Apocrine Hidrocystoma of the Nail: A Unique Case.

ABSTRACT: Apocrine hidrocystomas are benign, cystic neoplastic lesions resulting from the apocrine secretory component of the sweat gland. They most commonly occur on the head and neck, with predilection to the periorbital area. Less frequent sites include the axilla, nipple, external auditory canal, foreskin, conjunctiva, lower lip, and fingers, among others. The authors report a unique case of a nail bed hidrocystoma in a 55-year-old woman, a site not previously described.

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA. METHODS: We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool. RESULTS: Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo. CONCLUSION: Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

Measuring the impact of monoclonal antibody therapies.

Objective: Monoclonal antibody (Mab) treatments have significantly improved the quality and quantity of life, but they are some of the most expensive treatments, resulting in a degree of hesitancy to introduce new Mab agents. A system for estimating the effect of Mab drugs, in general, would optimally inform health strategy and fully realize how a single scientific discovery can deliver health benefits. We evaluated such a method with several well-established Mab regimens. Methods: We selected five different Mab regimens in oncology and rheumatology in England. We carried out two systematic literature reviews and meta-analyses to assess health outcomes (Health Assessment Questionnaire-Disability Index for rheumatoid arthritis; overall mortality for melanoma) from real-world data and compared them to the outcomes from randomized control trials (RCTs). We applied economic modeling to estimate the net monetary benefits for health outcomes for the estimated patient population size for each Mab regimen. Results: Meta-analyses of 27 eligible real-world data (RWD) sets and 26 randomized controlled trial (RCT) sets found close agreement between the observed and expected health outcomes. A Markov model showed the net positive monetary benefit in three Mab regimens and the negative benefit in two regimens. However, because of limited access to NHS data, the economic model made several assumptions about the number of treated patients and the cost of treatment to the NHS, the accuracy of which may affect the estimation of the net monetary benefit. Conclusion: RCT results reliably inform the real-world experience of Mab treatments. Calculation of the net monetary benefit by the algorithm described provides a valuable overall measure of the health impact, subject to the accuracy of data inputs. This study provides a compelling case for building a comprehensive, systematized, and accessible database and related analytics, on all Mab treatments within health services.

Genetic and clinical variables act synergistically to impact neurodevelopmental outcomes in children with single ventricle heart disease.

BACKGROUND: Recent large-scale sequencing efforts have shed light on the genetic contribution to the etiology of congenital heart defects (CHD); however, the relative impact of genetics on clinical outcomes remains less understood. Outcomes analyses using genetics are complicated by the intrinsic severity of the CHD lesion and interactions with conditionally dependent clinical variables. METHODS: Bayesian Networks were applied to describe the intertwined relationships between clinical variables, demography, and genetics in a cohort of children with single ventricle CHD. RESULTS: As isolated variables, a damaging genetic variant in a gene related to abnormal heart morphology and prolonged ventilator support following stage I palliative surgery increase the probability of having a low Mental Developmental Index (MDI) score at 14 months of age by 1.9- and 5.8-fold, respectively. However, in combination, these variables act synergistically to further increase the probability of a low MDI score by 10-fold. The absence of a damaging variant in a known syndromic CHD gene and a shorter post-operative ventilator support increase the probability of a normal MDI score 1.7- and 2.4-fold, respectively, but in combination increase the probability of a good outcome by 59-fold. CONCLUSIONS: Our analyses suggest a modest genetic contribution to neurodevelopmental outcomes as isolated variables, similar to known clinical predictors. By contrast, genetic, demographic, and clinical variables interact synergistically to markedly impact clinical outcomes. These findings underscore the importance of capturing and quantifying the impact of damaging genomic variants in the context of multiple, conditionally dependent variables, such as pre- and post-operative factors, and demography.

Single ventricle congenital heart disease is a birth defect. In these children, the heart has only one effective blood-pumping chamber instead of two. Surgery can reroute the blood to use only one chamber, but multiple risk factors influence how well a child develops afterwards. Studying these risk factors can be challenging because they are interconnected, i.e. children with a genetic birth defect may be more likely to have a lower birthweight, and hence more likely to spend longer in hospital after surgery. Here, we used a statistical approach not commonly applied to study congenital heart disease and describe that whether a genetic variant (a small difference in a child's DNA) is important for how a child with single ventricle heart disease develops and grows after surgery depends on the presence of other risk factors.

JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications.

OBJECTIVES: To estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate. METHODS: Systematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool. RESULTS: In 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data. CONCLUSIONS: JAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons. PROSPERO REGISTRATION NUMBER: CRD42022362630.

Online Patient-Reported Outcome Measure Engagement Is Dependent on Demographics and Locality: Findings From an Observational Cohort.

OBJECTIVE: Online patient-reported outcome measures (PROMs) enable remote collection of perceptions of health status, function, and well-being. We aimed to explore patterns of PROM completion in patients with early inflammatory arthritis (EIA) recruited to the National Early Inflammatory Arthritis Audit (NEIAA). METHODS: NEIAA is an observational cohort study design; we included adults from this cohort with a new diagnosis of EIA from May 2018 to March 2020. The primary outcome was PROM completion at baseline, 3 months, and 12 months. Mixed effects logistic regression and spatial regression models were used to identify associations between demographics (age, gender, ethnicity, deprivation, smoking, and comorbidity), clinical commissioning groups, and PROM completion. RESULTS: Eleven thousand nine hundred eighty-six patients with EIA were included, of whom 5331 (44.5%) completed at least 1 PROM. Patients from ethnic minority backgrounds were less likely to return a PROM (adjusted odds ratio [aOR] 0.57, 95% CI 0.48-0.66). Greater deprivation (aOR 0.73, 95% CI 0.64-0.83), male gender (aOR 0.86, 95% CI 0.78-0.94), higher comorbidity burden (aOR 0.95, 95% CI 0.91-0.99), and current smoker status (aOR 0.73, 95% CI 0.64-0.82) also reduced odds of PROM completion. Spatial analysis identified 2 regions with high (North of England) and low (Southeast of England) PROM completion. CONCLUSION: We define key patient characteristics (including ethnicity) that influence PROM engagement using a national clinical audit. We observed an association between locality and PROM completion, with varying response rates across regions of England. Completion rates could benefit from targeted education for these groups.

COVID-19 admissions and mortality in patients with early inflammatory arthritis: results from a UK national cohort.

OBJECTIVE: To describe the risks and predictors of coronavirus disease 2019 (COVID-19) hospitalization and mortality among patients with early inflammatory arthritis (EIA), recruited to the National Early Inflammatory Arthritis Audit (NEIAA). METHODS: NEIAA is an observational cohort. We included adults with EIA from Feb 2020 to May 2021. Outcomes of interest were hospitalization and death due to COVID-19, using NHS Digital linkage. Cox proportional hazards were used to calculate hazard ratios for outcomes according to initial treatment strategy, with adjustment for confounders. RESULTS: From 14 127 patients with EIA, there were 143 hospitalizations and 47 deaths due to COVID-19, with incidence rates per 100 person-years of 0.93 (95% CI 0.79, 1.10) for hospitalization and 0.30 (95% CI 0.23, 0.40) for death. Increasing age, male gender, comorbidities and ex-smoking were associated with increased risk of worse COVID-19 outcomes. Higher baseline DAS28 was not associated with COVID-19 admissions [confounder adjusted hazard ratio (aHR) 1.10; 95% CI 0.97, 1.24] or mortality (aHR 1.11; 95% CI 0.90, 1.37). Seropositivity was not associated with either outcome. Higher symptom burden on patient-reported measures predicted worse COVID-19 outcomes. In unadjusted models, CS associated with COVID-19 death (HR 2.29; 95% CI 1.02, 5.13), and SSZ monotherapy associated with COVID-19 admission (HR 1.92; 95% CI 1.04, 3.56). In adjusted models, associations for CS and SSZ were not statistically significant. CONCLUSION: Patient characteristics have stronger associations with COVID-19 than the initial treatment strategy in patients with EIA. An important limitation is that we have not looked at treatment changes over time.

Detection of Antiviral Tissue Responses and Increased Cell Stress in the Pancreatic Islets of Newly Diagnosed Type 1 Diabetes Patients: Results From the DiViD Study.

Aims/hypothesis: The Diabetes Virus Detection (DiViD) study has suggested the presence of low-grade enteroviral infection in pancreatic tissue collected from six of six live adult patients newly diagnosed with type 1 diabetes. The present study aimed to compare the gene and protein expression of selected virally induced pathogen recognition receptors and interferon stimulated genes in islets from these newly diagnosed type 1 diabetes (DiViD) subjects vs age-matched non-diabetic (ND) controls. Methods: RNA was extracted from laser-captured islets and Affymetrix Human Gene 2.0 ST arrays used to obtain gene expression profiles. Lists of differentially expressed genes were subjected to a data-mining pipeline searching for enrichment of canonical pathways, KEGG pathways, Gene Ontologies, transcription factor binding sites and other upstream regulators. In addition, the presence and localisation of specific viral response proteins (PKR, MxA and MDA5) were examined by combined immunofluorescent labelling in sections of pancreatic tissue. Results: The data analysis and data mining process revealed a significant enrichment of gene ontologies covering viral reproduction and infectious cycles; peptide translation, elongation and initiation, as well as oxidoreductase activity. Enrichment was identified in the KEGG pathways for oxidative phosphorylation; ribosomal and metabolic activity; antigen processing and presentation and in canonical pathways for mitochondrial dysfunction, oxidative phosphorylation and EIF2 signaling. Protein Kinase R (PKR) expression did not differ between newly diagnosed type 1 diabetes and ND islets at the level of total RNA, but a small subset of ß-cells displayed markedly increased PKR protein levels. These PKR+ ß-cells correspond to those previously shown to contain the viral protein, VP1. RNA encoding MDA5 was increased significantly in newly diagnosed type 1 diabetes islets, and immunostaining of MDA5 protein was seen in α- and certain ß-cells in both newly diagnosed type 1 diabetes and ND islets, but the expression was increased in ß-cells in type 1 diabetes. In addition, an uncharacterised subset of synaptophysin positive, but islet hormone negative, cells expressed intense MDA5 staining and these were more prevalent in DiViD cases. MxA RNA was upregulated in newly diagnosed type 1 diabetes vs ND islets and MxA protein was detected exclusively in newly diagnosed type 1 diabetes ß-cells. Conclusion/interpretation: The gene expression signatures reveal that pathways associated with cellular stress and increased immunological activity are enhanced in islets from newly diagnosed type 1 diabetes patients compared to controls. The increases in viral response proteins seen in ß-cells in newly diagnosed type 1 diabetes provide clear evidence for the activation of IFN signalling pathways. As such, these data strengthen the hypothesis that an enteroviral infection of islet ß-cells contributes to the pathogenesis of type 1 diabetes.

Comparison of the polyphenol content and in vitro antioxidant capacity of fruit-based nutritional supplements commonly consumed by athletic and recreationally active populations.

Background: Polyphenol-rich fruit supplements are commonly consumed by recreationally active and athletic populations because of their proposed benefits to both exercise performance and recovery from prior exercise. While it has been proposed that 300 mg of polyphenols pre-exercise enhances performance and 1000 mg per day accelerates recovery from muscle damage, it is difficult for consumers to optimize their intake because the polyphenol content of most fruit supplements is not available. Therefore, this study aimed to profile the phenolic and anthocyanin content and in vitro antioxidant capacity of a range of polyphenol-rich fruit supplements on sale in the UK. Methods: Ten polyphenol-rich fruit supplements (six cherry, two pomegranate, one blueberry, and one New Zealand blackcurrant) commonly consumed by athletes were analyzed for total phenols (Folin-Ciocalteu method), total anthocyanins (pH differential method), and in vitro antioxidant capacity (ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). Results: The ten tested supplements varied markedly per serving in total phenolics (range: 13.8-1007.3 mg/gallic acid equivalents), anthocyanin content (range: 0.19-40.52 mg/cyanidin-3-glucoside), ORAC (range: 150-10,072 µmol of trolox equivalents), and FRAP (range: 72-14,320 µmol of Fe2+ equivalents). Different brands of tart cherry concentrate also exhibited a marked variation in their content of total phenolics (208-591 mg/GAE), anthocyanins (1.5-23.7 mg/cyd-3-glu), and antioxidant capacity (FRAP: 1724-4489 µmol of Fe2+ equivalents; ORAC: 6015-10,072 µmol of TE per serving) per serving. Conclusion: As expected, supplements based on different fruits contained different quantities of anthocyanins and polyphenols. However, there was also a substantial variation within different brands of tart cherry supplements. Because limited compositional information is available on the labels of most fruit-based supplements, the data in this article will enable consumers to select the required volume of the ten tested supplements to meet suggested recommendations for polyphenol intake to enhance performance (300 mg pre-exercise) and accelerate recovery (1000 mg per day) from prior exercise.

Single-fraction high-dose palliative radiotherapy for facial cutaneous squamous cell carcinoma: a case report.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a common malignancy affecting the skin, and its incidence increases with age; as such, it disproportionately affects the elderly. It is especially difficult to treat advanced skin cancers in elderly patients with dementia, who may not tolerate radiotherapy. CASE DESCRIPTION: A 100-year-old woman with advanced dementia was referred to dermatology for a large cSCC involving the nasal bridge and abutting the bilateral orbits. She was initially deemed a poor candidate for surgical resection, but over time the tumor grew and became increasingly destructive. Due to tumor growth causing symptoms and threatening vision, her family requested treatment. The patient was therefore referred to radiation oncology, and she received palliative radiation, using a single fraction of 16 gray (Gy) via a single electron field. Within 3 months, she had a clinical complete response, with no residual tumor and no persistent side effects from radiotherapy (RT). Ongoing follow-up revealed durable treatment response with no bothersome late toxicity. CONCLUSIONS: Single-fraction palliative radiotherapy is a suitable treatment option for durable palliation in elderly patients unable to undergo surgery and unable to tolerate conventional, fractionated RT in cases of symptomatic or rapidly-progressing non-melanoma skin cancers (NMSC). It is well-tolerated in frail patients or those with dementia.

Surgical delays of less than 1 year in Mohs surgery associated with tumor growth in moderately- and poorly-differentiated squamous cell carcinomas but not lower-grade squamous cell carcinomas or basal cell carcinomas: A retrospective analysis.

BACKGROUND: Evidence is controversial and limited concerning whether surgical delays are associated with tumor growth for cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas. OBJECTIVE: Identify tumor subpopulations that may demonstrate an association between tumor growth and surgical delay. METHODS: We retrospectively analyzed 299 SCCs and 802 basal cell carcinomas treated with Mohs surgery at a single institution. Time interval from biopsy to surgery represented surgical delay. Change in major diameter (ΔMD) from size at biopsy to postoperative defect represented tumor growth. Independent predictors of ΔMD were identified by multivariate analysis. Linear regression was then utilized to assess for whether the ΔMD from these independent predictors trended with surgical delay. RESULTS: Surgical delays ranged from 0 to 331 days. Among SCCs, histologic subtype and prior treatment were identified as independent predictors of ΔMD. Significant associations between ΔMD and surgical delay were found for poorly- and moderately-differentiated SCCs, demonstrating growth rates of 0.28 cm and 0.24 cm per month of delay, respectively. The ΔMD for SCCs with prior treatment and basal cell carcinoma subgroups did not vary with surgical delay. LIMITATIONS: Retrospective design, single center. CONCLUSION: Surgical delays of less than a year were associated with tumor growth for higher-grade SCCs, with effect sizes bearing potential for clinical significance.

Doubly Misdiagnosed: Exophiala Masquerading as Squamous Cell Carcinoma and Chromoblastomycosis.

ABSTRACT: Deep cutaneous fungal infections (DCFI) can arise in the setting of skin trauma and immunosuppression. DCFI may be secondary to chromoblastomycosis, which is typically characterized by pseudoepitheliomatous hyperplasia histologically and can be mistaken for squamous cell carcinoma. In addition, "copper penny" spore-like pigmented yeast forms on Grocott's methenamine silver stain can suggest chromoblastomycosis, but this finding is not specific. By contrast, phaeohyphomycosis characteristically exhibits circumscribed pseudocyst or abscess on histopathology, and both yeast and hyphae can be seen. Our case reports a DCFI with pseudoepitheliomatous hyperplasia and "copper penny" yeast forms, ultimately diagnosed as phaeohyphomycosis after isolating Exophiala spinifera on fungal culture.

Intraoperative Diagnosis of Histologic Change in Irradiated Skeletal Muscle.

ABSTRACT: Adjuvant radiation may be used to reduce the recurrence of high-risk cutaneous squamous cell carcinoma after resection. Adjuvant radiation can produce histologic changes in the skeletal muscle that mimic keratinocyte atypia, presenting a diagnostic challenge during subsequent resections. We present a case of cutaneous squamous cell carcinoma and histologic changes observed in a fresh frozen section that were consistent with degenerative changes of irradiated skeletal muscle that had a muscle-specific actin+, Melan-A-, and cytokeratin- immunophenotype on paraffin-embedded permanent sections. We also reviewed the literature of other similar reported findings on irradiated skeletal muscle.

Effect of Polyphenol-Rich Foods, Juices, and Concentrates on Recovery from Exercise Induced Muscle Damage: A Systematic Review and Meta-Analysis.

Objectives. To determine the effects of consuming polyphenol-rich foods, juices and concentrates on recovery from exercise-induced muscle damage (EIMD). Method. Eligibility criteria. Randomised and quasi-randomised placebo-controlled trials with a parallel or cross-over design evaluating the effects of consuming polyphenol-rich foods, juices and concentrates on recovery from EIMD in humans. Eligible studies included at least one of the primary outcome measures: maximal isometric voluntary contraction; MIVC, delayed onset muscle soreness; DOMS, or countermovement jump; CMJ. Information sources. AMED, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, PUBMED, SCOPUS (Elsevier), SPORTDiscus (EBSCO), and the UK Clinical Trials Gateway were searched from inception to September 2020. Risk of bias and quality of evidence. Risk of bias was assessed using Cochrane Risk of Bias 2 tool. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Synthesis of results. Random effects models were used to determine the effect of polyphenol supplementation on recovery from EIMD. Data are presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Results. Included studies. Twenty-five studies were included; 15 had a parallel, and 10 had a cross-over design. A total of 527 participants (male: n = 425; female: n = 102) were included in the meta-analysis. Synthesis of results. Consumption of polyphenol-rich foods, juices and concentrates accelerated recovery of MIVC immediately post-exercise (SMD = 0.23, 95% CI 0.04, 0.42; p = 0.02; low-quality evidence), 24 h (SMD = 0.39, 95% CI 0.15, 0.62; p = 0.001; low-quality evidence), 48 h (SMD = 0.48, 95% CI 0.28, 0.67; p < 0.001; moderate-quality evidence), 72 h (SMD = 0.29, 95% CI 0.11, 0.46; p = 0.001; low-quality evidence) and 96 h post-exercise (SMD = 0.50, 95% CI 0.16, 0.83; p = 0.004; very low-quality evidence). DOMS was reduced at 24 h (SMD = -0.29, 95% CI -0.47, -0.11; p = 0.002; low-quality evidence), 48 h (SMD = -0.28, 95% CI -0.46, -0.09; p = 0.003; low-quality evidence) and 72 h post-exercise (SMD = -0.46, 95% CI -0.69, -0.24; p < 0.001; very low-quality evidence). CMJ height was greater immediately post-exercise (SMD = 0.27, 95% CI 0.01, 0.53; p = 0.04; low-quality evidence), at 24 h (SMD = 0.47, 95% CI 0.11, 0.83; p = 0.01; very low-quality evidence), 48 h (SMD = 0.58, 95% CI 0.24, 0.91; p < 0.001; very low-quality evidence) and 72 h post-exercise (SMD = 0.57, 95% CI 0.03, 1.10; p = 0.04; very low-quality evidence). Polyphenol supplementation did not alter creatine kinase, c-reactive protein, and interleukin-6 at any time points. At 72 h post-exercise, protein carbonyls (SMD = -0.64, 95% CI -1.14, -0.14; p = 0.01) were reduced. Discussion. Limitations of evidence. Risk of bias was high for 10 studies and moderate for 15. Sensitivity analyses excluding the high risk of bias studies reduced the SMDs for MIVC and DOMS, and for CMJ effects at 24 and 48 h were no longer statistically significant. Interpretation. Consuming polyphenol-rich foods, juices and concentrates accelerated recovery of muscle function while reducing muscle soreness in humans. Maximal benefit occurred 48-72 h post-exercise, however, the certainty of the evidence was moderate to very low. Supplementation could be useful when there is limited time between competitive events and impaired recovery could negatively impact performance.