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The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356 -
Archives of Gynecology and Obstetrics May 2024Preeclampsia is a major cause of health problems for both pregnant women and unborn babies worldwide. However, the underlying causes of preeclampsia are not fully... (Review)
Review
PURPOSE
Preeclampsia is a major cause of health problems for both pregnant women and unborn babies worldwide. However, the underlying causes of preeclampsia are not fully understood, leading to limited effective treatments. The goal of this study is to enhance our knowledge of its causes, devise prevention strategies, and develop treatments.
METHODS
We performed a systematic literature search. Six models regarding the pathogenesis of preeclampsia are discussed in this review.
RESULTS
This review focuses on the latest advancements in understanding preeclampsia's origins. Preeclampsia is a complex condition caused by various factors, processes, and pathways. Reduced blood flow and oxygen to the uterus and placenta, heightened inflammatory reactions, immune imbalances, altered genetic changes, imbalanced blood vessel growth factors, and disrupted gut bacteria may contribute to its development.
CONCLUSION
Preeclampsia is thought to result from the interplay of these factors.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Placenta; Uterus
PubMed: 38421424
DOI: 10.1007/s00404-024-07393-6 -
Chest Oct 2023Several recently published randomized controlled trials have evaluated various noninvasive oxygenation strategies for the treatment of acute hypoxemic respiratory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several recently published randomized controlled trials have evaluated various noninvasive oxygenation strategies for the treatment of acute hypoxemic respiratory failure.
RESEARCH QUESTION
Which available noninvasive oxygen strategies are effective for acute hypoxic respiratory failure?
STUDY DESIGN AND METHODS
A systematic review of Medline, Embase, Cochrane CENTRAL, CINAHL, Web of Science, MedRxiv, and Research Square was conducted from inception to October 1, 2022. A random effects frequentist network meta-analysis was performed, and the results are presented using absolute risk difference per 1,000 patients. The Grading of Recommendations, Assessment, Development and Evaluation framework was used to rate the certainty of the evidence. Mortality, invasive mechanical ventilation, duration of hospitalization and ICU stay, ventilator-free days, and level of comfort are reported.
RESULTS
Thirty-six trials (7,046 patients) were included. It was found that helmet CPAP probably reduces mortality compared with standard oxygen therapy (SOT) (231 fewer deaths per 1,000; 95% CI, 126-273 fewer) (moderate certainty). A high-flow nasal cannula (HFNC) probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000; 95% CI, 40.5-157.5 fewer) (moderate certainty). All noninvasive oxygenation strategies may reduce the duration of hospitalization as compared with SOT (low certainty). Helmet bilevel ventilation (4.84 days fewer; 95% CI, 2.33-7.36 days fewer) and helmet CPAP (1.74 days fewer; 95% CI, 4.49 fewer-1.01 more) may reduce the duration of ICU stay as compared with SOT (both low certainty). SOT may be more comfortable than face mask noninvasive ventilation and no different in comfort compared with an HFNC (both low certainty).
INTERPRETATION
A helmet interface for noninvasive ventilation probably reduces mortality and the risk of mechanical ventilation, as well as the duration of hospital and ICU stay. An HFNC probably reduces the risk of invasive mechanical ventilation and may be as comfortable as SOT. Further research is necessary to understand the role of these interfaces in acute hypoxemic respiratory failure.
Topics: Humans; Adult; Network Meta-Analysis; Respiratory Insufficiency; Oxygen; Oxygen Inhalation Therapy; Hypoxia; Noninvasive Ventilation; Cannula; Respiratory Distress Syndrome
PubMed: 37085046
DOI: 10.1016/j.chest.2023.04.022 -
Journal of Cancer Research and Clinical... Dec 2023Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance.
METHODS
A systematic search of electronic databases was conducted to identify clinical studies that examined the correlation between biomarkers and treatment outcomes in the HNSCC patients. The included articles were screened and analyzed to extract data regarding overall survival (OS) and progression-free survival (PFS).
RESULTS
The relationship between the biomarkers included in the summary and prognosis was as follows: HPV positivity was associated with improved OS (HR = 0.76, 95% CI = 0.58-1.99), PFS (HR = 1.16, 95% CI = 0.81-1.67), and response (OR = 1.67, 95% CI = 1.37-2.99). PD-L1 positivity was associated with OS (HR = 0.71, 95% CI = 0.59-0.85), PFS (HR = 0.56 95% CI = 0.43-0.73), and response (OR = 2.16, 95% CI = 1.51-3.10). Neither HPV positivity nor PD-L1 positivity was associated with DCR. The following markers were collected for OS and PFS data and were associated with longer OS: lower Glasgow prognostic score (GPS/mGPS) grading, lower PS grading, high body mass index (BMI), low neutrophil-to-lymphocyte ratio (NLR), low platelet-to-lymphocyte ratio (PLR), high albumin (Alb), low lactate dehydrogenase (LDH). Factors associated with better PFS were lower GPS/mGPS grading, lower PS grading, high BMI, low NLR, high absolute lymphocyte count, and low LDH. Hyperprogressive disease was associated with worse OS and PFS. Fewer clinical studies have been completed on the tumor microenvironment and hypoxia, microsatellite instability/DNA mismatch repair, and microbiome and systematic analysis is difficult.
CONCLUSION
In our meta-analysis, different immune checkpoint factors were associated with different prognoses in HNSCC patients receiving immunotherapy. HPV, PD-L1, BMI, Alb, HPD, PS, GPS/mGPS, LDH, NLR, and PLR predicted the ICI outcome in HNSCC patients.
Topics: Humans; Prognosis; Immune Checkpoint Inhibitors; B7-H1 Antigen; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Biomarkers; Tumor Microenvironment
PubMed: 38078963
DOI: 10.1007/s00432-023-05504-5 -
Brain Sciences Nov 2023Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of... (Review)
Review
Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of studies investigating hypoxia (10-16% O) for ≥14 days in humans, as well as the neurobiological mechanisms triggered by hypoxia in animals, and suggests optimal treatment protocols to guide future studies. We followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020. Searches were performed on PubMed/MEDLINE, PsycInfo, EMBASE, and the Cochrane Library, in May-September 2023. Two authors independently reviewed the human studies with the following tools: (1) revised Cochrane collaboration's risk of bias for randomized trials 2.0; (2) the risk of bias in nonrandomized studies of interventions. We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer's disease markers. A total of 75% of human studies indicated cognitive and/or neurological benefits, although all studies were evaluated ashigh risk of bias due to a lack of randomization and assessor blinding. Low-dose intermittent or continuous hypoxia repeated for 30-240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted.
PubMed: 38137096
DOI: 10.3390/brainsci13121648 -
Journal of Gastrointestinal Cancer Dec 2023Obstructive sleep apnea (OSA), characterised by recurrent episodes of upper airway collapse, intermittent hypoxia (IH) and sleep fragmentation (SF), has been associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obstructive sleep apnea (OSA), characterised by recurrent episodes of upper airway collapse, intermittent hypoxia (IH) and sleep fragmentation (SF), has been associated with carcinogenesis in pre-clinical models. The relationship between OSA and colorectal cancer (CRC) in clinical studies is controversial.
AIM
The objective of this meta-analysis was to assess the association between OSA and CRC.
METHODS
Two independent investigators searched studies indexed in CINAHL, MEDLINE, EMBASE, the Cochrane Database and clinicaltrials.gov that were randomised controlled trials (RCT) or observational studies evaluating the relationship between OSA and CRC. Studies were included if they had available odds ratios (OR) and relative risks (RR) or if hazard ratios (HR) with 95% confidence intervals (CI) were available and a reference group composed of participants who did not have OSA. OR and 95% CI were calculated using a random-effect, generic inverse variance method.
RESULTS
We included four observational studies out of 85 records, comprising a combined cohort of 5,651,662 identified patients in the data analysis. Three studies used polysomnography to identify OSA. The pooled OR of CRC in patients with OSA was 1.49 (95% CI, 0.75 to 2.97). The statistical heterogeneity was high with I of 95%.
CONCLUSIONS
Our study is unable to conclusively point towards OSA being a risk factor in the development of CRC, despite the plausible biological mechanisms for this. Further well-designed prospective RCT assessing the risk of CRC in patients with OSA and the impact of OSA treatments on the incidence and prognosis of CRC are needed.
Topics: Humans; Sleep Apnea, Obstructive; Polysomnography; Risk Factors; Incidence; Colorectal Neoplasms
PubMed: 36813984
DOI: 10.1007/s12029-023-00919-2 -
Brain and Behavior Nov 2023Obstructive sleep apnea (OSA) is a common sleep disorder that causes intermittent hypoxia and sleep fragmentation, leading to attention impairment and other cognitive... (Review)
Review
BACKGROUND AND OBJECTIVE
Obstructive sleep apnea (OSA) is a common sleep disorder that causes intermittent hypoxia and sleep fragmentation, leading to attention impairment and other cognitive deficits. Magnetic resonance imaging (MRI) is a powerful modality that can reveal the structural and functional brain alterations associated with attention impairment in OSA patients. The objective of this systematic review is to identify and synthesize the evidence on MRI biomarkers and neuropsychological assessments of attention deficits in OSA patients.
METHODS
We searched the Scopus and PubMed databases for studies that used MRI to measure biomarkers related to attention alteration in OSA patients and reported qualitative and quantitative data on the association between MRI biomarkers and attention outcomes. We also included studies that found an association between neuropsychological assessments and MRI findings in OSA patients with attention deficits.
RESULTS
We included 19 studies that met our inclusion criteria and extracted the relevant data from each study. We categorized the studies into three groups based on the MRI modality and the cognitive domain they used: structural and diffusion tensor imaging MRI findings, functional, perfusion, and metabolic MRI findings, and neuropsychological assessment findings.
CONCLUSIONS
We found that OSA is associated with structural, functional, and metabolic brain alterations in multiple regions and networks that are involved in attention processing. Treatment with continuous positive airway pressure can partially reverse some of the brain changes and improve cognitive function in some domains and in some studies. This review suggests that MRI techniques and neuropsychological assessments can be useful tools for monitoring the progression and response to treatment of OSA patients.
Topics: Humans; Diffusion Tensor Imaging; Sleep Apnea, Obstructive; Brain; Magnetic Resonance Imaging; Biomarkers; Neuropsychological Tests
PubMed: 37743582
DOI: 10.1002/brb3.3262 -
Pain Jan 2024This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical... (Meta-Analysis)
Meta-Analysis
This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical trials (RCTs) on painful diabetic neuropathy (PDN), updating the previous literature by a decade. Four databases were searched for PDN trials published in the past 20 years, testing oral medications, adopting a parallel-group design. Magnitude of placebo or nocebo responses, Cochrane risk of bias, heterogeneity, and moderators were evaluated. Searches identified 21 studies (2425 placebo-treated patients). The overall mean pooled placebo response was -1.54 change in the pain intensity from baseline [95% confidence interval (CI): -1.52, -1.56, I 2 = 72], with a moderate effect size (Cohen d = 0.72). The pooled placebo 50% response rate was 25% [95% CI: 22, 29, I 2 = 50%]. The overall percentage of patients with adverse events (AEs) in the placebo arms was 53.3% [95% CI: 50.9, 55.7], with 5.1% [95% CI: 4.2, 6] of patients dropping out due to AEs. The year of study initiation was the only significant moderator of placebo response (regression coefficient = -0.06, [95% CI: -0.10, -0.02, P = 0.007]). More recent RCTs tended to be longer, bigger, and to include older patients (N = 21, rs = 0.455, P = 0.038, rs = 0.600, P = 0.004, rs = 0.472, P = 0.031, respectively). Our findings confirm the magnitude of placebo and nocebo responses, identify the year of study initiation as the only significant moderator of placebo response, draw attention to contextual factors such as confidence in PDN treatments, patients' previous negative experiences, intervention duration, and information provided to patients before enrollment.
Topics: Humans; Nocebo Effect; Diabetic Neuropathies; Placebo Effect; Pain Measurement; Diabetes Mellitus
PubMed: 37530658
DOI: 10.1097/j.pain.0000000000003000 -
Sleep Medicine Reviews Feb 2024Sleep disordered breathing is extremely common in pregnancy and is a risk factor for maternal complications. Animal models demonstrate that intermittent hypoxia causes... (Meta-Analysis)
Meta-Analysis Review
Sleep disordered breathing is extremely common in pregnancy and is a risk factor for maternal complications. Animal models demonstrate that intermittent hypoxia causes abnormal fetal growth. However, there are conflicting data on the association between maternal sleep disordered breathing and offspring growth in humans. We investigated this association by conducting a systematic review and meta-analysis. Sixty-three manuscripts, and total study population of 67, 671, 110 pregnant women were included. Thirty-one studies used subjective methods to define sleep disordered breathing, 24 applied objective methods and eight used international codes. Using a random effects model, habitual snoring, defined by subjective methods, and obstructive sleep apnea, diagnosed by objective methods, were associated with an increased risk for large for gestational age (OR 1.46; 95%CI 1.02-2.09 and OR 2.19; 95%CI 1.63-2.95, respectively), while obstructive sleep apnea, identified by international codes, was associated with an increased risk for small for gestational age newborns (OR 1.28; 95%CI 1.02-1.60). Our results support that maternal sleep disordered breathing is associated with offspring growth, with differences related to the type of disorder and diagnostic methods used. Future studies should investigate underlying mechanisms and whether treatment of sleep disordered breathing ameliorates the neonatal growth.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Fetus; Pregnancy Complications; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Snoring
PubMed: 37956482
DOI: 10.1016/j.smrv.2023.101868 -
European Journal of Neurology Dec 2023The prognosis of prolonged (28 days to 3 months post-onset) disorders of consciousness (pDoC) due to anoxic brain injury is uncertain. The present study aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The prognosis of prolonged (28 days to 3 months post-onset) disorders of consciousness (pDoC) due to anoxic brain injury is uncertain. The present study aimed to evaluate the long-term outcome of post-anoxic pDoC and identify the possible predictive value of demographic and clinical information.
METHOD
This is a systematic review and meta-analysis. The rates of mortality, any improvement in clinical diagnosis, and recovery of full consciousness at least 6 months after severe anoxic brain injury were evaluated. A cross-sectional approach searched for differences in baseline demographic and clinical characteristics between survivors and non-survivors, patients improved versus not improved, and patients who recovered full consciousness versus not recovered.
RESULTS
Twenty-seven studies were identified. The pooled rates of mortality, any clinical improvement and recovery of full consciousness were 26%, 26% and 17%, respectively. Younger age, baseline diagnosis of minimally conscious state versus vegetative state/unresponsive wakefulness syndrome, higher Coma Recovery Scale Revised total score, and earlier admission to intensive rehabilitation units were associated with a significantly higher likelihood of survival and clinical improvement. These same variables, except time of admission to rehabilitation, were also associated with recovery of full consciousness.
CONCLUSIONS
Patients with anoxic pDoC might improve over time up to full recovery of consciousness and some clinical characteristics can help predict clinical improvement. These new insights could support clinicians and caregivers in the decision-making on patient management.
Topics: Humans; Consciousness; Consciousness Disorders; Prognosis; Persistent Vegetative State; Brain Injuries
PubMed: 37246500
DOI: 10.1111/ene.15899