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Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 μg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/μl compared with 24.26 when CD4 count <50 cells/μl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.
Topics: Talaromyces; Humans; Paracoccidioides; Antifungal Agents; Coccidioides; World Health Organization; Mycoses; Paracoccidioidomycosis; Coccidioidomycosis; Microbial Sensitivity Tests
PubMed: 38935909
DOI: 10.1093/mmy/myad133 -
Medical Mycology Jun 2024In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority...
In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.
Topics: Candida tropicalis; Humans; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Candidiasis, Invasive; Incidence; Global Health; Risk Factors
PubMed: 38935905
DOI: 10.1093/mmy/myae040 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 14 studies were eligible for inclusion. Morbidity was frequent with moderate to severe impairment of quality of life in 60.3%, amputation in up to 38.5%, and recurrent or long-term disease in 31.8%-73.5% of patients. Potential risk factors included male gender (56.6%-79.6%), younger age (11-30 years; 64%), and farming occupation (62.1%-69.7%). Mycetoma was predominantly reported in Sudan, particularly in central Sudan (37%-76.6% of cases). An annual incidence of 0.1/100 000 persons and 0.32/100 000 persons/decade was reported in the Philippines and Uganda, respectively. In Uganda, a decline in incidence from 3.37 to 0.32/100 000 persons between two consecutive 10-year periods (2000-2009 and 2010-2019) was detected. A community-based, multi-pronged prevention programme was associated with a reduction in amputation rates from 62.8% to 11.9%. With the pre-specified criteria, no studies of antifungal drug susceptibility, mortality, and hospital lengths of stay were identified. Future research should include larger cohort studies, greater drug susceptibility testing, and global surveillance to develop evidence-based treatment guidelines and to determine more accurately the incidence and trends over time.
Topics: Humans; Mycetoma; Incidence; Antifungal Agents; World Health Organization; Risk Factors; Male; Female; Quality of Life
PubMed: 38935904
DOI: 10.1093/mmy/myae044 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.
Topics: Humans; Mucorales; Antifungal Agents; Mucormycosis; World Health Organization; Risk Factors; Invasive Fungal Infections; Microbial Sensitivity Tests; Prevalence; Drug Resistance, Fungal; Incidence; Global Health
PubMed: 38935901
DOI: 10.1093/mmy/myad130 -
Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Vaccines Jun 2024As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged,... (Review)
Review
As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports and case series published in three databases before January 2024 following PRISMA guidelines to understand the characteristics of possible causal relationships or coincidences. In total, 404 articles were screened respectively by title, abstracts, and full-texts. Thirty-four papers fulfilled the inclusion criteria and have been analyzed, covering 44 patients with new-onset AAV after COVID-19 vaccination with no prior history of COVID-19 infection. Data regarding patients' metrics, comorbidities, vaccination characteristics, symptoms, diagnostics, treatment, and outcomes were investigated and summarized. The cohort consisted predominantly of females. AAV diagnosis was confirmed via biopsy, with renal dysfunction as a prevailing manifestation. In most cases, the first symptoms of AAV developed after the second dose; moreover, Pfizer-BioNTech was the most frequently administered vaccine among the analyzed cohort. Primary treatment involved glucocorticoid therapy, with a mostly favourable response. This systematic review aims to raise awareness among clinicians in the field regarding this rare but possible complication, to promote the prompt recognition and diagnosis of de novo ANCA-positive small-vessel vasculitis in timely association with SARS-CoV-2 vaccination.
PubMed: 38932385
DOI: 10.3390/vaccines12060656 -
Medicina (Kaunas, Lithuania) May 2024: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to... (Review)
Review
: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to explore the association between inflammatory markers in saliva and PDs in MS patients, assessing the use of saliva as a non-invasive tool to monitor disease progression. : 82 publications were examined after a thorough search of scholarly databases to determine whether inflammatory markers were present in MS patients and whether they were associated with periodontal disease (PD). Quality and bias were assessed using the Newcastle-Ottawa Scale, resulting in eight articles that were thoroughly analyzed. : The results point to a strong correlation between MS and periodontal disorders, which may point to the same pathophysiological mechanism. It does, however, underscore the necessity of additional study to determine a definitive causal association. : The findings indicate a strong association between MS and PDs, likely mediated by systemic inflammatory responses detectable in saliva. The review highlights the importance of oral health in managing MS and supports the utility of saliva as a practical, non-invasive medium for monitoring systemic inflammation. Further research is necessary to confirm the causal relationships and to consider integrating salivary diagnostics into routine clinical management for MS patients.
Topics: Humans; Saliva; Multiple Sclerosis; Periodontal Diseases; Biomarkers; Inflammation
PubMed: 38929476
DOI: 10.3390/medicina60060859 -
Biomedicines Jun 2024The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of... (Review)
Review
BACKGROUND AND OBJECTIVES
The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of atezolizumab, examining its impact on survival outcomes, response rates, and safety measured by serious adverse events (SAEs).
MATERIALS AND METHODS
A literature search was conducted using PubMed, Scopus, and Web of Science, focusing on articles published up to February 2024. The review followed the PRISMA guidelines and synthesized outcomes from four randomized trial studies involving atezolizumab administered at 1200 mg IV every three weeks, alone or in combination with chemoradiotherapy.
RESULTS
A total of 284 patients received atezolizumab, the majority being advanced stage cervical cancer (IVA-IVB). Median follow-up times ranged from 9 weeks to 32.9 months. It was found that combining atezolizumab with standard therapies extended median progression-free survival (PFS) from 10.4 to 13.7 months and overall survival (OS) from 22.8 to 32.1 months, according to the phase III trial. Monotherapy and initial treatment settings with atezolizumab also showed promising efficacy, with disease-free survival rates at 24 months reaching 79% compared to 52% with standard therapy alone. However, the treatment was associated with high rates of SAEs, reaching up to 79% in more intensive treatment combinations.
CONCLUSIONS
Atezolizumab demonstrates significant potential in improving PFS and OS in patients with cervical cancer, supporting its inclusion as a first-line treatment option. Despite the efficacy benefits, the high incidence of SAEs necessitates careful patient selection and management strategies to mitigate risks. This systematic review supports the continued evaluation of atezolizumab in broader clinical trials to refine its therapeutic profile and safety measures in the context of cervical cancer treatment.
PubMed: 38927498
DOI: 10.3390/biomedicines12061291 -
European Respiratory Review : An... Apr 2024This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD.
METHODS
A structured search strategy (2000-2023) was applied to eight databases to identify studies evaluating the impact of exercise-based interventions (≥14 days in duration) on balance or falls in people with COPD. Pooled mean treatment effects (95% confidence intervals (CIs), 95% prediction intervals (PIs)) were calculated for outcomes reported in five or more studies. Inter-individual response variance and the promise of behaviour change techniques (BCTs) were explored.
RESULTS
34 studies (n=1712) were included. There were greater improvements in balance post intervention compared to controls for the Berg Balance Scale (BBS) (mean 2.51, 95% CI 0.22-4.80, 95% PI -4.60-9.63), Timed Up and Go (TUG) test (mean -1.12 s, 95% CI -1.69- -0.55 s, 95% PI -2.78-0.54 s), Single-Leg Stance (SLS) test (mean 3.25 s, 95% CI 2.72-3.77 s, 95% PI 2.64-3.86 s) and Activities-specific Balance Confidence (ABC) scale (mean 8.50%, 95% CI 2.41-14.58%, 95% PI -8.92-25.92%). Effect on falls remains unknown. Treatment effects were larger in male mixed-sex groups for the ABC scale and SLS test, and in balance training other exercise-based interventions for the BBS and TUG test. Falls history was not associated with changes in balance. Meta-analysis of individual response variance was not possible and study-level results were inconclusive. Eleven promising BCTs were identified (promise ratio ≥2).
CONCLUSION
Evidence for the effect of exercise-based interventions eliciting clinically important improvements in balance for people with COPD is weak, but targeted balance training produces the greatest benefits. Future exercise interventions may benefit from inclusion of the identified promising BCTs.
Topics: Humans; Accidental Falls; Postural Balance; Pulmonary Disease, Chronic Obstructive; Exercise Therapy; Male; Treatment Outcome; Female; Aged; Risk Factors; Middle Aged; Recovery of Function; Lung
PubMed: 38925795
DOI: 10.1183/16000617.0003-2024 -
Complementary Therapies in Medicine Jun 2024Oxidative stress and inflammation play critical roles in the pathogenesis of many chronic diseases. Dark chocolate (DC)/cocoa, as a rich source of polyphenols like... (Review)
Review
Effect of dark chocolate/ cocoa consumption on oxidative stress and inflammation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of controlled trials.
BACKGROUND
Oxidative stress and inflammation play critical roles in the pathogenesis of many chronic diseases. Dark chocolate (DC)/cocoa, as a rich source of polyphenols like flavonoids, has anti-inflammatory and antioxidant properties that may confer health benefits, but findings in this context are inconsistent.
OBJECTIVE
This systematic review and dose-response meta-analysis aimed to provide a comprehensive overview of the controlled trials (CTs) that have examined the effects of DC/cocoa on oxidative stress and inflammation biomarkers in adults.
SEARCH METHODS
Databases including PubMed, Web of Science, and Scopus, were searched for relevant studies through April 2024.
SELECTION CRITERIA
Studies assessed C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), nitric oxide (NO), P-selectin, E-selectin and thiobarbituric acid reactive substances (TBARS) in adults were included.
DATA ANALYSIS
Based on the random-effects model, we calculated WMDs, SMDs and 95 % confidence intervals (CIs). Sensitivity, sub-group, meta-regression and dose-response analyses were also conducted.
RESULTS
Thirty-three eligible CTs with 1379 participants were included. All studies reported the intervention types (cocoa powder, beverages and chocolate bars) and dosage. However, sixteen studies didn't do/report testing for purity and potency by independent groups. Also, none of the studies mentioned the risk of contamination with heavy metals. Another limitation was the lack of blinding assessment in studies. DC/cocoa significantly reduced MDA (SMD: -0.69, 95 %CI: -1.17, -0.2, p = 0.005) and increased NO levels (SMD: 2.43, 95 %CI: 1.11,3.75, p < 0.001); However, it has no significant effects on the other outcomes. Greater anti-inflammatory effects occurred at higher flavonoid doses (>450 mg/day) and for shorter durations (≤4 weeks) in the non-healthy participants. Non-linear dose-response relationships between cocoa dosage and CRP level and also between flavonoid dosage and IL-6 level were observed. Based on the GRADE evaluation, just CRP and MDA results were considered as high certainty evidence and the other outcomes results were categorized as very low to moderate certainty.
CONCLUSIONS
DC/cocoa may improve systemic oxidative status and inflammation in adults. However, further studies should be performed to determine its benefits.
PubMed: 38925412
DOI: 10.1016/j.ctim.2024.103061