Effect of direct oral anticoagulant therapy on pulmonary artery clot dissolution in intermediate high-risk pulmonary thromboembolism.

BACKGROUND: Direct oral anticoagulants are the established drugs for treating pulmonary thromboembolism. The advantage of direct oral anticoagulants over conventional therapy for clot lysis and right ventricular unloading in the acute phase remains unclear. This study aimed to evaluate the effect of acute treatment with direct oral anticoagulants on clot dissolution and right ventricular unloading in intermediate high-risk pulmonary thromboembolism. METHODS: Thirty patients with intermediate high-risk pulmonary thromboembolism admitted between November 2012 and December 2018 were included; 21 and 9 were treated with direct oral anticoagulants and conventional therapy, respectively. We compared the efficacy of clot dissolution and right ventricular unloading for intermediate high-risk pulmonary thromboembolism between direct oral anticoagulant and conventional therapy in the acute phase. Efficacy was assessed by computed tomography obstruction index, right/left ventricular ratio, and brain natriuretic peptide levels between baseline and at discharge. RESULTS: Computed tomography obstruction index, right ventricular/left ventricular ratio, and brain natriuretic peptide levels were significantly lower at discharge than at admission in both groups. The rate of improvement in computed tomography obstruction index was significantly higher in the direct oral anticoagulant therapy group than in the conventional therapy group (64 ± 15% vs. 47 ± 16%; p = 0.01). There were no significant differences in the rate of improvement in right ventricular/ left ventricular ratio and brain natriuretic peptide levels between the two groups. CONCLUSIONS: Compared with conventional therapy, direct oral anticoagulants significantly reduced pulmonary artery clot burden conventional therapy in the acute treatment of intermediate high-risk pulmonary thromboembolism.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary disease without pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.

Clinical outcomes of upfront combination therapy for portopulmonary hypertension.

Background: Limited data exists on upfront combination therapy for portopulmonary hypertension. We evaluated the clinical efficacy, long-term outcomes, and safety of upfront combination therapy in patients with portopulmonary hypertension. Methods: We performed a retrospective, single-center cohort study involving a final analysis of 33 consecutive patients diagnosed with portopulmonary hypertension who were taking pulmonary arterial hypertension-specific medication. We compared hemodynamic parameters, risk profiles, composite clinical worsening events, and safety between monotherapy (n = 23) and upfront combination therapy (n = 10). Results: Twenty-seven patients (82 %) were classified into the Child-Pugh A stage. The change ratios of pulmonary vascular resistance (-32 % vs. -57 %, P = 0.006) were significantly better with upfront combination therapy. Upfront combination therapy also showed significant improvement in risk profiles. Kaplan-Meier analysis showed that the composite event-free rate was significantly lower in patients who received upfront combination therapy than in those who received monotherapy (P = 0.016), although no statistical differences were observed in all-cause death. In the univariate Cox proportional hazards analysis, upfront combination therapy was a factor for decreasing composite clinical worsening outcomes (hazard ratio 0.190, 95 % confidence interval 0.042-0.854; P = 0.030). No significant hepatic impairments were observed over 2 years of follow-up in the upfront combination group. Conclusions: In patients with portopulmonary hypertension, upfront combination therapy significantly improved symptoms and short-term hemodynamics, and reduced long-term clinical worsening events without serious adverse effects. This study's findings suggest that patients with portopulmonary hypertension presenting with mild hepatic impairment benefit from upfront combination therapy.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Systemic AA Amyloidosis Secondary to Metastatic Renal Cell Carcinoma in a Hemodialysis Patient with Intractable Diarrhea.

We describe an autopsied case of systemic AA amyloidosis secondary to metastatic renal cell carcinoma presenting intractable diarrhea. Severe diarrhea was the major symptom for the diagnosis of AA amyloidosis. No renal symptoms which are common in AA amyloidosis secondary to renal cell carcinoma were shown because hemodialysis following bilateral nephrectomy had already been started 9 years before. Treatment against metastatic tumors as a solution of AA amyloidosis could not be performed because of bad performance status and the patient died 5 months after the diagnosis. Autopsy findings revealed that AA amyloid deposition was seen in multi-organs including the intestine. The metastatic tumors were histologically compatible as metastasis of renal cell carcinoma. There was no other cause of chronic inflammation such as inflammatory arthritis. We concluded that chronic inflammation provoked by the metastatic tumors of renal cell carcinoma was a major cause of systemic AA amyloidosis. Intestinal AA amyloidosis with malabsorption was the cause of death. Clinicians should keep it in mind that solid organ malignancy can be a cause of AA amyloidosis and renal cell carcinoma is the most common carcinomatous cause. This case is particularly instructive in that progression of amyloidosis may be missed in hemodialysis patients with anuria and that gastrointestinal symptoms can be the primary indicators of systemic amyloidosis. Endoscopic examination including biopsy is important for the diagnosis and early treatment of amyloidosis.

Smoking history and severe atrophic gastritis assessed by pepsinogen are risk factors for the prevalence of synchronous gastric cancers in patients with gastric endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs. METHODS: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study. RESULTS: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737). CONCLUSION: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated.

Commercially available novel device to prevent the diffusion of droplets from subjects undergoing esophagogastroduodenoscopy: A pilot study with its prototype.

Introduction: Under the current pandemic situation of the coronavirus disease 2019 (COVID-19), we have newly developed a commercially available device named Endomask to prevent the diffusion of droplets from subjects undergoing esophagogastroduodenoscopy (EGD). Herein, we evaluate the efficacy and safety of the device, and also evaluate the stress of the device on the operators and the subjects of EGD. Methods: The efficacy of the device was evaluated using an experimental model that simulated the environment of EGD. The safety of the device was evaluated clinically by means of measuring the oxygen saturation and the expiratory carbonic dioxide partial pressure of subjects with our device during EGD. The stress of the device on the operability of the endoscopists and the respiration of the subjects were evaluated using questionnaires. Results: In the experiments with Endomask, the percentage of the area with simulated droplets was significantly reduced compared to that without our device (median, 0.24% vs. 6.96%, p = 0.009). The saturation of oxygen and the expiratory carbonic dioxide partial pressure of subjects with the device did not show significant change at any recording times. Neither the operators nor the subjects felt serious stress from examination with the device. Conclusions: Endomask could remarkably and safely prevent the diffusion of droplets without serious stress. Endomask is expected to contribute to a reduction of the infectious risk of SARS-CoV-2 in endoscopy units during COVID-19 pandemic.

Using Polyethylene Glycol 3350 Plus Electrolytes in Constipated Hemodialysis Patients: A Case Series.

Appropriate management of constipation in hemodialysis patients has not been established, although constipation is the most frequent gastrointestinal complication in dialysis patients. We herein report the efficacy and safety of polyethylene glycol in constipated hemodialysis patients assessed prospectively. Seven patients using stimulant laxatives participated in this study. Polyethylene glycol was administered to reduce stimulant laxatives during the six-week intervention period. The amount of stimulant laxatives decreased and spontaneous bowel movements with ideal stool consistency increased significantly after the intervention. No serious adverse effects were observed throughout this study. In conclusion, polyethylene glycol can be a useful tool for managing constipated hemodialysis patients.

Spontaneous reactivation of hepatitis B virus with S gene mutations in an elderly patient with diabetic nephropathy.

Generally, reactivation of hepatitis B virus (HBV) infection is induced by the administration of immunosuppressants or anticancer agents, but reactivation without such drugs has rarely been reported. Here we report an elder case with spontaneous reactivation of HBV replication accompanied by hepatitis B surface antigen (HBsAg) mutations. A 69-year-old man with a history of diabetes mellitus and chronic kidney disease (CKD) was found to be positive for HBsAg (0.072 IU/ml) in June 2018. In May 2019, marked hepatic dysfunction and increased HBsAg (2533.2 IU/ml) were observed when he visited the hospital due to diarrhea and worsening of CKD. At that time, hepatitis B surface antibody (HBsAb) was positive (268.9 mIU/ml) and HBV DNA was 6.0 log IU/ml. After treatment with entecavir, HBV DNA and HBsAg rapidly decreased. Full-genome HBV sequence analysis revealed that the patient was infected with HBV of subgenotype B1 and it had an "a" determinant mutation M133L in the S gene coding HBsAg. Notably, both HBsAg and HBsAb were positive at the time of HBV reactivation, suggesting that the HBV with these mutations escaped from neutralization by HBsAb. This case suggests that immune escape mutations could play an important role in spontaneous HBV reactivation.

Endoscopic Findings of Esophageal Adenosquamous Carcinoma Diagnosed by Endoscopic Mucosal Resection.

Adenosquamous carcinoma (ASC) is a rare histological type of esophageal carcinoma. Esophagogastroduodenoscopy for the health checkup of a 71-year-old male revealed the presence of a slightly elevated lesion like a submucosal tumor at the lower part of the esophagus. The center of it was slightly depressed, and the depressed area was not stained by iodine. Magnifying endoscopy with narrow-band imaging revealed reticular pattern vessels in the depressed area, whereas no irregularity of the microvascular pattern of the surrounding area was evident. One of the biopsied specimens taken from the depressed area was diagnosed as squamous intraepithelial neoplasia, but a malignant tumor with submucosal invasion was suspected based on the findings of endoscopic ultrasonography. Endoscopic mucosal resection using a cap-fitted endoscope was performed, and the lesion was diagnosed as esophageal ASC histologically. Carcinomas that formed nested and ductal structures existed in the lamina propria and invaded to the submucosa. Almost all of them were covered by non-invasive intraepithelial neoplasia, whereas small erosion was seen in the central depressed area. The growing pattern of ASC was quite different from that of typical differentiated squamous cell carcinomas. When we do endoscopic examination for an esophageal lesion like submucosal tumor, we have to consider the possibility of an esophageal carcinoma that has a similar growing pattern. If reticular pattern vessels are seen with magnifying endoscopy, the existence of an invasive carcinoma is suspected, and additional endoscopic ultrasonography is recommended. Possible efforts to gain histological findings have to be made using bowling biopsy, endoscopic resection, and so on.

Application of Novel Sialoglyco Particulates Enhances the Detection Sensitivity of the Equine Influenza Virus by Real-Time Reverse Transcriptase Polymerase Chain Reaction.

Sialoglyco particulates carrying an N-glycolylneuraminyl-α-(2 → 3)-N-acetyllactosamine (Neu5Gcα2,3LacNAc) residue that displays a high level of affinity for the equine influenza virus (EIV) were generated using sialoglycopolypeptide and hexyl-containing hybrid silica particulates. The particulates were spherical with a diameter of approximately 950 nm and found to have good dispersibility in aqueous solution. Interaction between the sialoglyco particulates and the EIV was investigated by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) of the EIV genome captured on the particulates. The number of EIV-specific genes detected by rRT-PCR on a nasal swab obtained from infected horses clearly increased when the sample was treated with sialoglyco particulates. Our results show these novel sialoglyco particulates can be used as a highly sensitive tool for detecting low levels of EIV that were previously undetectable in the early or late stage of infection.

From Linear to Nonlinear Responses of Thermal Pure Quantum States.

We propose a self-validating scheme to calculate the unbiased responses of quantum many-body systems to external fields of arbitrary strength at any temperature. By switching on a specified field to a thermal pure quantum state of an isolated system, and tracking its time evolution, one can observe an intrinsic thermalization process driven solely by many-body effects. The transient behavior before thermalization contains rich information on excited states, giving the linear and nonlinear response functions at all frequencies. We uncover the necessary conditions to clarify the applicability of this formalism, supported by a proper definition of the nonlinear response function. The accuracy of the protocol is guaranteed by a rigorous upper bound of error exponentially decreasing with system size, and is well implemented in the simple ferromagnetic Heisenberg chain, whose response at high fields exhibits a nonlinear band deformation. We further extract the characteristic features of excitation of the spin-1/2 kagome antiferromagnet; the wave-number-insensitive linear responses from the possible spin liquid ground state, and the significantly broad nonlinear peaks which should be generated from numerous collisions of quasiparticles, that are beyond the perturbative description.

Free space optical secret key agreement.

Free space optical (FSO) communications are enabling high-speed global wireless networks. Thanks to the highly directional nature of laser beam, they also yield a greater security advantage over radio frequency counterparts. When combined with a scheme of secret key agreement (SKA), FSO-SKA can establish at high speed a symmetric secret key which cannot be decrypted even by unbounded computer resources. Although there have been many theoretical studies on SKA, experimental investigations have been quite lacking, especially on quantifying eavesdropping risks and secret key rates in realistic environment. Here, we report the first full-field implementations of FSO-SKA in a 7.8-km terrestrial link with a probing station, enabling the estimation of eavesdropping risks. We attain the final key rates from 100 kbps to 7.77 Mbps under various atmospheric and beaming conditions even with total losses of 55dB or higher, in which known quantum key distribution schemes attain impractically low key rates.

Free-space optical wiretap channel and experimental secret key agreement in 7.8 km terrestrial link.

Secret key agreement using physical properties of a wireless channel is becoming a promising scheme to establish a secret key between two users, especially in short-distance radio frequency (RF) communications. In this scheme, the existence of codes or key distillation that can make the leaked information to an eavesdropper arbitrarily small can be derived in an information theoretical way, given a priori knowledge on the channel linking a sender (Alice), a legitimate receiver (Bob), and an eavesdropper (Eve), which is called the wiretap channel. In practice, however, it is often difficult for Alice and Bob to get sufficient knowledge on Eve. In this study, we implement a free-space optical wiretap channel in a 7.8 km-terrestrial link and study how to estimate Eve's tapping ability, demonstrating high speed secret key agreement in the optical domain under a certain restricted condition of line-of-sight.

Secret key rates for intensity-modulated dual-threshold detection key distribution under individual beam splitting attacks.

We investigate the secret key rates for the recently proposed intensity-modulated dual-threshold key distribution [T. Ikuta and K. Inoue, New J. Phys. 18 (2016)] under beam splitting attacks. We show that previous assumptions on an eavesdropper that performs hard decision measurements on the channel, overestimates the secret key rate. We discuss the impact of an eavesdropper that can measure full soft information and give the secret key rates under forward and reverse reconciliation. Further, we perform simulations for different system assumptions and show the optimal modulation depths for these systems. We also outline an attack on this protocol based on photon counting that prohibits secret key generation.

Magnetically Tunable Vibration Transmissibility for Polyurethane Magnetic Elastomers.

The effect of a weak magnetic field on vibration transmissibility was investigated for magnetic elastomers with various volume fractions of magnetic particles. Polyurethane elastomers without magnetic particles exhibited a natural frequency at 53 Hz and were insensitive to a magnetic field of 60 mT. The natural frequency for magnetic elastomers with a volume fraction of 0.23 was 115 Hz at 0 mT, and increased to 134 Hz at 60 mT. The vibration transmissibility was independent of the magnetic field. A linear relation between the natural frequency and (G/m)1/2 was observed (G: storage modulus, m: mass), indicating that the observed vibration is basically described by a simple harmonic oscillation.

Quantum photonic network and physical layer security.

Quantum communication and quantum cryptography are expected to enhance the transmission rate and the security (confidentiality of data transmission), respectively. We study a new scheme which can potentially bridge an intermediate region covered by these two schemes, which is referred to as quantum photonic network. The basic framework is information theoretically secure communications in a free space optical (FSO) wiretap channel, in which an eavesdropper has physically limited access to the main channel between the legitimate sender and receiver. We first review a theoretical framework to quantify the optimal balance of the transmission efficiency and the security level under power constraint and at finite code length. We then present experimental results on channel characterization based on 10 MHz on-off keying transmission in a 7.8 km terrestrial FSO wiretap channel.This article is part of the themed issue 'Quantum technology for the 21st century'.

The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter.

BACKGROUND/AIMS: The treatment strategy for non-ampullary duodenal neuroendocrine tumors (NAD-NETs) ≤20 mm in diameter has not been established. In this study, we aimed to evaluate the detailed characteristics of NAD-NETs ≤20 mm in diameter to clarify the risk factors of subsequent metastasis. METHODS: The patients with NAD-NETs ≤20 mm in diameter who had been treated at 12 institutions between 1992 and 2013 were enrolled. Clinical records were retrieved, and histopathological findings of all cases were centrally reviewed by 2 pathologists. RESULTS: We studied 49 patients with a mean follow-up period of 66.5 months. Thirty-five patients were initially treated with endoscopic resection (ER), and 14 with surgery. A univariate analysis revealed the ORs and 95% CIs of the risk factors for metastasis were lymphovascular invasion (12.5 [2.01-77.9]), multiple tumors (9.75 [1.46-65.4]), a tumor size of 11-20 mm (6.67 [1.21-36.6]), and World Health Organization grade G2 (7.13 [1.16-43.9]). Five-year overall and disease-specific survival rates were 86.1 and 97.2%, respectively. CONCLUSION: This is the first study to demonstrate the risk factors of metastasis in NAD-NETs ≤20 mm in diameter. These findings may be helpful for determining the appropriate therapeutic approach and the clinical strategy of treatment following ER.