Development and external validation of the DOAT and DOATS scores: simple decision support tools to identify disease progression among nonelderly patients with mild/moderate COVID-19.

BACKGROUND: During the fifth wave of the coronavirus disease 2019 (COVID-19) pandemic in Japan, which took place between June and September 2021, a significant number of COVID-19 cases with deterioration occurred in unvaccinated individuals < 65 years old. However, the risk factors for COVID-19 deterioration in this specific population have not yet been determined. This study developed a prediction method to identify COVID-19 patients < 65 years old who are at a high risk of deterioration. METHODS: This retrospective study analyzed data from 1,675 patients < 65 years old who were admitted to acute care institutions in Fukushima with mild-to-moderate-1 COVID-19 based on the Japanese disease severity criteria prior to the fifth wave. For validation, 324 similar patients were enrolled from 3 hospitals in Yamagata. Logistic regression analyses using cluster-robust variance estimation were used to determine predictors of disease deterioration, followed by creation of risk prediction scores. Disease deterioration was defined as the initiation of medication for COVID-19, oxygen inhalation, or mechanical ventilation starting one day or later after admission. RESULTS: The patients whose condition deteriorated (8.6%) tended to be older, male, have histories of smoking, and have high body temperatures, low oxygen saturation values, and comorbidities, such as diabetes/obesity and hypertension. Stepwise variable selection using logistic regression to predict COVID-19 deterioration retained comorbidities of diabetes/obesity (DO), age (A), body temperature (T), and oxygen saturation (S). Two predictive scores were created based on the optimism-corrected regression coefficients: the DOATS score, including all of the above risk factors, and the DOAT score, which was the DOATS score without oxygen saturation. In the original cohort, the areas under the receiver operating characteristic curve (AUROCs) of the DOATS and DOAT scores were 0.81 (95% confidence interval [CI] 0.77-0.85) and 0.80 (95% CI 0.76-0.84), respectively. In the validation cohort, the AUROCs for each score were both 0.76 (95% CI 0.69-0.83), and the calibration slopes were both 0.80. A decision curve analysis confirmed the clinical practicability of both scores in the validation cohort. CONCLUSIONS: We established two prediction scores that can quickly evaluate the risk of COVID-19 deterioration in mild/moderate patients < 65 years old.

Telepathology in intraoperative frozen section consultation of breast cancer sentinel node biopsy in Fukushima, Japan following the 2011 triple disaster: diagnostic accuracy and required time during the early implementation phase.

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic.

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

Long-term Experience on Breast Cancer-related Lymphedema in the Coastal Area of Fukushima, Japan After the 2011 Triple Disaster.

BACKGROUND/AIM: Disasters can jeopardize breast cancer care and Japan's triple disaster in 2011 (earthquake, tsunami, and nuclear accident) is no exception. However, detailed information is lacking regarding the care of breast cancer related lymphedema (BCRL) following the disaster. We aimed to explore the process by which local patients become aware of BCRL, the problems faced, and the support they require. We also aimed to clarify the effects of the 2011 disaster on experiences related to lymphedema in the target population. PATIENTS AND METHODS: Patients who developed BCRL after breast cancer treatment were recruited from Iwaki city, a municipality located in the southern coastal region of Fukushima (N=16). In-depth, semi-structured, face-to-face interviews were conducted, and the obtained data were appraised using thematic analysis. RESULTS: Five themes related to BCRL were identified: 1) the process of becoming aware of BCRL, 2) troubles or worries/concerns due to BCRL, 3) information sources regarding BCRL management, 4) strategies to cope with BCRL, and 5) the adverse impacts of the 2011 disaster on BCRL management. CONCLUSION: Except for the disaster context, the themes are in line with those of previous studies conducted in the non-disaster context. Nonetheless, there were limited but non-negligible adverse effects of the 2011 disaster on long-term local BCRL management. The findings of this study demonstrate the necessity for individualizing coping strategies against BCRL among healthcare professionals in the Fukushima coastal area and beyond.

Duration and Influencing Factors of Postoperative Urinary Incontinence after Robot-Assisted Radical Prostatectomy in a Japanese Community Hospital: A Single-Center Retrospective Cohort Study.

OBJECTIVES: Post-operative urinary incontinence (PUI) after robotic-assisted radical prostatectomy (RARP) is an important complication; PUI occurs immediately after postoperative urethral catheter removal, and, although approximately 90% of patients improve within one year after surgery, it can significantly worsen their quality of life. However, information is lacking on its nature in community hospital settings, particularly in Asian countries. The purposes of this study were to investigate the time required to recover from PUI after RARP and to identify its associated factors in a Japanese community hospital. METHODS: Data were extracted from the medical records of 214 men with prostate cancer who underwent RARP from 2019 to 2021. We then calculated the number of days elapsed from the surgery to the initial outpatient visit confirming PUI recovery among the patients. We estimated the PUI recovery rate using the Kaplan-Meier product limit method and evaluated associated factors using the multivariable Cox proportional hazards model. RESULTS: The PUI recovery rates were 5.7%, 23.4%, 64.6%, and 93.3% at 30, 90, 180, and 365 days following RARP, respectively. After an adjustment, those with preoperative urinary incontinence experienced significantly slower PUI recovery than their counterparts, while those with bilateral nerve sparing experienced recovery significantly sooner than those with no nerve sparing. CONCLUSION: Most PUI improved within one year, but a proportion of those experiencing recovery before 90 days was smaller than previously reported.

The necessity of proactive measures from healthcare providers highlighted by delayed breast cancer diagnosis due to COVID-19: A case report.

Key Clinical Message: During disasters, multiple factors can cause significant delays in medical visits. Regular patient monitoring, high-risk individual alerts, and telemedicine enhancements can potentially alleviate these issues and ensure timely interventions. Abstract: During the COVID-19 pandemic, a Japanese woman in her 70s delayed her regular breast cancer checkup for over 2 years. During disasters, health priorities tend to decline, necessitating proactive measures from healthcare providers, such as augmenting collaboration among healthcare professionals and identifying high-risk individuals.

Real-world clinical outcomes of treatment with molnupiravir for patients with mild-to-moderate coronavirus disease 2019 during the Omicron variant pandemic.

It is unclear whether molnupiravir has a beneficial effect on vaccinated patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here evaluated the efficacy of molnupiravir in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron variant surge in Fukushima Prefecture, Japan. We enrolled patients with mild-to-moderate COVID-19 who were admitted to hospitals between January and April, 2022. Clinical deterioration after admission was compared between molnupiravir users (n = 230) and non-users (n = 690) after 1:3 propensity score matching. Additionally, we performed forward stepwise multivariate logistic regression analysis to evaluate the association between clinical deterioration after admission and molnupiravir treatment in the 1:3 propensity score-matched subjects. The characteristics of participants in both groups were balanced as indicated by covariates with a standardized mean difference of < 0.1. Regarding comorbidities, there was no imbalance between the two groups, except for the presence of hypertension, dyslipidemia, diabetes mellitus, and cardiac disease. The clinical deterioration rate was significantly lower in the molnupiravir users compared to the non-users (3.90% vs 8.40%; P = 0.034). Multivariate logistic regression analysis demonstrated that receiving molnupiravir was a factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.206-0.973; P = 0.042), independent of other covariates. This real-world study demonstrates that molnupiravir contributes to the prevention of deterioration in COVID-19 patients after hospitalization during the Omicron variant phase.

Possible association of Typhoon Hagibis and the COVID-19 pandemic on patient delay in breast cancer patients: A case report.

Little is known on how different types of disasters interact in their impacts on patient care. We experienced a breast cancer patient whose initial presentation was delayed for 2 years due to the COVID-19 pandemic and Typhoon Hagibis. Increasing awareness is needed on the combined impacts of disasters on breast cancer management.

Strangulated transomental hernia in virgin abdomen: laparoscopic surgery with a small laparotomy may be useful to assess the indeterminate viability of the bowel.

A 66-year-old female without prior history of abdominal surgery visited the emergency department with a complain of sudden intensive lower abdominal pain. Closed loop bowel obstruction was discovered on contrast-enhanced computed tomography, leading to a laparoscopic examination of 5 h after the onset. During laparoscopy, 100 cm of distal jejunum with borderline viability was found incarcerated in a gap of the greater omentum. A 3-cm small incision was made at the umbilical trocar site to observe the bowel after it was released laparoscopically. When viewed under the shadowless lamp, the affected bowel appeared reddish, with peristalsis and a palpated mesentery artery. The surgical team determined no need for resection. The postoperative recovery went smoothly without any complications. Laparoscopic surgery for transomental hernias can be performed safely even in patients with borderline bowel viability, and observing bowel extra-peritoneally with a small incision could be helpful for laparoscopic surgery for internal hernias with borderline viability.

Why only me? A case report of a breast cancer patient with unresolved trauma from a past disaster experience developing a mental disorder.

Little is known about how the psychological stress of having experienced a natural disaster affects cancer patients. We experienced a patient who was treated with breast cancer after having been stricken by a typhoon, which resulted in significant psychological damage. Treatment strategies should incorporate patients' mental health appropriately after disasters.

Association between COVID-19 incidence and postponement or cancellation of elective surgeries in Japan until September 2020: a cross-sectional, web-based survey.

OBJECTIVES: This study aimed to examine whether and how the COVID-19 pandemic has affected the postponement or cancellation of elective surgeries in Japan. DESIGN AND SETTING: A cross-sectional, web-based, self-administered survey was conducted nationwide from August 25 to September 30 2020. We used data from the Japan 'COVID-19 and Society' Internet Survey collected by a large internet research agency, Rakuten Insight, which had approximately 2.2 million qualified panellists in 2019. PARTICIPANTS: From a volunteer sample of 28 000 participants, we extracted data from 3678 participants with planned elective surgeries on any postponement or cancellation of elective surgeries. OUTCOME MEASURES: The main outcome measure was any postponement or cancelltion of elective surgeries. In addition, for all respondents, we extracted data on sociodemographic, health-related characteristics, psychological characteristics and prefectural-level residential areas. We used weighted logistic regression approaches to fulfil the study objectives, minimising potential bias relating to web-based surveys. RESULTS: Of the 3678 participants, 431 (11.72%) reported experiencing postponement or cancellation of their elective surgeries. Notably, the participants living in prefectures where the declaration of the state of emergency was made on 7 April 2020 were significantly more likely to experience postponement or cancellation of elective surgeries than those residing in prefectures with the state of emergency beginning on 16 April 2020 (174 (26.02%) vs 153 (12.15%)). CONCLUSIONS: The proportion of patients whose elective surgery had been postponed was limited during Japan's first wave of the COVID-19 pandemic, although the declaration of a state of emergency increased the likelihood of postponement. It is imperative to increase awareness of the secondary health effects related to policy intervention in pandemics and other health crises and to use appropriate countermeasures such as standard infectious control measures and triage of surgical patients.

Interruption of breast cancer care and importance of inter-hospital cooperation during the COVID-19 pandemic: A case report of advanced breast cancer in Fukushima, Japan.

We experienced the case of a patient with advanced breast cancer who failed to receive comprehensive care despite regular video conferencing with her physician during the COVID-19 pandemic, resulting in delayed detection of liver metastasis. Inter-hospital collaboration is required to provide uninterrupted cancer care to those disproportionately affected by crises.

A call for individualized evacuation strategies for floods: A case report of secondary surgical site infection in a postsurgery breast cancer patient in Fukushima, Japan, following Typhoon Hagibis in 2019.

Recognition of Individual and environmental risks is crucial to alleviate damage inflicted by disasters. In particular, an awareness of floods and their health risks in patients' residences is important for patients and their healthcare professionals.

Understanding the response of dendritic cells to activation by streptococcal preparation OK-432.

BACKGROUND: The streptococcal preparation OK-432 induces maturation of T cells and dendritic cells (DCs). However, the mechanisms by which OK-432 induces DC maturation are not well understood. MATERIALS AND METHODS: The effects of OK-432 and TNF-alpha on peripheral blood mononuclear cells (PBMCs) were compared. Antibody-based approaches were used to detect proteins characteristic of antigen-presenting cells and cytokines. Cytotoxicity was evaluated by measuring the release of LDH after incubation of effector and target cells. The TLR-4 levels were measured by real-time quantitative PCR. RESULTS: Changes in cell surface marker levels were detected in both treatment groups but OK-432 had a greater effect on induction of Th-1-type cytokines. Furthermore, TLR-4 mRNA was up-regulated in cells from two out of five patients in response to OK-432, but not in response to TNF-alpha. CONCLUSION: OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.

[Experimental study for a combination chemo-immunotherapy using dendritic cells].

This study was designed to seek for the optimal anticancer agents for a combination of chemotherapy and specific immunotherapy using dendritic cells (DC) in gastric cancer. We investigated the immuno-suppressive activity of anticancer agents on human peripheral blood mononuclear cells (PBMC), apoptosis inducing activity on gastric cancer cells and expression of Toll-like receptor (TLR)-4 mRNA on immatureDCs (iDCs) by paclitaxel (TXL) and docetaxel (TXT). We further compared the cytotoxicity of cytotixic T lymphocytes (CTLs) induced by DCs pulsed with tumor cell lysate and apoptotic cells induced by TXT. Although most of the anticancer agents demonstrated the suppression activity on proliferation of PBMC in a dose dependent manner, TXT, doxifluridine and irinotecan did not show the suppressive activity on PBMC even in the highest drug concentration. About 60% of gastric cancer cells demonstrated apoptosis after a 24-48 hour treatment with both TXL and TXT. Expression of TLR-4 mRNA in iDCs was up-regulated by TXT, not by TXL, and peaked at 2 hours after the treatment. CTLs induced by DCs pulsed with tumor cell lysate and apoptotic cells showed a similar killing activity to target cells. These results suggest that TXT appears to be an optimal anticancer agent for a combination therapy with chemotherapy and tumor specific immunotherapy using dendritic cells in gastric cancer.

Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK19, and CK20 mRNA in patients with gastric cancer.

BACKGROUND: To determine the significance of bone marrow disseminated tumor cells in gastric cancer, we investigated the mRNA expression levels of carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and cytokeratin 20 (CK20) using the real-time quantitative reverse-transcription polymerase chain reaction (RQ-PCR). METHODS: Bone marrow samples were aspirated from the sternum at the time of surgery in 65 patients with resectable gastric cancer. Total RNA was extracted from bone marrow; and the expression levels of CEA, CK19, and CK20 mRNA were determined by RQ-PCR using an ABI PRISM 7000 and quantified against the GAPDH mRNA level. RESULTS: The detection limits of these genes were determined in the gastric cancer cell line MKN-45 and the colon cancer cell line C-1, which had been serially diluted in peripheral blood mononuclear cells (PBMCs). A rate of 1 cancer cell/million PBMCs was obtained by detecting CEA and CK19 mRNA in MKN-45 and by detecting CK20 mRNA in C-1. In the clinical samples, only 1 of the 65 gastric cancer patients (1.5%) who had stage IV disease was positive for CEA, CK19, and CK20 mRNA; none of CEA, CK19, or CK20 mRNA was positive in the remaining 64 patients. No significant correlation was observed between disseminated cancer cells in bone marrow and clinicopathological features, including simultaneous or metachronous hepatic metastasis and patient survival. CONCLUSION: The incidence of disseminated cancer cells in bone marrow in our study appears low, unlike that in previous reports. The significance of disseminated cancer cells in bone marrow may also be quite low in gastric cancer.