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Journal of Clinical Medicine Jun 2024Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder connected with a distinctive facial appearance, various skeletal malformations, delayed bone age,...
Floating-Harbor syndrome (FHS) is an extremely rare genetic disorder connected with a distinctive facial appearance, various skeletal malformations, delayed bone age, and expressive language delays. It is caused by heterozygous mutations in the Snf2-related CREBBP activator protein (SRCAP) gene. The aim of this paper is to describe the case of a 14-year-old male with FHS, referring to a review of the literature, and to collect all reported symptoms. In addition, the orthodontic treatment of the patient is described. For this, the electronic databases PubMed and Scopus were searched using the keyword "Floating-Harbor syndrome". Similar to previous cases in the literature, the patient presented with short stature; a triangular face with a large bulbous nose; deep-set eyes and narrow eyelid gaps; a wide mouth with a thin vermilion border of the upper lip; and dorsally rotated, small ears. They also presented some less-described symptoms, such as macrodontia and micrognathia. Moreover, mild mental retardation, microcephaly, and delayed psychomotor development were found. On the basis of an extraoral, intraoral examination, X-rays, and CBCT, he was diagnosed with overbite, canine class I and angle class III, on both sides. To the best of our knowledge, orthodontic treatment of this disease has not been assessed in detail so far, so this is the first case.
PubMed: 38929963
DOI: 10.3390/jcm13123435 -
Neurologia I Neurochirurgia Polska 2024Drug-resistant epilepsy (DRE) remains poorly-controlled in c.33% of patients, and up to 50% of patients suffering from DRE are deemed not to be suitable candidates for... (Review)
Review
INTRODUCTION
Drug-resistant epilepsy (DRE) remains poorly-controlled in c.33% of patients, and up to 50% of patients suffering from DRE are deemed not to be suitable candidates for resective surgery. For these patients, deep brain stimulation (DBS) may constitute the last resort in the treatment of DRE.
STATE OF THE ART
We undertook a systematic review of the current literature on DBS efficacy and the safety of two thalamic nuclei-anterior nucleus of the thalamus (ANT) and the centromedian nucleus of the thalamus in the management of patients with DRE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL) was conducted.
CLINICAL IMPLICATIONS
We found 30 articles related to ANT DBS and 13 articles related to CMN DBS which were further analysed. Based on the clinical research articles, we found a mean seizure frequency reduction for both thalamic nuclei. For ANT DBS, the mean seizure frequency reduction ranged from 48% to 75%, and for CMN DBS from 46.7% to 91%. The responder rate (defined as at least 50% reduction in seizure frequency) was reported to be 53.2-75% for patients after ANT DBS and 50-90% for patients after CMN DBS.
FUTURE DIRECTIONS
ANT and CMN DBS appear to be safe and efficacious treatments, particularly in patients with refractory partial seizures and primary generalised seizures. ANT DBS reduces most effectively seizures originating in the temporal and frontal lobes. CMN DBS reduces mostly primary generalised tonic-clonic and atypical absences and atonic seizures. Seizures related to Lennox-Gastaut syndrome respond very favourably to CMN DBS.
Topics: Humans; Deep Brain Stimulation; Drug Resistant Epilepsy; Anterior Thalamic Nuclei; Intralaminar Thalamic Nuclei; Treatment Outcome
PubMed: 38864766
DOI: 10.5603/pjnns.98258 -
Brain : a Journal of Neurology Jun 2024Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair...
Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
Topics: Animals; Female; Humans; Male; Mice; Acyltransferases; Carboxylic Ester Hydrolases; Mutation, Missense; Phenotype; Phospholipases; Retinal Diseases
PubMed: 38735647
DOI: 10.1093/brain/awae055 -
International Journal of Molecular... Apr 2024This study examines the impact of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) on various aspects of children's health-from the realms... (Review)
Review
This study examines the impact of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) on various aspects of children's health-from the realms of growth and puberty to the nuanced characteristics of metabolic syndrome, diabetes, liver pathology, carcinogenic potential, and cardiovascular disorders. A comprehensive literature review was conducted using PubMed, with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method employing specific keywords related to child health, obesity, and insulin-like growth factors. This study reveals associations between insulin-like growth factor 1 and birth weight, early growth, and adiposity. Moreover, insulin-like growth factors play a pivotal role in regulating bone development and height during childhood, with potential implications for puberty onset. This research uncovers insulin-like growth factor 1 and insulin-like growth factor 2 as potential biomarkers and therapeutic targets for metabolic dysfunction-associated liver disease and hepatocellular carcinoma, and it also highlights the association between insulin-like growth factors (IGFs) and cancer. Additionally, this research explores the impact of insulin-like growth factors on cardiovascular health, noting their role in cardiomyocyte hypertrophy. Insulin-like growth factors play vital roles in human physiology, influencing growth and development from fetal stages to adulthood. The impact of maternal obesity on children's IGF levels is complex, influencing growth and carrying potential metabolic consequences. Imbalances in IGF levels are linked to a range of health conditions (e.g., insulin resistance, glucose intolerance, metabolic syndrome, and diabetes), prompting researchers to seek novel therapies and preventive strategies, offering challenges and opportunities in healthcare.
Topics: Pregnancy; Child; Female; Humans; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Metabolic Syndrome; Obesity; Insulin-Like Peptides; Diabetes Mellitus
PubMed: 38612776
DOI: 10.3390/ijms25073966 -
Alzheimer's Research & Therapy Apr 2024Measurement of beta-amyloid (Aβ) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Measurement of beta-amyloid (Aβ) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of developing a clinical syndrome in the presence of these protein changes (A+ and T+) remains unclear. By performing a systematic review and meta-analysis, we investigated the risk of mild cognitive impairment (MCI) or dementia in the non-demented population with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal fluid examination.
METHODS
A systematic search of prospective and retrospective studies investigating the association of Aβ and p-tau with cognitive decline was performed in three databases (MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were pooled using a random-effects model. The effect of neurodegeneration was not studied due to its non-specific nature.
RESULTS
A total of 18,162 records were found, and at the end of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aβ42 or Aβ42/40 analysis and amyloid PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects (11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73 [95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95% CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion (13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression showed that the ORs for Aβ exposure decreased with age in MCI. (beta = -0.04 [95% CI -0.03 to -0.083]).
CONCLUSIONS
Identifying Aβ-positive individuals, irrespective of the measurement technique employed (CSF or PET), enables the detection of the most at-risk population before disease onset, or at least at a mild stage. The inclusion of tau status in addition to Aβ, especially in A+T+ cases, further refines the risk assessment. Notably, the higher odds ratio associated with Aβ decreases with age.
TRIAL REGISTRATION
The study was registered in PROSPERO (ID: CRD42021288100).
Topics: Humans; Prospective Studies; Retrospective Studies; Amyloidogenic Proteins; Cognitive Dysfunction; Dementia
PubMed: 38610055
DOI: 10.1186/s13195-024-01455-2 -
Journal of Clinical Medicine Feb 2024The prevalence of obstructive sleep apnea (OSA) is suggested to differ according to different age groups. While its prevalence has been extensively investigated among... (Review)
Review
BACKGROUND
The prevalence of obstructive sleep apnea (OSA) is suggested to differ according to different age groups. While its prevalence has been extensively investigated among middle-aged and old individuals, very few studies have summarized its prevalence among young adults. The present study aimed to conduct a systematic review and meta-analysis of OSA prevalence among healthy adults aged 18-30 years in the general population.
METHODS
A search of Embase, Medline, and Web of Science databases for articles reporting the prevalence of OSA among young adults confirmed by objective diagnostic methods was completed by two reviewers. Studies identified and included in the review were summarized qualitatively. Additionally, a meta-analysis of prevalence rates was conducted using a random effects model.
RESULTS
11 articles out of 5898 met the inclusion criteria and were included in the meta-analysis. The diagnostic thresholds, scoring criteria, and the type of used device varied substantially among all the studies. We found that the pooled prevalence of OSA among young adults was 16% (CI 95%, 8-29%, I = 92%, τ = 1.47).
CONCLUSION
The prevalence of OSA among young adults was found to be ~16%. However, a few factors diverged prevalence between the studies, such as hypopnea definition, AHI threshold, and type of device. Most of the studies included examined healthy volunteers, suggesting that the disease burden may be underestimated. Findings from our review highlight the need to include OSA-related assessment and intervention in the overall health care of young adults. By early detection and offered treatment, further complications related to comorbidities may be omitted.
PubMed: 38592210
DOI: 10.3390/jcm13051386 -
Critical Care Explorations Apr 2024We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and... (Review)
Review
OBJECTIVES
We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness.
DATA SOURCES
We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials.
STUDY SELECTION
We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP.
DATA EXTRACTION
We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia, superinfections/secondary infections, neuropsychiatric effects, and neuromuscular weakness.
DATA SYNTHESIS
We included 47 RCTs ( = 13,893 patients). Corticosteroids probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95% CI, 0.87-1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or secondary infections (RR, 0.97; 95% CI, 0.89-1.05; absolute risk reduction, 0.5%; moderate certainty) and may have no effect on neuromuscular weakness (RR, 1.22; 95% CI, 1.03-1.45; ARI, 1.4%; low certainty) or neuropsychiatric events (RR, 1.19; 95% CI, 0.82-1.74; ARI, 0.5%; low certainty). Conversely, they increase the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11-1.31; ARI, 5.4%; high certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI, 1.29-1.96; ARI, 2.3%; moderate certainty).
CONCLUSIONS
In ARDS, sepsis, and CAP, corticosteroids are associated with hyperglycemia and probably with hypernatremia but likely have no effect on gastrointestinal bleeding or secondary infections. More data examining effects of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular weakness, would clarify the safety of this class of drugs in critical illness.
PubMed: 38567382
DOI: 10.1097/CCE.0000000000001071 -
Antibodies (Basel, Switzerland) Mar 2024Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or... (Review)
Review
Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or pregnancy morbidity. Due to various suspected causes, deficient or insufficient levels of vitamin D in the serum have been reported in patients with PAPS; however, the reports have been sporadic and inconclusive. This systematic review and meta-analysis aimed to comprehensively evaluate the serum vitamin D levels in patients with PAPS compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42019132128) and a systematic literature search was conducted through Google Scholar, PubMed, Web of Science, Scopus, and ScienceDirect databases without restricting language and year. Pooled prevalence, mean difference (MD), and odds ratio (OR) along with 95% confidence intervals (CI) were determined by using a random effects model. Study quality was assessed by the Joana Brigg's Institute (JBI) protocol and publication bias was evaluated by a trim and fill funnel plot, Begg's, and Egger's tests. The pooled prevalence of vitamin D deficiency and insufficiency was found to be 32.2% [95% CI: 16.3-48.2] and 61.5% [95% CI: 40.2-82.8], respectively. Serum levels of vitamin D were considerably lower in the PAPS patients compared to controls (MD: -5.75, 95% CI: -9.73 to -1.77; = 0.005). Multiple sensitivity analyses showed that the results remained statistically significant, demonstrating the robustness of this meta-analysis. No significant publication bias was detected in determining the MD of serum vitamin D levels in PAPS and controls. In conclusion, PAPS patients had greater rates of vitamin D deficiency or insufficiency, higher frequency of thrombosis, and lower serum vitamin D levels than healthy individuals.
PubMed: 38534213
DOI: 10.3390/antib13010022 -
Kardiologia Polska 2024Cardiovascular disease is a leading cause of mortality worldwide and is likely to rise. Acute coronary syndrome (ACS) is consequent on inflammation. As a common and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiovascular disease is a leading cause of mortality worldwide and is likely to rise. Acute coronary syndrome (ACS) is consequent on inflammation. As a common and cost-effective inflammatory biomarker, the neutrophil-to-lymphocyte ratio (NLR) may be beneficial in cardiovascular medicine.
AIMS
This meta-analysis examines the diagnostic and prognostic performance of the NLR in ACS.
METHODS
We systematically searched PubMed Central, Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov databases. The search spanned from databases inception to January 10, 2024. The findings were aggregated into normalized mean differences with 95% confidence intervals.
RESULTS
Ninety articles, with 45 990 participants, were included. Pooled analysis of the NLR varied and was higher in ST-segment elevation myocardial infarction (STEMI) vs. non-ST-segment elevation myocardial infarction patients (4.94 ± 3.24 vs. 3.24 ± 2.74), acute myocardial infarction vs. unstable angina (4.47 ± 3.43 vs. 2.97 ± 1.58), ACS vs. stable angina (SA) (5.45 ± 4.28 vs. 2.46 ± 2.15), and ACS vs. controls (5.31 ± 4.01 vs. 2.46 ± 2.45). The NLR also was associated with ACS mortality, with survivors having lower results (3.67 ± 2.72 vs. 5.56 ± 3.93). Subanalysis showed that differences in the NLR were observed in STEMI survivors (4.28 ± 3.24 vs. 6.79 ± 3.98). Of ACS patients with major cardiovascular events (MACE) vs. without MACE, the NLR was 6.29 ± 4.89 vs. 3.82 ± 4.12. In STEMI patients, the NLR differed between those with and without MACE (6.99 ± 5.27 vs. 4.99 ± 4.12).
CONCLUSIONS
The NLR is an effective tool for differentiating between different types of ACS. A high NLR is associated with ACS and increased MACE at 30 days. The NLR also appears to be a good predictor of MACE risk, at least in STEMI patients.
Topics: Humans; Prognosis; Acute Coronary Syndrome; ST Elevation Myocardial Infarction; Neutrophils; Lymphocytes; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention
PubMed: 38493452
DOI: 10.33963/v.phj.99554 -
Journal of Psychosomatic Research Jun 2024This systematic review aims to analyze the existing literature investigating respiratory functioning in people with Persistent Somatic Symptoms (PSS) compared to healthy...
OBJECTIVE
This systematic review aims to analyze the existing literature investigating respiratory functioning in people with Persistent Somatic Symptoms (PSS) compared to healthy controls, to identify patterns of respiratory disturbances by symptom or syndrome, and describe any respiratory outcomes consistent across diagnoses.
METHODS
A systematic review following PRISMA guidelines was conducted. A comprehensive search was carried out across five databases (PubMed (NCBI), PsycArticles (Ovid), Web of Science (Core Collection), Embase, and Scopus) using two customised search strings for persistent somatic symptoms and objective respiratory parameters. Title/abstract screening and data extraction were carried out independently by two reviewers. The modified Newcastle-Ottawa Scale was used for quality assessment of the studies. Studies investigating baseline respiratory functioning in adult patients with PSS compared to healthy controls, using at least one objective respiratory were included.
RESULTS
18 studies met the inclusion criteria for the review, with a pooled sample size of n = 3245. Chronic pain conditions were found to be the most prevalent subset of diagnoses of interest, comprising six of the studies. 10 studies included measures of lung capacity, flow and/or volume, nine studies reported measures of ventilation, and four studies investigated respiratory muscle functioning. 13 of the included studies reported significant differences in at least one objective respiratory measure between groups (at rest). Scores on self-reported measures of dysnpea and breathlessness were higher in patients compared to healthy controls, while objective respiratory outcomes were varied.
CONCLUSION
The current systematic review is consistent with previous literature suggesting more pronounced experiences of breathlessness in patients with PSS, and significant disparities between reported dyspnea and objective respiratory outcomes. Research investigating the uncoupling between subjective and objective respiratory outcomes is needed to understand the mechanisms behind breathing disturbances in PSS.
Topics: Humans; Medically Unexplained Symptoms; Observational Studies as Topic; Respiration Disorders
PubMed: 38388305
DOI: 10.1016/j.jpsychores.2024.111607