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Journal of Gastrointestinal and Liver... Jun 2024The environmental factors, apart from gluten ingestion predisposing to coeliac disease are poorly known. Smoking is associated with many immune-mediated diseases, but...
BACKGROUND AND AIMS
The environmental factors, apart from gluten ingestion predisposing to coeliac disease are poorly known. Smoking is associated with many immune-mediated diseases, but research on coeliac disease is scarce. This study aims to investigate how smoking affects the clinical presentation, presence of comorbidities and response to gluten-free diet in coeliac disease.
METHODS
Altogether 815 adults with coeliac disease participated in a nationwide cross-sectional study. Participants were interviewed and smoking habits (never, former, or current smoker), clinical presentation of coeliac disease and presence of comorbidities were elicited. Serology and severity of small bowel mucosal lesions at diagnosis were gathered from the participants' medical records and follow-up serology was measured. Gastrointestinal symptoms and psychological well-being were assessed using validated questionnaires.
RESULTS
Current smokers were more often male and were diagnosed at younger ages than never or former smokers. There were no differences between the groups in clinical presentation, severity of symptoms or mucosal lesions at diagnosis or in dietary compliance and clinical, serological, and histological recovery. Musculoskeletal disorders, particularly osteoporosis and osteopenia, were more common in never smokers than in other groups (14.5% vs. 5.1% and 4.1%, p<0.001), and cardiovascular disorders were diagnosed more often in former smokers (36.2% vs. 23.5% and 21.9%, p=0.003).
CONCLUSIONS
Smoking does not seem to have an impact on the clinical presentation, severity of symptoms or mucosal damage in coeliac disease. Histological and clinical recovery as well as seroconversion on gluten-free diet are not affected by smoking status.
Topics: Humans; Celiac Disease; Male; Female; Cross-Sectional Studies; Middle Aged; Diet, Gluten-Free; Adult; Cigarette Smoking; Aged; Treatment Outcome; Comorbidity; Risk Factors; Smokers; Ex-Smokers; Intestinal Mucosa
PubMed: 38944862
DOI: 10.15403/jgld-5364 -
Journal of Gastrointestinal and Liver... Jun 2024
Topics: Humans; Terminology as Topic; Non-alcoholic Fatty Liver Disease
PubMed: 38944849
DOI: 10.15403/jgld-5518 -
Aging Jun 2024The genomic landscape of clear cell renal cell carcinoma (ccRCC) has a considerable intra-tumor heterogeneity, which is a significant obstacle in the field of precision...
Unfolding the mysteries of heterogeneity from a high-resolution perspective: integration analysis of single-cell multi-omics and spatial omics revealed functionally heterogeneous cancer cells in ccRCC.
The genomic landscape of clear cell renal cell carcinoma (ccRCC) has a considerable intra-tumor heterogeneity, which is a significant obstacle in the field of precision oncology and plays a pivotal role in metastasis, recurrence, and therapeutic resistance of cancer. The mechanisms of intra-tumor heterogeneity in ccRCC have yet to be fully established. We integrated single-cell RNA sequencing (scRNA-seq) and transposase-accessible chromatin sequencing (scATAC-seq) data from a single-cell multi-omics perspective. Based on consensus non-negative matrix factorization (cNMF) algorithm, functionally heterogeneous cancer cells were classified into metabolism, inflammatory, and EMT meta programs, with spatial transcriptomics sequencing (stRNA-seq) providing spatial information of such disparate meta programs of cancer cells. The bulk RNA sequencing (RNA-seq) data revealed high clinical prognostic values of functionally heterogeneous cancer cells of three meta programs, with transcription factor regulatory network and motif activities revealing the key transcription factors that regulate functionally heterogeneous ccRCC cells. The interactions between varying meta programs and other cell subpopulations in the microenvironment were investigated. Finally, we assessed the sensitivity of cancer cells of disparate meta programs to different anti-cancer agents. Our findings inform on the intra-tumor heterogeneity of ccRCC and its regulatory networks and offers new perspectives to facilitate the designs of rational therapeutic strategies.
PubMed: 38944814
DOI: 10.18632/aging.205974 -
BMC Infectious Diseases Jun 2024An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy.
METHODS
This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations.
RESULTS
A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low.
CONCLUSIONS
This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.
Topics: Humans; Azithromycin; Terbutaline; Pneumonia, Mycoplasma; Child; Anti-Bacterial Agents; Mycoplasma pneumoniae; Drug Therapy, Combination; Administration, Inhalation; Treatment Outcome; Randomized Controlled Trials as Topic; Child, Preschool
PubMed: 38944667
DOI: 10.1186/s12879-024-09564-x -
Nature Communications Jun 2024One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and... (Randomized Controlled Trial)
Randomized Controlled Trial
One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex. Associations between baseline values and all-cause 24-week mortality were analysed using Cox models, and for cause-specific mortality used Fine & Gray models, including prophylaxis randomisation, viral load, CD4, WHO stage, age, BMI, and site as covariates; and weighted according to inverse probability of selection into the substudy. Higher baseline CRP, IFN-γ, IL-6 and IP-10 were associated with higher all-cause mortality; and higher IL-23, IL-2 and RANTES with lower all-cause mortality. Associations varied by cause of death: tuberculosis-associated mortality was most strongly associated with higher CRP and sST2, and cryptococcosis-associated mortality with higher IL-4 and lower IL-8. Changes in I-FABP (p = 0.002), faecal alpha-1 antitrypsin (p = 0.01) and faecal myeloperoxidase (p = 0.005) between baseline and 4 weeks post-ART were greater in those receiving enhanced versus cotrimoxazole prophylaxis. Our findings highlight how the immune milieu shapes outcomes following ART initiation, and how adjunctive antimicrobials can modulate the gut environment in advanced HIV.
Topics: Humans; HIV Infections; Biomarkers; Africa South of the Sahara; Male; Female; Adult; Adolescent; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load; Young Adult; Anti-HIV Agents; Child
PubMed: 38944653
DOI: 10.1038/s41467-024-49317-7 -
Vaccine Jun 2024Maternal immunisation is a powerful tool to protect both pregnant women and their children. A new maternal RSV vaccine holds promise to protect newborns from...
Maternal immunisation is a powerful tool to protect both pregnant women and their children. A new maternal RSV vaccine holds promise to protect newborns from RSV-associated illness in the first few months of life, but no official recommendation has been made in Germany. Since RSV causes a significant burden of paediatric hospital admissions, we consider it a pertinent opportunity to review barriers to maternal vaccination in Germany, which might also apply to other settings. Access to vaccination for pregnant women in Germany is shaped by an interplay of legal, regulatory, institutional, and sociocultural factors, with a less permissive clinical research environment, delays in recommendation and roll-out, and lower acceptance by healthcare professionals and the population. Actionable recommendations to improve availability and uptake include coordination with other national regulatory bodies to reduce delays, awareness and literacy campaigns for health professionals and the general public, and capacity building for vaccine clinical research.
PubMed: 38944576
DOI: 10.1016/j.vaccine.2024.06.061 -
International Journal of Infectious... Jun 2024In Japan, influenza activity was low throughout the COVID-19 pandemic until the 2022-23 season, when the first influenza outbreak occurred since the 2020-21 season. In...
In Japan, influenza activity was low throughout the COVID-19 pandemic until the 2022-23 season, when the first influenza outbreak occurred since the 2020-21 season. In our influenza surveillance during the COVID-19 pandemic, co-infection with SARS-CoV-2 and influenza virus had not been detected; however, in January 2024, we identified three pediatric outpatients co-infected with these viruses: one with SARS-CoV-2 Omicron EG.5 sublineage HK.3 and influenza A(H3N2) and two with SARS-CoV-2 Omicron BA.2.86 sublineage JN.1.5 and influenza A(H1N1)pdm09. We evaluated the susceptibility of SARS-CoV-2 against RNA-dependent RNA polymerase inhibitors (remdesivir and molnupiravir) and 3C-like protease inhibitors (nirmatrelvir and ensitrelvir), and that of influenza viruses against neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and the cap-dependent endonuclease inhibitor baloxavir. All viruses tested were susceptible to these antiviral drugs and did not possess amino acid substitutions associated with reduced antiviral susceptibility. The patients were treated with anti-influenza drugs and did not develop severe symptoms despite the co-infection. Since SARS-CoV-2 and influenza viruses continue to evolve, continuous monitoring of their circulation remains essential to assess public health measures and support clinical management.
PubMed: 38944411
DOI: 10.1016/j.ijid.2024.107134 -
Gene Jun 2024Vascular calcification is prevalent in chronic kidney disease (CKD). Genetic causes of CKD account for 10-20% of adult-onset disease. Vascular calcification is thought...
Vascular calcification is prevalent in chronic kidney disease (CKD). Genetic causes of CKD account for 10-20% of adult-onset disease. Vascular calcification is thought to be one of the most important risk factors for increased cardiovascular morbidity and mortality in CKD patients and is detectable in 80% of patients with end stage kidney disease (ESKD). Despite the high prevalence of vascular calcification in CKD, no single gene cause has been described. We hypothesized that variants in vascular calcification genes may contribute to disease pathogenesis in CKD, particularly in families who exhibit a predominant vascular calcification phenotype. We developed a list of eight genes that are hypothesized to play a role in vascular calcification due to their involvement in the ectopic calcification pathway: ABCC6, ALPL, ANK1, ENPP1, NT5E, SLC29A1, SLC20A2, and S100A12. With this, we assessed exome data from 77 CKD patients, who remained unsolved following evaluation for all known monogenic causes of CKD. We also analyzed an independent cohort (Ontario Neurodegenerative Disease Research Initiative (ONDRI), n = 520) who were screened for variants in ABCC6 and compared this to a control cohort of healthy adults (n = 52). We identified two CKD families with heterozygous pathogenic variants (R1141X and A667fs) in ABCC6. We identified 10 participants from the ONDRI cohort with heterozygous pathogenic or likely pathogenic variant in ABCC6. Replication in a healthy control cohort did not reveal any variants. Our study provides preliminary data supporting the hypothesis that ABCC6 may play a role in vascular calcification in CKD. By screening CKD patients for genetic causes early in the diagnostic pathway, patients with genetic causes associated with vascular calcification can be preventatively treated with new therapeutics with aims to decrease mortality.
PubMed: 38944164
DOI: 10.1016/j.gene.2024.148731 -
Journal of Vascular Surgery. Venous and... Jun 2024The aim of this study is to share our experience in treating patients with LMs over a span of 14 years, evaluating its efficacy and safety, particularly with the use of...
OBJECTIVE
The aim of this study is to share our experience in treating patients with LMs over a span of 14 years, evaluating its efficacy and safety, particularly with the use of ethanol as sclerosant of choice.
METHODS
A retrospective review of pediatric patients diagnosed and later treated for LMs between 2008 and 2022 was conducted. We collected patient demographics, LM characteristics, treatment strategies and outcomes, including response to treatment and complications.
RESULTS
The cohort included 36 patients (24 males), first presenting clinically at a median age of 5 months (range 0-12 years). LMs were macrocystic (17), microcystic (3), and mixed types (16). In most patients (22) the malformation involved the cervicofacial area. Twenty-five patients underwent 54 procedures, averaging 2 procedures per patient (range 1-13). Sclerotherapy resulted in 90% of patients exhibiting some response of the LM (p=0.005). Ethanol was used in most procedures (31) and proved most efficacious, facilitating partial or complete response of the malformations in all cases compared to 72% with other sclerosants (p=0.06). Sclerotherapy exhibited low complication rates among all sclerosants used (7%, p=0.74).
CONCLUSION
Sclerotherapy is a safe and effective intervention for pediatric LMs. Ethanol demonstrated comparable efficacy and safety to other sclerosants, highlighting its potential as a preferred treatment option. This study supports the tailored use of sclerotherapy, guided by a thorough understanding of the risks and benefits, to provide optimized care for patients with LMs.
PubMed: 38944113
DOI: 10.1016/j.jvsv.2024.101938 -
The Lancet. Oncology Jun 2024There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for...
BACKGROUND
There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer.
METHODS
The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population.
FINDINGS
Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater.
INTERPRETATION
Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer.
FUNDING
Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.
PubMed: 38944050
DOI: 10.1016/S1470-2045(24)00269-9