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Journal of Perinatal Medicine Jul 2024This case series aims to evaluate the long-term outcomes of congenital cytomegalovirus (CMV) infection in a population treated with valaciclovir during pregnancy. The...
OBJECTIVES
This case series aims to evaluate the long-term outcomes of congenital cytomegalovirus (CMV) infection in a population treated with valaciclovir during pregnancy. The study focuses on assessing the prevalence of long-term sequelae in infants with confirmed CMV fetal infection.
METHODS
A retrospective analysis was conducted on 33 pregnancies corresponding to 34 fetus with confirmed CMV congenital infection. They were followed from November 2004 to December 2020. Valaciclovir treatment was initiated after confirmation of fetal infection, and fetal outcomes were monitored through serial ultrasounds, neurosonography, and fetal magnetic resonance imaging (MRI). Postnatal assessments included: PCR confirmation, symptoms evaluation at birth, and long-term follow-up protocols for visual, auditory, and neurodevelopmental assessment.
RESULTS
Therapy was started at a median gestational age of 24 weeks. Of the 34 newborns 79.4 % were asymptomatic at birth. Median follow-up time was 6 years and 32.35 % developed long-term sequelae. Neurosensorial hearing loss (SNHL) was the predominant sequelae. In the cases which developed sequelae 54.5 % had imaging findings, and all with major findings developed long-term sequelae.
CONCLUSIONS
In our treated population we had a higher asymptomatic rate at birth comparing with a non-treated population, similar to those found in previous studies. We had a long-term sequelae rate of 32.35 %, similar to recent studies on non-treated population, although we registered a slightly lower rate of SNHL. A larger multicenter studies with a longer follow-up time, where treatment is started in the first trimester, is of the utmost importance, so we can truly understand the correlation between these imaging findings, therapy and long-term sequelae.
PubMed: 38943320
DOI: 10.1515/jpm-2023-0535 -
Health Technology Assessment... Jun 2024Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be approximately 10-15%, and around 80% remain asymptomatic. At present, cholecystectomy is the default option for people with symptomatic gallstone disease.
OBJECTIVES
To assess the clinical and cost-effectiveness of observation/conservative management compared with laparoscopic cholecystectomy for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones in secondary care.
DESIGN
Parallel group, multicentre patient randomised superiority pragmatic trial with up to 24 months follow-up and embedded qualitative research. Within-trial cost-utility and 10-year Markov model analyses. Development of a core outcome set for uncomplicated symptomatic gallstone disease.
SETTING
Secondary care elective settings.
PARTICIPANTS
Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion.
INTERVENTIONS
Participants were randomised 1: 1 at clinic to receive either laparoscopic cholecystectomy or observation/conservative management.
MAIN OUTCOME MEASURES
The primary outcome was quality of life measured by area under the curve over 18 months using the Short Form-36 bodily pain domain. Secondary outcomes included the Otago gallstones' condition-specific questionnaire, Short Form-36 domains (excluding bodily pain), area under the curve over 24 months for Short Form-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation.
RESULTS
Between August 2016 and November 2019, 434 participants were randomised (217 in each group) from 20 United Kingdom centres. By 24 months, 64 (29.5%) in the observation/conservative management group and 153 (70.5%) in the laparoscopic cholecystectomy group had received surgery, median time to surgery of 9.0 months (interquartile range, 5.6-15.0) and 4.7 months (interquartile range 2.6-7.9), respectively. At 18 months, the mean Short Form-36 norm-based bodily pain score was 49.4 (standard deviation 11.7) in the observation/conservative management group and 50.4 (standard deviation 11.6) in the laparoscopic cholecystectomy group. The mean area under the curve over 18 months was 46.8 for both groups with no difference: mean difference -0.0, 95% confidence interval (-1.7 to 1.7); -value 0.996; = 203 observation/conservative, = 205 cholecystectomy. There was no evidence of differences in quality of life, complications or need for further treatment at up to 24 months follow-up. Condition-specific quality of life at 24 months favoured cholecystectomy: mean difference 9.0, 95% confidence interval (4.1 to 14.0), < 0.001 with a similar pattern for the persistent symptoms score. Within-trial cost-utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1033). A non-significant quality-adjusted life-year difference of -0.019 favouring cholecystectomy resulted in an incremental cost-effectiveness ratio of £55,235. The Markov model continued to favour observation/conservative management, but some scenarios reversed the findings due to uncertainties in longer-term quality of life. The core outcome set included 11 critically important outcomes from both patients and healthcare professionals.
CONCLUSIONS
The results suggested that in the short term (up to 24 months) observation/conservative management may be a cost-effective use of National Health Service resources in selected patients, but subsequent surgeries in the randomised groups and differences in quality of life beyond 24 months could reverse this finding. Future research should focus on longer-term follow-up data and identification of the cohort of patients that should be routinely offered surgery.
TRIAL REGISTRATION
This trial is registered as ISRCTN55215960.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/71) and is published in full in ; Vol. 28, No. 26. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Gallstones; Cholecystectomy, Laparoscopic; Cost-Benefit Analysis; Male; Female; Middle Aged; Quality of Life; Quality-Adjusted Life Years; Conservative Treatment; Adult; Technology Assessment, Biomedical; Aged; United Kingdom; Markov Chains
PubMed: 38943314
DOI: 10.3310/MNBY3104 -
BMC Infectious Diseases Jun 2024Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines,...
BACKGROUND
Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs) may control of inflammation through the production of regulatory cytokines, including IL10 and TGF-β. In this study we determined the frequencies of CD4 + and CD8 + Tregs in a HAM/TSP population, compared to asymptomatic carriers and uninfected individuals, as well as investigated the profiles of regulatory and inflammatory cytokines.
METHODS
Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-β-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells.
RESULTS
Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group.
CONCLUSIONS
A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-β may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.
Topics: Humans; T-Lymphocytes, Regulatory; Male; Female; Paraparesis, Tropical Spastic; Interleukin-10; Middle Aged; Human T-lymphotropic virus 1; Transforming Growth Factor beta; Adult; Viral Load; Aged; HTLV-I Infections; Carrier State
PubMed: 38943078
DOI: 10.1186/s12879-024-09494-8 -
Neurological Sciences : Official... Jun 2024Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS)...
Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.
PubMed: 38943019
DOI: 10.1007/s10072-024-07674-7 -
Communications Biology Jun 2024Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes...
Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes to late-stage diagnoses and poor survival. Highly vascularized and immune infiltrated microenvironment are prominent features of ccRCC, yet the interplay between vasculature and immune cells, disease progression and response to therapy remains poorly understood. Using droplet-based single-cell RNA sequencing we profile 50,236 transcriptomes from paired tumor and healthy adjacent kidney tissues. Our analysis reveals significant heterogeneity and inter-patient variability of the tumor microenvironment. Notably, we discover a previously uncharacterized vasculature subpopulation associated with epithelial-mesenchymal transition. The cell-cell communication analysis reveals multiple modes of immunosuppressive interactions within the tumor microenvironment, including clinically relevant interactions between tumor vasculature and stromal cells with immune cells. The upregulation of the genes involved in these interactions is associated with worse survival in the TCGA KIRC cohort. Our findings demonstrate the role of tumor vasculature and stromal cell populations in shaping the ccRCC microenvironment and uncover a subpopulation of cells within the tumor vasculature that is associated with an angiogenic phenotype.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Single-Cell Analysis; Tumor Microenvironment; Gene Expression Profiling; Phenotype; Gene Expression Regulation, Neoplastic; Endothelial Cells; Transcriptome; Epithelial-Mesenchymal Transition; Male; Female
PubMed: 38942917
DOI: 10.1038/s42003-024-06478-x -
British Dental Journal Jun 2024Introduction Impacted mandibular third molars can be asymptomatic or cause some pathologies, such as distal caries and odontogenic cysts and tumours. This study...
Introduction Impacted mandibular third molars can be asymptomatic or cause some pathologies, such as distal caries and odontogenic cysts and tumours. This study investigates the prevalence of distal caries of the mandibular second molar adjacent to the mesioangular or horizontally partially erupted mandibular third molar and its relationship regarding decayed, missing and filled teeth (DMFT) risk group, age, side (left-right) and sex.Methods The study included patients who had an appointment for mesioangular or horizontally positioned and partially erupted mandibular third molar surgery. Before the surgery, the DMFT score, age, sex and side were recorded. After extraction, the second molar was clinically examined for distal caries. The prevalence of distal caries and the correlation between the DMFT risk group, age, sex and side were determined.Results The study was conducted on 514 patients and involved 639 teeth. Men and patients in the moderate- or high-risk group are significantly prone to developing distal caries of the second molar. No statistically significant relationship exists regarding age group, side and position.Conclusion Sex and DMFT risk groups affect the prevalence of distal caries in second molars adjacent to the mesioangular or horizontally partially erupted third molars. The prophylactic extraction should be considered in men and patients in the moderate- or high-risk group.
Topics: Humans; Male; Female; Dental Caries; Molar, Third; Cross-Sectional Studies; Risk Factors; Adult; Mandible; Molar; Prevalence; Young Adult; Adolescent; Middle Aged; Tooth, Impacted; DMF Index; Tooth Extraction; Sex Factors
PubMed: 38942867
DOI: 10.1038/s41415-024-7508-3 -
Bioprocess and Biosystems Engineering Jun 2024The most prevalent form of inflammatory bowel disease (IBD), ulcerative colitis (UC), is characterized by persistent inflammation of the colorectal mucosa. It is...
The most prevalent form of inflammatory bowel disease (IBD), ulcerative colitis (UC), is characterized by persistent inflammation of the colorectal mucosa. It is asymptomatic, whereas Crohn's disease (CD) causes patchy lesions in the gastrointestinal tract. Men and women suffer equally from ulcerative colitis, which usually strikes in the second and third decades of life and becomes more common in senior citizens. In the present study, we produced zinc oxide nanoparticles using the natural herbal plant, Cassia alata. Zinc oxide nanoparticles have remarkable antimicrobial and antitumor benefits in the field of biomedical science. Furthermore, the synthesized zinc oxide nanoparticles (ZnO NPs) were characterized using UV, XRD, FTIR, and SEM analyses. The XRD analysis confirmed the crystallite nature and purity of the synthesized nanoparticles. Zinc oxide nanoparticles with a uniform size and partially agglomerated morphology were verified by SEM analysis. We investigated the protective effects of environmentally friendly zinc oxide nanoparticles in dextran sodium sulfate-induced ulcerative colitis mouse models. Green synthesized Cassia alata zinc oxide nanoparticles (CA ZnO NPs) reversed weight loss, disease activity index, colon shortening, and colon histological damage. Zinc oxide nanoparticles reduce hypersensitivity, oxidative stress, and inflammation, and protect the mucosal layer. Green synthesized CA ZnO NPs demonstrated protection against dextran sodium sulfate-induced ulcerative colitis via anti-inflammatory activity.
PubMed: 38942827
DOI: 10.1007/s00449-024-03047-8 -
Scientific Reports Jun 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, causes a spectrum of symptoms ranging from mild upper to severe lower respiratory tract infections. However, the dynamics of nucleocapsid (N) protein antigenemia and RNAemia are not fully understood. We conducted a cohort study involving 117 patients with clinically confirmed COVID-19, focusing on the kinetics of antigenemia and RNAemia and their association with various clinical characteristics. The patients had a median age of 66.0 years (52.0-79.0 years), with a gender distribution of 46.2% male and 53.8% female. Antigenemia reached 100% in fatal cases during the first week after admission. The sensitivity/specificity of antigenemia for diagnosis were 64.7%/73.0% at admission, 69.1%/100% in Week 1, and 66.3%/100% in Week 2. Additionally, the rates of antigenemia in asymptomatic patients were 27.3% upon admission and 22.0% in Week 1, respectively; however, no antigenemia was in samples collected in Week 2. Viral RNAemia was not detected in asymptomatic patients, but RNAemia viral loads were elevated in fatal cases. Kaplan-Meier survival curves demonstrated a higher mortality rate when antigenemia concentrations were elevated in the follow-up samples (P = 0.005). Our study provides a comprehensive analysis of the kinetics of viral N-protein antigenemia and RNAemia according to disease severity and clinical classification. Our findings suggest that highest concentrations of antigenemia in fatal cases occur in the first week after admission, indicating that early elevated antigenemia may serve as a marker of mortality risk.
Topics: Humans; Male; COVID-19; Female; Middle Aged; Aged; SARS-CoV-2; RNA, Viral; Severity of Illness Index; Antigens, Viral; Coronavirus Nucleocapsid Proteins; Cohort Studies; Phosphoproteins
PubMed: 38942808
DOI: 10.1038/s41598-024-65489-0 -
Journal of Vascular Surgery Jun 2024Outcomes for weekend surgical interventions are associated with higher rates of mortality and complications compared to weekday interventions. While prior investigations...
OBJECTIVE
Outcomes for weekend surgical interventions are associated with higher rates of mortality and complications compared to weekday interventions. While prior investigations have reported the 'weekend effect' for carotid endarterectomy (CEA), this association remains unclear for Transcarotid Artery Revascularization (TCAR) and Transfemoral Carotid Artery Stenting (TFCAS). We investigated the weekend effect for all three carotid revascularization methods.
METHODS
We queried the Vascular Quality Initiative (VQI) for patients undergoing CEA, TCAR, and TFCAS between 2016-2022. Chi-square and logistic regression modeling analyzed outcomes including in-hospital stroke, death, MI, and 30-day mortality by weekend vs. weekday intervention. Backward stepwise regression was utilized to identify significant confounding variables and were ultimately included in each final logistic regression model. Logistic regression of outcomes was substratified by symptomatic status. Secondary multivariable analysis compared outcomes between the three revascularization methods by weekend vs. weekday interventions.
RESULTS
155,962 procedures were analyzed including 103,790 CEA, 31,666 TCAR and 20,506 TFCAS. Of these, 1988 CEA, 246 TCAR and 820 TFCAS received weekend interventions. Logistic regression demonstrated no significant differences for TCAR, and increased odds of in-hospital stroke/death/MI for CEA [OR:1.31,(1.04-1.65)] and TFCAS [OR:1.46,(1.09-1.96)] weekend procedures. Asymptomatic TCAR patients had nearly triple the odds of 30-day mortality [OR:2.85,(1.06-7.68), P=0.038]. Similarly, odds of in-hospital death were nearly tripled for asymptomatic CEA [OR:2.89,(1.30-6.43), P=0.009] and asymptomatic TFCAS [OR:2.78,(1.34-5.76), P=0.006] patients. Secondary analysis demonstrated that CEA and TCAR had no significant differences for all outcomes. TFCAS was associated with increased odds of stroke and death compared to CEA and TCAR.
CONCLUSION
In this observational cohort study, we found that weekend carotid revascularization is associated with increased odds of complications and mortality. Furthermore, asymptomatic weekend patients perform worse in the CEA and TFCAS procedural groups. Among the three revascularization methods, TFCAS is associated with the highest odds of perioperative stroke and mortality. As such, our findings suggest that TFCAS procedures should be avoided over the weekend, in favor of CEA or TCAR. In patients who are poor candidates for CEA, TCAR offers the lowest morbidity and mortality for weekend procedures.
PubMed: 38942398
DOI: 10.1016/j.jvs.2024.06.163 -
Journal of Forensic and Legal Medicine Jun 2024Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and...
Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and life-threatening condition. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, was previously used for obesity treatment but is now banned due to its cardiovascular side effects. Although fatalities related to PCC and adverse events associated with sibutramine have been frequently reported individually, there is no documented literature addressing PCC-induced by sibutramine. Here we report a rare case of fatal sibutramine-induced PCC in a previously asymptomatic young female with undiagnosed pheochromocytoma. The 25-year-old patient took a weight-loss pill containing sibutramine for the first time and subsequently experienced nausea, vomiting, chest tightness, and other symptoms. She went to hospital about 6 hours after taking the pill but died approximately 4 hours later despite the resuscitation efforts. An autopsy revealed a pheochromocytoma in the right adrenal gland. The cause of death was attributed to sibutramine-induced PCC. To our knowledge, this is the first report to document the occurrence of sibutramine-induced PCC.
PubMed: 38941912
DOI: 10.1016/j.jflm.2024.102711