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Heart & Lung : the Journal of Critical... Jun 2024Progressive exercise intolerance is a hallmark of pulmonary hypertension (pH), severely impacting patients' independence and quality of life (QoL). Accumulating evidence... (Review)
Review
Respiratory, cardiovascular and musculoskeletal mechanisms involved in the pathophysiology of pulmonary hypertension: An updated systematic review of preclinical and clinical studies.
BACKGROUND
Progressive exercise intolerance is a hallmark of pulmonary hypertension (pH), severely impacting patients' independence and quality of life (QoL). Accumulating evidence over the last decade shows that combined abnormalities in peripheral reflexes and target organs contribute to disease progression and exercise intolerance.
OBJECTIVE
The aim of this study was to review the literature of the last decade on the contribution of the cardiovascular, respiratory, and musculoskeletal systems to pathophysiology and exercise intolerance in pH.
METHODS
A systematic literature search was conducted using specific terms in PubMed, SciELO, and the Cochrane Library databases for original pre-clinical or clinical studies published between 2013 and 2023. Studies followed randomized controlled/non-randomized controlled and pre-post designs.
RESULTS
The systematic review identified 25 articles reporting functional or structural changes in the respiratory, cardiovascular, and musculoskeletal systems in pH. Moreover, altered biomarkers in these systems, lower cardiac baroreflex, and heightened peripheral chemoreflex activity seemed to contribute to functional changes associated with poor prognosis and exercise intolerance in pH. Potential therapeutic strategies acutely explored involved manipulating the baroreflex and peripheral chemoreflex, improving cardiovascular autonomic control via cardiac vagal control, and targeting specific pathways such as GPER1, GDF-15, miR-126, and the JMJD1C gene.
CONCLUSION
Information published in the last 10 years advances the notion that pH pathophysiology involves functional and structural changes in the respiratory, cardiovascular, and musculoskeletal systems and their integration with peripheral reflexes. These findings suggest potential therapeutic targets, yet unexplored in clinical trials, that could assist in improving exercise tolerance and QoL in patients with pH.
PubMed: 38941771
DOI: 10.1016/j.hrtlng.2024.06.001 -
Frontiers in Genome Editing 2024With scientific progress and the development of new genomic techniques (NGTs), the spectrum of organisms modified for various purposes is rapidly expanding and includes...
Horizon scanning of potential environmental applications of terrestrial animals, fish, algae and microorganisms produced by genetic modification, including the use of new genomic techniques.
With scientific progress and the development of new genomic techniques (NGTs), the spectrum of organisms modified for various purposes is rapidly expanding and includes a wide range of taxonomic groups. An improved understanding of which newly developed products may be introduced into the market and released into the environment in the near and more distant future is of particular interest for policymakers, regulatory authorities, and risk assessors. To address this information need, we conducted a horizon scanning (HS) of potential environmental applications in four groups of organisms: terrestrial animals (excluding insects and applications with gene drives), fish, algae and microorganisms. We applied a formal scoping review methodology comprising a structured search of the scientific literature followed by eligibility screening, complemented by a survey of grey literature, and regulatory websites and databases. In all four groups of organisms we identified a broad range of potential applications in stages of basic as well as advanced research, and a limited number of applications which are on, or ready to be placed on, the market. Research on GM animals including fish is focused on farmed animals and primarily targets traits which increase performance, influence reproduction, or convey resistance against diseases. GM algae identified in the HS were all unicellular, with more than half of the articles concerning biofuel production. GM algae applications for use in the environment include biocontrol and bioremediation, which are also the main applications identified for GM microorganisms. From a risk assessor's perspective these potential applications entail a multitude of possible pathways to harm. The current limited level of experience and limited amount of available scientific information could constitute a significant challenge in the near future, for which risk assessors and competent authorities urgently need to prepare.
PubMed: 38938511
DOI: 10.3389/fgeed.2024.1376927 -
The Lancet. Oncology Jul 2024Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations.
METHODS
We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679.
FINDINGS
46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I=99·8%; 10·24 [8·48-12·35], I=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only.
INTERPRETATION
Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents.
FUNDING
US National Cancer Institute, National Institutes of Health.
Topics: Humans; Organ Transplantation; HIV Infections; Neoplasms; Incidence; Transplant Recipients; Immunocompromised Host; Risk Factors; Risk Assessment; Female; Male
PubMed: 38936380
DOI: 10.1016/S1470-2045(24)00189-X -
Medical Mycology Jun 2024Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges,...
Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4-32 mg/l), while resistance to amphotericin B (MIC: 0.125-0.16 mg/l), itraconazole (MICs: 0.004-0.125 mg/l), and voriconazole (MICs: 0.004-0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat.
Topics: Humans; Histoplasmosis; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Histoplasma; Prevalence; Immunocompromised Host
PubMed: 38935903
DOI: 10.1093/mmy/myae039 -
Frontiers in Surgery 2024Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and...
BACKGROUND
Advancements in surgical techniques have improved outcomes in patients undergoing pancreatic surgery. To date there have been no meta-analyses comparing robotic and laparoscopic approaches for distal pancreatectomies (DP) in patients with pancreatic adenocarcinoma (PDAC). This systematic review and network meta-analysis aims to explore the oncological outcomes of laparoscopic distal pancreatectomy (LDP), robotic distal pancreatectomy (RDP) and open distal pancreatectomy (ODP).
METHODS
A systematic search was conducted for studies reporting laparoscopic, robotic or open surgery for DP. Frequentist network meta-analysis of oncological outcomes (overall survival, resection margins, tumor recurrence, examined lymph nodes, administration of adjuvant therapy) were performed.
RESULTS
Fifteen studies totalling 9,301 patients were included in the network meta-analysis. 1,946, 605 and 6,750 patients underwent LDP, RDP and ODP respectively. LDP (HR: 0.761, 95% CI: 0.642-0.901, = 0.002) and RDP (HR: 0.757, 95% CI: 0.617-0.928, = 0.008) were associated with overall survival (OS) benefit when compared to ODP. LDP (HR: 1.00, 95% CI: 0.793-1.27, = 0.968) was not associated with OS benefit when compared to RDP. There were no significant differences between LDP, RDP and ODP for resection margins, tumor recurrence, examined lymph nodes and administration of adjuvant therapy.
CONCLUSION
This study highlights the longer OS in both LDP and RDP when compared to ODP for patients with PDAC.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42022336417).
PubMed: 38933652
DOI: 10.3389/fsurg.2024.1369169 -
Bulletin of the World Health... Jul 2024To conduct a systematic review on the effects of multisectoral interventions for health on health system performance. (Review)
Review
OBJECTIVE
To conduct a systematic review on the effects of multisectoral interventions for health on health system performance.
METHODS
We conducted a systematic review according to the preferred reporting items for systematic review and meta-analysis protocols. We searched for peer-reviewed journal articles in PubMed®, Scopus, Web of Science, Cumulated Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews on 31 August 2023 (updating on 28 February 2024). We removed duplicates, screened titles and abstracts, and then conducted a full-text eligibility and quality assessment.
FINDINGS
We identified an initial 1118 non-duplicate publications, 62 of which met our inclusion and exclusion criteria. The largest proportions of reviewed studies focused on multisectoral interventions directly related to specific health outcomes (66.1%; 41 studies) and/or social determinants of health (48.4%; 30 studies), but without explicit reference to overall health system performance. Most reviewed publications did not address process indicators (83.9%; 52/62) or discuss sustainability for multisectoral interventions in health (72.6%; 45/62). However, we observed that the greatest proportion (66.1%; 41/62) considered health system goals: health equity (68.3%; 28/41) and health outcomes (63.4%; 26/41). Although the greatest proportion (64.5%; 40/62) proposed mechanisms explaining how multisectoral interventions for health could lead to the intended outcomes, none used realistic evaluations to assess these.
CONCLUSION
Our review has established that multisectoral interventions influence health system performance through immediate improvements in service delivery efficiency, readiness, acceptability and affordability. The interconnectedness of these effects demonstrates their role in addressing the complexities of modern health care.
Topics: Humans; Delivery of Health Care; Social Determinants of Health
PubMed: 38933474
DOI: 10.2471/BLT.23.291246 -
Nutrients Jun 2024Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive years. The disease's multifactorial etiology involves genetic, environmental, and hormonal components. Recent studies have highlighted the potential impact of dietary factors, particularly unsaturated fatty acids, on the modulation of SLE due to their anti-inflammatory properties. This meta-analysis aims to evaluate the association between unsaturated fatty acid consumption and the risk, progression, and clinical manifestations of SLE, providing evidence-based guidance for dietary management.
METHODS
We conducted a comprehensive search across major medical databases up to January 2024, focusing on studies that examined the intake of unsaturated fatty acids and the impact of such intake on SLE. Using the PICOS (population, intervention, comparator, outcomes, study design) framework, we included randomized controlled trials and case-control studies, assessing outcomes such as SLE activity, measured by SLE Disease Activity Index (SLEDAI) or the British Isles Lupus Assessment Group (BILAG) index, inflammation biomarkers. Studies were analyzed using either a fixed- or random-effects model based on heterogeneity ( statistic), with sensitivity analyses performed to assess the robustness of the findings.
RESULTS
Our search included 10 studies, encompassing a wide variety of designs and populations. The meta-analysis showed that a diet rich in unsaturated fatty acids is significantly associated with a reduction in SLEDAI scores (pooled SMD) of -0.36, 95% CI: -0.61 to -0.11, = 0.007, indicating a beneficial effect on disease activity. Additionally, we found that unsaturated fatty acid intake has a significant impact on HDL levels, suggesting a positive effect on lipid profiles. However, no significant effects were observed on levels of the inflammatory marker IL-6 or other lipid components (LDL and cholesterol). With minimal heterogeneity among studies ( ≤ 15%), sensitivity analysis confirmed the stability and reliability of these results, highlighting the potential role of unsaturated fatty acids in SLE management.
CONCLUSIONS
This meta-analysis suggests that dietary intake of unsaturated fatty acids may play a positive role in reducing SLE activity and may significantly affect HDL levels without having significant effects on inflammation markers or other lipid profiles. These findings support the inclusion of unsaturated fatty acids in the dietary management of SLE patients, although further research is required to refine dietary recommendations and explore the mechanisms underlying these associations.
Topics: Lupus Erythematosus, Systemic; Humans; Fatty Acids, Unsaturated; Female; Diet; Male; Biomarkers; Adult
PubMed: 38931327
DOI: 10.3390/nu16121974 -
Molecules (Basel, Switzerland) Jun 2024Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on... (Review)
Review
Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.
Topics: Oxidative Stress; Ozone; Oxidation-Reduction; Humans; Mitochondria; Reactive Oxygen Species; Animals; Antioxidants; Biomarkers
PubMed: 38930804
DOI: 10.3390/molecules29122738 -
Minerva Anestesiologica Jun 2024Decision-making about organ donation (OD) is influenced by interrelated cognitive and non-cognitive factors. The identification of these factors in the general...
INTRODUCTION
Decision-making about organ donation (OD) is influenced by interrelated cognitive and non-cognitive factors. The identification of these factors in the general population and among healthcare professionals (HCP) in Italy are key ethical and scientific requirements to inform targeted communication and policy-making interventions, and to promote decision-making processes that are truly informed.
EVIDENCE ACQUISITION
A systematic review of articles published between January 1, 1999, and January 31, 2024 was performed by searching four databases using these terms: "organ donation" AND (attitude OR opinion OR knowledge OR awareness OR intention OR beliefs OR norms OR perception) AND (Italy OR Italian). The reference sections of included articles were scrutinized for additional references.
EVIDENCE SYNTHESIS
Most respondents (lay citizens and HCPs) were in favor of OD, but many (mainly but not exclusively lay citizens) would not authorize OD in the event of death of a family member. Lack of knowledge about OD and the gap between demand and supply of organs, fear of body mutilation, doubts about the criteria for brain death diagnosis, doubts about the wishes of the deceased family member, and distrust towards medical doctors and the healthcare system were the most commonly reported reasons, confirming that cognitive and non-cognitive factors are at play.
CONCLUSIONS
The majority of the Italian population supports OD, but cognitive and non-cognitive barriers are present even among HCPs. Communication campaigns, encouraging family discussions about OD, providing better education for HCPs (including medical and nursing students), and making it easier to sign OD cards may promote informed decision-making and possibly increase consent rates.
PubMed: 38922284
DOI: 10.23736/S0375-9393.24.18098-4 -
The Iowa Orthopaedic Journal 2024Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined....
BACKGROUND
Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined. Recent data suggests that the collagen-degrading menstrual hormone relaxin may cyclically impact female ACL tissue quality. This review aims to identify any correlation between menstrual relaxin peaks and rates of female ACL injury.
METHODS
A systematic review was performed, utilizing the MEDLINE, EMBASE, and CINAHL databases. Included studies had to directly address relaxin/female ACL interactions. The primary outcome variable was relaxin proteolysis of the ACL, at cellular, tissue, joint, and whole-organism levels. The secondary outcome variable was any discussed method of moderating relaxin levels, and the clinical results if available.
RESULTS
AllThe numerous relaxin receptors on female ACLs upregulate local collagenolysis and suppress local collagen production. Peak serum relaxin concentrations (SRC) occur during menstrual cycle days 21-24; a time phase associated with greater risk of ACL injury. Oral contraceptives (OCPs) reduce SRC, with a potential ACLprotective effect.
CONCLUSION
A reasonable correlative and plausible causative relationship exists between peak relaxin levels and increased risk of ACL injury in females, and further investigation is warranted. .
Topics: Humans; Relaxin; Female; Anterior Cruciate Ligament Injuries; Menstrual Cycle; Athletic Injuries; Athletes
PubMed: 38919370
DOI: No ID Found