-
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 -
Critical Care Medicine Mar 2022Sepsis is a life-threatening organ dysfunction caused by a host's unregulated immune response to eliminate the infection. After hospitalization, sepsis survivors often...
OBJECTIVES
Sepsis is a life-threatening organ dysfunction caused by a host's unregulated immune response to eliminate the infection. After hospitalization, sepsis survivors often suffer from long-term impairments in memory, attention, verbal fluency, and executive functioning. To understand the effects of sepsis and the exacerbated peripheral inflammatory response in the brain, we asked the question: What are the findings and inflammatory markers in the brains of deceased sepsis patients? To answer this question, we conducted this systematic review by the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
DATA SOURCES
Relevant studies were identified by searching the PubMed/National Library of Medicine, PsycINFO, EMBASE, Bibliographical Index in Spanish in Health Sciences, Latin American and Caribbean Health Sciences Literature, and Web of Science databases for peer-reviewed journal articles published on April 05, 2021.
STUDY SELECTION
A total of 3,745 articles were included in the primary screening; after omitting duplicate articles, animal models, and reviews, 2,896 articles were selected for the study. These studies were selected based on the title and abstract, and 2,772 articles were still omitted based on the exclusion criteria.
DATA EXTRACTION
The complete texts of the remaining 124 articles were obtained and thoroughly evaluated for the final screening, and 104 articles were included.
DATA SYNTHESIS
The postmortem brain had edema, abscess, hemorrhagic and ischemic injuries, infarction, hypoxia, atrophy, hypoplasia, neuronal loss, axonal injuries, demyelination, and necrosis.
CONCLUSIONS
The mechanisms by which sepsis induces brain dysfunction are likely to include vascular and neuronal lesions, followed by the activation of glial cells and the presence of peripheral immune cells in the brain.
Topics: Atrophy; Autopsy; Biomarkers; Brain; Humans; Inflammation; Magnetic Resonance Imaging; Sepsis
PubMed: 34402457
DOI: 10.1097/CCM.0000000000005307 -
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 -
Transplantation Proceedings 2021Risk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of everolimus (EVR) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Risk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of everolimus (EVR) in minimizing this risk when combined with a reduced CnI dose.
BACKGROUND
To systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post-liver transplantation.
METHODS
We searched MEDLINE, Scopus, and the Cochrane Library for randomized controlled trials comparing EVR- and CnI-based regimens post-liver transplantation. Assessment of studies and data extraction were undertaken independently.
RESULTS
Eight studies were selected, describing 769 patients. Cockcroft-Gault GFR was higher at one (P = .05), 3, and 5 years (P = .030) in patients on EVR compared to those receiving CnI therapy. The composite endpoint of efficacy failure was similar between the 2 arms after 1, 3, and 5 years of study. More patients discontinued EVR due to adverse effects in 1 year; however, no difference was noted after 3 or 5 years. A higher rates of proteinuria, peripheral edema, and incisional hernia occurred in patients on EVR.
CONCLUSIONS
The analysis confirms noninferiority of EVR and reduced CnI combination. Combination regimen resulted in better renal function compared to standard CnI therapy.
Topics: Calcineurin Inhibitors; Everolimus; Female; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Tacrolimus
PubMed: 33390288
DOI: 10.1016/j.transproceed.2020.09.021 -
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 -
International Journal of Clinical... May 2021We aimed to perform a systematic review and meta-analysis to examine the efficacy and safety of mirogabalin in patients with diabetic peripheral neuropathic pain (DPNP). (Meta-Analysis)
Meta-Analysis
AIM
We aimed to perform a systematic review and meta-analysis to examine the efficacy and safety of mirogabalin in patients with diabetic peripheral neuropathic pain (DPNP).
METHODS
We searched four databases from inception to 1st July 2020. We included all randomised controlled trials (RCTs) which assessed the effectiveness and safety of mirogabalin in patients with DPNP. We evaluated the quality of the included RCTs using the Cochrane risk of bias assessment tool. We pooled dichotomous outcomes as risk ratios and continuous outcomes as mean differences with 95% confidence intervals, both under the random- or fixed-effects model.
RESULTS
Three RCTs matched our inclusion criteria with a total of 1732 patients with DPNP: 1057, 534 and 141 patients received mirogabalin, placebo and pregabalin, respectively. The quality of included RCTs was marked as moderate-to-high. Mirogabalin treatment was significantly associated with a significant reduction in the average daily pain score (ADPS) compared with placebo over 7 weeks. Compared with pregabalin, mirogabalin was significantly associated with more decrease in ADPS only after 3, 4 and 5 weeks. The proportion of patients with ≥30% and ≥50% reduction in the ADPS was significantly higher in the mirogabalin vs placebo and pregabalin groups. Compared with placebo, mirogabalin was significantly associated with more adverse events of dizziness, increased weight, peripheral oedema and somnolence. The safety profile was comparable between mirogabalin and pregabalin.
CONCLUSIONS
Our systematic review and meta-analysis revealed that in patients with DPNP, mirogabalin treatment was superior to placebo and pregabalin in decreasing the ADPS over time. Besides, mirogabalin was largely safe and associated with some adverse events that could be managed conservatively.
Topics: Analgesics; Bridged Bicyclo Compounds; Diabetes Mellitus; Humans; Neuralgia; Pregabalin; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32991782
DOI: 10.1111/ijcp.13744 -
Survey of Ophthalmology 2021Radiation maculopathy and radiation-induced macular edema are common, sight-threatening complications after radiotherapy, especially that used for uveal melanoma. While... (Review)
Review
Radiation maculopathy and radiation-induced macular edema are common, sight-threatening complications after radiotherapy, especially that used for uveal melanoma. While many treatment and preventive strategies have been proposed, management of these conditions is still challenging. Initially, treatments were based on the use of retinal laser, but the outcomes were poor. Subsequently, management has shifted toward injection of intravitreal antivascular endothelial growth factor or corticosteroids. We reviewed current clinical evidence, which mostly relies on small sample-sized and retrospective studies, for the management of radiation maculopathy and, in particular, radiation-induced macular edema. At present, the first-line approach is usually intravitreal antivascular endothelial growth factor. Intravitreal dexamethasone implantation may be an option for those with suboptimal response or contraindications to antivascular endothelial growth factor agents. Possible preventive treatments that require future study are intravitreal bevacizumab and ranibizumab, peripheral laser photocoagulation, and subtenon triamcinolone acetonide.
Topics: Angiogenesis Inhibitors; Bevacizumab; Glucocorticoids; Humans; Intravitreal Injections; Macular Edema; Retrospective Studies; Triamcinolone Acetonide; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 32918934
DOI: 10.1016/j.survophthal.2020.08.007 -
Annales de Cardiologie Et D'angeiologie Oct 2020Cardiovascular disease is the leading cause of death worldwide. Conceptually, endothelial dysfunction, inflammatory conditions and oxidative stress are at the forefront...
Cardiovascular disease is the leading cause of death worldwide. Conceptually, endothelial dysfunction, inflammatory conditions and oxidative stress are at the forefront of the onset and development of most cardiovascular diseases, particularly coronary artery disease and heart failure. Serum albumin has many physiological properties, including in particular antioxidant, anti-inflammatory, anticoagulant and anti-platelet aggregation activity. It also plays an essential role in the exchange of fluids across the capillary membrane. Hypoalbuminemia is a powerful prognostic marker in the general population as well as in many disease states. In the more specific context of cardiovascular disease, low serum albumin is independently associated with the development of various deleterious conditions such as coronary artery disease, heart failure, atrial fibrillation, stroke and venous thromboembolism. Low serum albumin has also emerged as a potent prognostic parameter in patients with cardiovascular disease regardless of usual prognostic markers. Remarkably, its potent prognostic value persists after adjusting for causative confounders such as malnutrition and inflammation. This prognostic value probably refers primarily to the syndrome of malnutrition-inflammation and the severity of comorbidities. Nevertheless, several recent meta-analyses strongly support the hypothesis that hypoalbuminemia may act as an unrecognized, potentially modifiable risk factor contributing to the emergence and progression of cardiovascular disease, primarily by exacerbating oxidative stress, inflammation and platelet aggregation, and by favouring peripheral congestion and pulmonary edema. Currently, it is unknown whether prevention and correction of low serum albumin offers a benefit to patients with or at risk for cardiovascular disease, and further studies are critically needed in this setting.
Topics: Atrial Fibrillation; Cardiac Surgical Procedures; Cardiovascular Diseases; Coronary Artery Disease; Disease Progression; Heart Defects, Congenital; Heart Failure; Humans; Hypoalbuminemia; Prognosis; Risk Factors; Serum Albumin; Stroke; Venous Thromboembolism
PubMed: 32797938
DOI: 10.1016/j.ancard.2020.07.012