Diagnostic accuracy of direct reverse transcription-polymerase chain reaction using guanidine-based and guanidine-free inactivators for SARS-CoV-2 detection in saliva samples.

This study aimed to evaluate diagnostic accuracy of SARS-CoV-2 RNA detection in saliva samples treated with a guanidine-based or guanidine-free inactivator, using nasopharyngeal swab samples (NPS) as referents. Based on the NPS reverse transcription-polymerase chain reaction (RT-PCR) results, participants were classified as with or without COVID-19. Fifty sets of samples comprising NPS, self-collected raw saliva, and saliva with a guanidine-based, and guanidine-free inactivator were collected from each group. In patients with COVID-19, the sensitivity of direct RT-PCR using raw saliva and saliva treated with a guanidine-based and guanidine-free inactivator was 100.0%, 65.9%, and 82.9%, respectively, with corresponding concordance rates of 94.3% (κ=88.5), 82.8% (κ=64.8), and 92.0% (κ=83.7). Among patients with a PCR Ct value of <30 in the NPS sample, the positive predictive value for the three samples was 100.0%, 80.0%, and 96.0%, respectively. The sensitivity of SARS-CoV-2 RNA detection was lower in inactivated saliva than in raw saliva and lower in samples treated with a guanidine-based than with a guanidine-free inactivator. However, in individuals contributing to infection spread, inactivated saliva showed adequate accuracy regardless of the inactivator used. Inactivators can be added to saliva samples collected for RT-PCR to reduce viral transmission risk while maintaining adequate diagnostic accuracy.

Trifluridine and Tipiracil Hydrochloride Combination-Induced Interstitial Pneumonia: A Case Report.

We report a case of a 62-year-old male who was diagnosed with advanced rectal cancer. The attending gastro-enterologist initiated chemotherapy using capecitabine plus oxaliplatin and bevacizumab; however, this treatment regimen was discontinued, as the patient developed a skin rash. Once the skin rash improved, chemotherapy was re-initiated using a combination of trifluridine and tipiracil hydrochloride (TAS-102). The patient developed high fever and dyspnea 2 months after initiation of TAS-102. Chest high-resolution computed tomography showed bilateral diffuse ground glass opacities in all lung lobes with traction bronchiectasis. At this time, the gastro-enterologist consulted our department. The patient was put on non-invasive positive pressure ventilation due to worsening respiratory symptoms. The patient was suspected to develop TAS-102-induced interstitial pneumonia based on positive TAS-102 drug-induced lymphocyte stimulation test. The patient's respiratory symptoms and radiological findings improved after corticosteroid treatment. The corticosteroid dose was gradually decreased by 5 mg. Thereafter, chemotherapy was re-initiated using different anti-cancer agents.

Prognostic analysis of pulmonary hypertension with lung parenchymal lesion: Comparison of mortality with and without connective tissue disease.

BACKGROUND: The prognosis of pulmonary hypertension (PH) associated with connective tissue diseases related to interstitial pneumonia (CTD-IP PH) is relatively good among patients with PH and lung disease. However, the impact of pulmonary vasodilator treatment on the prognosis of CTD-IP PH compared with that of PH-induced chronic lung disease (group-3 PH) remains unclear. METHODS: From 2012 to 2022, 50 patients with lung parenchymal lesions diagnosed with PH (mean pulmonary arterial pressure >20 mmHg) at Juntendo University Hospital were divided into two groups: CTD-IP PH (30 patients) and group 3-PH (20 patients). The impact of pulmonary vasodilator treatment and the use of long-term oxygen therapy (LTOT) on the prognosis of each group was examined retrospectively. RESULTS: The prognosis of CTD-IP PH was significantly better compared to group-3 PH. While the treatment with pulmonary vasodilators did not affect the prognosis in group 3-PH, the prognosis of the patients treated with vasodilators in the CTD-IP PH group was significantly better than that of the non-treated patients. Treatment with multi-pulmonary vasodilators did not affect the prognosis in CTD-IP PH. Although the prognosis for the patients with LTOT was poor in all registered patients in the present study, treatment with pulmonary vasodilators improved the prognosis even under the use of LTOT in CTD-IP PH (P = 0.002). In a multivariate analysis of the CTD-IP PH group, pulmonary vasodilator treatment was an independent factor for better prognosis. CONCLUSION: Treatment with a pulmonary vasodilator for CTD-IP PH may improve the prognosis, even in patients requiring LTOT.

Pneumatosis intestinalis with free air in the abdominal cavity caused by nintedanib.

This is the first case confirmed the association between PI development and nintedanib by the reproducibility of PI development. In patients taking a combination treatment with corticosteroid and nintedanib, clinicians should be careful regarding the development of PI although the patient improved only after discontinuation of nintedanib treatment.

Unexpected Complications 25 Years after Coil Embolization for Pulmonary Arteriovenous Fistula.

An 87-year-old woman who had undergone coil embolization 25 years ago for pulmonary arteriovenous fistula, which was diagnosed following repeated cerebral infarction, presented with massive hemoptysis. The coils migrated and were excreted in stool following hemoptysis during long-term follow-up. Although the technical success rate of coil embolization for pulmonary arteriovenous malformations is extremely high, and coil embolization-related complications are rare, little is known about the long-term complications. We herein report the clinical course of our case, review previous reports related to coil migration as a long-term complication, and discuss the associated mechanism.

Protocol of an Exploratory Single-Arm Study to Evaluate the Safety and Immunogenicity of KD-414 as a Booster Vaccine for SARS-CoV-2 in Healthy Adults (KAPIVARA).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is currently ongoing, and there have been significant efforts in the development of COVID-19 vaccines. However, the neutralizing antibody titers in vaccinated individuals are reported to progressively decrease over time. Japanese pharmaceutical companies have published the results of Phase I and II studies on the safety and efficacy of different vaccines. Final clinical trials will be conducted with the aim of practical application by March 2023. To effectively utilize vaccines developed by Japanese companies, the efficacy and safety of a booster dose (i.e., third vaccination) must be evaluated among individuals who have received three doses of different vaccines. METHODS: This protocol describes a study that aims to examine the effect of a booster dose of "KD-414", a novel Japanese inactivated vaccine, on antibody titers among participants involved in a previous study. Volunteers in this protocol will be recruited from participants in the previous study and immunized with KD-414 after obtaining consent. The antibody titers, before and after immunization with KD-414, among participants who previously received two doses of the BNT162b2 mRNA vaccine, will be comparatively analyzed. DISCUSSION: The reactogenicity and immunogenicity of seven different COVID-19 vaccines including an inactivated vaccine as a third dose after two doses of ChAdOx1 nCov-19 or BNT162b2, has been tested previously, and found to be superior to control (quadrivalent meningococcal conjugate vaccine) regardless of which vaccine had been received during the initial course. This suggests that many types of third booster doses are efficacious. It is anticipated that this study will provide evidence of the safety and immunogenicity of KD-414 as a booster vaccine, which will have profound public health implications.

A single-center descriptive study of untraced sources of infection among new cases of coronavirus disease in Tokyo, Japan.

We investigated possible sources of newly infected patients with coronavirus disease (COVID-19) after the fourth wave in order to explore unknown sources. Retrospective chart review on all the confirmed patients with COVID-19 admitted to the National Center for Global Health and Medicine (NCGM) in Tokyo, Japan was conducted from May 22 through June 29, 2021. Among the 22 participants, 14 (64%) had a history of known high-risk infection behaviors. Of those, 12 reported that their activities involved eating and drinking. In addition, there were 24 high-risk situations, of those, 21 (88%) were related to indoor dining, and masks were not worn in 22 situations (92%). New source of infection has not been identified. In situations with a high known risk of infection, many cases were related to eating and drinking, and insufficient use of masks was evident. Raising risk awareness on infection prevention and control of COVID-19 is urgently needed.

The influence of serum uric acid on renal function in patients with calcium or uric acid stone: A population-based analysis.

OBJECTIVES: To determine the influence of serum uric acid (UA) levels on renal impairment in patients with UA stone. MATERIALS AND METHODS: We retrospectively analyzed 463 patients with calcium oxalate and/or calcium phosphate stones (CaOx/CaP), and 139 patients with UA stones. The subjects were divided into the serum UA-high (UA ≥ 7.0 mg/dL) or the UA-low group (UA < 7.0 mg/dL). The control group comprised 3082 community-dwelling individuals that were pair-matched according to age, sex, body mass index, comorbidities, hemoglobin, serum albumin, and serum UA using propensity score matching. We compared renal function between controls and patients with UA stone (analysis 1), and between patients with CaOx/CaP and with UA stone (analysis 2). Logistic regression analysis was used to evaluate the impact of the hyperuricemia on the development of stage 3 and 3B chronic kidney disease (CKD) (analysis 3). RESULTS: The renal function was significantly associated with serum UA levels in the controls and patients with CaOx/CaP and UA stones. In pair-matched subgroups, patients with UA stone had significantly lower renal function than the control subjects (analysis 1) and patients with CaOx/CaP stones (analysis 2) regardless of hyperuricemia. Multivariate logistic regression analysis revealed that patients with UA stone, CaOx/CaP, hyperuricemia, presence of cardiovascular disease, higher body mass index, older age and lower hemoglobin had significantly higher risk of stage 3 and 3B CKD (analysis 3). CONCLUSION: Patients with UA stones had significantly worse renal function than controls and CaOx/CaP patients regardless of hyperuricemia. Urolithiasis (CaOx/CaP and UA stone) and hyperuricemia had an association with impaired renal function. Our findings encourage clinicians to initiate intensive treatment and education approaches in patients with urolithiasis and/or hyperuricemia in order to prevent the progression of renal impairment.

Clinical relevance of aortic calcification in urolithiasis patients.

BACKGROUND: The aim of the present study is to investigate the clinical relevance of aortic calcification in urolithiasis patients. METHODS: Between January 2010 and September 2014, 1221 patients with urolithiasis were treated in Oyokyo Kidney Research Institute and Hirosaki University Hospital. Among these, 287 patients (Stone group) on whom adequate data were available were included in this retrospective study. We also selected 148 subjects with early stage (pT1N0M0) renal cell carcinoma from 607 renal cell carcinoma patients who underwent radical nephrectomy at Hirosaki University Hospital (Non-stone group) as control subjects. Validity of the Non-stone group was evaluated by comparison with pair-matched 296 volunteers from 1166 subjects who participated in the Iwaki Health Promotion Project in 2014. Thereafter, age, body mass index, aortic calcification index (ACI), renal function, serum uric acid concentrations, and comorbidities (diabetes, hypertension, or cardiovascular disease) were compared between the Non-stone and Stone groups. Independent factors for higher ACI and impaired renal function were assessed using multivariate logistic regression analysis. RESULTS: We confirmed relevance of Non-stone group patients as a control subject by comparing the pair-matched community-dwelling volunteers. Backgrounds of patients between the Non-stone and Stone groups were not significantly different except for the presence of hypertension in the Stone group. ACI was not significantly high in the Stone group compared with the Non-stone group. However, age-adjusted ACI was greater in the Stone group than the Non-stone group. Among urolithiasis patients, ACI was significantly higher in uric acid containing stone patients. The number of patients with stage 3B chronic kidney disease (CKD) was significantly higher in the Stone group than in the Non-stone group (12% vs. 4%, P = 0.008). Multivariate logistic regression analysis showed higher aortic calcification index (>13%), and being a stone former were independent factors for stage 3B CKD at the time of diagnosis. CONCLUSION: Aortic calcification and being a stone former had harmful influence on renal function. This study was registered as a clinical trial: UMIN: UMIN000022962.

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

BACKGROUND: Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. METHODS: Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 or <60 mL/min/1.73 m2, respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. RESULTS: The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m2, and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. CONCLUSIONS: Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. TRIAL REGISTRATION: This study was registered as a clinical trial: UMIN000023577.

Hepatoid carcinoma of the skin: spontaneous rat skin hepatoid carcinoma with eosinophilic globules and crystals immunoreactive to alpha-1-antitrypsin.

We present a case of hepatoid carcinoma of the abdominal skin in a male Wistar rat. Histopathologically, this carcinoma resembled human hepatocellular carcinoma with respect to trabecular-sinusoidal structures. Carcinoma tissues contain numerous eosinophilic globules and crystals, and in this case, we found the characteristic eosinophilic globules in the hepatoid carcinoma cells and the crystals in the extracellular portions. Vivid carcinoma cells full of eosinophilic globules were present near the necrotic areas in tumor tissue, wherein quadrate crystals unstained with eosin were observed. PAS staining after diastase digestion revealed that the globules were PAS positive and diastase resistant. In addition, we found that the hepatoid carcinoma cells were immunoreactive for alpha-1-antitrypsin (anti-A1AT) antibody with the globules and crystals staining peripherally, and a central unstained region. Ultrastructural study of intracytoplasmic globules and extracellular crystals revealed that the fringe of each globule and crystal had no limiting membrane and showed the same level of electron density. These findings suggest that the characteristic crystals in this tumor may have originated from the globules that were emitted from the carcinoma cells after their death as a result of saturation with intracytoplasmic globules.

FBP17 Mediates a Common Molecular Step in the Formation of Podosomes and Phagocytic Cups in Macrophages.

Macrophages act to protect the body against inflammation and infection by engaging in chemotaxis and phagocytosis. In chemotaxis, macrophages use an actin-based membrane structure, the podosome, to migrate to inflamed tissues. In phagocytosis, macrophages form another type of actin-based membrane structure, the phagocytic cup, to ingest foreign materials such as bacteria. The formation of these membrane structures is severely affected in macrophages from patients with Wiskott-Aldrich syndrome (WAS), an X chromosome-linked immunodeficiency disorder. WAS patients lack WAS protein (WASP), suggesting that WASP is required for the formation of podosomes and phagocytic cups. Here we have demonstrated that formin-binding protein 17 (FBP17) recruits WASP, WASP-interacting protein (WIP), and dynamin-2 to the plasma membrane and that this recruitment is necessary for the formation of podosomes and phagocytic cups. The N-terminal EFC (extended FER-CIP4 homology)/F-BAR (FER-CIP4 homology and Bin-amphiphysin-Rvs) domain of FBP17 was previously shown to have membrane binding and deformation activities. Our results suggest that FBP17 facilitates membrane deformation and actin polymerization to occur simultaneously at the same membrane sites, which mediates a common molecular step in the formation of podosomes and phagocytic cups. These results provide a potential mechanism underlying the recurrent infections in WAS patients.

Progression of atherosclerosis in hemodialysis patients: effect of adiponectin on carotid intima media thickness.

AIM: We investigated the parameters related to the progression of common carotid artery intima media thickness (IMT) in hemodialysis (HD) patients. METHODS: IMT was examined in 85 patients by ultrasonography at baseline and after 12 months. The difference in IMT between these two time points was calculated (DeltaIMT). We defined DeltaIMT< or =0.00 as 'progression', and DeltaIMT0.00 as 'stable'. Body fat distribution was calculated on computed tomography. Total adiponectin (T-Ad) and high molecular weight adiponectin (H-Ad) were measured by ELISA. RESULTS: There were no significant differences between the two groups in all profiles except for the ratio of H-Ad to T-Ad (HMWR) at baseline. In the 'progression' group, IMT increased from 1.56+/-0.89 to 1.77+/-0.94 mm (p<0.001) and visceral fat area (60.3+/-30.7 to 69.2+/-37.5, cm2; p<0.01) increased. In the 'stable' group, HMWR increased from 31.3+/-5.4 to 37.6+/-7.3% (p<0.001). Multiple logistic regression analysis selected DeltaHMWR (p=0.031, odds ratio=0.928) independently of IMT progression. The correlation coefficient was -0.254 (p=0.019) between DeltaIMT and DeltaHMWR. CONCLUSIONS: We found that an increase in HMWR was related to the stable state of IMT in HD patients.

Carotid intima media thickness and aortic calcification index closely relate to cerebro- and cardiovascular disorders in hemodialysis patients.

AIM: Atherosclerosis can be evaluated by carotid intima media thickness (IMT), the aortic calcification index (ACI), and pulse wave velocity (PWV). We investigated which test was most closely related to cerebro- and cardiovascular disorders (CCVD) in hemodialysis patients. METHODS: Maximum IMT (max-IMT), ACI, and PWV were examined in 110 hemodialysis patients, using carotid ultrasonography, abdominal CT and a blood pressure pulse wave instrument, respectively. Blood hemoglobin A1c (HbA1c), serum total cholesterol, high density lipoprotein cholesterol, triglyceride, total protein, albumin, high sensitivity C reactive protein (hs-CRP), and tumor necrosis factor alpha were measured. The patients were divided into two groups; with and without CCVD and the degree of atherosclerosis was evaluated in each group. RESULTS: Compared to the CCVD (-) group, the CCVD (+) group showed significantly higher percentages of males and diabetic patients, higher levels of HbA1c (5.14 vs 4.83%) and hs-CRP (0.320 vs 0.167 mg/dL), an older age group (64.5 vs 57.5 years), a greater max-IMT (2.05 vs 1.19 mm), and a higher ACI (71.8 vs 41.0%); and significantly lower diastolic blood pressure (82.8 vs 89.2 mmHg). Multiple logistic regression analysis showed that the factors influencing the development of CCVD were age (odds ratio: 1.092), ACI (odds ratio: 1.025), and max-IMT (odds ratio: 2.006). However, PWV did not significantly relate to CCVD. CONCLUSIONS: In hemodialysis patients, the ACI and max-IMT were significantly associated with CCVD, but the association of PWV was weak. A prospective cohort study is warranted to determine the risk factors for CCVD in hemodialysis patients.