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Cureus Nov 2023Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, severity continues to rise worldwide. This systematic review seeks... (Review)
Review
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, severity continues to rise worldwide. This systematic review seeks to examine the prevalence of diabetes and its associated comorbid conditions, aiming to provide insights into the multifaceted impact of diabetes on a broader scale. DM exhibits a positive correlation with advancing age, and it's strongly influenced by genetic predisposition. In recent years, there has been a discernible global increase in the prevalence of type 1 diabetes (T1D), as evidenced by extensive epidemiological studies. Individuals with DM frequently have a positive familial history, and the presence of DM in both parents or solely the mother significantly amplifies genetic susceptibility. Moreover, non-genetic factors, such as acute psychological stressors, obesity, pregnancy, and smoking play a pivotal role in the development of DM. Notably, urinary tract infections (UTIs) are a common comorbidity in patients with type 2 diabetes (T2D) and all patients with T1D. T2D is prevalent, particularly among females, and its incidence rises with age. UTIs are prevalent among individuals with diabetes, particularly females, with Escherichia coli (E. coli) isolates being the primary etiological agents responsible for UTI inflammation. Insulin resistance is a common feature in both prediabetes and prehypertension, serving as a precursor to these conditions. The increasing incidence of T2D in regions with high tuberculosis (TB) prevalence emphasizes the significance of understanding DM as a substantial TB risk factor. DM is associated with a threefold elevation in TB risk and a twofold increase in unfavorable outcomes during TB treatment. Notably, the global prevalence of DM has led to a larger population of TB patients with comorbid DM than TB patients coinfected with HIV. Diabetes and sepsis contribute significantly to worldwide morbidity and mortality, with diabetic individuals experiencing more post-sepsis complications and increased mortality. The coexistence of hypertension and T2D is a common comorbidity, with hypertension incidence being twice as high among individuals with diabetes compared to those without, often linked to insulin resistance and a heightened risk of diabetes onset.
PubMed: 38146555
DOI: 10.7759/cureus.49374 -
Frontiers in Immunology 2023Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42020193027.
Topics: Humans; Immunotherapy, Adoptive; T-Lymphocytes; Lymphoma, Non-Hodgkin; B-Lymphocytes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Sialic Acid Binding Ig-like Lectin 2
PubMed: 37180149
DOI: 10.3389/fimmu.2023.1178403 -
Virchows Archiv : An International... Apr 2022Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has... (Meta-Analysis)
Meta-Analysis Review
Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0-3.7). We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2% (95% CI, 2.3-4.2) versus 1.7% (95% CI, 0.0-6.2) (p 0.24). We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.
Topics: Adenocarcinoma in Situ; Carcinoma in Situ; Cystadenocarcinoma, Serous; Fallopian Tube Neoplasms; Female; Humans; Incidence; Ovarian Neoplasms; Reproducibility of Results; Salpingectomy
PubMed: 34850262
DOI: 10.1007/s00428-021-03244-w -
International Journal of Environmental... Sep 2023Conduct a systematic review concerning the literature that reflects whether the callous and unemotional traits present in childhood and/or adolescence are precursors in... (Review)
Review
OBJECTIVE
Conduct a systematic review concerning the literature that reflects whether the callous and unemotional traits present in childhood and/or adolescence are precursors in the development of female psychopathy in adulthood.
MATERIALS AND METHODS
A systematic review involved consulting three databases-EBSCO, the Web of Science, and PubMed-for peer-reviewed and quantitative studies within the period 2000-2023. Nine articles with quality of three and above were included.
RESULTS
The presence of callous and unemotional traits designates a group of youth that show characteristics associated with psychopathy, specifically when predicting a more severe and chronic pattern of antisocial behaviour. Children with high rates of callous and unemotional traits, who show symptoms of attention deficit hyperactivity disorder in combination with severe conduct problems, are most likely to show features associated with psychopathy. The multidimensional psychopathy construct is considered a better predictor of future and stable antisocial behaviour than the callous and unemotional traits alone model.
CONCLUSIONS
According to the studies selected, the callous and unemotional traits in childhood seem to be precursors of female psychopathy in adulthood, but only because of the way they seem to enhance conduct problems, disruptive behaviour disorders, and, as a possible outcome, delinquency and antisocial traits, which may be precursors of future psychopathy.
Topics: Adolescent; Child; Female; Humans; Antisocial Personality Disorder; Databases, Factual; Phenotype; Problem Behavior; PubMed
PubMed: 37754645
DOI: 10.3390/ijerph20186786 -
Pancreatology : Official Journal of the... Nov 2023Intraductal papillary mucinous neoplasms (IPMNs) are a cystic precursor to pancreatic cancer. IPMNs deemed clinically to be at high-risk for malignant progression are...
BACKGROUND
Intraductal papillary mucinous neoplasms (IPMNs) are a cystic precursor to pancreatic cancer. IPMNs deemed clinically to be at high-risk for malignant progression are frequently treated with surgical resection, and pathological examination of the pancreatectomy specimen is a key component of the clinical care of IPMN patients.
METHODS
Systematic literature reviews were conducted around eight topics of clinical relevance in the examination of pathological specimens in patients undergoing resection of IPMN.
RESULTS
This review provides updated perspectives on morphological subtyping of IPMNs, classification of intraductal oncocytic papillary neoplasms, nomenclature for high-grade dysplasia, assessment of T stage, distinction of carcinoma associated or concomitant with IPMN, role of molecular assessment of IPMN tissue, role of intraoperative assessment by frozen section, and preoperative evaluation of cyst fluid cytology.
CONCLUSIONS
This analysis provides the foundation for data-driven approaches to several challenging issues in the pathology of IPMNs.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Intraductal Neoplasms; Adenocarcinoma, Mucinous; Retrospective Studies; Pancreatic Neoplasms
PubMed: 37604731
DOI: 10.1016/j.pan.2023.08.002 -
Annals of Oncology : Official Journal... Jun 2017Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association.
METHODS
We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model.
RESULTS
For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions.
CONCLUSIONS
Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer.
Topics: Adenoma; Adult; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Weight Gain
PubMed: 28327995
DOI: 10.1093/annonc/mdx080 -
Environmental Pollution (Barking, Essex... Sep 2021Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia... (Meta-Analysis)
Meta-Analysis Review
Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (OR: 1.75, 95%CI: 1.08-2.85; OR: 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.
Topics: Case-Control Studies; Environmental Exposure; Female; Humans; Infant; Male; Maternal Exposure; Occupational Exposure; Paternal Exposure; Pesticides; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 34380208
DOI: 10.1016/j.envpol.2021.117376 -
Proadrenomedullin and neonatal sepsis: a systematic review and meta-analysis of diagnostic accuracy.European Journal of Pediatrics Jan 2022The association of proadrenomedullin and neonatal sepsis has been examined in numerous studies. The object of our meta-analysis is to evaluate differences in... (Meta-Analysis)
Meta-Analysis Review
The association of proadrenomedullin and neonatal sepsis has been examined in numerous studies. The object of our meta-analysis is to evaluate differences in proadrenomedullin among neonates with sepsis and health neonates. We systematically searched the following databases: MEDLINE, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and WHO (International Clinical Trials Register Platform) using a structured algorithm. Statistical analysis was conducted using Revman 5.3 and R software. Included studies in the meta-analysis were assessed using the Newcastle-Ottawa scale. Proadrenomedullin levels were found significantly higher in neonates with sepsis than healthy neonates with an SMD equal with 3.07 [95% CI 1.71, 4.42 (p < 10, I = 98%)]. The optimal cutoff point of pro-ADM was calculated at 17.559 with a sensitivity of 0.879 (0.458; 0.984) and a specificity of 0.994 (0.820; 1.000), and an AUC of 0.905. Subgroup analysis, leave-one-out meta-analysis, and meta-regression were performed in an effort to lower inter-study heterogeneity. Sensitivity analysis was conducted by excluding high risk of bias studies and those contributing to the overall heterogeneity shown by the Baujat plot. Publication bias was assessed using a funnel plot and the trim-and-fill method. Certainty assessment was evaluated using the GRADE score.Conclusion: The findings of our meta-analysis suggest that proadrenomedullin is elevated in neonates with sepsis. However, future prospective cohort studies need to be conducted in order to assess its diagnostic accuracy. What is Known: • Proadrenomedullin has been found increased in adult patients with infectious diseases such as community acquired pneumonia. • Proadrenomedullin plays a major role in the pathophysiology of sepsis in adults. What is New: • Proadrenomedullin is increased in neonates with sepsis. • Future cohort studies need to be conducted in order to elucidate the value of proadrenomedullin in a safer way.
Topics: Adrenomedullin; Humans; Infant, Newborn; Neonatal Sepsis; Prospective Studies; Protein Precursors; Sepsis
PubMed: 34342678
DOI: 10.1007/s00431-021-04214-9 -
Frontiers in Genetics 2022Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding...
Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding and non-coding genes, and bioactive substances. Exosomes participate in information transmission between cells and regulate processes such as cell proliferation, migration, angiogenesis, and phenotypic transformation. They have broad prospects in the occurrence, development, and treatment of many diseases including orthopedics. Exosomes derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, osteoclasts, and their precursors are recognized to play pivotal roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. This articlesummarizes the characteristics of exosomes and their research progress in bone remodeling, bone tumors, vascular skeletal muscle injury, spinal cord injury, degenerative disc diseases, cartilage degeneration, osteoarthritis, necrosis of the femoral head, and osteoporosis.
PubMed: 36081990
DOI: 10.3389/fgene.2022.915141 -
Journal of Neural Transmission (Vienna,... Mar 2023The origins of the male preponderance in autism incidence remain unclear. The idea that perinatal factors associated with sex differentiation (e.g., steroid hormone... (Review)
Review
The origins of the male preponderance in autism incidence remain unclear. The idea that perinatal factors associated with sex differentiation (e.g., steroid hormone pathways) may increase the possibility of the emergence of autism is complementary to the hypothesis that female individuals are intrinsically less likely to develop autism. Empirical evidence for the mechanistic roles of in utero steroid hormones in autism etiology is accumulating but inconsistent. We conducted a systematic review using rigorous criteria for the measurements of steroids and vitamin D exposure, to summarize the potential contributing roles of prenatal and early postnatal steroids and vitamin D alterations to the emergence of autism. We searched PubMed, PsychInfo, Scopus, and included 22 studies for qualitative synthesis. Among them, six studies examined the association of autism diagnoses in offspring and levels of steroids and precursor steroid hormones in the fetal environment, eight studies examined the associations between autism and maternal and fetal blood vitamin D levels during pregnancy and at birth, and eight studies examined the associations between offspring autism diagnoses and maternal hyperandrogenemia diagnosed before pregnancy. We identified promising and complex results regarding the relations between steroid metabolism and autism. The interpretation of findings was limited by the mostly observational study designs, insufficient investigation of the effects of offspring sex, confounders and their cumulative effects on the development of the child, and unclear impact of the timing of steroids exposure and their effects on fetal neurodevelopment.
Topics: Child; Pregnancy; Infant, Newborn; Male; Humans; Female; Vitamin D; Autistic Disorder; Incidence; Family; Hormones; Observational Studies as Topic
PubMed: 36752873
DOI: 10.1007/s00702-022-02582-6