Systematic Review Of Clinical Studies Research Articles

The gut microbiome in alcohol use disorder and alcohol-associated liver disease: A systematic review of clinical studies.

Evidence suggests that a relationship exists between the gut microbiome and the pathogenesis of alcohol use disorder (AUD) and alcohol-associated liver disease (AALD). This systematic review identified studies that investigated the gut microbiome in individuals with an AUD or an AALD. A search was conducted on October 27, 2022, in PubMed, Web of Science, and Embase databases. Fifty studies satisfied eligibility criteria. Most studies found evidence for gut dysbiosis in individuals with AUD and AALD. Microbiome intervention studies have mostly been conducted in AALD patients; fecal microbial transplant interventions show the most promise. Because most studies were conducted cross-sectionally, the causal relationship between the gut microbiome and alcohol use is unknown. Furthermore, almost all studies have been conducted in predominantly male populations, leaving critical questions regarding sex differences and generalizability of the findings. The study summaries and recommendations provided in this review seek to identify areas for further research and to highlight potential gut microbial interventions for treating AUD and AALD.

Assessment of Native Myocardial T1 Mapping for Early Detection of Anthracycline-Induced Cardiotoxicity in Patients with Cancer: a Systematic Review and Meta-analysis.

Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger's test. According to the Qtest, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.

A Systematic Review of Clinical Studies Investigates the Role of Serum Prolactin Levels in Women with Uterine Fibroids

A Systematic Review of Clinical Studies Investigates the Role of Serum Prolactin Levels in Women with Uterine Fibroids

Probiotics in autism spectrum disorders: a systematic review of clinical studies and future directions.

It is hypothesized that gut dysbiosis, a typical feature of patients with autism spectrum disorder (ASD), could be involved in the origin of this neurodevelopmental disorder. Therefore, the use of probiotics to restore gastrointestinal (GI) equilibrium might be a promising therapeutic strategy due to its capacity to balance the gut-brain axis and behavioral responses. To summarize current knowledge on the use of probiotics to treat core clinical ASD symptoms and concomitant GI signs, compare the design of published studies with those of ongoing trials, assess the near future of this field, and provide recommendations for improving novel studies. The literature search was conducted in February 2020 and updated in March 2021, using a broad range of bibliographic and clinical trial-specific databases. Data were extracted using a standardized form, and articles reporting on 28 clinical studies (already published or still ongoing) were included. The risk of bias in clinical studies was evaluated using the Cochrane Collaboration Risk of Bias Assessment tool for randomized trials and the Risk of Bias in Nonrandomized Studies-Interventions tool for nonrandomized trials. The results suggest that probiotics improve ASD-like social deficits, GI symptoms, and gut microbiota profile. However, inconsistencies among studies and their methodological limitations make it difficult to draw any conclusions regarding the efficacy of probiotics in ASD. This review provides specific suggestions for future research to improve the quality of the studies. Although ongoing studies have improved designs, the available knowledge does not permit solid conclusions to be made regarding the efficacy of probiotics in ameliorating the symptoms (psychiatric and/or GI) associated with ASD. Thus, more high-quality research and new approaches are needed to design effective probiotic strategies for ASD.

Ozone Treatment for the Management of Caries in Primary Dentition: A Systematic Review of Clinical Studies.

Dental caries in children is a frequent and debilitating condition, whose management is often challenging. The aim of this systematic review was to investigate the effectiveness of ozone applications for the treatment of caries in primary dentition. According to PRISMA guidelines, a systematic literature search was performed up to 6 January 2024. Clinical studies using ozone to treat caries of deciduous teeth were considered for inclusion. Out of the 215 records retrieved, seven studies were eventually included in the review, all of which used gaseous ozone. Four studies were judged at high risk of bias, two at low risk, and one of some concerns. The great heterogeneity of designs, outcomes, and protocols made it impossible to conduct a meta-analysis. Despite some limitations, the evidence yielded by the included studies suggests that ozone application, regardless of the protocol applied, is comparable to other interventions in terms of clinical outcomes and anti-bacterial activity, with no reported adverse effects and good patient acceptance. Therefore, ozone application may be a non-invasive approach to treat caries in primary dentition, especially in very young and poorly cooperative patients. Further standardized and rigorous studies are, however, needed to identify the best clinical protocols for this specific field.

Zingiber officinale Roscoe (Ginger) and its Bioactive Compounds in Diabetes: A Systematic Review of Clinical Studies and Insight of Mechanism of Action

Zingiber officinale Roscoe (Ginger) belongs to the Zingiberaceae family, which is renowned for its rich nutritional and phytochemical composition, and has been validated for its anti-diabetic and anti-inflammatory properties via in vitro, in vivo, and clinical studies. Nonetheless, a comprehensive review of these pharmacological studies, especially clinical studies, together with an analysis of the mechanism of action of the bioactive compounds is still lacking. This review provided a comprehensive and updated analysis of the anti-diabetic efficacy of Z. officinale and its compounds ginger enone, gingerol, paradol, shogaol, and zingerone. The present systematic review was conducted using the PRISMA guidelines. Scopus, ScienceDirect, Google Scholar, and PubMed were the main databases used for retrieving information from inception to March 2022. From the findings obtained, Z. officinale can be regarded as a therapeutic species showing significant improvement in clinical studies on glycemic parameters (Fasting blood glucose (FBG), hemoglobin A1C (HbA1c), and insulin resistance). In addition, the bioactive compounds of Z. officinale act via several mechanisms as revealed by in vitro and in vivo studies. Overall, these mechanisms were by increasing glucose-stimulated insulin secretion, sensitising insulin receptors and raising glucose uptake, translocation of GLUT4, inhibition of advanced glycation end product-induced increase of reactive oxygen species, regulation of hepatic gene expression of enzymes associated with glucose metabolism, regulation of the level of pro-inflammatory cytokines, amelioration of the pathological injuries of kidneys, protective effect on the morphology of β-cells as well as its antioxidant mechanisms, among others. Z. officinale and its bioactive compounds displayed promising results in in vitro and in vivo systems, nevertheless, it is highly recommended that human trials be conducted on these compounds since clinical studies are the core of medical research and considered the final stages of the drug development process.

Cardiac Toxicity in the Treatment of Light Chain Amyloidosis: Systematic Review of Clinical Studies.

Light chain amyloidosis (AL) is a progressive and a fatal disease that primarily affects cardiac tissue. Although the current approach to anti-amyloidosis treatments has managed to reduce amyloidosis morbimortality, the dynamics of cardiac adverse events are unknown. to provide evidence about reported cardiac toxicity during treatment of AL amyloidosis through a systematic review of the literature. A search was performed for registered clinical trials on ClinicalTrials.gov filtered for AL amyloidosis up to December 31, 2022. Studies were filtered by those that reported intervention in patients with AL amyloidosis and that had reported adverse events. The type of study, the intervention performed, and the frequency of reported cardiac adverse events were discriminated from each trial. 25 clinical trials were analyzed, representing a population of 1,542 patients, among whom 576 (38.95%) adverse events were reported, 326 being serious (SAE) and 242 nonserious (nSAE). The most frequent SAEs were cardiac failure, atrial fibrillation, and cardiac arrest, while the most frequent nSAEs were palpitations, atrial fibrillation, and sinus tachycardia. cardiac toxicity during treatment for amyloidosis seems common, and it is important to evaluate the relationship of therapies with its occurrence.

Topical Chinese patent medicines for chronic musculoskeletal pain: systematic review and trial sequential analysis

PurposeChronic musculoskeletal pain (CMP) is defined as persistent or recurrent pain that occurs in the joints, musculo-soft tissue, spine or bones for more than three months and is not completely curable. Although topical Chinese patent medicine (CPM) is the most extensively utilized medication in Asia and is widely used for pain management, its efficacy remains controversial. This article presents a systematic review of clinical studies on the therapeutic properties of topical CPM for CMP patients to better inform clinical decision-making and provide additional and safer treatment options for patients with CMP.MethodWe performed a comprehensive search on PubMed, Cochrane Library, web of science and Chinese databases (CNKI and WanFang data) from 2010 to 2022. In all the studies, knee osteoarthritis, cervical spondylosis, low back pain, and periarthritis of shoulder met the International Pain Association definition of chronic musculoskeletal pain. We included only randomized controlled trials (RCTs) using topical CPM primarily for chronic musculoskeletal pain in adults. To determine the effect of topical CPM on clinical symptoms, we extracted the Visual Analog Scale (VAS, range 0–10) and the Western Ontario and McMaster Universities Arthritis Index pain scores (WOMAC pain, range 0–20), in which the lower the score, the better the results. We also accepted the comprehensive outcome criteria developed by the Chinese National Institute of Rheumatology as an endpoint (total effectiveness rate, range 0–100%, higher score = better outcome), which assesses the overall pain, physical function and wellness. Finally, trial sequential analysis of VAS pain score and total effectiveness rate was performed using TSA software.ResultsTwenty-six randomized controlled trials (n = 3180 participants) compared topical CPM with oral Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (n = 15), topical NSAIDs (n = 9), physiotherapy (n = 5), exercise therapy (n = 4), and intra-articular Sodium hyaluronate injection (n = 2). Sixteen studies found that topical CPM was statistically significant in improving CMP pain (measured by VAS pain and Womac pain scores)(p < 0.05), and 12 studies found topical CPMs to be more clinically effective (assessed by ≥ 30% reduction in symptom severity) in treating patients with CMP (p < 0.05). Trial sequential analysis indicates that the current available evidence is robust, and further studies cannot reverse this result. In most of the studies, randomisation, allocation concealment and blinding were not sufficiently described, and no placebo-controlled trials were identified.ConclusionMost studies showed superior analgesic effects of topical CPM over various control treatments, suggesting that topical CPM may be effective for CMP and is an additional, safe and reasonable treatment option. These reported benefits should be validated in higher-quality RCTs.

99mTc-MIBI washout rate as a marker of myocardial mitochondrial dysfunction: A systematic review and meta-analysis

BACKGROUND: This review outlines the features of the pharmacokinetics of the perfusion radiopharmaceutical 99mTc-MIBI, which allows the assessment of myocardial mitochondrial dysfunction, and shows the main clinical applications of the phenomenon of increased 99mTc-MIBI washout rate.&#x0D; AIM: To systematize the data of fundamental (experimental) and clinical studies evaluating and estimating mitochondrial dysfunction according to myocardial perfusion scintigraphy data and perform meta-analysis of clinical studies in this field.&#x0D; MATERIALS AND METHODS: PubMed, Scopus, Google Scholar, and eLibrary databases were searched until mid-2023. The following keywords, their combinations, and Russian-language counterparts were used: mitochondrial dysfunction, 99mTc-MIBI, 99mTc-Tetrofosmin, myocardial perfusion scintigraphy, reverse redistribution, washout, and washout rate. In the meta-analysis, a random-effects model was used to calculate the mean difference estimate.&#x0D; RESULTS: Forty articles were selected for systematic analysis: 13 were experimental, 24 were original clinical papers, 2 were clinical cases, and 1 was a review. Six studies using a case–control design were selected for the meta-analyses. The total number of patients in the systematic review and meta-analysis were 551 and 196, respectively. In the analysis of the literature, the severity of the reverse redistribution phenomenon and 99mTc-MIBI washout rate correlated with mitochondrial and myocardial microstructure, left ventricular contractility and hemodynamics, natriuretic peptide levels, exercise tolerance, coronary atherosclerosis severity, myocardial oxidative metabolism, and risk of cardiovascular events. The meta-analysis showed that the washout rate was statistically significantly accelerated in individuals with cardiac pathologies, relative to controls (mean difference score, 9.5771 [95%]; confidence interval, 6.6001–12.5540; z=6.3053, p 0.0001).&#x0D; CONCLUSION: The assessment of mitochondrial function by 99mTc-MIBI washout evaluation may provide additional insights into the functional status of cardiac muscles.

Clinical Features of Myeloid Neoplasms with Germline GATA2 Mutations–a Systematic Review of Clinical Studies Retrieved through Extensive Searching

Aims: Recent findings increasingly find individuals are being recognized as having germline predisposition to myeloid malignancies. GATA2 mutation is one of the most extensively studied germline mutations. However, until recently most of studies have focused on the mechanism of how GATA2 as one of the driver mutations causes malignancies. As regards the clinical features, such as the treatment and prognosis of myeloid neoplasms associated with germline GATA2 mutations, only small studies published, based on which they were insufficiently studied. Therefore, we did the systematic review to summarize the diagnosis, therapeutic methods and prognosis of myeloid malignant diseases associated with germline GATA2 mutations. Methods: Two reviewers independently comprehensively searched Pubmed and hand searched the professional journals and the reference lists of related and included articles from Jan 1 st, 1990 until May 1 st, 2023. They also independently screened and evaluated the retrieved records and then extracted data of included studies. Studies reported clinical materials on the diagnosis, treatment and prognosis of myeloid malignant patients with germline GATA2 mutations will be included and the clinical data will be summarized. Searching strategies were as follows: #1 germline or predispo* or somat* or famil* or germ line or congenit* or altera* or non-tumor; #2 gene* or genom* or sequenc* or muta* or SNP or abnormal* or translocat* or chromosom* or frameshift* or exom* or GATA; #3 “acute myeloid leukemia” “Leukemia, Myeloid, Acute” “Myelodysplastic Syndromes” “refractory anemia” “myeloid or myeloblast*” or AML or MDS; #4 #1 and #2 and #3 Results: 2457 records were retrieved and 23 studies with 396 patients were included. Screening process was shown in Figure 1. Studies included were all small sample sized. The diagnosis age was from three to 78 years old, most of the median ages of included studies were less than 30 years indicated carriers would have symptoms in young age, on the other hand, there were also patients who began having symptoms in old age (the oldest 78 years) or remained asymptomatic carriers without getting sick in the whole life. There was no sex difference. Emberger syndrome which caused lymphedema and MonoMAC and/or DCML (dendritic cell, monocyte, B-lymphocyte and NK-lymphocyte) deficiency syndromes that caused cytopenia and infections were generally appeared earlier before myeloid malignancies. Myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) are common malignant diseases for patients with germline GATA2 mutations predisposition. The morbidity was not able to be calculated based on the data available. MDS was the most common myeloid neoplasm compared with AML and CMML which were always transformed from MDS. Other hematologic malignancies were rare. The disease transformation was shown from refractory cytopenia to malignant clonal hematopoiesis that caused MDS, and then transformed into leukemia. In total, 311/396 (78.5%) patients developed malignant myeloid diseases. Nine studies had done the family pedigree analysis and there were 162 family members who had the germline GATA2 mutations predisposition, in which there were 32 asymptomatic carriers (19.7%). 128 patients were reported to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT), 81 (63.3%) were alive and 44 (34.4%) died of relapse or transplantation related complications. Three patients' outcome was unknown. In study Michael A. Spinner et al, survival rate was 54% by 4 years after allo-HSCT (21 patients included). Nearly all patients (15/18) with myeloid malignancies who did not receive transplantation had died. The most common cytogenetic abnormalities were monosomy 7 and trisomy 8, and other abnormalities were also common. Conclusions: Most of germline GATA2 mutation carriers will have symptoms in young age and many of them will progress into malignant myeloid diseases. Allo-HSCT was effective to treat symptomatic patients, especially for patients with malignant hematologic diseases, and furthermore that is the only curative treatment. Asymptomatic carriers are not rare and for them regular tests are essential. More clinical studies on germline GATA2 mutations for myeloid neoplasms are needed to clarify the clinical features in this setting and improve its treatment and prognosis.

Role of oral microbiota in Alzheimers disease: A systematic review of clinical studies

Alzheimers disease (AD) is one of the most common neurodegenerative diseases in the world, causing dementia among the elderly. Oral microbiome may be associated with AD. This systematic review summarizes the current role of the oral microbiome in the etiology and diagnosis of AD. Articles included were sourced primarily from electronic databases including PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library from January 2011 to August 2022 and in OpenGrey and Google Scholar for grey literature. Relevant studies were selected using a two-stage approach involving the screening of titles and abstracts and full-text evaluation by two authors. Risk of bias was also performed using the Newcastle Ottawa scale (NOS) before qualitative synthesis. 18 studies out of 1079 citations were included in this review. The median NOS rating (IQR) of the reviewed studies was 8 (7.25 9). Most studies suggested that there was an association between oral microbiome and AD. Some claimed that oral microbiome might be the risk factor of AD using disparate approaches. Others also detected antibodies to oral microorganisms among AD patients and observed a significantly different alpha diversity among patients with AD than controls. Although limited by the number of studies, this review found that a change in the oral microbiome may be indicative of AD severity. Oral microbiome may be associated with Alzheimers disease. Some microbial species may be risk factors or aid diagnosis for AD, however more research is still needed to establish their role in AD etiology and noninvasive diagnosis.

Is the Use of Ozonated Oil Effective in the Treatment of Oral Lesions? Systematic Review of Clinical Studies

The aim of this study was to perform a systematic review (SR) of the therapeutic effect of ozonated oil for oral lesions treatment. A SR was conducted according to the PRISMA guidelines. The Medline (PubMed), Embase, Cochrane Library, Scielo and LILACS were investigated, together with manual searches, to extract all publications until December 2020, including randomized and non-randomized clinical trials reporting the effects of ozonated oils on the management of oral lesions when compared with other methods. The risk of bias (RoB) of the studies included were assessed by using the RoB 2 tool and ROBINS-I. After analyzing the titles and reading the abstracts, 1932 articles were excluded; the remaining 25 passed a full-text evaluation. Ultimately, 13 articles were included in this SR. There was heterogeneity of the results regarding healing times and intervals of ozonated oil application for the treatment of each type of oral lesion, but in general, there was a shorter healing time when ozonated oil was used as therapy, and no adverse effects were reported. Despite the limited information found and the lack of rigorous methodological standards for the use of ozonated oil on oral lesions, a positive effect was suggested. The findings indicated an advantage in terms of shorter healing times when compared with other conventional treatments. No adverse effects were reported, showing safety and reliability for patient’s treatment.

43591 The Coronation of Thiamidol: A Systematic Review of Clinical Studies Investigating the Topical Use of Thiamidol in Combating Hyperpigmentation

43591 The Coronation of Thiamidol: A Systematic Review of Clinical Studies Investigating the Topical Use of Thiamidol in Combating Hyperpigmentation

Lithium in bipolar depression: A review of the evidence.

Lithium is widely used as treatment of acute mania and as prophylactic therapy for bipolar disorder. International and national guidelines also consider lithium as a possible treatment of acute bipolar depression. Research on the use of lithium in bipolar depression, however, seems to be limited compared to the data available for its efficacy in the other phases of bipolar disorder. To provide a systematic review of the evidence for lithium in the treatment of acute bipolar depression and provide directions for further research. A systematic review of clinical studies investigating the use of lithium in bipolar depression was performed using preferred reporting items for systematic reviews and meta-analyses guidelines in Pubmed, Embase and Psychinfo using the medical subjects headings and free text terms "lithium," "bipolar depression," "dosage," "serum concentration" and "bipolar disorders." This review included 15 studies with a total of 1222 patients, between the age of 18 and 65, suffering from bipolar depression of which 464 were treated with lithium. There are currently only limited and low-quality data on the efficacy of lithium as a treatment of bipolar depression. It appears that there have been no placebo controlled randomized controlled trials with lithium concentrations that are considered to be therapeutic. The older studies suffered from limitations such as small sample sizes, insufficient treatment lengths, and insufficient monitoring of serum concentrations. In contrast to data for the treatment of mania and prophylaxis, robust data on the efficacy of lithium in bipolar depression is currently lacking, making it impossible to make conclusions regardingefficacy or inefficacy, for which further research is needed.

Neuroendocrine Biomarkers of Herbal Medicine for Major Depressive Disorder: A Systematic Review and Meta-Analysis.

Major depressive disorder (MDD) is a medical condition involving persistent sadness and loss of interest; however, conventional treatments with antidepressants and cognitive behavioral therapy have limitations. Based on the pathogenesis of MDD, treatments using herbal medicines (HM) have been identified in animal studies. We conducted a systematic review of clinical studies to identify neurobiological outcomes and evaluate the effectiveness of HM in treating MDD. A meta-analysis was performed by searching nine databases from their inception until 12 September 2022, including 31 randomized controlled trials with 3133 participants, to examine the effects of HM on MDD using neurobiological biomarkers and a depression questionnaire scale. Quality assessment was performed using a risk of bias tool. Compared to antidepressants alone, HM combined with an antidepressant significantly increased concentrations of serotonin (SMD = 1.96, 95% CI: 1.24-2.68, p < 0.00001, I2 = 97%), brain-derived neurotrophic factor (SMD = 1.38, 95% CI: 0.92-1.83, p < 0.00001, I2 = 91%), and nerve growth factors (SMD = 2.38, 95% CI: 0.67-4.10, p = 0.006, I2 = 96%), and decreased cortisol concentrations (SMD = -3.78, 95% CI: -4.71 to -2.86, p < 0.00001, I2 = 87%). Although HM or HM with an antidepressant benefits MDD treatment through improving neuroendocrine factors, these findings should be interpreted with caution because of the low methodological quality and clinical heterogeneity of the included studies.

Complications associated with vertical bone augmentation techniques in implant dentistry: A systematic review of clinical studies published in the last ten years

Vertical bone augmentation procedures are increasingly necessary in daily practice. However, it has been reported that vertical ridge augmentation is one of the least predictable techniques in terms of complications. The aim of this systematic review was to evaluate and compare complications in relation to the different procedures used for vertical bone augmentation prior to implant placement. This review was conducted according to PRISMA guidelines. An electronic search was carried out in four databases: The National Library of Medicine (MEDLINE/PubMed); Web of Science; SCOPUS; and Cochrane Central Register of Controlled Trials (CENTRAL). The Newcastle–Ottawa Quality Assessment Scale, the Cochrane Collaboration tool for assessing risk of bias, and The Joanna Briggs Institute Critical Appraisal tool were used to assess the quality of evidence in the studies reviewed. Twenty-five studies with a total of 749 vertically augmented sites were included in the review. Complication rates varied among the different procedures: 51.02% for distraction osteogenesis, 38.01% for bone blocks, and 16.80% for guided bone regeneration. Vertical bone augmentation procedures prior to implant placement are associated with frequent surgical complications and should be approached with caution due to their possible impact on clinical treatment success.

Bromelain-based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long-term outcomes.

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy.

Searching for the Best Treatment for Ramp Lesions: A Systematic Review and Network Meta-Analysis.

Ramp lesions are a common occurrence in patients with anterior cruciate ligament (ACL) tears. These lesions can be difficult to diagnose due to their concealed nature, and their treatment is crucial due to the stabilizing function of the medial meniscocapsular region. The optimal treatment option for ramp lesions varies depending on the size and stability of the lesion. The purpose of this study was to evaluate the best treatment option for ramp lesions based on the stability of the lesion, including no treatment, biological treatment, and arthroscopic repair. We hypothesize that stable lesions have a favorable prognosis with techniques that do not require the use of meniscal sutures. In contrast, unstable lesions require appropriate fixation, either through an anterior or posteromedial portal. This study is a systematic review and meta-analysis with a level of evidence IV. The study used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for a systematic review of clinical studies reporting outcomes of ramp lesion treatment. The PubMed/MEDLINE database was searched using Mesh and non-Mesh terms related to ramp lesions, medial meniscus ramp lesions, and meniscocapsular injuries. The inclusion criteria encompassed clinical studies in English or Spanish that reported the treatment of ramp meniscal lesions, with a follow-up of at least six months and inclusion of functional results, clinical stability tests, radiological evaluation, or arthroscopic second look. The analysis included 13 studies with 1614 patients. Five studies distinguished between stable and unstable ramp lesions using different criteria (displacement or size) for assessment. Of the stable lesions, 90 cases received no treatment, 64 cases were treated biologically (debridement, edge-curettage, or trephination), and 728 lesions were repaired. There were 221 repaired unstable lesions. All different methods of repair were registered. In stable lesions, three studies were included in a network meta-analysis. The best-estimated treatment for stable lesions was biological (SUCRA 0.9), followed by repair (SUCRA 0.6), and no treatment (SUCRA 0). In unstable lesions, seven studies using International Knee Documentation Committee Subjective Knee Form (IKDC) and 10 studies using Lysholm for functional outcomes showed significant improvement from preoperative to postoperative scores after repair, with no differences between repairing methods. We recommend simplifying the classification of ramp lesions as stable or unstable to determine treatment. Biological treatment is preferred for stable lesions rather than leaving them in situ. Unstable lesions, on the other hand, require repair, which has been associated with excellent functional outcomes and healing rates.

Paper 18: A Prospective, Randomized Trial of the Modified Jobe vs. Modified Docking Techniques for Ulnar Collateral Ligament Reconstruction in the Elbow

Objectives: Overhead throwing athletes, notably pitchers, subject the elbow to tremendous valgus stress, and numerous studies have demonstrated an increasing incidence of ulnar collateral ligament of the elbow (UCL) injury. However, surgical reconstruction has transformed this injury from career-ending to career-interruptive. Two primary techniques exist for UCL reconstruction (UCLR): 1) the Modified Jobe and 2) the Modified Docking techniques. Prior biomechanical comparisons have reported equivalent ulnohumeral stability. Systematic reviews of clinical studies have suggested that the Docking technique may result in improved rates of return to play (RTP) and fewer complications, but these comparisons have been indirect and complicated by changes in technique. Our objective was to perform the first prospective, randomized comparison of UCLR utilizing the Modified Jobe or Modified Docking technique as measured by Kerlan-Jobe Orthopaedic Clinic (KJOC) score, Andrews-Timmerman score, and Conway-Jobe score. As secondary outcomes, we sought to compare pre- and postoperative imaging characteristics, required tourniquet times, rate of complications, and RTP data. We hypothesized that no difference exists between the two techniques with regard to any of the above outcomes. Methods: This study was a single-surgeon, prospective, randomized trial comparing the Modified Jobe and Modified Docking techniques for primary UCLR. Patients were eligible if they had clinical and radiographic evidence of UCL injury and participated in overhead sports. Patients were excluded if they were not an overhead athlete, lacked clinical and radiographic evidence of a UCL tear, or had a history of previous elbow surgery. An a priori power analysis was performed utilizing historic data from both techniques to generate a sample size of 80 (40 in each group). All patients were randomized to one of the two techniques for UCLR using a standardized, contralateral gracilis autograft. All patients underwent the same postoperative rehabilitation protocol including throwing and batting progressions. Patient reported outcomes (PROs; KJOC score, Andrews-Timmerman score, and Conway-Jobe score) were obtained preoperatively and at 6 months, 1 year, 18 months, and 2 years postoperative. Pre- and post-operative imaging including both stress ultrasound (SUS) and magnetic resonance (MRI/MRA) were obtained. Additional information including demographics, intraoperative data, complications, and RTP data were collected. T-tests or Mann-Whitney U tests were used to calculate differences between continuous data. Chi-Square or Fisher’s Exact were used for categorical data. Results: There were 40 patients (38M/2F) enrolled in the Jobe group and 40 patients (39M/1F) enrolled in the Docking group. Demographics including sex ratio, age, time between injury and surgery, and sport and level of play were similar between groups. Detailed patient demographic data is given in Table 1. Six patients in the Jobe group and eight patients in the Docking group underwent concomitant anterior subcutaneous UNT (p=0.769). Gracilis autograft harvest and closure required similar mean tourniquet time in both groups (28.7 minutes in Jobe group vs 28.3 minutes in Docking group; p=0.721). However, UCLR required significantly longer upper extremity tourniquet time in the Jobe group (101.0 minutes vs. 92.0 minutes; p=0.008). Preoperatively, patients reported similar levels of function via all PROs. Postoperatively at 6 months, 1 year and 18 months, both groups reported similar PROs. At two years, patients reported similar scores in terms of Andrews Timmerman and Conway Jobe scores, however the Docking group reported significantly higher mean KJOC scores (75.0 vs 85.0; p=0.025). Following surgery, both groups took a similar mean time to swing a bat, to begin tossing, and to begin a mound program. Of the patients that returned for two year follow up in clinic, 28/32 in the Jobe group returned to play at a mean of 13.4 months, compared to 27/27 in the Docking group who returned to play at 14.3 months (p=0.166). Detailed patient outcome data is given in Table 2. All grafts were intact and showed progressive healing on MR and SUS at final radiographic follow-up. There were no significant differences in the rate of complications. One patient in the Docking group required reoperation with revision ulnar nerve decompression with transposition for persistent ulnar nerve symptoms. No patient in the Jobe group required reoperation. Conclusions: This study is the first and only prospective, randomized trial evaluating the outcomes of the Modified Jobe and Modified Docking techniques for UCLR. The study identified high rates of good-to-excellent results with equivalent RTP rates and time to RTP for both techniques. Surgeons should continue to utilize the technique with which they are most comfortable, but the Docking technique demonstrated reduced tourniquet times and superior KJOC scores at 2 years. [Table: see text][Table: see text]

Cannabinoids in Treating Parkinson's Disease Symptoms: A Systematic Review of Clinical Studies.

Background: Parkinson's disease (PD) is a serious neurodegenerative condition impacting many individuals worldwide. There is a need for new non-invasive treatments of PD. Cannabinoids in the form of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) may offer utility as treatment, and our objective was hence to conduct a systematic review regarding the clinical evidence for the efficacy and safety of cannabinoids in treating PD. Methods: Screening, data extraction, and quality assessments were all conducted by multiple reviewers, with discrepancies resolved by consensus. Results: After conducting searches in 4 different databases, 673 articles were screened. Thirteen articles were deemed eligible for inclusion in this review. It was shown that cannabis, CBD, and nabilone (a synthetic form of THC) were capable of consistently improving motor symptoms more than a placebo. All treatments improved various non-motor symptoms, particularly with cannabis improving pain intensity, and CBD improving psychiatric symptoms in a dose-dependent manner. Adverse effects were usually minor, and, in the case of CBD, rare (except at very high doses). Conclusion: Cannabinoids have been shown to safely offer important potential in treating motor symptoms in PD and some non-motor symptoms. More large-scale randomized control trials for specific forms of cannabinoid treatments are required to determine their overall efficacy.