Living with COVID-19: mass gatherings and minimizing risk.

During the COVID-19 pandemic, it has been important to both minimize the risk of infection and restore daily life. As a typical example, mass gathering events, such as sporting events, are gradually becoming more common, thanks to the measures taken to contain COVID-19. Some pilot studies have been launched at governments' initiative to investigate the risk of infection without measures such as face masks and physical distancing at mass gathering events, but the ethics of these studies should be carefully considered. On the other hand, it is still beneficial to implement infection control measures at mass gathering events and, in parallel, to estimate the risk of infection with measures in place, especially under a lack of vaccination progress or the spread of mutant strains possibly resistant to vaccines. To help improve compliance with measures taken by spectators and organizers and to ensure their effectiveness, we have conducted quantitative evaluations of the implementation of such measures by monitoring CO2 concentrations, assessing the proportion of people wearing face masks and analysing human flow at the event. This approach allows us to share our observations with stakeholders and participants, enabling us to protect the culture of mass gathering events, minimize the risk of infection and restore a sense of well-being in daily life.

Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma.

OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

Percentage of CD19+ Cells in Peripheral Blood Lymphocytes After Rituximab-Based Desensitization as a Predictor of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

BACKGROUND: Rituximab (RIT) is effective as a part of the desensitization therapy before ABO-incompatible kidney transplantation (ABOi-KTx), and a single dose of RIT at 375 mg/m2 or less is recommended. However, adequate RIT dose recommendations have not yet been established for individual recipients. Therefore, we evaluated the relationship between the proportion of B cells in peripheral blood and acute antibody-mediated rejection (AAMR). METHODS: Forty-four consecutive ABOi-KTx recipients were enrolled in this retrospective study. Before transplantation, subjects were treated with RIT at various doses, ranging from 65 to 400 mg/body (46-263 mg/m2), followed by plasmapheresis and intravenous immunoglobulin as a desensitization therapy. The percentage of CD19+ cells in the total peripheral blood lymphocytes population (%CD19) was determined the day before transplantation. Transplant recipients were divided into 2 groups according to pretransplant %CD19, as follows: low %CD19 group, ≤ 1.2% (n = 35) and high %CD19 group, > 1.2% (n = 9). The relationship between %CD19 and incidence of AAMR was evaluated, and the predicting factors for AAMR incidence were determined by univariate and multivariate analyses. RESULTS: The incidence of AAMR was significantly higher in the high %CD19 group than in the low %CD19 group (44.4% vs 5.7%, P = .006). Furthermore, multivariate analysis showed that %CD19 > 1.2% was the only independent factor to predict AAMR, with an odds ratio of 14.31 (P = .038). CONCLUSION: High %CD19 values after rituximab administration in ABOi-KTx recipients implies insufficient depletion of B cells, which can lead to AAMR.

Optimal Settings for Double Filtration Plasmapheresis With Targeted Removal Rate of Preexisting Antibody in Antibody-Incompatible Kidney Transplant.

BACKGROUND: Elimination of preexisting donor-reactive antibodies is essential for antibody-incompatible kidney transplantation. Double filtration plasmapheresis (DFPP) using albumin (Alb) replacement fluid (Rf) removes immunoglobulin more selectively than plasma exchange; however, fixed-dose treatment can result in insufficient removal of antibody or excess loss of osmotic pressure and subsequent hypotension. The aim of this study was to determine the optimal setting (volume and concentration of Rf) of DFPP to remove donor-reactive antibodies. MATERIALS AND METHODS: One hundred seventeen DFPPs were performed in 41 patients for kidney transplant in an ABO-incompatible or crossmatch-positive setting. A formula for Rf volume was determined based on volume-removal rate (RR) curve of IgG. Another formula for Alb concentration of Rf was also established to keep plasma volume within pre-DFPP plasma volume ± 10% calculated by post- to pre-DFPP hematocrit ratio to avoid hypotensive events. RESULTS: RR-IgG was obtained based on patient data: Rf (mL) = BW (kg) × eX, [X = (RR-IgG + 10.757)/25.603] (R2 = 0.401, P < .001). Rf Alb concentration was determined by AlbRf ≥ (2.982 - 2.36 × RR-IgG) × Albpre + (2.36 × RR-IgG - 0.236) × pre-DFPP total protein. CONCLUSIONS: Optimal volume and concentration of Alb Rf can be calculated using our formulae with targeted RR-IgG.

Investigation of antibody to severe fever with thrombocytopenia syndrome virus (SFTSV) in blood samples donated in a SFTS-endemic area in Japan.

The risk of transfusion-transmitted infection (TTI) for severe fever with thrombocytopenia syndrome virus (SFTSV) is a concern because person-to-person transmission resulting from contact with SFTSV-contaminated blood has been reported. To obtain information regarding the risk of TTI-SFTSV, antibody testing was performed for blood samples donated in an severe fever with thrombocytopenia syndrome-endemic area in Japan. No antibody-positive samples were detected among 3990 samples. This finding suggested that there were few cases of SFTSV infection among donors and that the risk of TTI-SFTSV was also estimated low in Japan.

Highly Immunogenic DQB1 Mismatch Eplets Are Associated With Development of Chronic Active Antibody-Mediated Rejection: A First Report From Japan.

BACKGROUND: De novo donor-specific antibody (dnDSA), especially against class II HLA, correlates with chronic active antibody-mediated rejection (CAAMR), which eventually leads to graft loss. It would be helpful if we could identify the patients at high risk of dnDSA development in terms of histocompatibility. Structure-based matching strategy assessing mismatched epitopes/eplets by comparing polymorphic amino acid sequences can predict the risk of development of dnDSA and CAAMR. However, it has not been evaluated in Japanese patients whose diversity in HLA is limited. PATIENTS AND METHODS: We retrospectively studied 55 living related kidney transplant patients and ascertained donor and recipient HLA-A, -B, -DRB1, and -DQB1. The number of mismatched eplets was determined using an algorithm, HLAMatchmaker version 3. The relationship between characteristics of mismatched eplets and development of CAAMR was evaluated. RESULTS: There were 8 patients in the CAAMR group and 47 in the control group. The numbers of mismatched HLAs (3.6 ± 1.2 in CAAMR and 3.7 ± 2.0 in control groups), mismatched eplets (32.2 ± 10.4 in CAAMR and 34.4 ± 19.8 in control groups), mismatched DRB1 eplets (11.2 ± 4.3 in CAAMR and 11.5 ± 7.9 in control groups), and mismatched DQB1 eplets (9.2 ± 4.3 in CAAMR and 10.5 ± 7.3 in control groups) were not significantly different. Significantly more patients had at least one highly immunogenic mismatched eplet (62.5% in CAAMR and 25.5% in control groups; P = .024 by χ2 test). CONCLUSIONS: The presence of highly immunogenic mismatched eplets is associated with development of CAAMR.

Does the Age of Donor Kidneys Affect Nocturnal Polyuria in Patients With Successful Real Transplantation?

BACKGROUND: We investigated whether the age of donor kidneys influences the incidence of nocturnal polyuria in patients with successful renal transplantation (RTX). METHODS: Eighty-five patients (45 men and 40 women) undergoing RTX (median age, 47 years) were included in this study. Twenty-four-hour bladder diaries were kept for 3 days, and nocturnal polyuria was defined as a nocturnal polyuria index (nocturnal urine volume/24-hour urine volume) of >0.33. Risk factors for nocturnal polyuria were analyzed in patients with RTX by means of the Mann-Whitney U test, χ2 test, and a logistic regression analysis. RESULTS: End-stage renal disease (ESRD) developed from diabetes mellitus in 16 patients (19%). Sixty-five patients (76%) received pre-transplant dialysis, with a median duration of 5 years. The median serum creatinine level and body mass index at the most recent visit were 1.2 mg/dL and 21.2 kg/m2, respectively. On the basis of the 24-hour bladder diaries, nocturnal polyuria was identified in 48 patients (56%). A logistic regression analysis revealed that diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria (odds ratio, 8.95; 95% confidence interval, 2.01-65.3; P = .0028). The age of donor kidneys at examination did not affect the incidence of nocturnal polyuria (P = .9402). CONCLUSIONS: Nocturnal polyuria was not uncommon in patients with successful RTX. Diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria, whereas the age of donor kidneys at examination did not affect the incidence of nocturnal polyuria. Thus, nocturnal polyuria is caused by recipient factors but not donor factors.

Impact of renal transplantation on glucose tolerance in Japanese recipients with impaired glucose tolerance.

AIMS: To investigate changes in glucose tolerance, insulin secretion and insulin sensitivity in Japanese recipients before and 1 year after renal transplantation. METHODS: We conducted a study of Japanese recipients without diabetes who underwent renal transplantation at Hokkaido University Hospital. A 75-g oral glucose tolerance test was performed before and 1 year after renal transplantation in these recipients. Insulin sensitivity was estimated using the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Insulin secretion was evaluated based on the insulin secretion sensitivity index-2 (ISSI-2). RESULTS: Of the 62 renal transplant recipients, 31 were diagnosed as having impaired glucose tolerance before transplantation. Among these 31 recipients, after 1 year, four had developed new-onset diabetes after transplantation, and nine had impaired glucose tolerance. Unexpectedly, 18 changed from impaired to normal glucose tolerance. When these recipients with impaired glucose tolerance were classified into a non-amelioration group and an amelioration group, the ISSI-2 was significantly reduced, with no significant changes in the Matsuda index or HOMA-IR, in the non-amelioration group 1 year after renal transplantation. By contrast, ISSI-2 and Matsuda index values were significantly increased, with no significant changes in HOMA-IR values in the amelioration group. CONCLUSIONS: More than half of Japanese renal transplant recipients with impaired glucose tolerance had normal glucose tolerance 1 year after renal transplantation. These results suggest that an increase in insulin secretion and whole insulin sensitivity was associated with improvement in glucose tolerance in these recipients.

Diagnosis and treatment of bone metastasis: comprehensive guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients' outcomes.

Phase I/II study of S-1 in combination with sorafenib for metastatic renal cell carcinoma.

BACKGROUND: The potential of S-1 for the treatment of metastatic renal cell carcinoma (mRCC) has been shown in two phase II studies. We aimed to assess the safety, tolerance, pharmacokinetics and clinical activity of S-1 combined with sorafenib in patients with mRCC. PATIENTS AND METHODS: In this multicenter, single-arm, open-label, phase I/II study of S-1 plus sorafenib, we recruited patients with clear-cell or papillary renal cell carcinoma who had received a maximum of one prior cytokine-based regimen. The phase I primary end points were the maximum tolerated dose (MTD) and recommended dose (RD). S-1 was administered orally at 60, 80, 100 or 120 mg/day on days 1-28 of a 42-day cycle in combination with sorafenib (400 or 800 mg/day), given daily with dose adjustment. In phase II, the primary end point was to assess the overall response rate (ORR) at the RD. RESULTS: Nine patients were enrolled into phase I and 21 (including 6 patients who received the RD in the phase I portion) were enrolled into phase II. In the phase I portion, the MTD could not be determined, and the RD was defined as S-1 80 mg/m(2)/day on days 1-28 + sorafenib 800 mg/day on days 1-42. In the phase II portion, 21 patients were fully assessable for efficacy and safety. The confirmed ORR was 52% [95% confidence interval (CI) 29.8-74.3], including one complete response (5%) and 10 partial responses (48%). The median progression-free survival was 9.9 (95% CI 6.5-17.1) months. The most frequently reported treatment-related adverse event for all grades was hand-foot skin reaction (100%). The major reasons for dose reduction were hand-foot skin reaction (38%) and rash (14%). CONCLUSION: Combination therapy with S-1 plus sorafenib is effective and tolerable for patients with mRCC. However, skin events management is important in S-1 plus sorafenib combination therapy.

Efficacy of the Mirasol pathogen reduction technology system against severe fever with thrombocytopenia syndrome virus (SFTSV).

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne virus in the Bunyaviridae family. This virus has recently been found in China, Japan and Korea. The risk of transfusion-transmitted SFTSV infection (TTI-SFTSV) is a concern because person-to-person transmission resulting from contact with SFTSV-contaminated blood has been reported. Therefore, we investigated the efficacy of the Mirasol pathogen reduction technology (PRT) system for inactivating SFTSV in vitro. The Mirasol PRT system achieved a > 4.11 log10 reduction value (LRV) for SFTSV. In conclusion, we showed that the Mirasol PRT system could potentially be used to reduce the risk of TTI-SFTSV.

Traumatic pediatric spinal cord injury: long-term outcomes of lower urinary tract function.

Long-term urodynamic and urological outcomes were evaluated in pediatric patients following traumatic spinal cord injury (SCI). The medical charts of three pediatric patients following traumatic SCI were retrospectively reviewed. The level of the injury was cervical in two patients and thoracic in one. Two patients, whose initial urodynamics demonstrated voluntary or reflex detrusor contraction with synergic sphincter relaxation, managed to void; however, urinary management was switched in one of these patients from voiding to clean intermittent catheterization (CIC) with anti-cholinergic agents because of a treatment for urinary incontinence. There were also no episodes of hydronephrosis, vesicoureteral reflux (VUR) or renal dysfunction in these two patients. Although one patient with hyperreflexic bladder was initially managed with CIC and anti-cholinergic agents, detrusor myectomy was ultimately performed because of severe VUR associated with the progressive worsening of lower urinary tract (LUT) function. Careful follow-ups including urodynamics are mandatory for children with progressively deteriorated LUT function or problematic urinary incontinence.

Detoxification mechanism of asbestos materials by microwave treatment.

The detoxification mechanism of asbestos materials was investigated through simulations and experiments. The permittivities of pure CaO and Mg3Si4O12, as quasi-asbestos materials, were measured using the cavity perturbation method. The real and imaginary parts of the relative permittivity (ɛr' and ɛr″) of CaO are functions of temperature, and numerical simulations revealed the thermal distributions in an electromagnetic field with respect to both asbestos shape and material configuration based on permittivity. Optical microscopic observation revealed that the thickness of chrysotile fibers decreased as a result of CaO heating. The heating mechanism of asbestos materials has been determined using CaO phase, and the detoxification mechanism of asbestos materials was discussed based on the heating mechanism.

Indoor air quality and thermal comfort in temporary houses occupied after the Great East Japan Earthquake.

UNLABELLED: Thermal conditions and indoor concentrations of aldehydes, volatile organic compounds (VOCs), and NO2 were investigated in 19 occupied temporary houses in 15 temporary housing estates constructed in Minamisoma City, Fukushima, Japan. The data were collected in winter, spring, and summer in January to July 2012. Thermal conditions in temporary log houses in the summer were more comfortable than those in pre-fabricated houses. In the winter, the indoor temperature was uncomfortably low in all of the houses, particularly the temporary log houses. Indoor air concentrations for most aldehydes and VOCs were much lower than the indoor guidelines, except for those of p-dichlorobenzene, acetaldehyde, and total VOCs. The indoor p-dichlorobenzene concentrations exceeded the guideline (240 µg/m(3)) in 18% of the temporary houses, and the 10(-3) cancer risk level (91 µg/m(3)) was exceeded in winter in 21% due to use of moth repellents by the occupants. Indoor acetaldehyde concentrations exceeded the guideline (48 µg/m(3) ) in about half of the temporary houses, likely originating from the wooden building materials. Indoor NO2 concentrations in the temporary houses were significantly higher in houses where combustion heating appliances were used (0.17 ± 0.11 ppm) than in those where they were not used (0.0094 ± 0.0065 ppm). PRACTICAL IMPLICATIONS: In the winter, log-house-type temporary houses are comfortable in terms of humidity, dew condensation, and fungi based on the results of questionnaires and measurements, whereas pre-fabricated temporary houses are more comfortable in terms of temperature. In the summer, log-house-type temporary houses are comfortable in terms of temperature and humidity. More comfortable temporary housing in terms of temperature and humidity year-round is needed. Indoor air concentrations of p-dichlorobenzene and NO2 were quite high in some temporary houses due to occupants' activities, such as use of moth repellents and combustion heating appliances. The government should provide recommendations for safe use of temporary houses by occupants.

A randomized multicenter phase II trial on the efficacy of a hydrocolloid dressing containing ceramide with a low-friction external surface for hand-foot skin reaction caused by sorafenib in patients with renal cell carcinoma.

BACKGROUND: The purpose of this study was to investigate the usefulness of a hydrocolloid dressing containing ceramide for hand-foot skin reaction (HFSR) on the soles of the feet in metastatic renal cell carcinoma (RCC) patients treated with sorafenib. PATIENTS AND METHODS: Patients with grade 1 HFSR on the soles of the feet were randomly assigned in to two groups. One group received a hydrocolloid dressing containing ceramide (arm A) and the other received 10% urea cream (arm B). Patients in both groups applied treatment to the affected sites on the soles of the feet, but not to the hands. The primary end point was the incidence of grade 2 or 3 HFSR on the soles of the feet in the first 4 weeks. RESULTS: Thirty-three patients were assessed (17 in arm A and 16 in arm B), and there were no significant differences in baseline characteristics between the two groups. During the observation period of this study, grade 2 or 3 HFSR on the soles of the feet was found in 29% of patients in arm A and was significantly less than the 69% in arm B (P=0.03). The incidence of HFSR on the hands, however, was similar in both arms. The median time to grade 2 or 3 HFSR on the soles of the feet was also significantly longer in arm A than in arm B (P=0.03). CONCLUSIONS: These results indicate that a hydrocolloid dressing containing ceramide prevented the worsening of HFSR caused by sorafenib in metastatic RCC patients. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000002016.

Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis.

BACKGROUND: Molecules that are highly expressed in tumour endothelial cells (TECs) may be candidates for specifically targeting TECs. Using DNA microarray analysis, we found that the lysyl oxidase (LOX) gene was upregulated in TECs compared with its expression in normal endothelial cells (NECs). LOX is an enzyme that enhances invasion and metastasis of tumour cells. However, there are no reports on the function of LOX in isolated TECs. METHODS: TECs and NECs were isolated to investigate LOX function in TECs. LOX inhibition of in vivo tumour growth was also assessed using ß-aminopropionitrile (BAPN). RESULTS: LOX expression was higher in TECs than in NECs. LOX knockdown inhibited cell migration and tube formation by TECs, which was associated with decreased phosphorylation of focal adhesion kinase (Tyr 397). Immunostaining showed high LOX expression in human tumour vessels in vivo. Tumour angiogenesis and micrometastasis were inhibited by BAPN in an in vivo tumour model. CONCLUSION: LOX may be a TEC marker and a possible therapeutic target for novel antiangiogenic therapy.

Indoor air quality, air exchange rates, and radioactivity in new built temporary houses following the Great East Japan Earthquake in Minamisoma, Fukushima.

This study measured air exchange rates, indoor concentrations of aldehydes and volatile organic compounds (VOCs), and radioactivity levels at 19 temporary houses in different temporary housing estate constructed in Minamisoma City following the Great East Japan Earthquake. The 19 surveyed houses represented all of the companies assigned to construct temporary houses in that Minamisoma City. Data were collected shortly after construction and before occupation, from August 2011 to January 2012. Mean air exchange rates in the temporary houses were 0.28/h, with no variation according to housing types and construction date. Mean indoor concentrations of formaldehyde, acetaldehyde, toluene, ethylbenzene, m/p-xylene, o-xylene, styrene, p-dichlorobenzene, tetradecane, and total VOCs (TVOCs) were 29.2, 72.7, 14.6, 6.35, 3.05, 1.81, 7.29, 14.3, 8.32, and 901 µg/m(3), respectively. The levels of acetaldehyde and TVOCs exceeded the indoor guideline (48 µg/m(3)) and interim target (400 µg/m(3)) in more than half of the 31 rooms tested. In addition to guideline chemicals, terpenes (α-pinene and d-limonene) and acetic esters (butyl acetate and ethyl acetate) were often detected in these houses. The indoor radiation levels measured by a Geiger-Müller tube (Mean: 0.22 µSv/h) were lower than those recorded outdoors (Mean: 0.42 µSv/h), although the shielding effect of the houses was less than for other types of buildings.