-
Osteoarthritis and Cartilage Jun 2024Hemophilia A and B are rare X-linked genetic bleeding disorders due to a complete or partial deficiency in the coagulation factors VIII or IX, respectively. The main... (Review)
Review
Hemophilia A and B are rare X-linked genetic bleeding disorders due to a complete or partial deficiency in the coagulation factors VIII or IX, respectively. The main treatment for hemophilia is prophylactic and based on coagulation factor replacement therapies. These treatments have significantly reduced bleeding and improved the patients' quality of life. Nevertheless, repeated joint bleedings (hemarthroses), even subclinical hemarthroses, can lead to hemophilic arthropathy (HA). This disabling condition is characterized by chronic pain due to synovial inflammation, cartilage and bone destruction requiring ultimately joint replacement. HA resembles to rheumatoid arthritis because of synovitis but HA is considered as having similarities with osteoarthritis as illustrated by the migration of immune cells, production of inflammatory cytokines, synovial hypertrophy and cartilage damage. Various drugs have been evaluated for the management of HA with limited success. The objective of the review is to discuss new therapeutic approaches with a special focus on the studies that have investigated the potential of using mesenchymal stromal cells (MSCs) in the management of HA. A systematic review of the literature has been made. Most of the studies have focused on the interest of MSCs for the delivery of missing factors VIII or IX but in some studies, more insight on the effect of MSC injection on synovial inflammation or cartilage structure were provided and put in perspective for possible clinical applications.
Topics: Humans; Hemarthrosis; Hemophilia A; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Hemophilia B
PubMed: 38160743
DOI: 10.1016/j.joca.2023.12.007 -
Journal of Strength and Conditioning... Apr 2024Molinari, T, Radaelli, R, Rech, A, Brusco, CM, Markarian, AM, and Lopez, P. Moderators of resistance training effects in healthy young women: A systematic review and... (Meta-Analysis)
Meta-Analysis
Molinari, T, Radaelli, R, Rech, A, Brusco, CM, Markarian, AM, and Lopez, P. Moderators of resistance training effects in healthy young women: A systematic review and meta-analysis. J Strength Cond Res 38(4): 804-814, 2024-To systematically review and analyze the effects of resistance-based exercise programs and potential moderators of change in body fat percentage, whole-body fat and lean mass, muscle hypertrophy, muscle strength, and muscle power/rapid force in healthy young women (between 18 and 35 years). A systematic search was undertaken in 7 databases from inception to May 2022. Eligible randomized controlled trials examined the effects of resistance-based exercise programs on outcomes of interest in healthy young women. Meta-analysis was undertaken with a 3-level mixed-effects model. Associations between standardized mean difference (SMD) and potential moderators (number of sessions, weekly volume, and intensity) were tested by meta-regression models. Statistical significance was set at an α level of 0.05, whereas an α level of 0.05-0.10 was also considered for potential moderators of resistance training effects. Forty articles ( n = 1,312) were included. Resistance-based exercise programs resulted in a significant improvement of 0.4 SMD (95% confidence intervals [95% CI]: 0.2 to 0.5, p < 0.001) in lean mass/muscle hypertrophy and 1.2 SMD (95% CI: 0.9 to 1.5, p < 0.001) in muscle strength. A higher number of sessions was associated with changes in lean mass/muscle hypertrophy ( β = 0.01 ± 0.00, p = 0.009), whereas a higher weekly volume approached statistical significance to moderate changes in muscle strength ( β = 0.01 ± 0.01, p = 0.053). Body fat percentage (-0.4 SMD, 95% CI: -0.6 to -0.1, p = 0.006) and muscle power/rapid force (0.6 SMD, 95% CI: 0.2 to 1.1, p = 0.011) were significantly improved. In conclusion, a higher resistance training volume was associated with greater improvements in lean mass/muscle hypertrophy, muscle strength, and body fat percentage, whereas muscle power/rapid force improvements were observed irrespective of prescription characteristics. These findings may help in designing resistance training programs for muscle hypertrophy, strength and power, and body fat percentage in healthy women.
Topics: Humans; Female; Resistance Training; Health Status; Exercise; Muscle Strength; Hypertrophy
PubMed: 38090747
DOI: 10.1519/JSC.0000000000004666 -
Circulation. Genomic and Precision... Dec 2023The diagnosis of Fabry disease (FD) has relevant implications related to the management. Thus, a clear assignment of variant pathogenicity is crucial. This systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The diagnosis of Fabry disease (FD) has relevant implications related to the management. Thus, a clear assignment of variant pathogenicity is crucial. This systematic review and meta-analysis aimed to investigate the prevalence of FD in high-risk populations and newborns and evaluate the impact of different variant classifications on the estimated prevalence of FD.
METHODS
We searched the EMBASE and PubMed databases on February 21, 2023. Observational studies evaluating the prevalence of FD and reporting the identified variants were included. variants were re-evaluated for their pathogenicity significance using the American College of Medical Genetics and Genomics criteria and the ClinVar database. The pooled prevalence of FD among different settings was calculated. The study was registered on PROSPERO (CRD42023401663) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.
RESULTS
Of the 3941 studies identified, 110 met the inclusion criteria. The pooled prevalence of FD was significantly different according to the clinical setting and criteria used for the pathogenicity assessment. Using the American College of Medical Genetics and Genomics criteria, the pooled prevalence was 1.2% in patients with left ventricular hypertrophy/hypertrophic cardiomyopathy (26 studies; 10 080 patients screened), 0.3% in end-stage renal disease/chronic kidney disease (38 studies; 62 050 patients screened), 0.7% in stroke (25 studies; 15 295 patients screened), 0.7% in cardiac conduction disturbance requiring pacemaker (3 studies; 1033 patients screened), 1.0% in small-fiber neuropathy (3 studies; 904 patients screened), and 0.01% in newborns (15 studies; 11 108 793 newborns screened). The pooled prevalence was different if the variants were assessed using the ClinVar database, and most patients with a discrepancy in the pathogenicity assignment carried 1 of the following variants: p.A143T, p.D313Y, and p.E66Q.
CONCLUSIONS
This systematic review and meta-analysis describe the prevalence of FD among newborns and high-risk populations, highlighting the need for a periodic reassessment of the variants in the context of recent clinical, biochemical, and histological data.
REGISTRATION
URL: https://crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023401663.
Topics: Humans; Infant, Newborn; Fabry Disease; alpha-Galactosidase; Prevalence; Hypertrophy, Left Ventricular; Stroke
PubMed: 38047356
DOI: 10.1161/CIRCGEN.123.004252 -
Endocrine Practice : Official Journal... Feb 2024We aimed to evaluate the effects of thyroid-stimulating hormone (TSH) suppression therapy on cardiac structure and function in patients with differentiated thyroid... (Meta-Analysis)
Meta-Analysis Review
Effect of Thyroid-Stimulating Hormone Suppression Therapy on Cardiac Structure and Function in Patients With Differentiated Thyroid Cancer After Thyroidectomy: A Systematic Review and Meta-Analysis.
OBJECTIVE
We aimed to evaluate the effects of thyroid-stimulating hormone (TSH) suppression therapy on cardiac structure and function in patients with differentiated thyroid cancer (DTC) following thyroidectomy.
METHODS
Two investigators independently searched the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant studies published from inception to January 6, 2023, without any restrictions on language. Standard mean differences and 95% confidence intervals were calculated using fixed or random effects models. Thirteen clinical outcomes were analyzed, mainly evaluating cardiac morphology, systolic function, and diastolic function.
RESULTS
Thirteen studies were included in the quantitative analysis. Compared to healthy controls, left ventricular mass index, left ventricular posterior wall thickness, interventricular septal thickness, and isovolumic relaxation time values increased; the ratio of E-wave velocity to A-wave velocity and E-wave velocity values decreased. The left ventricular ejection fraction and cardiac output did not change in patients with DTC who underwent long-term TSH suppression therapy. Interventricular septal thickness values were significantly correlated with the duration of TSH suppression therapy.
CONCLUSION
Long-term TSH suppression therapy leads to cardiac hypertrophy and impaired cardiac diastolic function in patients with DTC. These changes may be related to the duration of TSH suppression therapy. Large prospective studies with long follow-up periods are needed to validate these findings.
Topics: Humans; Thyroxine; Stroke Volume; Thyroidectomy; Prospective Studies; Thyrotropin; Ventricular Function, Left; Thyroid Neoplasms
PubMed: 38007181
DOI: 10.1016/j.eprac.2023.11.006 -
Handchirurgie, Mikrochirurgie,... Dec 2023Lipoedema is a symmetrically localised, painful hypertrophy of subcutaneous adipose tissue in the extremities with marked disproportion to the trunk, and almost...
BACKGROUND
Lipoedema is a symmetrically localised, painful hypertrophy of subcutaneous adipose tissue in the extremities with marked disproportion to the trunk, and almost exclusively affects females. Despite being first described over 80 years ago, the aetiology and pathogenesis of the disease are largely unknown and are currently the subject of intensive research efforts.
METHODS
To summarise the current evidence-based literature on the cellular pathologies and aetiology of lipoedema, a PRISMA-based systematic review was conducted within the National Library of Medicine and Cochrane databases.
RESULTS
A total of 53 studies were identified and included in this review. The results were classified and summarised into categories.
CONCLUSION
Although there has been a significant increase in research activity and recent publication of extensive studies with a histological and molecular genetic focus, the fundamental aetiology and pathology of lipoedema remains largely unclear. The current data shows discrepancies across studies, particularly with regard to the "oedematous" component of lipoedema. The frequently present comorbidities "lymphoedema" and "obesity", primarily in advanced stages of lipoedema, complicate the diagnostic differentiation and clear definition of study cohorts in scientific research.
Topics: United States; Female; Humans; Lipedema; Lymphedema; Obesity; Extremities; Pain
PubMed: 37984363
DOI: 10.1055/a-2183-7414 -
Prenatal Diagnosis Nov 2023Several factors associated with poor outcome in patients with prenatally diagnosed sacrococcygeal teratoma (SCT) have been found. However, the prognostic accuracy of... (Meta-Analysis)
Meta-Analysis Review
Several factors associated with poor outcome in patients with prenatally diagnosed sacrococcygeal teratoma (SCT) have been found. However, the prognostic accuracy of these factors has not been well established. Therefore, we aimed to systematically review the prognostic accuracy of factors associated with poor outcome in these patients. We queried Search Premier, COCHRANE Library, EMCARE, EMBASE, PubMed, ScienceDirect, and Web of Science databases to identify studies regarding patients with prenatally diagnosed SCT. Poor outcome was defined as termination of pregnancy (TOP), intrauterine fetal death (IUFD), or perinatal death. We estimated the odds ratio of factors associated with poor outcome. Eleven studies (447 patients) were included. Overall mortality, including TOP, was 34.9%. Factors associated with poor outcome in fetuses with prenatally diagnosed SCT were cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, and placentomegaly. A tumor volume to fetal weight ratio (TFR) of >0.12 before a gestational age of 24 weeks is predictive of poor outcome. The prognostic accuracy of factors associated with poor outcome in fetuses prenatally diagnosed with SCT seems promising. Factors associated with cardiac failure such as cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, placentomegaly, and TFR >0.12 were found to be predictive of poor outcome.
Topics: Pregnancy; Female; Humans; Infant; Prognosis; Hydrops Fetalis; Ultrasonography, Prenatal; Teratoma; Cardiomegaly; Sacrococcygeal Region
PubMed: 37964422
DOI: 10.1002/pd.6457 -
Journal of Clinical Neuromuscular... Dec 2023Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle...
OBJECTIVES
Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research.
METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies.
RESULTS
We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases).
CONCLUSIONS
IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.
Topics: Male; Middle Aged; Humans; Female; Isaacs Syndrome; Thymoma; Anticonvulsants; Thymus Neoplasms; Autoantibodies; Potassium Channels, Voltage-Gated; Carbamazepine; Receptors, Cholinergic; Steroids; Recurrence
PubMed: 37962197
DOI: 10.1097/CND.0000000000000460 -
European Archives of... Apr 2024Inferior turbinate hypertrophy is not a rare problem in children, it causes chronic nasal obstruction which can severely impact the quality of life. This study aimed to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Inferior turbinate hypertrophy is not a rare problem in children, it causes chronic nasal obstruction which can severely impact the quality of life. This study aimed to investigate the efficacy and safety of turbinate reduction surgery in children with impaired nasal breathing due to hypertrophied inferior turbinate that's refractory to medical treatment.
METHODS
We included 23 articles with various study designs: randomized controlled trials, single-arm clinical trials, and prospective and retrospective cohort studies. We searched PubMed, Scopus, Cochrane Library, and Web of Science with the relevant keywords till April 9th, 2023. The inclusion criteria were studied with the three prespecified study design that addressed children under 18 years who underwent turbinate reduction with any technique and evaluating the improvement whether by objective or subjective methods.
RESULTS
Studies used objective measures favor turbinate surgery except two that showed no significant difference between pre and postoperative results. All studies used subjective measures showed an improvement postoperatively except one study. Complication rates are rare, with crust formation is being the commonest (6.03%), however, the procedure is generally safe in children. In addition, follow-up periods varied widely between 2 weeks and more than 5 years.
CONCLUSION
Turbinate reduction in children is an effective as a treatment method for nasal blockage due to inferior turbinate hypertrophy which is resistant to medical treatment. It is a safe procedure with low rates of complications, however, due to the heterogenicity of the study designs, with a possible risk of bias we could not conduct a meta-analysis besides our systematic review.
Topics: Child; Humans; Adolescent; Turbinates; Treatment Outcome; Prospective Studies; Retrospective Studies; Quality of Life; Nasal Obstruction; Hypertrophy
PubMed: 37943317
DOI: 10.1007/s00405-023-08327-9 -
Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
Biomedical Papers of the Medical... Mar 2024Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation... (Meta-Analysis)
Meta-Analysis Review
Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.
Topics: Child; Animals; Humans; Aged; 8-Hydroxy-2'-Deoxyguanosine; Creatinine; DNA Damage; Comet Assay; Hypertension
PubMed: 37916467
DOI: 10.5507/bp.2023.044