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Acta Neuropathologica Communications May 2023COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous...
INTRODUCTION
COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples.
MATERIAL AND METHODS
We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022.
RESULTS
In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples.
CONCLUSION
This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature.
Topics: Humans; COVID-19; SARS-CoV-2; RNA, Viral; Lung; Central Nervous System; Nervous System Diseases
PubMed: 37165453
DOI: 10.1186/s40478-023-01566-1 -
Malaria Journal May 2023Understanding malaria epidemiology is a critical step toward efficient malaria control and elimination. The objective of this meta-analysis was to derive robust... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Understanding malaria epidemiology is a critical step toward efficient malaria control and elimination. The objective of this meta-analysis was to derive robust estimates of malaria prevalence and Plasmodium species from studies conducted in Mauritania and published since 2000.
METHODS
The present review followed the PRISMA guidelines. Searches were conducted in various electronic databases such as PubMed, Web of Science, and Scopus. To obtain pooled prevalence of malaria, meta-analysis was performed using the DerSimonian-Laird random-effects model. Methodological quality of eligible prevalence studies was assessed using Joanna Briggs Institute tool. Inconsistency and heterogeneity between studies were quantified by the I index and Cochran's Q test. Publication bias was assessed with funnel plots and Egger's regression tests.
RESULTS
A total of 16 studies with a good individual methodological quality were included and analysed in this study. The overall random effects pooled prevalence of malaria infection (symptomatic and asymptomatic) across all included studies was 14.9% (95% confidence interval [95% CI]: 6.64, 25.80, I = 99.8%, P < 0.0001) by microscopy, 25.6% (95% CI: 8.74, 47.62, I = 99.6%, P < 0.0001) by PCR and 24.3% (95% CI: 12.05 to 39.14, I = 99.7%, P < 0.0001) by rapid diagnostic test. Using microscopy, the prevalence of asymptomatic malaria was 1.0% (95% CI: 0.00, 3.48) against 21.46% (95% CI: 11.03, 34.21) in symptomatic malaria. The overall prevalence of Plasmodium falciparum and Plasmodium vivax was 51.14% and 37.55%, respectively. Subgroup analysis showed significant variation (P = 0.039) in the prevalence of malaria between asymptomatic and symptomatic cases.
CONCLUSION
Plasmodium falciparum and P. vivax are widespread in Mauritania. Results of this meta-analysis implies that distinct intervention measures including accurate parasite-based diagnosis and appropriate treatment of confirmed malaria cases are critical for a successful malaria control and elimination programme in Mauritania.
Topics: Humans; Prevalence; Mauritania; Malaria; Malaria, Vivax; Plasmodium; Plasmodium vivax; Plasmodium falciparum; Malaria, Falciparum
PubMed: 37131226
DOI: 10.1186/s12936-023-04569-4 -
BMJ Open Apr 2023To assess the diagnostic accuracy of stool specimens to diagnose pulmonary tuberculosis (PTB) in adults.
OBJECTIVE
To assess the diagnostic accuracy of stool specimens to diagnose pulmonary tuberculosis (PTB) in adults.
DESIGN
Systematic review.
DATA SOURCES
MEDLINE (Ovid), Embase (Ovid), Web of Science and the Cochrane database were searched from inception to 9 March 2023-10 March 2023 using a comprehensive search strategy; reference lists of selected articles and relevant review articles were manually searched.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies in English reporting diagnostic performance of stool specimens against respiratory specimens using mycobacterial culture or smear microscopy or Xpert assay to diagnose PTB in adults were eligible for this systematic review.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened the retrieved citations and extracted data. The risk of bias and applicability of results were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Narrative data synthesis was performed.
RESULTS
A total of 1658 citations were screened, and 28 full-text articles were assessed. Nine studies met the inclusion criteria. The reported sensitivity and specificity of stool culture varied between 21.4% and 63.9%, and 61.5% and 100%, respectively. In stool smear microscopy, sensitivities and specificities ranged from 12.1% to 53.9%, and from 79.5% to 100%, respectively. The reported sensitivities of PCR assays, including Xpert assays, ranged from 69.7% to 100%, with specificities ranging from 69.8% to 100%. Most of the studies had a low risk of bias and a low applicability concern in all domains.
CONCLUSION
This systematic review could not conclude on the diagnostic accuracy of stool specimens for PTB diagnosis in adults. Further studies are required to evaluate the accuracy of stool specimens in adults to enable meta-analyses in updates of this review as well as other systematic reviews.
PROSPERO REGISTRATION NUMBER
CRD42021245203.
Topics: Adult; Humans; Tuberculosis, Pulmonary; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Sensitivity and Specificity; Bias
PubMed: 37105702
DOI: 10.1136/bmjopen-2022-062135 -
Frontiers in Immunology 2023Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors.... (Review)
Review
Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1β, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1β, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA.
Topics: Humans; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Arthritis, Gouty; Inflammasomes; Polymorphism, Genetic; Genetic Predisposition to Disease; Cytokines
PubMed: 37051231
DOI: 10.3389/fimmu.2023.1137822 -
Materials (Basel, Switzerland) Mar 2023The aim of this systematic review was to perform a qualitative synthesis of in vitro studies which evaluate and compare the penetration of calcium silicate-based sealers... (Review)
Review
The aim of this systematic review was to perform a qualitative synthesis of in vitro studies which evaluate and compare the penetration of calcium silicate-based sealers into dentinal tubules. A systematic advanced search was performed in Scopus, Embase, Medline (via PubMed), Web of Science, and Cochrane databases on the 1 December 2022. In vitro studies that compared the tubular penetration of at least two calcium silicate-based sealers in extracted human teeth were eligible. PRILE 2021 guidelines were used for the assessment of the risk of bias included studies. The search identified a total of 680 preliminary records, among which 12 studies were eligible for review. The most used methodology to evaluate sealer penetration was the use of a fluorochrome together with the tested sealers and the analysis of their penetration under confocal laser microscopy. Regarding the results of the included studies, calcium silicate-based sealers exhibit a favorable dentinal tubule penetration. Tubular penetration, however, can be affected by factors such as the irrigation protocol, sealer activation, the filling method used, and root canal morphology. EndoSequence BC Sealer showed the highest sealer penetration among the tested sealers. The influence of different fluorochromes on the results of dentinal tubule penetration studies should also be further explored. The in vitro nature of the included studies limits the applicability of the results into the clinical setting. Prospero registration: CRD42022383896.
PubMed: 37049028
DOI: 10.3390/ma16072734 -
PLoS Neglected Tropical Diseases Mar 2023Taenia solium is a tapeworm that causes taeniosis in humans and cysticercosis in humans and pigs. Within Eastern and Southern Africa (ESA), information on the presence...
BACKGROUND
Taenia solium is a tapeworm that causes taeniosis in humans and cysticercosis in humans and pigs. Within Eastern and Southern Africa (ESA), information on the presence of human taeniosis and cysticercosis seems scarce. This systematic review aimed to describe the current information available and gaps in the epidemiology of human T. solium infections in ESA.
METHODS/PRINCIPLE FINDINGS
Scientific literature published between 1st January 2000 and 20th June 2022 in international databases [MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Scopus (Elsevier), African Index Medicus (via WHO Global Index Medicus), and Open Grey] was systematically reviewed for ESA. The study area included 27 countries that make up the ESA region. Information on either taeniosis, cysticercosis or NCC was available for 16 of 27 countries within the region and a total of 113 reports were retained for the review. Most case reports for cysticercosis and NCC were from South Africa, while Tanzania had the most aggregated cysticercosis reports. Eleven countries reported on NCC with seven countries reporting data on NCC and epilepsy. Unconfirmed human T. solium taeniosis cases were reported in nine countries while two countries (Madagascar and Zambia) reported confirmed T. solium cases. The cysticercosis seroprevalence ranged between 0.7-40.8% on antigen (Ag) ELISA and between 13.1-45.3% on antibody (Ab) ELISA. Based on immunoblot tests the Ab seroprevalence was between 1.7-39.3%, while the proportion of NCC-suggestive lesions on brain CT scans was between 1.0-76% depending on the study population. The human taeniosis prevalence based on microscopy ranged between 0.1-14.7%. Based on Copro Ag-ELISA studies conducted in Kenya, Rwanda, Tanzania, and Zambia, the highest prevalence of 19.7% was reported in Kenya.
CONCLUSIONS
Despite the public health and economic impact of T. solium in ESA, there are still large gaps in knowledge about the occurrence of the parasite, and the resulting One Health disease complex, and monitoring of T. solium taeniosis and cysticercosis is mostly not in place.
Topics: Humans; Swine; Animals; Seroepidemiologic Studies; Taeniasis; Cysticercosis; Taenia solium; Africa, Southern; Tanzania; Prevalence; Swine Diseases
PubMed: 37000841
DOI: 10.1371/journal.pntd.0011042 -
Frontiers in Medicine 2023To evaluate the subclinical changes in corneal dendritic cell density (CDCD) and corneal subbasal nerve density (CSND) in asymptomatic contact lens (CL) wearers. (Review)
Review
PURPOSE
To evaluate the subclinical changes in corneal dendritic cell density (CDCD) and corneal subbasal nerve density (CSND) in asymptomatic contact lens (CL) wearers.
METHODS
Databases including PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for trials and studies reporting the changes of corneal CDCD and CSND in contact lens wearers published until 25 June 2022. PRISMA guidelines as well as recommended meta-analysis practices were followed. Meta-analysis was conducted using RevMan V.5.3 software.
RESULTS
After the screening, 10 studies with 587 eyes of 459 participants were included. Seven studies reported the data of CDCD. Compared with the control group, CDCD in the CL wearers was higher (18.19, 95% CI 18.8-27.57, = 0.0001). Type of confocal microscopy (IVCM), wear duration, and frequency of lens change were sources of heterogeneity. The difference in CSND between CL wearers and the control group was insignificant, and subgroup analysis did not reveal a source of heterogeneity.
CONCLUSION
Overall, CDCD increased in CL wears, while CSND did not show significant differences. IVCM is a feasible tool to assess subclinical changes in CL wearers.
PubMed: 36993811
DOI: 10.3389/fmed.2023.1149803 -
PLOS Global Public Health 2023People living with HIV (PLHIV) admitted to hospital have a high risk of death. We systematically appraised evidence for interventions to reduce mortality among...
People living with HIV (PLHIV) admitted to hospital have a high risk of death. We systematically appraised evidence for interventions to reduce mortality among hospitalised PLHIV in low- and middle-income countries (LMICs). Using a broad search strategy with terms for HIV, hospitals, and clinical trials, we searched for reports published between 1 Jan 2003 and 23 August 2021. Studies of interventions among adult HIV positive inpatients in LMICs were included if there was a comparator group and death was an outcome. We excluded studies restricted only to inpatients with a specific diagnosis (e.g. cryptococcal meningitis). Of 19,970 unique studies identified in search, ten were eligible for inclusion with 7,531 participants in total: nine randomised trials, and one before-after study. Three trials investigated systematic screening for tuberculosis; two showed survival benefit for urine TB screening vs. no urine screening, and one which compared Xpert MTB/RIF versus smear microscopy showed no difference in survival. One before-after study implemented 2007 WHO guidelines to improve management of smear negative tuberculosis in severely ill PLHIV, and showed survival benefit but with high risk of bias. Two trials evaluated complex interventions aimed at overcoming barriers to ART initiation in newly diagnosed PLHIV, one of which showed survival benefit and the other no difference. Two small trials evaluated early inpatient ART start, with no difference in survival. Two trials investigated protocol-driven fluid resuscitation for emergency-room attendees meeting case-definitions for sepsis, and showed increased mortality with use of a protocol for fluid administration. In conclusion, ten studies published since 2003 investigated interventions that aimed to reduce mortality in hospitalised adults with HIV, and weren't restricted to people with a defined disease diagnosis. Inpatient trials of diagnostics, therapeutics or a package of interventions to reduce mortality should be a research priority. Trial registration: PROSPERO Number: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019150341.
PubMed: 36963024
DOI: 10.1371/journal.pgph.0001557 -
BMC Oral Health Mar 2023Ultrasonically-activated irrigation (UAI) is effective in root canal irrigation but may damage canal walls. EDDY is a sonic activation system with flexible working tips... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ultrasonically-activated irrigation (UAI) is effective in root canal irrigation but may damage canal walls. EDDY is a sonic activation system with flexible working tips that cause no harm to dentinal walls. This review explores the intracanal cleaning efficacy of EDDY compared with UAI in vitro.
METHODS
The systematic review was registered in the PROSPERO database (CRD42021235826). A literature search was conducted in six electronic databases. In vitro studies that compared the removal of smear layer, debris, soft tissue or microbes in root canals between EDDY and UAI were included. Data extraction and quality assessment were performed. Meta-analyses were conducted on smear layer removal and debris elimination with the standardized mean difference (SMD). Heterogeneity was measured using the I test and the Chi test. The random-effect model was used when I > 50%, or p < 0.1, otherwise the fixed-effect model was applied. The level of significance was set at p < 0.05.
RESULTS
19 articles were included in this systematic review and 7 articles were included in meta-analyses. Meta-analyses on smear layer removal showed unimportant differences between EDDY and UAI at any canal third (coronal [SMD = 0.08, 95% confidence interval (95%CI): -0.29 to 0.45; p = 0.44, I = 0%]; middle [SMD = 0.02, 95% CI: -0.44 to 0.47; p = 0.94, I = 0%]; apical [SMD = 0.01, 95%CI: -0.35 to 0.38; p = 0.70, I = 0%]). Meta-analyses on debris removal evaluated by scanning electron microscope (coronal [SMD = 0.03, 95% CI: -0.41 to 0.46; p = 0.27, I = 23%]; middle [SMD = -0.24, 95% CI: -0.83 to 0.35; p = 0.80, I = 0%]; apical [SMD = 0.24, 95%CI: -0.20 to 0.67; p = 0.36, I = 2%]) and micro-CT (SMD = 0.36, 95% CI: -0.67 to 1.40; p = 0.03, I = 70%) both found insignificant differences. No meta-analysis was undertaken on soft-tissue removal and disinfection due to the various study designs, but the qualitative analyses implied that EDDY achieved similar performance to UAI in both aspects.
CONCLUSIONS
Limited evidence indicated that EDDY was comparable to UAI in removing smear layer, debris, soft tissue and microbes ex vivo. Considering UAI may damage canal walls, EDDY might be a substitute for UAI in irrigation activation. But more randomized clinical trials are required to explore the clinical extrapolation of the results in this review.
Topics: Humans; Dental Pulp Cavity; Root Canal Preparation; Smear Layer; Root Canal Irrigants; Therapeutic Irrigation; Microscopy, Electron, Scanning; Sodium Hypochlorite
PubMed: 36932445
DOI: 10.1186/s12903-023-02875-6 -
Journal of Clinical Medicine Feb 2023(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have... (Review)
Review
(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have assessed the pathological characteristics and outcomes of biopsy-proven kidney IRAEs. (2) Methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane for case reports, case series, and cohort studies for patients with biopsy-proven kidney IRAEs. All data were used to describe pathological characteristics and outcomes, and individual-level data from case reports and case series were pooled to analyze risk factors associated with different pathologies and prognoses. (3) Results: In total, 384 patients from 127 studies were enrolled. Most patients were treated with PD-1/PD-L1 inhibitors (76%), and 95% presented with acute kidney disease (AKD). Acute tubulointerstitial nephritis/acute interstitial nephritis (ATIN/AIN) was the most common pathologic type (72%). Most patients (89%) received steroid therapy, and 14% (42/292) required RRT. Among AKD patients, 17% (48/287) had no kidney recovery. Analyses of pooled individual-level data from 221 patients revealed that male sex, older age, and proton pump inhibitor (PPI) exposure were associated with ICI-associated ATIN/AIN. Patients with glomerular injury had an increased risk of tumor progression (OR 2.975; 95% CI, 1.176, 7.527; = 0.021), and ATIN/AIN posed a decreased risk of death (OR 0.164; 95% CI, 0.057, 0.473; = 0.001). (4) Conclusions: We provide the first systematic review of biopsy-proven ICI-kidney IRAEs of interest to clinicians. Oncologists and nephrologists should consider obtaining a kidney biopsy when clinically indicated.
PubMed: 36835884
DOI: 10.3390/jcm12041349