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Frontiers in Neuroscience 2021Peripheral neuropathy can be caused by diabetes mellitus and HIV infection, and often leaves patients with treatment-resistant neuropathic pain. To better treat this...
Peripheral neuropathy can be caused by diabetes mellitus and HIV infection, and often leaves patients with treatment-resistant neuropathic pain. To better treat this condition, we need greater understanding of the pathogenesis, as well as objective biomarkers to predict treatment response. Magnetic resonance imaging (MRI) has a firm place as a biomarker for diseases of the central nervous system (CNS), but until recently has had little role for disease of the peripheral nervous system. To review the current state-of-the-art of peripheral nerve MRI in diabetic and HIV symmetrical polyneuropathy. We used systematic literature search methods to identify all studies currently published, using this as a basis for a narrative review to discuss major findings in the literature. We also assessed risk of bias, as well as technical aspects of MRI and statistical analysis. Protocol was pre-registered on NIHR PROSPERO database. MEDLINE, Web of Science and EMBASE databases were searched from 1946 to 15th August 2020 for all studies investigating either diabetic or HIV neuropathy and MRI, focusing exclusively on studies investigating symmetrical polyneuropathy. The NIH quality assessment tool for observational and cross-sectional cohort studies was used for risk of bias assessment. The search resulted in 18 papers eligible for review, 18 for diabetic neuropathy and 0 for HIV neuropathy. Risk of bias assessment demonstrated that studies generally lacked explicit sample size justifications, and some may be underpowered. Whilst most studies made efforts to balance groups for confounding variables (age, gender, BMI, disease duration), there was lack of consistency between studies. Overall, the literature provides convincing evidence that DPN is associated with larger nerve cross sectional area, T2-weighted hyperintense and hypointense lesions, evidence of nerve oedema on Dixon imaging, decreased fractional anisotropy and increased apparent diffusion coefficient compared with controls. Analysis to date is largely restricted to the sciatic nerve or its branches. There is emerging evidence that various structural MR metrics may be useful as biomarkers in diabetic polyneuropathy, and areas for future direction are discussed. Expanding this technique to other forms of peripheral neuropathy, including HIV neuropathy, would be of value. (identifier: CRD 42020167322) https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=167322.
PubMed: 34621152
DOI: 10.3389/fnins.2021.727311 -
The role of matrix metalloproteinase-9 and its inhibitor TIMP-1 in burn injury: a systematic review.International Journal of Burns and... 2021Matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are key mediators of acute inflammation and regulators... (Review)
Review
Matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), are key mediators of acute inflammation and regulators of the wound healing process. The aim of this systematic review was to determine the local and systemic involvement of the MMP-9/TIMP-1 system following burn injury. Two databases (Scopus and MEDLINE) were searched for all studies reporting MMP-9 and/or TIMP-1 after burn injury. Based on our eligibility criteria, we reviewed 24 studies involving 508 burns patients in 11 clinical studies and 367 animals in 13 preclinical studies. Local, systemic, and peripheral gene expression, protein levels and activity of MMP-9 and TIMP-1 were assessed. Increased MMP-9 was reported at the site of injury early after burn trauma in all studies, and remained elevated in non-healing wounds. Increased TIMP-1 expression in burn wounds occurred later than MMP-9, and was persistent in hypertrophic burn scars. Similar to local expression, systemic MMP-9 and TIMP-1 concentrations were significantly elevated after burn injury in response to upregulation of proinflammatory cytokines. While no association was found between systemic MMP-9 concentration and extent of injury or outcome, serum or plasma TIMP-1 showed good correlation with survival and burn severity. This review also found evidence of the MMP-9/TIMP-1 system contributing to secondary tissue damage distant from the burn site, including burn-associated musculoskeletal damage and acute lung injury. In addition, increased MMP-9 synthesis and activity in the brain after peripheral burn may lead to blood-brain barrier dysfunction and cerebral edema, a significant contributor to mortality. This systematic review provides an overview of the available evidence of the role of MMP-9 and TIMP-1 in burn injury pathophysiology and finds that TIMP-1 may be a promising biomarker in outcome prognostication of burns patients. Large-scale studies of both pediatric and adult burns patients with increased female representation and repeated sampling are recommended to validate the reliability of TIMP-1 as a prognostic marker following burn injury.
PubMed: 34557330
DOI: No ID Found -
International Ophthalmology Jan 2022The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a... (Review)
Review
INTRODUCTION
The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a system-wide thromboembolic state, leading to serious cardiovascular, cerebrovascular and peripheral vascular manifestations. However, our knowledge regarding retinal manifestations due to systemic COVID-19 is minimal. This systematic review has comprehensively summarized all retinal manifestations secondary to COVID-19 disease recorded till date since the beginning of the pandemic.
METHODS
All studies published till November 27, 2020, which have reported retinal manifestations in COVID-19 patients were systematically reviewed using the PRISMA statement.
RESULTS
We included 15 articles: 11 case reports and four cross-sectional case series. The most commonly reported manifestations which did not affect visual acuity were retinal hemorrhages and cotton wool spots. The most common vision threatening manifestation was retinal vein occlusion with associated macular edema. Rarely, patients may also present with retinal arterial occlusions and ocular inflammation. These manifestations may occur from as soon as within a week after the onset of COVID-19 symptoms to more than 6 weeks after.
CONCLUSION
Mostly causing milder disease, COVID-19 may however lead to severe life-threatening thromboembolic complications, and systemic antithrombotic therapy has been suggested as a prophylactic and therapeutic management strategy for patients affected with serious systemic disease. However, both sick and apparently healthy patients may suffer from various retinal complications which may lead to loss of vision as well. No consensus regarding management of retinal complications with anticoagulants or anti-inflammatory medications have been proposed; however, they may be tackled on individual basis.
Topics: COVID-19; Cross-Sectional Studies; Humans; Pandemics; Retina; SARS-CoV-2
PubMed: 34379290
DOI: 10.1007/s10792-021-01996-7 -
Hand (New York, N.Y.) Sep 2022This systematic review investigates complications and recurrence of Dupuytren's contracture in metacarpophalangeal joints (MCPJs) and/or proximal interphalangeal joints...
This systematic review investigates complications and recurrence of Dupuytren's contracture in metacarpophalangeal joints (MCPJs) and/or proximal interphalangeal joints (PIPJs) of fingers treated with collagenase clostridium histolyticum (CCH). A review of the literature on Dupuytren's disease was performed using PRISMA guidelines. Included publications described complications and/or recurrences for contractures ≥20° in MCPJs and/or PIPJs treated with CCH. Successful treatments reduced contractures to ≤5° immediately. Treatment-related adverse events (AEs) were classified as minor, major surgical, and major nonsurgical. Contracture recurrence involved return of fixed-flexion contracture ≥20° in a successfully treated finger in patients with ≥12 months of follow-up. Of 2675 patients (3753 joints), 94% experienced ≥1 treatment-related AE, most commonly peripheral edema (64%), pain in extremity (53%), and contusion (51%). Major surgical complications occurred in 9 patients (1.0%). Major nonsurgical complications occurred in 2 patients, specifically nonrupture tendon injury and anaphylaxis. Of 1488 patients (2069 joints), recurrences were reported in 23% of successfully treated joints (n = 466; 20% MCPJs, 28% PIPJs), on average 12 to 24 months after treatment. MCPJs achieved greater success than PIPJs in initial contracture reduction (77% versus 36%). CCH is a safe, effective treatment to improve hand function in Dupuytren's contracture. Most AEs are minor and self-resolving, although the risk of major AEs still exists. Following treatment, 23% of successfully treated joints experience recurrence, typically within 12 to 24 months but sometimes as early as 6 months. Surgeons are encouraged to discuss these risks with patients for shared decision-making regarding optimal treatment modalities.
Topics: Collagenases; Dupuytren Contracture; Humans; Injections, Intralesional; Microbial Collagenase; Recurrence
PubMed: 33478271
DOI: 10.1177/1558944720974119 -
Neuro-oncology Apr 2021Malignant peripheral nerve sheath tumors (MPNST) carry a dismal prognosis and require early detection and complete resection. However, MPNSTs are prone to sampling... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant peripheral nerve sheath tumors (MPNST) carry a dismal prognosis and require early detection and complete resection. However, MPNSTs are prone to sampling errors and biopsies or resections are cumbersome and possibly damaging in benign peripheral nerve sheath tumor (BPNST). This study aimed to systematically review and quantify the diagnostic accuracy of noninvasive tests for distinguishing MPNST from BPNST.
METHODS
Studies on accuracy of MRI, FDG-PET (fluorodeoxyglucose positron emission tomography), and liquid biopsies were identified in PubMed and Embase from 2000 to 2019. Pooled accuracies were calculated using Bayesian bivariate meta-analyses. Individual level-patient data were analyzed for ideal maximum standardized uptake value (SUVmax) threshold on FDG-PET.
RESULTS
Forty-three studies were selected for qualitative synthesis including data on 1875 patients and 2939 lesions. Thirty-five studies were included for meta-analyses. For MRI, the absence of target sign showed highest sensitivity (0.99, 95% CI: 0.94-1.00); ill-defined margins (0.94, 95% CI: 0.88-0.98); and perilesional edema (0.95, 95% CI: 0.83-1.00) showed highest specificity. For FDG-PET, SUVmax and tumor-to-liver ratio show similar accuracy; sensitivity 0.94, 95% CI: 0.91-0.97 and 0.93, 95% CI: 0.87-0.97, respectively, specificity 0.81, 95% CI: 0.76-0.87 and 0.79, 95% CI: 0.70-0.86, respectively. SUVmax ≥3.5 yielded the best accuracy with a sensitivity of 0.99 (95% CI: 0.93-1.00) and specificity of 0.75 (95% CI: 0.56-0.90).
CONCLUSIONS
Biopsies may be omitted in the presence of a target sign and the absence of ill-defined margins or perilesional edema. Because of diverse radiological characteristics of MPNST, biopsies may still commonly be required. In neurofibromatosis type 1, FDG-PET scans may further reduce biopsies. Ideal SUVmax threshold is ≥3.5.
Topics: Bayes Theorem; Fluorodeoxyglucose F18; Humans; Nerve Sheath Neoplasms; Neurofibrosarcoma; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 33326583
DOI: 10.1093/neuonc/noaa280 -
Archives of Cardiovascular Diseases 2020The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK)... (Meta-Analysis)
Meta-Analysis
Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.
BACKGROUND
The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized.
AIM
To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting.
METHODS
We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data.
RESULTS
MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach.
CONCLUSIONS
In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.
Topics: Adverse Drug Reaction Reporting Systems; Aged; Antineoplastic Agents; Cardiovascular Diseases; Databases, Factual; Female; Fibrosarcoma; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Patient Safety; Pharmacovigilance; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32418884
DOI: 10.1016/j.acvd.2020.03.014 -
Frontiers in Pharmacology 2019Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials...
Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.
Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials regarding the non-cardiovascular safety. This was the focus of our study. We systematically searched MEDLINE, EMBASE, and Cochrane Library (5 Sep 2018) for randomized controlled trials (RCTs) that reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and their 95% confidence intervals (CIs) were pooled using random-effects models. Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were identified. SGLT2 inhibitors were associated with a lower risk of serious adverse events (RR 0.90, 95% CI 0.86 to 0.94, < 0.001), death (RR 0.78, 95% CI 0.64 to 0.94, < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, < 0.05), arthralgia (RR 0.72, 95% CI 0.54 to 0.96, < 0.05), hypertension (RR 0.61, 95% CI 0.50 to 0.75, < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 0.72, < 0.001) compared to placebo. SGLT2 inhibitors were associated with higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, < 0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 4.32, < 0.001). Other significant effects were observed for osmotic diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, < 0.001), volume-related AEs (RR 1.26, 95% CI 1.08 to 1.46, < 0.05), renal-related AEs (RR 1.36, 95% CI 1.02 to 1.80, < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, < 0.001), and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, < 0.05). Subgroup and sensitivity analyses strengthened the robustness of primary results. Results from RCTs confirmed lower risk of death, serious adverse events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) patients treated with SGLT2 inhibitors when compared with placebo. The use of SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, volume depletion effects, renal related AEs, and higher blood ketone bodies when compared with placebo.
PubMed: 31616297
DOI: 10.3389/fphar.2019.01066 -
Drug Design, Development and Therapy 2019Immune checkpoint inhibitors have developed rapidly and have demonstrated antitumor activity in various cancers. To evaluate the safety and efficacy of atezolizumab in...
PURPOSE
Immune checkpoint inhibitors have developed rapidly and have demonstrated antitumor activity in various cancers. To evaluate the safety and efficacy of atezolizumab in treating cancers, we conducted this meta-analysis.
METHODS
Embase, PubMed, MEDLINE, the Central Register of Controlled Trials of the Cochrane Library, and the American Society of Clinical Oncology database were searched for relevant studies. The primary outcomes were any grade adverse events (AEs) and grade ≥3 AEs. The secondary outcomes were overall objective response rate, pooled 6-month progression-free survival (PFS) rate, 1-year overall survival (OS) rate, median PFS, and median OS.
RESULTS
Our meta-analysis was based on 14 clinical trials with 3,266 patients. The total risk of any grade AEs reached 69%, while grade ≥3 AEs happened in only 13% of participants. The overall atezolizumab-related death rate was 0.17%. Major common AEs involved fatigue (24.5%), decreased appetite (13.2%), nausea (12.3%), diarrhea (10.8%), pyrexia (10.7%), pruritus (9.6%), cough (9.5%), edema peripheral (8.6%), and rash (8.4%). The most common severe AEs were fatigue (2.2%), anemia (1.9%), and dyspnea (1.9%). Meanwhile, we found that 6% patients reached complete response and 16% partial response. The pooled 6-month PFS rate and 1-year OS rate were 0.36 (95% CI: 0.31-0.41) and 0.55 (95% CI: 0.49-0.61), respectively. The median PFS varied from 1.5 to 6.1 months, and the median OS ranged from 5.9 to 28.9 months.
CONCLUSION
Atezolizumab has a considerable potential in treating cancers with an acceptable risk profile.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Humans; Neoplasms
PubMed: 30787594
DOI: 10.2147/DDDT.S188893 -
BMC Sports Science, Medicine &... 2018Swimming induced pulmonary oedema is an uncommon occurrence and usually presents during strenuous distance swimming in cold water. The prevalence is most likely...
BACKGROUND
Swimming induced pulmonary oedema is an uncommon occurrence and usually presents during strenuous distance swimming in cold water. The prevalence is most likely underreported and the underlying mechanisms are controversial. The purpose of this study was to summarize the evidence with regards to prevalence, pathophysiology and treatment of swimming induced pulmonary oedema in endurance athletes.
METHODS
Medline, Embase, Scopus and Google Scholar were searched and level I-IV from 1970 to 2017 were included. For clinical studies, only publications reporting on swimming-induced pulmonary oedema were considered. Risk of bias was assessed with the ROBINS-I tool, and the quality of evidence was assessed with the Cochrane GRADE system. For data synthesis and analysis, a best evidence synthesis was used.
RESULTS
A total of 29 studies were included (174 athletes). The most common symptom was cough, dyspnoea, froth and haemoptysis. The risk of bias for the clinical studies included 13 with moderate risk, 3 with serious, and 4 with critical. Four of the pathophysiology studies had a moderate risk, 3 a serious risk, and 1 a critical risk of bias. A best evidence analysis demonstrated a strong association between cold water immersion and in increases of CVP (central venous pressure), MPAP (mean pulmonary arterial pressure), PVR (peripheral vascular resistance) and PAWP (pulmonary arterial wedge pressure) resulting in interstitial asymptomatic oedema.
CONCLUSION
The results of this study suggest a moderate association between water temperature and the prevalence of SIPE. The presence of the clinical symptoms cough, dyspnoea, froth and haemoptysis are strongly suggestive of SIPE during or immediately following swimming. There is only limited evidence to suggest that there are pre-existing risk factors leading to SIPE with exposure to strenuous physical activity during swimming. There is strong evidence that sudden deaths of triathletes are often associated with cardiac abnormalities.
PubMed: 30410770
DOI: 10.1186/s13102-018-0107-3 -
AJNR. American Journal of Neuroradiology Sep 2018Accurate diagnosis of tumefactive demyelinating lesions is clinically important to avoid unnecessary invasive biopsy or inappropriate treatment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate diagnosis of tumefactive demyelinating lesions is clinically important to avoid unnecessary invasive biopsy or inappropriate treatment.
PURPOSE
We aimed to evaluate conventional and advanced MR imaging findings of tumefactive demyelinating lesions and determine the diagnostic performance of MR imaging for differentiating tumefactive demyelinating lesions from primary brain tumor.
DATA SOURCES
A systematic search of Ovid MEDLINE and EMBASE up to December 6, 2017, was conducted.
STUDY SELECTION
Original articles describing MR imaging findings in patients with tumefactive demyelinating lesions were selected.
DATA ANALYSIS
The pooled incidences of conventional MR imaging findings of tumefactive demyelinating lesions were obtained with the DerSimonian and Liard random-effects model. The pooled sensitivity and specificity of MR imaging for differentiating tumefactive demyelinating lesions from primary brain tumor were obtained using the bivariate random-effects model.
DATA SYNTHESIS
Nineteen eligible studies with 476 patients with tumefactive demyelinating lesions were included. The pooled incidence of open ring or incomplete rim enhancement was 35% (95% CI, 24%-47%), which was significantly higher than the incidence of closed ring or complete rim enhancement (18% [95% CI, 11%-29%]; = .0281). The pooled incidences of T2 hypointense rim, absent or mild mass effect, and absent or mild perilesional edema were 48%, 67%, and 57%, respectively. On advanced MR imaging, tumefactive demyelinating lesions showed a high apparent diffusion coefficient, peripheral restricted diffusion, and low cerebral blood volume. The pooled sensitivity and specificity of MR imaging for differentiating tumefactive demyelinating lesions from primary brain tumor were 89% (95% CI, 82%-93%) and 94% (95% CI, 89%-97%), respectively.
LIMITATIONS
Seventeen of 19 studies were retrospective studies.
CONCLUSIONS
Conventional MR imaging findings may help differentiate tumefactive demyelinating lesions from primary brain tumor, though further study is needed to determine the added value of advanced MR imaging.
Topics: Adult; Brain Neoplasms; Demyelinating Diseases; Diagnosis, Differential; Female; Humans; Magnetic Resonance Imaging; Male; Neuroimaging; Sensitivity and Specificity
PubMed: 30115676
DOI: 10.3174/ajnr.A5775