comprehensive description of how UK podiatrists conduct nail surgery for onychocryptosis.

Structure- and Property-Based Optimization of Efficient Pan-Bromodomain and Extra Terminal Inhibitors to Identify Oral and Intravenous Candidate I-BET787.

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins are important epigenetic regulators that elicit their effect through binding histone tail N-acetyl lysine (KAc) post-translational modifications. Recognition of such markers has been implicated in a range of oncology and immune diseases and, as such, small-molecule inhibition of the BET family bromodomain-KAc protein-protein interaction has received significant interest as a therapeutic strategy, with several potential medicines under clinical evaluation. This work describes the structure- and property-based optimization of a ligand and lipophilic efficient pan-BET bromodomain inhibitor series to deliver candidate I-BET787 (70) that demonstrates efficacy in a mouse model of inflammation and suitable properties for both oral and intravenous (IV) administration. This focused two-phase explore-exploit medicinal chemistry effort delivered the candidate molecule in 3 months with less than 100 final compounds synthesized.

Biomarkers of neurodegeneration in schizophrenia: systematic review and meta-analysis.

QUESTION: Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve. STUDY SELECTION AND ANALYSIS: We reviewed papers that compared postmortem findings, hippocampal MRI volume or cerebrospinal fluid (CSF) markers of AD, between patients with schizophrenia with evidence of cognitive impairment (age ≥45 years) with controls. We subsequently performed a meta-analysis of postmortem studies that compared amyloid-ß plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired patients with schizophrenia to normal controls or an AD group. FINDINGS: No studies found a significant increase of APs or NFTs in cognitively impaired patients with schizophrenia compared with controls. All postmortem studies that compared APs or NFTs in patients with schizophrenia to an AD group found significantly more APs or NFTs in AD. No studies found a significant differences in CSF total tau or phosphorylated tau between patients with schizophrenia and controls. The two studies which compared CSF Aß42 between patients with schizophrenia and controls found significantly decreased CSF Aß42 in schizophrenia compared with controls. Hippocampal volume findings were mixed. CONCLUSIONS: Studies have not found higher rates of AD-related pathology in cognitively impaired individuals with schizophrenia compared with controls. Higher rates of dementia identified in population studies may reflect a lack of specificity in clinical diagnostic tools used to diagnose dementia.

Development of Allosteric Small Molecule APOBEC3B Inhibitors from In Silico Screening.

APOBEC3B cytosine deaminase contributes to the mutational burdens of tumors, resulting in tumor progression and therapy resistance. Small molecule APOBEC3B inhibitors have potential to slow or mitigate these detrimental outcomes. Through molecular dynamics (MD) simulations and computational solvent mapping analysis, we identified a novel putative allosteric pocket on the C-terminal domain of APOBEC3B (A3Bctd), and virtually screened the ChemBridge Diversity Set (N~110,000) against both the active and potential allosteric sites. Selected high-scoring compounds were subsequently purchased, characterized for purity and composition, and tested in biochemical assays, which yielded 13 hit compounds. Orthogonal NMR assays verified binding to the target protein. Initial selectivity studies suggest these compounds preferentially target A3Bctd over related deaminase APOBEC3A (A3A), and MD simulations indicate this selectivity may be due to the steric repulsion from H56 that is unique to A3A. Taken together, our studies represent the first virtual screening effort against A3Bctd that has yielded candidate inhibitors suitable for further development.

Brain vital sign monitoring of sleep deprivation detects situational cognitive impairment.

Objective, rapid evaluation of cognitive function is critical for identifying situational impairment due to sleep deprivation. The present study used brain vital sign monitoring to evaluate acute changes in cognitive function for healthy adults. Thirty (30) participants were scanned using portable electroencephalography before and after either a night of regular sleep or a night of total sleep deprivation. Brain vital signs were extracted from three established event-related potential components: (1) the N100 (Auditory sensation); (2) the P300 (Basic attention); and (3) the N400 (Cognitive processing) for all time points. As predicted, the P300 amplitude was significantly reduced in the sleep deprivation group. The findings indicate that it is possible to detect situational cognitive impairment due to sleep deprivation using objective, rapid brain vital sign monitoring.

Th17-inducing dendritic cell vaccines stimulate effective CD4 T cell-dependent antitumor immunity in ovarian cancer that overcomes resistance to immune checkpoint blockade.

BACKGROUND: Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated by stimulating IL-15 while blocking p38 MAPK in bone marrow-derived DCs, followed by antigen pulsing. METHODS: ID8 tumor cells were injected intraperitoneally into mice. Mice were treated with Th17-DC or conventional DC (cDC) vaccine alone or with immune checkpoint blockade (ICB). Systemic immunity, tumor associated immunity, tumor size and survival were examined using a variety of experimental strategies. RESULTS: Th17-DC vaccines increased Th17 T cells in the tumor microenvironment, reshaped the myeloid microenvironment, and improved mouse survival compared with cDC vaccines. ICB had limited efficacy in OC, but Th17-inducing DC vaccination sensitized it to anti-PD-1 ICB, resulting in durable progression-free survival by overcoming IL-10-mediated resistance. Th17-DC vaccine efficacy, alone or with ICB, was mediated by CD4 T cells, but not CD8 T cells. CONCLUSIONS: These findings emphasize using biologically relevant immune modifiers, like Th17-DC vaccines, in OC treatment to reshape the tumor microenvironment and enhance clinical responses to ICB therapy.

Nurses' Experience Implementing an Automated Video Monitoring System to Decrease the Risk of Patient Falls during a Global Pandemic.

Healthcare is a complex sociotechnical system where information systems (IS) and information technology (IT) intersect to solve problems experienced by patients and providers alike. One example of IS/IT in hospitals is the Ocuvera automated video monitoring system (AVMS), which has been implemented in more than 30 hospitals. The purpose of this study was to evaluate nurses' attitudes toward AVMS implementation over time as they received the training program developed for this intervention. Consistent with the job demands-resources (JDR) model, we found that perceptions of AVMS usefulness increased over time and were positively associated with perceptions of social influence and behavioral control. These results were consistent with our finding that there was a significant decrease in the risk of unassisted falls from the bed from baseline to intervention. Leaders in hospital systems and healthcare organizations may want to consider implementing an AVMS as researchers continue to test, verify, and demonstrate the effectiveness of these interventions for improving patient well-being.

Patient and primary care practitioners' perspectives on consultations for fibromyalgia: a qualitative evidence synthesis.

BACKGROUND: Fibromyalgia presents a challenge to both the patients experiencing symptoms and the staff aiming to treat them. This qualitative review aimed to synthesise how patients and practitioners experience primary care consultations, develop a rounded picture of how they perceive each other, the challenges to primary care consultation and how they might be tackled. METHODS: CINAHL, Embase, CENTRAL and Medline were searched from inception to November 2021. Qualitative studies were included if they explored the perspectives and experiences of either fibromyalgia patients or primary care practitioners. Quantitative data, studies not published in English, not set in primary care or that did not distinguish the type of patient or clinician were excluded. Included studies were analysed using thematic synthesis and their quality assessed. RESULTS: In total, 30 studies met the inclusion criteria. Thematic synthesis identified three overarching themes: (1) life turned upside down - exploring the chaos experienced by patients as they seek help; (2) negative cycle - highlighting how patient and practitioner factors can create a detrimental cycle; and (3) breaking the cycle - validating patient-doctor relationships underpinned by clear communication can help break the negative cycle. CONCLUSIONS: Fibromyalgia patients experience uncertainty and chaos that can clash with the attitudes of GPs and the help they can feasibly provide. Difficult consultations in which neither the GP nor patient are satisfied can easily occur. Promoting supportive, reciprocal and open patient-doctor relationships is essential. Future research is required to further explore GP attitudes and to develop an intervention that could improve consultations, patient outcomes and GP satisfaction.

A systematic review and meta-analysis of randomised controlled trials of surgical treatments for ingrown toenails part II: healing time, post-operative complications, pain, and participant satisfaction.

BACKGROUND: When performing nail surgery, clinicians must choose from a multitude of procedures and variations within each procedure. Much has been published to guide this decision making, but there are a lack of up to date robust systematic reviews to assess the totality of this evidence. METHODS: Five databases (MEDLINE, Embase, CINAHL, Web of Science and CENTRAL) and two registers (Clinicaltrials.gov and ISRCTN) were searched to January 2022 for randomised trials evaluating the effects of a surgical intervention(s) for ingrown toenails. Two independent reviewers screened records, extracted data, assessed risk of bias and certainty of evidence. Data on co-primary outcomes of symptom relief and symptomatic regrowth were presented in our first paper. This paper presents data for the secondary outcomes and further discussion. RESULTS: Of 3,928 records identified, 36 randomised trials were included in the systematic review. Healing time appears to be reduced with shorter application of phenol. A reduced healing time was also apparent was with the addition of curettage, although this may also increase the risk of post-operative bleeding and pain. Post operative bleeding was also reportedly lower in people who received local anaesthetic with epinephrine but no tourniquet. Use of phenol with nail bed excision may decrease the risk of infection. Lower pain scores were reported when using partial matrixectomy and surgical interventions with phenol. Shorter duration of pain was reported with phenolisation and wedge resection. Participant satisfaction was high overall. CONCLUSION: This second paper reports secondary outcomes from a robust systematic review of randomised trials on surgical treatment of ingrown toenails. Despite the large volume of clinical trials conducted on the topic, few clinical conclusions can be drawn due to the poor quality of these studies. Further high-quality clinical trials are needed to answer fundamental questions in the surgical treatment of ingrown toenails.

Racial and Ethnic Differences Among Active-Duty Service Members in Use of Mental Health Care and Perceived Mental Health Stigma: Results From the 2018 Health Related Behaviors Survey.

INTRODUCTION: The prevalence of mental health disorders is rising among US service members; however, research is limited on their use of mental health care. The objective of our study was to determine whether racial and ethnic disparities exist in the use of mental health care and perceived mental health stigma among active-duty service members. METHODS: We obtained data from a sample of 17,166 active-duty service members who participated in the 2018 Department of Defense Health Related Behavior Survey (HRBS). Racial and ethnic groups included Black, Hispanic, White, and other. Yes-no questions about use of mental health care and perceived mental health stigma were our outcome variables. We used multiple logistic regression to assess racial and ethnic differences in mental health care use and perceived mental health stigma by service members. Significance was set at P <.05. RESULTS: In 2018, approximately 25.5% of service members self-reported using mental health services, and 34.2% self-reported perceived mental health stigma. Hispanic service members (AOR = 0.78) and service members in the "other" racial and ethnic group (AOR = 0.81) were less likely than their White counterparts to have used mental health care. Black (AOR = 0.68) and Hispanic (AOR = 0.86) service members were less likely than their White counterparts to self-report perceived mental health stigma. CONCLUSION: The 2018 HRBS showed racial and ethnic differences in mental health care use and perceived stigma among US active-duty service members. Perceived stigma was a barrier to use of mental health care among service members with a mental health condition. Culture-sensitive programs customized for different racial and ethnic groups are needed to promote mental health care and reduce perceptions of stigma associated with its use.

TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation.

TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT's intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting independently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action.

Global assessment of marine plastic exposure risk for oceanic birds.

Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.

Why do people take part in vaccine trials? A mixed methods narrative synthesis.

OBJECTIVES: To understand why individuals do or do not take part in vaccine trials, exploring the motivators and barriers to identify effective strategies to optimise recruitment in vaccine research. METHODS: Qualitative studies and quantitative surveys capturing data on reasons for trial participation/decline were included. Six databases were searched from 1996 to October 2021. Two reviewers independently screened and assessed risk of bias. Results were reported narratively and analysed using thematic analysis. RESULTS: We included 32 studies (17 qualitative; 12 quantitative; 3 mixed-methods) that covered a wide range of populations, geographical areas and disease types. Eight themes were identified 1) altruism; 2) potential for personal benefit; 3) perceived risks; 4) trust or distrust; 5) social networks; 6) stigma; 7) practical implications; 8) research vanguard. CONCLUSION: Our findings provide a detailed description of how potential participants weigh up their decisions to participate in vaccine trials, which could inform the planning and implementation of studies to enhance recruitment. PRACTICE IMPLICATIONS: Clinical trial researchers should consider a patient-centered approach to recruitment, tailoring promoting material and attempt to understand fears, stigma and perceived risks. In addition, recognising the importance of trust and the key role friends, communities, family, and those in supervisory positions play in decisions.

A systematic review and meta-analysis of randomised controlled trials on surgical treatments for ingrown toenails part I: recurrence and relief of symptoms.

BACKGROUND: Ingrown toenails are a common nail pathology. When conservative treatments are ineffective, a surgical approach is often utilised. Despite recent narrative reviews, there is a need for an up-to-date and rigorous systematic review of surgical methods for treating ingrown toenails. METHODS: Five databases (MEDLINE, Embase, CINAHL, Web of Science and CENTRAL) and two registers (Clinicaltrials.gov and ISRCTN) were searched to January 2022 for randomised trials evaluating the effects of a surgical intervention(s) for ingrown toenails with a follow-up of at least 1 month. Two independent reviewers screened records, extracted data, assessed risk of bias and certainty of evidence. RESULTS: Of 3,928 records identified, 36 (3,756 participants; 62.7% males) surgical interventions were included in the systematic review and 31 studies in the meta-analysis. There was very low quality evidence that using phenol with nail avulsion vs nail avulsion without phenol reduces the risk of recurrence (risk ratio [RR] 0.13 [95% CI 0.06 to 0.27], p < 0.001). No favourable effect was observed between chemical or surgical vs conservative management (0.55 [0.19 to 1.61], p = 0.280; 0.72 [0.33 to 1.56], p = 0.410), chemical or surgical vs other (e.g., CO2 laser, electrocautery) (1.61 [0.88 to 2.95], p = 0.120; 0.58 [0.25 to 1.37], p = 0.220), chemical vs surgical (0.75 [0.46 to 1.21], p = 0.230), surgical vs surgical (0.42 [0.21 to 0.85]), chemical vs chemical (0.19 [0.01 to 3.80], p = 0.280), surgical vs surgical + chemical (3.68 [0.20 to 67.35], p = 0.380), chemical vs surgical + chemical (1.92 [0.06 to 62.30], p = 0.710), local anaesthetic vs local anaesthetic + adrenaline (1.03 [0.22 to 4.86], p = 0.970), chemical timings 30 s vs 60 s (2.00 [0.19 to 21.41]) or antibiotics vs no antibiotics (0.54 [0.12 to 2.52], p = 0.430). Central toenail resection was the only procedure to significantly relieve symptoms (p = 0.001) but data were only available up to 8 weeks post-surgery. CONCLUSION: Despite the high number of publications, the quality of research was poor and the conclusions that can be inferred from existing trials is limited. Phenolisation of the nail matrix appears to reduce the risk of recurrence following nail ablation, and with less certainty 1 min appears to be the optimum time for application. Despite this being a widely performed procedure there remains a lack of good quality evidence to guide practice.