Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland.

Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular system is commonly involved. Acute heart failure (AHF) is the most severe complication of MIS-C, leading to cardiogenic shock. The aim of the study was to characterise the course of MIS-C with a focus on cardiovascular involvement, based on echocardiographic (echo) evaluation, in 498 children (median age 8.3 years, 63% boys) hospitalised in 50 cities in Poland. Among them, 456 (91.5%) had cardiovascular system involvement: 190 (48.2%) of patients had (most commonly atrioventricular) valvular insufficiency, 155 (41.0%) had contractility abnormalities and 132 (35.6%) had decreased left ventricular ejection fraction (LVEF < 55%). Most of these abnormalities improved within a few days. Analysis of the results obtained from two echo descriptions (a median of 5 days apart) revealed a >10% increase in LVEF even in children with primarily normal LVEF. Lower levels of lymphocytes, platelets and sodium and higher levels of inflammatory markers on admission were significantly more common among older children with contractility dysfunction, while younger children developed coronary artery abnormality (CAA) more often. The incidence of ventricular dysfunction might be underestimated. The majority of children with AHF improved significantly within a few days. CAAs were relatively rare. Children with impaired contractility as well as other cardiac abnormalities differed significantly from children without such conditions. Due to the exploratory nature of this study, these findings should be confirmed in further studies.

Common inherited variants of PDCD1, CD274 and HAVCR2 genes differentially modulate the risk and prognosis of adenocarcinoma and squamous cell carcinoma.

BACKGROUND: To investigate the association between single nucleotide polymorphisms (SNPs) of PDCD1, CD274, and HAVCR2 genes with the risk and outcomes of non-small cell lung cancer (NSCLC) subtypes: squamous cell lung cancer (LUSC) and lung adenocarcinoma (LUAD). METHODS: TaqMan SNP genotyping assays or polymerase chain reaction-restriction fragment length polymorphism methods were used to determine genotypes of: PDCD1: rs36084323, rs7421861, rs11568821, rs2227981, rs10204525; CD274: rs822335, rs10815225, rs17718883, rs2297136, rs4742098, rs4143815; HAVCR2: rs10057302, rs1036199. Among 383 NSCLC patients, 112 were diagnosed with LUAD and 116 with LUSC. The control group consisted of 433 unrelated, cancer-free subjects. RESULTS: A CC genotype of rs4143815 and GG genotype of rs4742098 were associated with two times higher risk of developing LUSC (CC vs. GG + GC, OR = 2.31; 95% CI = 1.32, 4.06; P = 0.003; GG vs. AA + AG, OR = 2.26; 95% CI = 1.17, 4.36; P = 0.016, respectively). Moreover, rs4143815 was an independent predictor of the age at diagnosis of LUAD. The carriers of C allele were diagnosed 4.81 years later (95% CI = 1.47, 8.15; P = 0.006) than patients with the GG genotype. The rs10057302 CA genotype was an independent predictor of overall survival in LUSC (adjusted HR = 0.13; 95% CI = 0.02, 0.93; P = 0.043). NSCLC carriers of rs11568821 T allele had almost double the risk of death (adjusted HR = 2.05; 95% CI = 1.28, 3.29; P = 0.003) compared to carriers of CC genotype. CONCLUSIONS: Our results provided additional evidence that SNPs of genes for PD-1, PD-L1 and TIM-3 differentially modulate the risk and prognosis of LUSC and LUAD.

Cholesterol lowering drug use and breast cancer survival: the Multiethnic Cohort Study.

PURPOSE: Prior studies conducted primarily in white populations have suggested that pre-diagnostic cholesterol lowering drugs (CLDs) improved survival among women with breast cancer (BC). However, this association had not been well characterized in diverse racial/ethnic populations. We investigated whether pre-diagnostic CLD use is associated with all-cause and BC-specific mortality among female BC cases of the Multiethnic Cohort (MEC). METHODS: CLD use was ascertained through questionnaires administered in 2003-2008. A total of 1448 incident BC cases were identified by linkage to SEER cancer registries in Hawaii and California from 2003 to 2014. Multivariable Cox regression was conducted to estimate hazard ratios (HR) and 95% confidence intervals (CI) of the associations of pre-diagnostic CLD use with all-cause and BC-specific mortality, adjusting for tumor characteristics, first course of treatment, health behaviors, co-morbidities, and demographics. Subgroup analyses by stage and hormone receptor status were conducted for all-cause mortality. RESULTS: There were 224 all-cause and 87 BC-specific deaths among the 1448 BC cases during a median follow-up of 4.5 years after diagnosis. Women with BC who ever used CLDs had a 27% lower hazard of all-cause mortality (HR 0.73, 95% CI 0.54-0.98) and 17% lower hazard of BC-specific mortality (HR 0.83, 95% CI 0.49-1.39) compared to never users. CLD use reduced mortality among women with advanced-stage tumors and hormone receptor-positive breast tumors (HR 0.54 95% CI 0.33-0.90; HR 0.69, 95% CI 0.48-0.99, respectively). CONCLUSION: These findings demonstrate an improved survival associated with CLD use prior to diagnosis in a multiethnic population of women with BC.