We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The ...amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells.
Background and purpose
Stroke assistance is facing changes and new challenges since COVID‐19 became pandemic. A variation on the patient influx might be one of the greater concerns, due to fewer ...people coming to emergency departments or coming too late. However, no data quantifying this have been published until now. The aim was to analyse the impact of the COVID‐19 epidemic outbreak on hospital stroke admissions and their characteristics in our region.
Methods
The data of every patient admitted to any hospital of our healthcare system with a diagnosis of ischaemic stroke between 30 December 2019 and 19 April 2020 were reviewed. Demographic and clinical data were recorded and compared between periods before and after the setting of the state of emergency secondary to the COVID‐19 outbreak.
Results
In total, 354 patients with ischaemic stroke were admitted in our study period. There was a weekly average of 27.5 cases before the setting of the state of emergency against 12 afterwards (P < 0.001). This drop in stroke cases occurred progressively from week 11, persisting in time despite the decrease in confirmed cases of COVID‐19. No differences in the proportion of intravenous thrombolysis (21.1% vs. 21.5%, P = 0.935) or endovascular therapy (12.4% vs. 15.2%, P = 0.510) were found, nor in other demographic or clinical characteristics except for median onset‐to‐door time (102 vs. 183 min, P = 0.015).
Conclusions
This observational study offers the perspective of a whole region in one of the countries more heavily stricken by the SARS‐CoV‐2 epidemic and shows that the decrease of stroke events, since the beginning of the COVID‐19 outbreak, happened globally and without any specific patient distribution.
Early restrictive-constrictive physiology in a cardiac allograft recipient Ortiz-Bautista, Carlos; Puerto García-Martín, Elena; Morán-Fernández, Laura ...
Revista portuguesa de cardiologia,
July-August 2017, 2017 Jul - Aug, 2017-07-00, 20170701, 2017-07-01, Letnik:
36, Številka:
7-8
Journal Article
The ankle-brachial index (ABI) is widely used to diagnose subclinical peripheral artery disease (PAD) in the general population, but data assessing its prevalence and related factors in different ...chronic kidney disease (CKD) stages are scarce. The aim of this study is to evaluate the prevalence and associated factors of pathological ABI values in CKD patients.
NEFRONA is a multicentre prospective project that included 2445 CKD patients from 81 centres and 559 non-CKD subjects from 9 primary care centres across Spain. A trained team collected clinical and laboratory data, performed vascular ultrasounds and measured the ABI.
PAD prevalence was higher in CKD than in controls (28.0 versus 12.3%, P < 0.001). Prevalence increased in more advanced CKD stages, due to more patients with an ABI ≥1.4, rather than ≤0.9. Diabetes was the only factor predicting both pathological values in all CKD stages. Age, female sex, carotid plaques, higher carotid intima-media thickness, higher high-sensitivity C-reactive protein (hsCRP) and triglycerides, and lower 25-hydroxi-vitamin D were independently associated with an ABI ≤0.9. Higher phosphate and hsCRP, lower low-density lipoprotein (LDL)-cholesterol and dialysis were associated with an ABI ≥1.4. A stratified analysis showed different associated factors in each CKD stage, with phosphate being especially important in earlier CKD, and LDL-cholesterol being an independent predictor only in Sage 5D CKD.
Asymptomatic PAD is very prevalent in all CKD stages, but factors related to a low or high pathological ABI differ, revealing different pathogenic pathways. Diabetes, dyslipidaemia, inflammation and mineral-bone disorders play a role in the appearance of PAD in CKD.
ABSTRACT
Background
Hyperkalemia is common among patients with chronic kidney disease (CKD) but there is scarce information on differential risk factors and outcomes for men and women. For instance, ...smoking has been suggested to be a risk factor for hyperkalemia, but specific analysis of the sex-specific impact of smoking on hyperkalemia in CKD is lacking.
Methods
We studied serum potassium levels in 2891 participants from the NEFRONA cohort: 483 controls (47% women) and 2408 CKD patients (38% women) without prior cardiovascular disease (CVD), assessing whether smoking is a risk factor for hyperkalemia, and if hyperkalemia is associated with outcomes separately for men and women.
Results
Median potassium levels and prevalence of hypo and hyperkalemia were higher in CKD participants than in controls. Serum potassium levels were higher and hyperkalemia and severe hyperkalemia more prevalent in men than in women with non-dialysis CKD (G3–G5). The highest prevalence of hyperkalemia for each gender was found in CKD G4-G5 and hemodialysis patients for men (46%) and in hemodialysis (54%) for women. Gender-specific etiological multivariate analysis identified current smoking as a risk factor for hyperkalemia only in men. Hyperkalemia was independently associated with stopping RAASi, an outcome which was more common in women. Hyperkalemia was also associated to higher risk of cardiovascular events within 4 years in men. In conclusion, hyperkalemia is common among men and women with CKD, but the prevalence, risk factors and outcomes may differ by gender. Specifically, current smoking is a driver of hyperkalemia in men.
Graphical Abstract
Graphical Abstract
Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. ...Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer.
Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1.
Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P <.01), high mucinous component (P <.01), and poor differentiation (P =.002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations.
We conclude that the incidence of molecularly confirmed HNPCC (one 0.3% of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.
ABSTRACT
Background
Chronic kidney disease (CKD) is associated with increased atherosclerotic burden and higher risk for cardiovascular events (CVE). Atherosclerosis has a significant genetic ...component and, in CKD, it is influenced by mineral metabolism alterations. Therefore, genetic modifications of mineral metabolism–related proteins could affect atherosclerosis in CKD patients. In the present study we investigated the role of single nucleotide polymorphisms (SNPs) of the matrix gamma-carboxy glutamic acid protein (MGP) on atherosclerosis progression and CVE in a CKD cohort.
Methods
A total of 2187 CKD patients from the Observatorio Nacional de Aterosclerosis en Nefrologia (NEFRONA) study were genotyped for SNPs present in the matrix gamma-carboxy glutamic acid (Gla) protein (MGP) gene. Atheromatosis was detected by vascular ultrasound. Progression of atheromatosis, defined as an increase in territories with plaque, was assessed after 24 months. Patients were followed for 48 months for CVE. Association of SNPs with plaque progression was assessed by logistic regression and their capacity to predict CVE by Cox regression.
Results
Three SNPs of the MGP gene were analyzed. No association of the rs4236 or the rs1800801 SNPs was detected with any of the outcomes. However, patients homozygotes for the minor allele of the rs1800802 SNP showed higher adjusted risk for plaque progression odds ratio 2.3 (95% confidence interval 1.06–4.9) and higher risk of suffering a CVE hazard ratio 2.16 (95% confidence interval 1.13–4.12) compared with the rest of genotypes. No association of the SNP with total or dp-ucMGP levels was found in a subsample.
Conclusions
The rs1800802 polymorphism of MGP is associated with plaque progression and CVE in CKD patients.
Graphical Abstract
Graphical Abstract
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