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Frontiers in Endocrinology 2024Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.
METHODS
A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25 of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.
RESULTS
Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was , with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in , , , , , , and/or ) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The point mutations/indels were distributed throughout . Overall, (16%, 37/225) and -variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. mutations occurred more frequently in PNETs with mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.
DISCUSSION
The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Sequence Analysis, DNA; Mutation
PubMed: 38868744
DOI: 10.3389/fendo.2024.1351624 -
PloS One 2024Prevention of mother-to-child transmission (PMTCT) of HIV service is conceptualized as a series of cascades that begins with all pregnant women and ends with the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prevention of mother-to-child transmission (PMTCT) of HIV service is conceptualized as a series of cascades that begins with all pregnant women and ends with the detection of a final HIV status in HIV-exposed infants (HEIs). A low rate of cascade completion by mothers' results in an increased risk of HIV transmission to their infants. Therefore, this review aimed to understand the uptake and determinants of key PMTCT services cascades in East Africa.
METHODS
We searched CINAHL, EMBASE, MEDLINE, Scopus, and AIM databases using a predetermined search strategy to identify studies published from January 2012 through to March 2022 on the uptake and determinants of PMTCT of HIV services. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool. A random-effects model was used to obtain pooled estimates of (i) maternal HIV testing (ii) maternal ART initiation, (iii) infant ARV prophylaxis and (iv) early infant diagnosis (EID). Factors from quantitative studies were reviewed using a coding template based on the domains of the Andersen model (i.e., environmental, predisposing, enabling and need factors) and qualitative studies were reviewed using a thematic synthesis approach.
RESULTS
The searches yielded 2231 articles and we systematically reduced to 52 included studies. Forty quantitative, eight qualitative, and four mixed methods papers were located containing evidence on the uptake and determinants of PMTCT services. The pooled proportions of maternal HIV test and ART uptake in East Africa were 82.6% (95% CI: 75.6-88.0%) and 88.3% (95% CI: 78.5-93.9%). Similarly, the pooled estimates of infant ARV prophylaxis and EID uptake were 84.9% (95% CI: 80.7-88.3%) and 68.7% (95% CI: 57.6-78.0) respectively. Key factors identified were the place of residence, stigma, the age of women, the educational status of both parents, marital status, socioeconomic status, Knowledge about HIV/PMTCT, access to healthcare facilities, attitudes/perceived benefits towards PMTCT services, prior use of maternal and child health (MCH) services, and healthcare-related factors like resource scarcity and insufficient follow-up supervision.
CONCLUSION
Most of the identified factors were modifiable and should be considered when formulating policies and planning interventions. Hence, promoting women's education and economic empowerment, strengthening staff supervision, improving access to and integration with MCH services, and actively involving the community to reduce stigma are suggested. Engaging community health workers and expert mothers can also help to share the workload of healthcare providers because of the human resource shortage.
Topics: Infant; Humans; Female; Pregnancy; HIV Infections; Infectious Disease Transmission, Vertical; Acquired Immunodeficiency Syndrome; Pregnancy Complications, Infectious; Africa, Eastern
PubMed: 38635647
DOI: 10.1371/journal.pone.0300606 -
BMJ Open Jan 2024Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2...
UNLABELLED
Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2 infection. This systematic literature review summarises the heterogeneous methodology used to measure PCC across real-world studies and highlights trends by region, age group, PCC follow-up period and data source.
METHODS
Medline, EMBASE and the Cochrane Library were searched and supplemented with conference and grey literature searches. Eligible studies included individuals with (1) PCC or (2) a positive SARS-CoV-2 test or COVID-19 diagnosis who were followed over time. Included studies were published in English between 1 January 2020 and 14 November 2022.
FINDINGS
Of 291 publications included, 175 (60%) followed individuals with confirmed COVID-19 over time for PCC and 116 (40%) used a prespecified PCC definition. There was substantial heterogeneity in study design, geography, age group, PCC conditions/symptoms assessed and their classification and duration of follow-up. Among studies using a prespecified PCC definition, author-defined criteria (51%) were more common than criteria recommended by major public health organisations (19%). Measurement periods for PCC outcomes from date of acute COVID-19 test were primarily 3 to <6 months (39.2%), followed by 6 to <12 months (27.5%) and <3 months (22.9%). When classified by organ/system, constitutional-related PCC were the most frequently assessed in adult (86%) and paediatric (87%) populations. Within constitutional symptoms, fatigue was most frequently assessed in adult (91.6%) and paediatric (95.0%) populations, followed by fever/chills (37.9% and 55%, respectively).
CONCLUSIONS
PCC definitions are heterogenous across real-world studies, which limits reliable comparisons between studies. However, some similarities were observed in terms of the most frequently measured PCC-associated symptoms/conditions, which may aid clinical management of patients with PCC.CRD42022376111.
Topics: Humans; Child; COVID-19; SARS-CoV-2; COVID-19 Testing; Post-Acute COVID-19 Syndrome
PubMed: 38233057
DOI: 10.1136/bmjopen-2023-077886 -
Communications Medicine Oct 2023Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to...
BACKGROUND
Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention.
METHODS
We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022.
RESULTS
From 10347 studies, 116 studies (n = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses.
CONCLUSIONS
GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.
PubMed: 37794119
DOI: 10.1038/s43856-023-00366-x -
Phlebology Oct 2023Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep venous thrombosis (DVT). Biomarkers are potentially valuable clinical tools for handling PTS....
Biomarkers and the post-thrombotic syndrome: A systematic review of biomarkers associated with the occurrence of the post-thrombotic syndrome after lower extremity deep venous thrombosis.
INTRODUCTION
Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep venous thrombosis (DVT). Biomarkers are potentially valuable clinical tools for handling PTS. The purpose of this review was to examine which biomarkers are associated with the development of PTS in adults with lower extremity DVT.
METHODS
We performed a systematic review of all English language prospective studies of biomarkers and PTS published in PubMed and EMBASE. Studies were included if diagnosing DVT by diagnostic imaging and assessing PTS by clinical scales, for example, the Villalta scale. Biomarkers of thrombophilia and pathological clot properties were not assessed. Data was reported qualitatively.
RESULTS
15 prospective studies were included. Studies varied widely in study design and methods of data analysis. Forty-six different biomarkers were examined, with seven being measured in two or more studies. The most frequently studied biomarkers were D-dimer, CRP, and IL-6. Associations between PTS and D-dimer were predominantly significant, while results on CRP and IL-6 were inconsistent. ICAM-1 was consistently associated with PTS in all studies and at all timepoints. IL-10 was significantly related to PTS development in the largest study and at all time points. Adiponectin, tPA, HRG and TAFI, MMP-1 and -8, and TIMP-1 and -2 were significantly associated with PTS in single studies.
CONCLUSION
(1) Further research on biomarkers and PTS is clearly warranted. (2) Significant differences in study designs made it difficult to draw reliable conclusions regarding individual biomarkers. We suggest the implementation of a standardized framework for the study of biomarkers and PTS, to make comparison of future studies more feasible. (3) D-dimer, ICAM-1, IL-10, MMP-1 and 8, TIMP-1, TIMP-2, and adiponectin are clinical biomarkers of particular interest to include in future studies of PTS. Large scale systemic quantitative proteomic analyses of DVT patients could help identify novel biomarkers of interest in PTS-patients.
Topics: Adult; Humans; Adiponectin; Biomarkers; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-6; Lower Extremity; Matrix Metalloproteinase 1; Postthrombotic Syndrome; Prospective Studies; Proteomics; Risk Factors; Tissue Inhibitor of Metalloproteinase-1; Venous Thrombosis
PubMed: 37620994
DOI: 10.1177/02683555231186681