Prognostic Implication of Longitudinal Changes of Left Ventricular Global Strain After Chemotherapy in Cardiac Light Chain Amyloidosis

AimCardiac involvement is the main prognostic determinant in AL amyloidosis. We sought to determine the prognostic significance of longitudinal change of left ventricular (LV) global longitudinal strain (GLS) in cardiac light chain (AL) amyloidosis patients undergoing chemotherapy.Methods and ResultWe retrospectively investigated 117 cardiac AL amyloidosis patients who underwent chemotherapy from 2005 to 2019. All patients underwent comprehensive 2D conventional transthoracic echocardiography at baseline and after completion of first-line chemotherapy. Speckle tracking analysis of images was performed offline. Absolute value of LV GLS was expressed as [LV GLS] and change of [LV GLS] after chemotherapy was expressed as Δ [LV GLS]. Clinical outcomes including cardiac response and all-cause mortality were analyzed.Baseline clinical and echocardiographic parameters were similar in patients with and without CR. Δ [LV GLS] significantly differed between the CR and non-CR groups (0.4 ± 2.8% in the CR group vs. −0.6 ± 2.5% in the non-CR group, P-value = 0.046). Δ [LV GLS] showed satisfactory predictive performance for all-cause mortality (cut-off value = 0.8%, AUC 0.643, 95% CI [0.537–0.748]). Adding Δ [LV GLS] to the Mayo stage + pre-chemotherapy [LV GLS] model showed incremental prognostic value (C-index: 0.637 vs. 0.708; Relative Integrated Discrimination Index 0.07, P-value = 0.003; Net Reclassification Improvement 0.54, P-value < 0.001). Δ [LV GLS] showed good correlation with cardiac response (AUC 0.820, 95% CI [0.737–0.904]).ConclusionIn cardiac amyloidosis patients who underwent chemotherapy, longitudinal change of [LV GLS] after chemotherapy showed significant association with overall survival as well as cardiac response

Quilty Lesions in the Endomyocardial Biopsies after Heart Transplantation

Background The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients. Methods A total of 1190 EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions, acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy was diagnosed by computed tomography coronary angiography. Clinical information, including the patients’ survival was retrieved by a review of medical records. Results Eighty-eight patients (75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellular rejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patient sdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesions from transplantation was longer than that of acute cellular rejections. We found a significant association between Quilty lesions and cardiac allograft vasculopathy. No significant relationship was found between Quilty lesions and the patients’ survival. Conclusions Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection

The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia.

Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases

Data of methylome and transcriptome derived from human dilated cardiomyopathy

AbstractAlterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1]

Optimal timing of surgery for prenatally diagnosed choledochal cysts

ObjectiveCholedochal cysts are increasingly being diagnosed antenatally. The appropriate time of surgical treatment has the greatest impact on the prognosis of choledochal cyst treatment. The purpose of this study was to compare the clinical outcomes of prenatally diagnosed choledochal cysts in infants according to the surgical treatment timing.MethodsWe retrospectively reviewed the medical records of infants who underwent surgery for choledochal cysts with antenatal diagnoses. We investigated each patient's demographic information, type of choledochal cyst, serum liver enzyme levels, and surgical outcomes according to the surgical intervention timing.ResultsBetween May 2006 and December 2020, 93 infants underwent surgery to treat choledochal cysts; among them, 68 had antenatally suspected choledochal cysts. Of the 68 patients, 21 developed symptoms directly after birth. While 38 patients remained asymptomatic, 9 developed symptoms before operation. To compare surgical outcomes, asymptomatic patients were divided into early (13 cases) and late (25 cases) operation groups based on an age benchmark of 30 days. The early surgical group experienced longer times to resume a full diet (6.0 ± 1.6 vs. 4.5 ± 0.7, p < 0.001) and longer postoperative hospital stays (11 ± 3.9 vs. 7.5 ± 0.8, p < 0.001). Surgical complications occurred in two patients in the early operation group. Minimally invasive surgery was performed in 12 patients in the late operation group. In both groups, postoperative liver function recovered at 6 months, with no significant difference.ConclusionThe results of this study showed longer hospital stays, increased diet durations, and postoperative complications in early surgery patients. However, liver function recovery was not different between the early and late operation groups. Thus, asymptomatic patients should be closely monitored, and we recommend that definitive surgical intervention be postponed until 4 months of age or until weight reaches 7 kg

Successful removal of kinked J-guide wire under fluoroscopic guidance during central venous catheterization -A case report-

Guidewire-associated complications that occur during the process of central venous catheterization include its kinking, looping, knotting and breakage. The removal of a looped or knotted guidewire is problematic because it can cause vessel damage, major hemorrhage, or embolization of a fractured guidewire. We report a case of guidewire kinking and its successful removal under fluoroscopic guidance

Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates.

Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing

Depression and suicide risk prediction models using blood-derived multi-omics data

More than 300 million people worldwide experience depression; annually, ~800,000 people die by suicide. Unfortunately, conventional interview-based diagnosis is insufficient to accurately predict a psychiatric status. We developed machine learning models to predict depression and suicide risk using blood methylome and transcriptome data from 56 suicide attempters (SAs), 39 patients with major depressive disorder (MDD), and 87 healthy controls. Our random forest classifiers showed accuracies of 92.6% in distinguishing SAs from MDD patients, 87.3% in distinguishing MDD patients from controls, and 86.7% in distinguishing SAs from controls. We also developed regression models for predicting psychiatric scales with R2 values of 0.961 and 0.943 for Hamilton Rating Scale for Depression???17 and Scale for Suicide Ideation, respectively. Multi-omics data were used to construct psychiatric status prediction models for improved mental health treatment