Background
The incidence of postoperative atrial fibrillation (POAF) after pulmonary lobectomy ranges from 6.4 to 12.6%. This study aimed to analyze the postoperative risk factors and prognosis for ...POAF in lobectomy for lung cancer.
Methods
Data were collected from patients undergoing pulmonary lobectomy from April 2010 to March 2019. We analyzed risk factors for POAF among perioperative factors and compared postoperative complications or overall survival between POAF and non-POAF groups. We classified POAF as either the temporary or non-temporary type and compared perioperative factors, postoperative complications, and overall survival.
Results
POAF was identified in 49 (5.2%) of the 947 lobectomies. The POAF group included more males, patients with poor performance status (PS), history of paroxysmal atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD), and intraoperative blood transfusions. Poor PS, COPD, previous paroxysmal AF, and intraoperative blood transfusion were independent risk factors for POAF in multivariate analysis. The POAF group had a poorer prognosis than the non-POAF group (
p
= 0.0045). POAF was divided into 29 temporary and 20 non-temporary types. The onset date of non-temporary-type POAF was significantly later than that of the transient type (
P
< 0.01), and diabetes mellitus was significantly higher in non-temporary-type POAF. Non-temporary-type POAF had a significantly poorer prognosis in terms of overall survival (
p
= 0.005).
Conclusions
Poor PS, COPD, history of PAF, and intraoperative blood transfusion were independent risk factors for POAF. Non-temporary-type POAF occurred significantly later than transient type and caused poorer prognosis after lobectomy for lung cancer.
During mammalian embryogenesis, de novo hematopoiesis occurs transiently in multiple anatomical sites including the yolk sac, dorsal aorta, and heart tube. A long-unanswered question is whether these ...local transient hematopoietic mechanisms are essential for embryonic growth. Here, we show that endocardial hematopoiesis is critical for cardiac valve remodeling as a source of tissue macrophages. Colony formation assay from explanted heart tubes and genetic lineage tracing with the endocardial specific Nfatc1-Cre mouse revealed that hemogenic endocardium is a de novo source of tissue macrophages in the endocardial cushion, the primordium of the cardiac valves. Surface marker characterization, gene expression profiling, and ex vivo phagocytosis assay revealed that the endocardially derived cardiac tissue macrophages play a phagocytic and antigen presenting role. Indeed, genetic ablation of endocardially derived macrophages caused severe valve malformation. Together, these data suggest that transient hemogenic activity in the endocardium is indispensable for the valvular tissue remodeling in the heart.
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•Hemogenic endocardium is a source of cardiac macrophages in cardiac valves•Endocardial macrophages are more phagocytic than macrophages from other source(s)•Genetic ablation of endocardial macrophages induces defects in valve formation•Endocardially derived macrophages are indispensable for normal valve remodeling
Shigeta et al. found that a subset of macrophages in the heart valves originates locally from the fetal endocardium. This local type of macrophages is more phagocytic than other macrophages and critical for the valve remodeling during cardiogenesis.
Heart failure and atherosclerosis share the underlying mechanisms of chronic inflammation followed by fibrosis. A highly conserved microRNA (miR), miR-33, is considered as a potential therapeutic ...target for atherosclerosis because it regulates lipid metabolism and inflammation. However, the role of miR-33 in heart failure remains to be elucidated.
To clarify the role of miR-33 involved in heart failure.
We first investigated the expression levels of miR-33a/b in human cardiac tissue samples with dilated cardiomyopathy. Increased expression of miR-33a was associated with improving hemodynamic parameters. To clarify the role of miR-33 in remodeling hearts, we investigated the responses to pressure overload by transverse aortic constriction in miR-33-deficient (knockout KO) mice. When mice were subjected to transverse aortic constriction, miR-33 expression levels were significantly upregulated in wild-type left ventricles. There was no difference in hypertrophic responses between wild-type and miR-33KO hearts, whereas cardiac fibrosis was ameliorated in miR-33KO hearts compared with wild-type hearts. Despite the ameliorated cardiac fibrosis, miR-33KO mice showed impaired systolic function after transverse aortic constriction. We also found that cardiac fibroblasts were mainly responsible for miR-33 expression in the heart. Deficiency of miR-33 impaired cardiac fibroblast proliferation, which was considered to be caused by altered lipid raft cholesterol content. Moreover, cardiac fibroblast-specific miR-33-deficient mice also showed decreased cardiac fibrosis induced by transverse aortic constriction as systemic miR-33KO mice.
Our results demonstrate that miR-33 is involved in cardiac remodeling, and it preserves lipid raft cholesterol content in fibroblasts and maintains adaptive fibrotic responses in the remodeling heart.
Background
The incidence of postoperative delirium after anatomical lung resection ranges from 5 to 16%. This study aimed to analyze the risk factors and prognosis of postoperative delirium in ...anatomical lung resection for lung cancer.
Methods
This study included 1351 patients undergoing anatomical lung resection between April 2010 and October 2020. We analyzed the perioperative risk factors of postoperative delirium. We also compared postoperative complications and survival between the delirium and non-delirium groups.
Results
Postoperative delirium was identified in 44 (3.3%) of 1351 patients who underwent anatomical lung resection for lung cancer. Age, peripheral vascular disease, depression, and current smoking status were independent risk factors for postoperative delirium in the multivariate analysis. The percentage of postoperative delirium was 0.6% in never smokers and 6.0% in current smokers. The delirium and non-delirium groups showed significant differences in overall survival (
p
= 0.0144) and non-disease-specific survival (
p
= 0.0080). After propensity score matching, the two groups did not significantly differ in overall survival (
p
= 0.9136), non-disease-specific survival (
p
= 0.8146), or disease-specific survival (
p
= 0.6804).
Conclusions
Age, peripheral vascular disease, depression, and current smoking status were considered independent risk factors for postoperative delirium in anatomical lung resection for lung cancer. Smoking cessation for at least four weeks before surgery is recommended for reducing incidence of post-operative delirium.
A combination of three post-transplant drugs, cyclophosphamide (PTCy), a calcineurin inhibitor, and mycophenolate mofetil, has long been used for prophylaxis of graft-versus-host-disease (GVHD) after ...HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT). Recently, this combination has been used following HLA-matched allo-HCT as well, but the optimal combination of drugs for GVHD prophylaxis in an HLA-matched setting remains unclear. This prospective phase II study evaluated the safety and efficacy of PTCy plus tacrolimus (TAC) for GVHD prophylaxis after allo-HCT from HLA-matched related donors (MRD) or HLA-matched unrelated donors (MUD). The cumulative incidences of grades II–IV and III–IV acute GVHD at 100 days post-transplantation were 18% and 5.9%, respectively, in the MRD group, and 18% and 9.1%, respectively, in the MUD group. The cumulative incidences of moderate to severe chronic GVHD at 1 year were 12% and 9.1% in the MRD and MUD groups, respectively. The 1-year overall survival rates in the MRD and MUD groups were 88% and 64%, respectively, and the 1-year GVHD-free, relapse free survival rates were 59% and 50%, respectively. These results suggest that GVHD prophylaxis with a less intensive double drug combination (PT/Cy and TAC) might be feasible after HLA-matched allo-HCT.
Clinical Trial Notation
This trial was a prospective single-center trial registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification number: UMIN000023890) and the Japan Registry of Clinical Trials (jRCTs051180143).
Familial hypercholesterolemia is an inherited disorder that remains underdiagnosed. Conventional genetic testing methods such as next-generation sequencing (NGS) or target PCR are based on the ...amplification process. Due to the efficiency limits of polymerase and ligase enzymes, these methods usually target short regions and do not detect large mutations straightforwardly. This study combined the long-read nanopore sequencing and CRISPR-Cas9 system to sequence the target DNA molecules without amplification. We originally designed and optimized the CRISPR-RNA panel to target the low-density lipoprotein receptor gene (LDLR) and proprotein convertase subtilisin/kexin type 9 gene (PCSK9) from human genomic DNA followed by nanopore sequencing. The average coverages for LDLR and PCSK9 were 106× and 420×, versus 1.2× for the background genome. Among them, continuous reads were 52x and 307x, respectively, and spanned the entire length of LDLR and PCSK9. We identified pathogenic mutations in both coding and splicing donor regions in LDLR. We also detected an 11,029 bp large deletion in another case. Furthermore, using continuous long reads generated from the benchmark experiment, we demonstrated how a false-positive 670 bp deletion caused by PCR amplification errors was easily eliminated.
Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study ...showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.
Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of cardiac valves and septa. However, ...little is known about the molecular mechanism of endocardial-hematopoietic transition. In the current study, we identified the regulatory network of endocardial hematopoiesis. Signal network analysis from scRNA-seq datasets revealed that genes in Notch and retinoic acid (RA) signaling are significantly downregulated in Nkx2-5-null endocardial cells. In vivo and ex vivo analyses validate that the Nkx2-5-Notch axis is essential for the generation of both hemogenic and cushion endocardial cells, and the suppression of RA signaling via Dhrs3 expression plays important roles in further differentiation into macrophages. Genetic ablation study revealed that these macrophages are essential in cardiac valve remodeling. In summary, the study demonstrates that the Nkx2-5/Notch/RA signaling plays a pivotal role in macrophage differentiation from hematopoietic progenitors.
Treatment of chronic myelogenous leukemia (CML) requires management of long-term use of tyrosine kinase inhibitors (TKIs). Although cardiovascular adverse events (CAEs) caused by off-target effects ...of TKIs can be life-threatening, the optimal method of monitoring for CAEs has not been established. Here, we comprehensively evaluated the clinical utility of various cardiovascular parameters, including ankle-brachial blood pressure index (ABI), cardiac ankle vascular index (CAVI), and carotid ultrasonography and electrocardiogram measurements, for monitoring and predicting CAEs in 74 patients with CML receiving TKIs. Based on concordance statistics, the predictive value of established risk factor models was significantly improved by addition of both ABI and CAVI, as follows: model 1 (hypertension, smoking history, and dyslipidemia), 0.680 versus 0.817 (
p
= 0.041); model 2 (hypertension, dyslipidemia, and diabetes mellitus), 0.685 vs. 0.830 (
p
= 0.047); and model 3 (age, hypertension, dyslipidemia and diabetes mellitus) 0.737 versus 0.818 (
p
= 0.044). However, no single cardiovascular parameter independently improved the predictive value of established risk factor models. In conclusion, addition of combined assessment of ABI and CAVI to established risk factors can improve prediction of future CAEs and may enable better clinical management of patients with CML receiving TKIs.
A 41-year-old woman presented with productive cough and exertional dyspnea. Bronchoscopy revealed an endobronchial tumor arising from the membrane proximal to the bifurcation of right upper bronchus, ...and the tumor was a typical carcinoid. The right main bronchus, right upper lobe bronchus, and intermediate bronchus were resected along with the tumor. Intraoperative pathological diagnosis of the bronchial stumps was negative, and bronchial reconstruction was subsequently performed. Two-thirds of the circumference of the right main bronchus and the right intermediate bronchus were anastomosed. The right upper lobe bronchus was anastomosed in an end-to-side fashion. The anastomotic site was covered by the intercostal muscles.
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