Carinal resection and reconstruction for recurrent lung cancer

A patient with a recurrent tumor in the trachea adjacent to the right main bronchus was treated by surgical resection 19 months after undergoing surgery for the primary cancer. The patient had previously undergone right upper lobectomy for T1N0M0 stage I squamous cell carcinoma. A carinal resection was performed which included 4 rings of the trachea, 2 rings of the righ main bronchus, and 1 ring of the left main bronchus. Reconstruction consisted of an end-to-end anastomosis of the trachea and left main bronchus, and an end-to-side anastomosis of the right and left main bronchi. The postoperative course was uneventful, and at present the patient is healthy 12 months following reoperation.     

Therapeutic effect of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in treatment of corneal alkali burns in mice

We evaluated the therapeutic efficacy of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in a corneal alkali burn model in mice. An alkali burn was produced with 1 N NaOH in the cornea of C57BL/6 mice under general anesthesia. SN50 (10 microg/microl) or vehicle was topically administered daily for up to 12 days. The eyes were processed for histological or immunohistochemical examination after bromodeoxyuridine labeling or for semi-quantification of cytokine mRNA. Topical SN50 suppressed nuclear factor-kappaB activation in local cells and reduced the incidence of epithelial defects/ulceration in healing corneas. Myofibroblast generation, macrophage invasion, activity of matrix metalloproteinases, basement membrane destruction, and expression of cytokines were all decreased in treated corneas compared with controls. To elucidate the role of tumor necrosis factor (TNF)-alpha in epithelial cell proliferation, we performed organ culture of mouse eyes with TNF-alpha, SN50, or an inhibitor of c-Jun N-terminal kinase (JNK) and examined cell proliferation in healing corneal epithelium in TNF-alpha-/- mice treated with SN50. An acceleration of epithelial cell proliferation by SN50 treatment was found to depend on TNF-alpha/JNK signaling. In conclusion, topical application of SN50 is effective in treating corneal alkali burns in mice.     

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis

Sarcoidosis is a multi‐systemic disease of unknown etiology that results in the development of non‐caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow‐up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.     

Timing of Uterine Artery Embolization for Leiomyoma during the Menstrual Cycle

PurposeTo investigate differences in outcomes of uterine artery embolization (UAE) for leiomyoma when performed during different phases of the menstrual cycle.Materials and MethodsIn this single-institution retrospective analysis, 111 premenopausal patients (median [range] age, 44 [33–52] years) undergoing UAE for symptomatic leiomyoma between June 2014 and February 2020 were included. Twenty-one patients underwent UAE in the menstrual phase (the early follicular phase), 27 in the late follicular phase, and 63 in the luteal phase. Baseline characteristics and technical and peri-procedural outcomes were compared among groups. Leiomyoma infarction on contrast-enhanced magnetic resonance imaging 1 week after UAE and 4-month outcomes, including changes in the Uterine Fibroid Symptom and Quality of Life questionnaire scores, the volume reduction rates of the uterus and largest leiomyoma, follicle stimulating hormone values, adverse events, and amenorrhea, were compared among groups.ResultsA 4-month follow-up was completed for all patients. No significant differences were observed among groups in baseline characteristics or technical and peri-procedural outcomes. There were no significant differences in the multivariate-adjusted 1-week infarction rates of all leiomyoma volumes (P = .161) or multivariate-adjusted 4-month outcomes, including changes in the Uterine Fibroid Symptom and Quality of Life questionnaire symptoms and total scores (P = .864 and P = .798, respectively), the volume reduction rates of the uterus and the largest leiomyoma (P = .865 and P = .965, respectively), and follicle stimulating hormone values (P = .186) among the groups. No significant differences were noted in the 4-month adverse events (P = .260) or amenorrhea (P = .793) among the groups.ConclusionsThe present study demonstrated no significant differences in the outcomes of UAE for leiomyoma when performed during different phases of the menstrual cycle.     

Electrocardiographic characteristics of repetitive monomorphic right ventricular tachycardia originating near the His-bundle

INTRODUCTION: Most idiopathic nonreentrant ventricular tachycardia (VT) and ventricular premature contractions (VPCs) arise from the right or left ventricular outflow tract (OT). However, some right ventricular (RV) VT/VPCs originate near the His-bundle region. The aim of this study was to investigate ECG characteristics of VT/VPCs originating near the His-bundle in comparison with right ventricular outflow tract (RVOT)-VT/VPCs. METHODS AND RESULTS: Ninety RV-VT/VPC patients underwent catheter mapping and radiofrequency ablation. ECG variables were compared between VT/VPCs originating from the RVOT and near the His-bundle. Ten patients had foci near the His-bundle (HIS group), with the His-bundle local ventricular electrogram preceding the QRS onset by 15-35 msec (mean: 22 msec) and His-bundle pacing produced a nearly identical ECG to clinical VT/VPCs. The HIS group R wave amplitude in the inferior leads (lead III: 1.0 +/- 0.6 mV) was significantly lower than that of the RVOT group (1.7 +/- 0.4 mV, P < 0.05). An R wave in aVL was present in 6 of 10 HIS group patients, while almost all RVOT group patients had a QS pattern in aVL. Lead I in HIS group exhibited significantly taller R wave amplitudes than RVOT group. HIS group QRS duration in the inferior leads was shorter than that of the RVOT group. Eight of 10 HIS group patients exhibited a QS pattern in lead V1 compared to 14 of 81 RVOT group patients. HIS group had larger R wave amplitudes in leads V5 and V6 than RVOT group. CONCLUSION: VT/VPCs originating near the His-bundle have distinctive ECG characteristics. Knowledge of the characteristic QRS morphology may facilitate catheter mapping and successful ablation.     

Sequential analysis of amino acid substitutions with hepatitis B virus in association with nucleoside/nucleotide analog treatment detected by deep sequencing

Taking nucleoside/nucleotide analogs is a major antiviral therapy for chronic hepatitis B infection. The problem with this treatment is the selection for drug‐resistant mutants. Currently, identification of genotypic drug resistance is conducted by molecular cloning sequenced by the Sanger method. However, this methodology is complicated and time‐consuming. These limitations can be overcome by deep sequencing technology. Therefore, we performed sequential analysis of the frequency of drug resistance in one individual, who was treated with lamivudine on‐and‐off therapy for 2 years, by deep sequencing. The lamivudine‐resistant mutations at rtL180M and rtM204V and the entecavir‐resistant mutation at rtT184L were detected in the first subject. The lamivudine‐ and entecavir‐resistant strain was still detected in the last subject. However, in the deep sequencing analysis, rt180 of the first subject showed a mixture in 76.9% of the methionine and in 23.1% of the leucine, and rt204 also showed a mixture in 69.0% of the valine and 29.8% of the isoleucine. During the treatment, the ratio of resistant mutations increased. At rt184, the resistant variants were detectable in 58.7% of the sequence, with the replacement of leucine by the wild‐type threonine in the first subject. Gradually, entecavir‐resistant variants increased in 82.3% of the leucine in the last subject. In conclusion, we demonstrated the amino acid substitutions of the serial nucleoside/nucleotide analog resistants. We revealed that drug‐resistant mutants appear unchanged at first glance, but actually there are low‐abundant mutations that may develop drug resistance against nucleoside/nucleotide analogs through the selection of dominant mutations.     

Unique protonation states of aspartate and topaquinone in the active site of copper amine oxidase

The oxidative deamination of biogenic amines, crucial in the metabolism of a wealth of living organisms, is catalyzed by copper amine oxidases (CAOs). In this work, on the ground of accurate molecular modeling, we provide a clear insight into the unique protonation states of the key catalytic aspartate residue Asp298 and the prosthetic group of topaquinone (TPQ) in the CAO of Arthrobacter globiformis (AGAO). This provides both extensions and complementary information to the crystal structure determined by our recent neutron diffraction (ND) experiment. The hybrid quantum mechanics/molecular mechanics (QM/MM) simulations suggest that the ND structure closely resembles a state in which Asp298 is protonated and the TPQ takes an enolate form. The TPQ keto form can coexist in the fully protonated state. The energetic and structural analyses indicate that the active site structure of the AGAO crystal is not a single state but rather a mixture of the different protonation and conformational states identified in this work.

Copper amine oxidases catalyze the oxidative deamination of biogenic amines. We investigated the unique protonation states in the active site using first-principle calculations.