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Revista Portuguesa de Cardiologia :... Jun 2024Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of... (Review)
Review
Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.
PubMed: 38945473
DOI: 10.1016/j.repc.2024.04.006 -
The Journal of Pediatrics Jun 2024To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to...
OBJECTIVE
To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to classify it by molecular genetics. and STUDY DESIGN: We categorized 186 retrospective cases of LO diagnosed between 2003 and 2023 into suspected Beckwith-Wiedemann spectrum (BWSp), PIK3CA-Related Overgrowth Spectrum (PROS), vascular overgrowth (VO) , or isolated (ILO), based on initial clinical assessments, to determine the appropriate first-tier molecular tests and tissue for analysis. Patients underwent testing for 11p15 epigenetic abnormalities or somatic variants in genes related to PI3K/AKT/mTOR, vascular proliferation, and RAS-MAPK cascades using blood or skin DNA. For cases with negative initial tests, a sequential cascade molecular approach was employed to improve diagnostic yield.
RESULTS
This approach led to a molecular diagnosis in 54% of cases, 89% of cases consistent with initial clinical suspicions and 11% reclassified. BWSp was the most common cause, with 43% of cases exhibiting 11p15 abnormalities. PROS had the highest confirmation rate, with 74% of clinically diagnosed patients showing a PIK3CA variant. VO demonstrated significant clinical overlap with other syndromes. Molecular diagnosis of ILO proved challenging, with only 21% of cases classifiable into a specific condition.
CONCLUSION
Despite, LO is underdiagnosed from a molecular viewpoint and to date has had no diagnostic guidelines, which would be crucial for addressing potential cancer predisposition, enabling precision medicine treatments, or guiding management. This study sheds light on the molecular etiology of LO, highlighting the importance of tailored diagnostic approach and of selecting appropriate testing to achieve the highest diagnostic yield.
PubMed: 38945442
DOI: 10.1016/j.jpeds.2024.114177 -
Cytokine Jun 2024The close link between immune and pathogenesis of venous thromboembolism (VTE) has been recognized, but not fully elucidated. The current study was designed to identify...
The close link between immune and pathogenesis of venous thromboembolism (VTE) has been recognized, but not fully elucidated. The current study was designed to identify immune microenvironment related signature and subtypes using explainable machine learning in VTE. We first observed an alteration of immune microenvironment in VTE patients and identified eight key immune cells involved in VTE. Then PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 were determined as key immune microenvironment-related genes, which could divide VTE patients into two subtypes with different immune and metabolic characteristics. Also, we found that prunetin and torin-2 may be most promising to treat VTE patients in Cluster 1 and 2, respectively. By comparing six machine learning models in both training and external validation sets, XGboost was identified as the best one to predict the risk of VTE, followed by the interpretation of each immune microenvironment-related gene contributing to the model. Moreover, CR2 and FPR2 had high accuracy in distinguishing VTE and control, which may act as diagnostic biomarkers of VTE, and their expressions were validated by qPCR. Collectively, immune microenvironment related PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 are key genes involved in the pathogenesis of VTE. The VTE risk prediction model and immune microenvironment subtypes based on those genes might benefit prevention, diagnosis, and the individualized treatment strategy in clinical practice of VTE.
PubMed: 38945040
DOI: 10.1016/j.cyto.2024.156685 -
European Journal of Medicinal Chemistry Jun 2024Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need...
Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need for chronic pharmacological treatments. The standard gold therapy of inflammation in asthmatic patients involves the use of glucocorticoids even if their chronic use is often related to serious adverse effects. Growing evidence suggests the biological relevance of hydrogen sulfide (HS) in the pathogenesis of airway diseases. Hence, aiming to associate the beneficial effects of steroidal anti-inflammatory drugs (SAIDs) to HS biological activity, we designed and synthesized novel multi-target molecules by chemically combining a group of glucocorticoids, usually employed in asthma treatment, with an isothiocyanate moiety, well-known for its HS releasing properties. Firstly, the synthesized compounds have been screened for their HS-releasing profile using an amperometric approach and for their in vitro effects on the degranulation process, using RBL-2H3 cell line. The physicochemical profile, in terms of solubility, chemical and enzymatic stability of the newly hybrid molecules, has been assessed at different physiological pH values and in esterase-rich medium (bovine serum albumin, BSA). The selected compound 5c, through both its corticosteroid and HS releasing component, has been evaluated in vivo in experimental model of asthma. The compound 5c inhibited in vivo all asthma features with a significative effect on the restoration of pulmonary structure and reduction of lung inflammation.
PubMed: 38944936
DOI: 10.1016/j.ejmech.2024.116636 -
Journal of Gastrointestinal and Liver... Jun 2024During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19...
BACKGROUND AND AIMS
During the coronavirus disease 2019 (COVID-19) pandemic a significant proportion of patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection developed secondary sclerosing cholangitis (SSC) as a hepatobiliary complication.
METHODS
17 patients were endoscopically diagnosed and treated with COVID-19 SSC from February 2020 until October 2022 at our center. We retrospectively reviewed and analyzed the data to define risk factors, establish endoscopic treatment options, and to estimate incidence and outcomes.
RESULTS
258 patients with COVID-19 infection were admitted to our tertiary center and mechanically ventilated. 10 patients developed COVID-19 SSC in-house, and 7 patients were transferred for further endoscopic treatment. All 17 patients were mechanically ventilated, received vasoactive substances and 12 of them were treated with extracorporeal membrane oxygenation therapy. Endoscopic retrograde cholangiography (ERC) was performed in all patients to establish the diagnosis of COVID-19 SSC and evaluate endoscopic treatment options. All ERCs revealed biliary casts. 9 patients had developed severe rarefication of the intrahepatic bile ducts and 4 showed biliary strictures. As endoscopic treatment approaches, casts were removed repeatedly, and strictures were dilated. During the study period, 14 patients died (82%). 3 patients are in follow-up to reassess the need for liver transplantation.
CONCLUSIONS
COVID-19 SSC was observed in 2.6 % of the patients with severe COVID-19 in our center. We show that endoscopic approaches offer the opportunity to extract casts and to treat biliary strictures. As the mortality rate of COVID-19 SSC is high, endoscopic treatment can be of great clinical relevance as a bridge to liver transplantation.
Topics: Humans; COVID-19; Male; Female; Cholangitis, Sclerosing; Middle Aged; Retrospective Studies; Cholangiopancreatography, Endoscopic Retrograde; Tertiary Care Centers; Aged; SARS-CoV-2; Adult; Treatment Outcome; Risk Factors; Liver Transplantation
PubMed: 38944874
DOI: 10.15403/jgld-5476 -
Journal of Gastrointestinal and Liver... Jun 2024
Topics: Humans; Colitis, Ulcerative; Disease Progression; Diverticulosis, Colonic; Colonoscopy; Male; Colitis; Middle Aged; Female; Biopsy; Treatment Outcome
PubMed: 38944872
DOI: 10.15403/jgld-5288 -
Journal of Gastrointestinal and Liver... Jun 2024Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral...
BACKGROUND AND AIMS
Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
MATERIALS
We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS
The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS
We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
Topics: Humans; Membrane Proteins; Polymorphism, Single Nucleotide; Lipase; Female; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Middle Aged; 17-Hydroxysteroid Dehydrogenases; Genetic Predisposition to Disease; Case-Control Studies; Hepatitis B, Chronic; Prognosis; Adult; Turkey; Risk Factors; Prospective Studies; Phenotype; Genetic Association Studies; Acyltransferases; Phospholipases A2, Calcium-Independent
PubMed: 38944871
DOI: 10.15403/jgld-5474 -
Journal of Gastrointestinal and Liver... Jun 2024
Topics: Humans; Mucormycosis; COVID-19; Melena; SARS-CoV-2; Male; Antifungal Agents; Middle Aged
PubMed: 38944868
DOI: 10.15403/jgld-5302 -
Journal of Gastrointestinal and Liver... Jun 2024
Topics: Humans; COVID-19; COVID-19 Vaccines; SARS-CoV-2; Vaccination; Liver Diseases; Chronic Disease
PubMed: 38944866
DOI: 10.15403/jgld-5619 -
Journal of Gastrointestinal and Liver... Jun 2024The "tumbling gallstone sign" is a diagnostic imaging finding described on radiologic examinations of the abdomen, in patients with cholelithiasis associated with...
The "tumbling gallstone sign" is a diagnostic imaging finding described on radiologic examinations of the abdomen, in patients with cholelithiasis associated with intermittent episodes of gallstone obstructive ileus. Best seen on serial radiographs or CT studies of the abdomen, this sign indicates a sudden change in position of the gallstone(s) within the intestinal lumen from the upper segments of the bowel to the lower segments of the bowel, causing transient mechanical bowel obstruction. The tumbling gallstone sign has been likened to that of the classic childrens' tumbling tower balancing game. On repeat CT scans, the dislodged gallstone(s) may be seen proceeding distally and impact in the ileum at a level lower than that seen on the previous CT scans, analogous to the tumbling gallstone sign.
Topics: Humans; Gallstones; Ileus; Tomography, X-Ray Computed; Intestinal Obstruction; Predictive Value of Tests
PubMed: 38944864
DOI: 10.15403/jgld-5332