Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Mpox Neutralizing Antibody Response to LC16m8 Vaccine in Healthy Adults.

Mpox Neutralizing Antibody Response to LC16m8 VaccineIn this study of 50 healthy volunteers in Japan, a smallpox vaccine (LC16m8) exhibited a robust neutralizing antibody response against two strains of the mpox virus. With a 94% "take" rate by day 14, seroconversion rates on day 28 were 72 and 70% against the Zr599 and Liberia strains, respectively, decreasing to 30% for both on day 168; no serious adverse events occurred.

Weekday Surgery Associated With Short-Term Outcomes in Patients With Colorectal Cancers.

INTRODUCTION: The "weekday effect" on elective surgery remains controversial. We aimed to examine the association between the day of surgery and short-term outcomes after elective surgery for stage I-III colorectal cancer (CRC). METHODS: We performed a multicenter retrospective analysis of 2574 patients who underwent primary colorectal resection for CRC between January 2017 and December 2019 at 15 institutions belonging to the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into two groups according to the day of surgery: Friday and non-Friday (Monday to Thursday). After propensity score matching (PSM), we compared 30-day mortality and postoperative outcomes. RESULTS: Out of the total, 368 patients underwent surgery on Fridays, and the remaining 2206 underwent surgery on non-Fridays. The overall mortality rate was 0.04% (n = 1). In 1685 patients with colon cancer, the proportion of American Society of Anesthesiologists scores was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM of patient, tumor, and operative characteristics, operative time was slightly more prolonged and blood loss was slightly greater in the Friday group; however, these differences were not clinically meaningful. In the 889 patients with rectal cancer, the proportion of patients with abnormal respiratory patterns was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM, the Friday group had a higher incidence of morbidity (≥ Clavien-Dindo 3a), higher incidence of digestive complications, and prolonged postoperative hospital stay. CONCLUSIONS: The results may be useful in determining the day of the week for CRC surgery, which requires more advanced techniques and higher skills.

Effect of body fat mass loss on prognosis of radical resection for pancreatic ductal adenocarcinoma based on bioelectrical impedance analysis.

BACKGROUND: Few reports have performed a prognostic analysis based on bioelectrical impedance analysis in patients with radical resection of pancreatic ductal adenocarcinoma (PDAC), and its usefulness in prognostic analysis remains unclear. This study aimed to evaluate body composition changes in patients undergoing radical resection for PDAC and analyze its impact on prognosis. METHODS: The medical records of radical resection for patients with PDAC were retrospectively reviewed, and the parameters of body composition, including body weight, skeletal muscle mass, body fat mass (BFM), and extracellular water-total body water ratio, from preoperatively to 12 months postoperatively, for each surgical procedure were measured based on direct segmental multifrequency bioelectrical impedance analysis with an InBody 770 (InBody Inc., Tokyo, Japan) device. The clinicopathological and prognostic factors were analyzed. RESULTS: Among 79 patients who underwent radical resection for PDAC, 36 (46%), 7 (8%), and 36 (46%) underwent pancreatoduodenectomy, total pancreatectomy, and distal pancreatectomy, respectively. The multivariate overall survival analysis demonstrated that BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021), lymph node metastasis (p = 0.014), and non-adjuvant chemotherapy (p <  0.001) were independent poor prognostic factors. Multivariate analysis revealed that preoperative BFM < 12 kg and preoperative albumin < 3.5 g/dL were independently associated with BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021 and p = 0.047, respectively). CONCLUSIONS: Loss of BFM in the early postoperative period may have a poor prognosis in radical resection of PDAC.

Clinical Effectiveness of Preoperative 18F-FDG PET/CT in Predicting Pathological Tumor Grade in Patients with Pseudomyxoma Peritonei Originating from Appendix: A Retrospective Cohort Study.

BACKGROUND: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard treatment for patients with pseudomyxoma peritonei (PMP). In some malignancies, the standard uptake value of positron emission tomography with 2-deoxy-2-18F-fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) is now accepted as a reliable indicator of neoplastic behavior. This study aimed to evaluate the association between the maximum standardized uptake value (SUVmax) and pathological grade in patients with PMP and to investigate the significance of SUVmax in the preoperative assessment of these patients. PATIENTS AND METHODS: In this retrospective single-center study, consecutively enrolled patients diagnosed with PMP of appendiceal origin underwent preoperative 18F-FDG PET/CT. SUVmax was calculated as the highest SUVmax value in the abdomen excluding the primary site. SUVmax was compared with the pathological grade (low or high grade) of PMP tumors according to the World Health Organization classification and further analyzed with respect to the estimated cutoff point, sensitivity, specificity, and receiver operating characteristic. RESULTS: In total, 160 patients were included. CRS was successfully performed in 93 patients and palliative debulking surgery in 67 patients. The pathological grade was high in 45 patients and low in 115. High-grade patients had a higher median SUVmax on 18F-FDG PET/CT than did low-grade patients (3.83 versus 2.34, p < 0.001). The highest area under the curve was 0.81, with a sensitivity of 77.8%, specificity of 72.3%, and cutoff point of 2.63. CONCLUSION: This study suggests that the SUVmax of preoperative 18F-FDG PET/CT is associated with the pathological grade in patients with PMP.

Prognostic factors of virus-associated pneumonia other than COVID-19 in adults.

OBJECTIVE: To determine prognostic factors of virus-associated pneumonia other than coronavirus disease 2019. METHODS: We retrospectively studied patients suffering from virus-associated community-acquired pneumonia, and who were admitted to Saitama Cardiovascular and Respiratory Center from 2002 to 2020. Prognostic factors were analyzed by univariable and multivariable regression analysis of patient demographics, laboratory data, chest imaging, severity on admission, and initial treatment. PATIENTS: HIV-positive patients, those with non-resected lung cancer or receiving chemotherapy, and those with COVID-19 were excluded. Included were 363 patients diagnosed by nucleic acid amplification method, paired sera, and rapid diagnostic tests. RESULTS: A CURB-65 score of ≥3 was significant by univariable analysis for 60-day mortality but was nonsignificant by multivariable analysis. The poor prognostic factors that were significant by multivariable analysis (p < 0.05) included immunosuppressive state due to systemic corticosteroid or immunosuppressant administration, acute kidney injury on admission, and corticosteroid administration initiated within 5 days or 5 days to 2 weeks from onset. CONCLUSION: A CURB-65 score of ≥3, which is considered to indicate severe pneumonia, was of limited value for predicting mortality of virus-associated pneumonia. We showed patients' underlying diseases and complications to be independent factors of poor prognosis for 60-day mortality. Timing of the initiation of corticosteroid administration remains to be elucidated.

Survival outcomes of patients with stage III colorectal cancer aged ≥ 80 years who underwent curative resection: the HiSCO-04 prospective cohort study.

BACKGROUND: The efficacy of adjuvant chemotherapy in elderly patients aged ≥ 80 years with stage III colorectal cancer remains unclear. In parallel with a multicenter prospective phase II trial evaluating the efficacy of uracil-tegafur and leucovorin as adjuvant chemotherapy (HiSCO-03), we conducted a prospective observational study of these patients to assess survival outcomes, including those ineligible for chemotherapy. METHODS: This multi-institutional prospective cohort study included 17 institutions in Hiroshima, Japan. Patients aged ≥ 80 years with stage III colorectal cancer who underwent curative resection were enrolled. The primary endpoint was 3-year disease-free survival, and the secondary endpoints were 3-year overall and relapse-free survival. Propensity score matching was used to assess the effects of adjuvant chemotherapy on survival outcomes. RESULTS: A total of 214 patients were analyzed between 2013 and 2018, including 99 males and 115 females with a median age of 84 years (range 80-101 years). Recurrence occurred in 58 patients and secondary cancers were observed in 17. The 3-year disease-free, overall, and relapse-free survival rates were 63.3%, 76.9%, and 62.9%, respectively. Adjuvant chemotherapy was administered to 65 patients with a completion rate of 52%. In a study of 80 patients that adjusted for background factors using propensity score matching, patients who completed the planned treatment showed improved disease-free survival (3-year disease-free survival: completed, 80.0%; not received, 65.5%; and discontinued, 56.3%; p = 0.029). CONCLUSIONS: Completion of adjuvant chemotherapy may improve the prognosis of patients with colorectal cancer aged ≥ 80 years, although the number of patients who would benefit from it is limited.

Association between social background and implementation of postoperative adjuvant chemotherapy for older patients undergoing curative resection of colorectal cancers, sub-analysis of the HiSCO-04 study.

PURPOSE: Adjuvant chemotherapy is recommended following colorectal cancer resection based on risk of recurrence. In older patients, treatment decisions should consider recurrence rates and tolerability, as well as functional prognosis, residual disease, and social factors. This study aims to investigate factors, including social background, influencing implementation of postoperative adjuvant chemotherapy in older patients undergoing curative resection for colorectal cancer. METHODS: This multi-institutional prospective cohort study included 15 institutions belonging to the Hiroshima Surgical study group for Clinical Oncology. We analyzed 159 older patients aged ≥ 80 years, who underwent curative resection for stage III colorectal cancer between December 2013 and June 2018, as sub-analysis of the HiSCO-04 study. RESULTS: In total, 62 (39.0%) patients underwent postoperative adjuvant chemotherapy. Four factors were significantly associated with its implementation: performance status < 2, Charlson Comorbidity Index < 2, prognostic nutritional index ≥ 40, and presence of a spouse or siblings as lifestyle supporters. No significant difference was found in the backgrounds between complete and incomplete postoperative adjuvant chemotherapy patients. CONCLUSION: Performance status, Charlson Comorbidity Index, nutritional status, and presence of a spouse or siblings as lifestyle supporters are possible factors influencing the implementation of postoperative adjuvant chemotherapy in older patients. To select appropriate treatment options, including postoperative adjuvant chemotherapy, it is essential to consider physical condition and comorbidities of older patients, thoroughly explain the situation to their families, and establish a support system to enhance understanding of the available treatment options.

Sitafloxacin- Versus Moxifloxacin-Based Sequential Treatment for Mycoplasma Genitalium Infections: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with increasing antibiotic resistance. The current treatment guidelines recommend moxifloxacin-sequential therapy for macrolide-resistant Mgenitalium or strains with unknown resistance profiles. However, it is unclear whether sitafloxacin, a 4th-generation fluoroquinolone antibiotic, is effective against resistant strains. OBJECTIVE: This study aims to assess and compare the efficacy and safety of sitafloxacin- and moxifloxacin-based treatment regimens for managing Mgenitalium infections. METHODS: We will conduct this randomized controlled trial at multiple centers in Japan. Eligible participants include adults aged 18 years or older with a confirmed Mgenitalium infection, as determined through the nucleic acid amplification test. Patients will be randomly assigned using a stratified approach based on the treatment facility and infection site. The interventions comprise oral sitafloxacin (200 mg) daily for 7 days (with optional pretreatment of oral doxycycline, 200 mg, daily for up to 7 days), with a control group receiving oral doxycycline (200 mg) daily for 7 days followed by moxifloxacin (400 mg) daily for another 7 days. The primary outcome is the treatment success rate with a superiority margin of 10%, as confirmed through the nucleic acid amplification test. Secondary outcomes encompass changes in the bacterial load at the urogenital or rectal sites and the emergence of posttreatment-resistant mutant strains. RESULTS: Enrollment commenced in June 2023 and will conclude in December 2024, with findings anticipated by 2025. The expected success rates fall within the range of 80% for sitafloxacin and 42% for moxifloxacin against Mgenitalium carrying the G248T (S83I) mutation, based on previous studies. Accordingly, with a 5% significance level (2-sided) and 80% statistical power, we aim to recruit 50 participants per group, factoring in a 10% expected dropout rate. CONCLUSIONS: This study will provide valuable insights into the efficacy and safety of sitafloxacin- versus moxifloxacin-based sequential therapy in treating Mgenitalium infections. These findings have the potential to influence clinical guidelines, favoring more effective therapeutic choices. The multicenter approach enhances the robustness of this study. However, a limitation is the potential insufficiency of statistical power to detect posttreatment-resistant mutant strains in each group, rendering posttreatment-resistance mutations a notable concern. In the future, we may need to increase the sample size to enhance power. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031230111); https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52565.

Physicochemical properties of the vacuolar membrane and cellular factors determine formation of vacuolar invaginations.

Vacuoles change their morphology in response to stress. In yeast exposed to chronically high temperatures, vacuolar membranes get deformed and invaginations are formed. We show that phase-separation of vacuolar membrane occurred after heat stress leading to the formation of the invagination. In addition, Hfl1, a vacuolar membrane-localized Atg8-binding protein, was found to suppress the excess vacuolar invaginations after heat stress. At that time, Hfl1 formed foci at the neck of the invaginations in wild-type cells, whereas it was efficiently degraded in the vacuole in the atg8Δ mutant. Genetic analysis showed that the endosomal sorting complex required for transport machinery was necessary to form the invaginations irrespective of Atg8 or Hfl1. In contrast, a combined mutation with the vacuole BAR domain protein Ivy1 led to vacuoles in hfl1Δivy1Δ and atg8Δivy1Δ mutants having constitutively invaginated structures; moreover, these mutants showed stress-sensitive phenotypes. Our findings suggest that vacuolar invaginations result from the combination of changes in the physiochemical properties of the vacuolar membrane and other cellular factors.

What was happening in the collaboration between general practitioners and public health nurses in the community: A qualitative study.

Background: Interprofessional collaboration in the community is becoming essential in primary care, particularly collaboration between public health nurses and general practitioners. However, the precise value of such collaboration has not been sufficiently studied. The purpose of this study was to conduct a qualitative analysis of collaboration between general practitioners and public health nurses in the community to explore the details of the phenomenon and its possible impact on the community. Methods: Since 2015, The University of Toyama has been implementing the Collaborative Health Activities Project, in which general practitioners and public health nurses work together to promote community health. Focus group and individual interviews were conducted with participating staff, and the data were analyzed qualitatively. Results: Fifteen themes were generated, in six categories. The categories were as follows: enhanced roles of public health nurses and physicians in the community, new perspectives on the community, public health nurses' sense of trust and empathy toward physicians, bonds of solidarity between public health nurses and physicians, proactive change in residents, and supporting "hangout places". Conclusion: The collaboration between general practitioners and public health nurses familiar with the same community fostered a sense of trust and empathy and created the bonds of solidarity between staff and residents. The results also suggest the collaboration may have a positive impact on the local community by inspiring residents to change proactively and supporting "hangouts" where residents and professionals can informally connect.

Efficacy and Safety of the Smallpox Vaccine for Postexposure Prophylaxis in Monkeypox: Protocol for an Open-Labeled, Single-Armed Study.

BACKGROUND: In May 2022, a case of monkeypox (currently known as "mpox") with no history of overseas travel was reported in the United Kingdom, followed by reports of infections reported in Europe, the United States, and other countries worldwide. Due to the significant overlap in immune responses among viruses of the genus Orthopoxvirus (including smallpox virus, mpox virus, and vaccinia virus), it is believed that cross-immunity can be achieved by administering the smallpox virus vaccine. In Japan, a smallpox vaccine (LC16m8 strain vaccine) has been approved; however, there was no regulatory approval for the mpox vaccine during the design of this study. Although it is believed that individuals exposed to the mpox virus may receive smallpox vaccination as mpox prophylaxis, the existing evidence is not clear. OBJECTIVE: The primary objective was to evaluate the efficacy of the LC16m8 strain vaccine, approved for smallpox in Japan, for postexposure prophylaxis against mpox when administered to close contacts of individuals with mpox. The secondary objective was to investigate the safety of the vaccine for postexposure prophylaxis against mpox. METHODS: The study aimed to enroll 100 vaccinated participants who had been identified as close contacts of individuals with mpox. Consent was obtained, and the participants are inoculated with the vaccine. Daily recordings of symptoms (body temperature, headache, rash, and side effects) were made until day 21 and then again on day 28. Furthermore, additional evaluations of adverse events were performed by the investigators on days 7, 14, 21, and 28. Considering that the maximum incubation period for mpox is 21 days, the primary end point is the presence or absence of the disease 21 days after close contact. The primary analysis focused on cases within 4 days of intense contact as it has been reported that vaccination within this timeframe can reduce the incidence of the disease. RESULTS: The first trial participant was enrolled on July 28, 2022, and the research period concluded in March 2023. The study results will be published in a peer-reviewed scientific journal. CONCLUSIONS: This study allowed us to investigate the efficacy and safety of the LC16m8 strain vaccine in postexposure prophylaxis against mpox. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031220137; https://jrct.niph.go.jp/en-latest-detail/jRCTs031220137. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46955.

An open-label, non-randomized study investigating the safety and efficacy of smallpox vaccine, LC16, as post-exposure prophylaxis for mpox.

Mpox is an acute exanthematous disease caused by the monkeypox virus. Since May 2022, it has spread as a community-acquired infection, mainly in Europe and the United States, and urgent measures to prevent this infection were also required in Japan. In this study, we investigated the post-exposure prophylaxis of mpox and safety after inoculating the smallpox vaccine. Participants in close contact with patients with mpox were inoculated with "Freeze-dried cell culture Smallpox Vaccine LC16," within 14 days after close contact. Six cases were registered, and all the participants were inoculated. No mpox symptoms or related complications were observed in the participants for 21 days after the close contact. Adverse events due to inoculation, such as rash, fever, lymphadenopathy, and local reaction at the inoculation site (comprising erythema, swelling, induration, and pain) were observed in the participants; however, all inoculation-related events were non-severe and non-serious, and the participants recovered during the 28-day observation period. The findings of this study suggest that inoculation with LC16 is an effective post-exposure prophylaxis in individuals who had close contact with patients with mpox. Further large-scale studies are warranted to validate these findings.

[Foreign Body in Chest Wall with Traumatic Pneumothorax Caused by Fang of Wild Boar].

We report a case of foreign body in chest wall with traumatic pneumothorax caused by fang of wild boar performed video-assisted thoracic surgery. The patient was a 69-year-old woman. She was attacked from behind by a wild boar during farm work. She was transferred to the emergency and critical care center of our hospital. She was in a state of hemorrhagic shock when arrived with multiple bite wounds on her back. Computed tomography( CT) scan revealed left pneumothorax and a foreign body in chest wall suspected to be a wild boar fang. Thoracoscopic surgery was performed to remove the foreign body.

Predictive factors associated with anastomotic leakage after resection of rectal cancer: a multicenter study with the Hiroshima Surgical study group of Clinical Oncology.

PURPOSE: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection. METHODS: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020. RESULTS: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection. CONCLUSIONS: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma.

Analysis of Acquisition of COVID-2019 Neutralizing Antibodies in Organ Transplant Recipients.

BACKGROUND: This study confirmed the kinetics of antibodies acquired by SARS-CoV-2 vaccination in solid-organ transplant recipients and examined their association with the development of COVID-19 and immunosuppressive status in organ transplant recipients. METHODS: We measured COVID-19 neutralizing antibody titer in 21 organ transplant recipients vaccinated with the COVID-19 vaccine and 14 nontransplant recipients (control group) 3 times before and at 1 and 6 months after the third dose of vaccine. By confirming the kinetics of the acquired antibodies, we examined the relevance of the background characteristics of organ transplant recipients, such as the development of infectious diseases and immunosuppressive status. RESULTS: The proportion of patients with neutralizing antibodies was significantly higher in the nontransplant group than in the transplant group. Neutralizing antibody titers were significantly lower in transplant recipients when they were compared before the third dose and 1 month later. In the transplant recipient group, 11 patients were positive, and 10 were negative for neutralizing antibodies. When the causal relationship between the neutralizing antibody titer and background was examined, a positive correlation was found between the antibody titer and the number of years since transplantation, and a negative correlation was found between the tacrolimus trough values, amount of mycophenolate mofetil or steroids taken internally, and antibody titer. CONCLUSION: This study suggests that the effectiveness of vaccination in transplant recipients is associated with the post-transplant period before vaccination and the dose of immunosuppressive agents.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Immunogenicity and safety of single booster dose of KD-414 inactivated COVID-19 vaccine in adults: An open-label, single-center, non-randomized, controlled study in Japan.

Although vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) induce effective immune responses, vaccination with booster doses is necessary because of waning immunity. We conducted an open-label, non-randomized, single-arm study in adults in Japan to assess the immunogenicity and safety of a single booster dose of the KD-414 purified whole-SARS-CoV-2-virion inactivated vaccine candidate after vaccination with a primary series of BNT162b2. The primary endpoint was serum neutralizing activity at 7 days after booster injection compared with the primary series of BNT162b2. The SARS-CoV-2-structural protein-binding antibody level and T cell response against SARS-CoV-2-Spike (S) peptides were also examined as secondary endpoints, and safety profile assessments were conducted. Twenty subjects who participated in a previous study declined an injection of KD-414 (non-KD-414 group) and received a booster dose of BNT162b2 instead. The non-KD-414 group was compared to the KD-414 group as a secondary outcome. A single dose of KD-414 induced lower serum neutralizing activity against the wild-type virus within 7 days compared to after the primary series of BNT162b2 but significantly induced anti-SARS-CoV-2-S1-receptor-binding domain-binding immunoglobulin G (IgG) antibodies and SARS-CoV-2-S peptide-specific CD4+ and CD8+ T cell responses. Local or systemic symptoms were significantly lower in the participants who received KD-414 than in those who received BNT162b2 as the third COVID-19 vaccine dose. The present data indicate that a single booster dose of KD-414 induces a substantial immune response in BNT162b2-primed individuals and has a good safety profile, thereby supporting further clinical trials to identify rational targets.

Evaluating the Immunogenicity and Safety of a Smallpox Vaccine to Monkeypox in Healthy Japanese Adults: A Single-Arm Study.

Monkeypox (mpox) is an acute exanthematous disease caused by the monkeypox virus (MPXV). Since May 2022, patients with mpox have been reported worldwide, mainly in Europe and the Americas. In Japan, LC16"KMB," which is a smallpox vaccine derived from a dried cell culture, against mpox, has been approved. Although inoculation with a smallpox vaccine has been recommended to prevent MPXV infection, the immunogenicity of the smallpox vaccine against the MPXV is unclear, and information regarding postvaccination safety is scarce. We present the protocol for a single-arm open-label study to investigate the immunogenicity and safety of LC16"KMB" against the MPXV in healthy Japanese adults. The primary endpoint is the seroconversion rate of neutralizing antibodies against the MPXV on postvaccination day 28. The secondary endpoints are the seroconversion rates against the MPXV on postvaccination days 14 and 168; the seroconversion rates against the vaccinia virus on postvaccination days 14, 28, and 168; the incidence of mpox until day 168; and adverse and serious adverse events until postvaccination days 28 and 168. These results will pave the way for larger comparative studies using other smallpox vaccines to evaluate the test vaccine's safety and efficacy in preventing mpox.