Clinical characteristics and prognostic factors of endometrial stromal sarcoma and undifferentiated uterine sarcoma confirmed by central pathologic review: A multi-institutional retrospective study from the Japanese Clinical Oncology Group.

OBJECTIVES: Low-grade and high-grade endometrial stromal sarcomas (LGESS and HGESS) and undifferentiated uterine sarcomas (UUS) are rare tumors whose pathological classification and staging system have changed recently. These tumors are reported to contain fusion genes. We aimed to clarify the genetic background, clinical features, prognostic factors, and optimal therapy of these tumors using a new classification and staging system. METHODS: We analyzed the clinical features and prognostic information of 72 patients with LGESS, 25 with HGESS, and 16 with UUS using central pathological review. Estrogen and progesterone receptors (PgRs) were examined by immunohistochemistry. JAZF1-SUZ12 and YWHAE-NUTM2A/B gene fusions were tested using real-time polymerase chain reaction. RESULTS: The 5-year overall survival (OS) rates of LGESS, HGESS, and UUS were 94%, 53%, and 25%, respectively. In LGESS, stage IV, incomplete surgery, and absence of PgR were associated with poor OS. The presence of JAZF1-SUZ12 fusion gene was not associated with OS. In HGESS, the relationship between stage and prognosis was unclear. None of the 3 patients with YWHAE-NUTM2A/B fusion gene died during follow-up. Adjuvant chemotherapy was associated with a favorable OS. Incomplete resection of UUS was associated with poor OS; however, residual tumors frequently occurred. Although most patients underwent adjuvant chemotherapy, their prognosis was extremely poor even in stage I disease. CONCLUSIONS: Prognosis of LGESS is generally good; however, stage IV, incomplete surgery, and PgR-negative tumors are associated with poor prognosis. Adjuvant chemotherapy may be useful for HGESS. Prognosis of UUS is extremely poor, even with adjuvant chemotherapy.

Antibody acquisition after second and third SARS-CoV-2 vaccinations in Japanese kidney transplant patients: a prospective study.

BACKGROUND: Kidney transplant patients have lower antibody acquisition after SARS-CoV-2 vaccination. The efficacy of vaccines in Japanese kidney transplant patients with specific characteristics, such as predominant living-donor, ABO-incompatible kidney transplant, and low-dose immunosuppression, requires verification. METHODS: We conducted a prospective study to estimate anti-SARS-CoV-2 antibody levels in 105 kidney transplant patients and 57 controls. Blood samples were obtained before vaccination, 1, 3, and 6 months after second vaccination, and 1 month after third vaccination. We investigated antibody acquisition rates, antibody levels, and factors associated with antibody acquisition. RESULTS: One month after second vaccination, antibody acquisition was 100% in the controls but only 36.7% in the kidney transplant group (P < 0.001). Antibody levels in positive kidney transplant patients were also lower than in the controls (median, 4.9 arbitrary units vs 106.4 arbitrary units, respectively, P < 0.001). Years after kidney transplant (odds ratio 1.107, 95% confidence interval 1.012-1.211), ABO-incompatible kidney transplant (odds ratio 0.316, 95% confidence interval 0.101-0.991) and mycophenolate mofetil use (odds ratio 0.177, 95% confidence interval 0.054-0.570) were significant predictors for antibody acquisition after second vaccination. After third vaccination, antibody positivity in the kidney transplant group increased to 75.3%, and antibody levels in positive patients were 71.7 arbitrary units. No factors were associated with de novo antibody acquisition. CONCLUSIONS: In Japanese kidney transplant patients, years after kidney transplant, ABO-incompatible kidney transplant and mycophenolate mofetil use were predictors for antibody acquisition after second vaccination. Third vaccination improves antibody status even in patients who were seronegative after the second vaccination.

Maoto, a traditional herbal medicine, for post-exposure prophylaxis for Japanese healthcare workers exposed to COVID-19: A single center study.

BACKGROUND: Little research has been done on post-exposure prophylaxis (PEP) for COVID-19. This study was done to determine if maoto, a traditional herbal medicine commonly used for diseases with symptoms similar to those of COVID-19, can be repurposed for post-exposure prophylaxis to prevent the spread of nosocomial infection with SARS-CoV-2. METHODS: A cohort analysis was done of the data of 55 health care workers (HCWs) whether to get infected with SARS-CoV-2 in a Japanese hospital experiencing a COVID-19 cluster in April of 2021. Of these subjects, maoto granules for medical use were prescribed for PEP to 42 HCWs and taken for three days in mid-April. Controls were 13 HCWs who rejected the use of maoto. Polymerase chain reaction was performed routinely once or twice a week or when a participant presented with symptoms of COVID-19. RESULT: There were no background differences between the maoto and control groups by profession, sex, or mean age. No severe adverse reactions were observed. During the observation period of 1 week, significantly fewer subjects were diagnosed with COVID-19 in the maoto group (N = 3, 7.1%) than in the control group (N = 6, 46.2%). The prophylactic effectiveness of maoto was 84.5%. CONCLUSION: Oral administration of maoto is suggested to be effective as PEP against nosocomial COVID-19 infection.

Recurrence of gastric cancer caused by implantation of tumor cells after curative endoscopic submucosal dissection.

A 93-year-old female underwent curative endoscopic submucosal dissection (ESD) for intramucosal gastric cancer (70 mm in diameter) in the antrum. The lesion showed an irregularly villous structure covered with mucus. En bloc resection was performed. The large resected specimen induced a longitudinal laceration on the right wall of the esophagogastric junction (EGJ) during retrieval. Unavoidably, we segmented the specimen in the stomach to facilitate retrieval. Histopathological evaluation of the specimen revealed well-to-moderately differentiated tubular and papillary adenocarcinoma. A new elevated lesion (15 mm in diameter) was found at the gastric side of the EGJ laceration scar 6 months after the first ESD, necessitating a second resection with ESD. Endoscopic, histopathological, and immunohistochemical features of the new lesion resembled those of the antral lesion. We assessed the new lesion as a recurrence of cancer caused by implantation of tumor cells in the mucosal laceration after ESD.We experienced recurrence caused by implantation of tumor cells in a mucosal laceration after curative gastric ESD. Endoscopist should be aware of the risk of implantation after gastric ESD.

Introduction of histological classification and cytology reporting format of the Japanese General Rules for the Description of Thyroid Cancer with a special focus on the differences of the WHO Histological Classification and The Bethesda System of Thyroid Cytology.

Histological classification and cytology reporting format described in General Rules for the Description of Thyroid Cancer, the 8th edition (2019) (the Japanese General Rules) were briefly introduced. Moreover, the differences between "the Japanese General Rules", and WHO Histological Classification, the 4th edition (2017) and The Bethesda System for Reporting Thyroid Cytopathology, the 2nd edition (2018) were also explained. The Japanese General Rules did not accept the borderline lesions of thyroid tumor which were newly shown in WHO Histological Classification. We believe it is not necessary to introduce these borderline lesions in daily practice in Japan. Borderline lesions were proposed for avoiding over-surgery for thyroid cancer patients. In the United States, when the patient is diagnosed as malignant on cytology, total thyroidectomy is generally recommended. However, there is no over-surgery in Japan, because surgeons have several choices of treatment for thyroid cancer patients. This article is the first that the Japanese General Rules was shown by foreign language. Therefore, this will be advantageous to us when we present our opinion concerning histology and cytology of thyroid tumor to the world.

Cytological examination of the thyroid in children and adolescents after the Fukushima Nuclear Power Plant accident: the Fukushima Health Management Survey.

The Fukushima Daiichi Nuclear Power Plant accident occurred on March 11 2011, following the Great East Japan Earthquake and tsunami. Radioactive materials, including I-131, were released into the environment after the accident. Shortly after, the prefectural government initiated the Fukushima Health Management Survey for monitoring the long-term health conditions of the residents of Fukushima Prefecture. In the survey, thyroid ultrasonography was scheduled for all people aged 18 years or younger who were living in Fukushima Prefecture at the time of disaster. The total number of examinees was approximately 370,000 in the Preliminary Baseline Survey (PBLS), and 380,000 in the first Full-scale Survey (FSS). First, thyroid ultrasonography was performed as the Primary Examination. When a thyroid nodule that meets the fine needle aspiration cytology (FNAC) guideline is detected, thyroid FNAC is performed. By the end of June 2017, the cytological specimens of 187 examinees had been interpreted as Malignant or Suspicious for Malignancy (SFM). In this article, the cytological results of whole categories are presented using the criteria of The Bethesda System for Reporting Thyroid Cytopathology. The total numbers of examinees with SFM or Malignant in PBLS and at the first FSS were 106 (62.0%) and 71 (38.0%), respectively. The data of the cytological results of SFM and Malignant were already reported. However, this is the first report of cytological data from categories other than SFM and Malignant. The results of the current study will contribute to future research into the thyroid conditions of children and adolescents.

A multi-center retrospective study of neuroendocrine tumors of the uterine cervix: Prognosis according to the new 2018 staging system, comparing outcomes for different chemotherapeutic regimens and histopathological subtypes.

OBJECTIVE: To analyze the clinical behavior of neuroendocrine tumors (NETs) of the uterine cervix, we conducted a multicenter, retrospective study of 193 patients. METHODS: We evaluated the prognosis of NETs according to the new International Federation of Gynecology and Obstetrics (FIGO) staging system, compared the clinical response to different chemotherapy regimens, and compared different histological subtypes of NETS. RESULTS: Diagnoses of the subjects were atypical carcinoid tumor (ACT, n = 37), small cell neuroendocrine carcinoma (SCNEC, n = 126), large cell neuroendocrine carcinoma (LCNEC, n = 22), and NET, not elsewhere classified (n = 8), according to central pathological review. According to FIGO 2018, 69, 17, 74, and 33 patients were at stage I, II, III, or IV, respectively. Five-year survival was 64.5%, 50.1%, 30.2%, and 3.4% for patients at stage I, II, III and IV. About 40% of patients with stage IIIC1 survived >5 years. On multivariate analyses, locally-advanced disease, para-aortic node metastasis, distant metastasis, and <4 cycles of chemotherapy were associated with poor survival. Histological subtype and pelvic node metastasis had no prognostic significance. Response rates to etoposide-platinum (EP) or irinotecan-platinum (CPT-P) regimens were 43.8% (28/64), but only 12.9% to a taxane-platinum (TC) regimen (4/31). The response rate for ACT was 8.7% (2/23), significantly less than the 36.6% for high-grade neuroendocrine carcinomas (HGNEC: both SCNEC and LCNEC, 41/111). CONCLUSIONS: Locally-advanced, extra-pelvic disease and insufficient chemotherapy were independent prognostic factors for cervical NET. HGNEC showed good responses to EP or CPT-P but not TC. Chemotherapy was less effective for ACT, which had a prognosis identical to HGNEC.

Prognostic factors and optimal therapy for stages I-II neuroendocrine carcinomas of the uterine cervix: A multi-center retrospective study.

PURPOSE: We aimed to determine appropriate treatment guidelines for patients with stages I-II high-grade neuroendocrine carcinomas (HGNEC) of the uterine cervix in a multicenter retrospective study. PATIENTS AND METHODS: We reviewed the clinicopathological features and prognoses of 93 patients with HGNEC of International Federation of Gynecology and Obstetrics (FIGO) stages I and II. All patients were diagnosed with HGNEC by central pathological review. RESULTS: The median overall survival (OS) and disease-free survival (DFS) were 111.3months and 47.4months, respectively. Eighty-eight patients underwent radical surgery, and five had definitive radiotherapy. The hazard ratio (HR) for death after definitive radiotherapy to death after radical surgery was 4.74 (95% confidence interval [CI], 1.01-15.90). Of the surgery group, 18 received neoadjuvant chemotherapy. Pathological prognostic factors and optimal adjuvant therapies were evaluated for the 70 patients. Forty-one patients received adjuvant chemotherapy with etoposide-platinum (EP) or irinotecan-platinum (CPT-P). Multivariate analyses identified the invasion of lymphovascular spaces as a significant prognostic factor for both OS and DFS. Pelvic lymph node metastasis was also a prognostic factor for DFS. Adjuvant chemotherapy with an EP or CPT-P regimen appeared to improve DFS (HR=0.27, 95% CI, 0.10-0.69). A trend toward improved OS was also observed, but was not statistically significant (HR=0.39, 95% CI, 0.15-1.01). CONCLUSION: Radical surgery followed by adjuvant chemotherapy with an EP or CPT-P regimen was optimal treatment for stages I and II HGNEC of the uterine cervix.

Histopathological analysis of anaplastic thyroid carcinoma cases with long-term survival: A report from the Anaplastic Thyroid Carcinoma Research Consortium of Japan.

The aim of this study was to clarify the histopathological features of anaplastic thyroid carcinoma in patients who achieved long-term survival. We reviewed 88 anaplastic thyroid carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 anaplastic thyroid carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be anaplastic thyroid carcinoma after central review. Of these, 12 were revised to papillary carcinoma with squamous cell carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with anaplastic thyroid carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in anaplastic thyroid carcinoma.

[Bronchial hamartoma in subsegmental bronchus; report of a case].

We report a rare surgical case of a bronchial hamartoma in subsegmental bronchus. A 70-year-old man was incidentally pointed out an abnormal chest shadow without any complaints. Chest computed tomography revealed a round nodule with diameter of 15 mm in the right upper lobe. The bronchoscopic examination revealed complete obstruction of right B2a by the tumor. Right S2 segmentectomy was done to make a definite diagnosis and to prevent possible obstructive pneumonia. Histopathological examination revealed that the tumor was a benign cartilage bronchial hamartoma.

Stage IV gastric adenocarcinoma with enteroblastic differentiation with 5-year relapse-free survival after D2 gastrectomy and chemotherapy: A case report.

BACKGROUND: Gastric adenocarcinoma with enteroblastic differentiation (GACED), a rare subtype of gastric cancer, is associated with a more aggressive behavior than conventional gastric adenocarcinomas. We report a rare case of stage IV GACED treated with D2 gastrectomy and postoperative chemotherapy. CASE PRESENTATION: A 39-year-old woman with acute upper abdominal pain immediately underwent surgery for gastric perforation. Afterward she was diagnosed with adenocarcinoma of the pylorus. D2 gastrectomy was performed and the final pathological diagnosis was stage IV GACED with positive peritoneal cytology. Postoperative chemotherapy was initiated with S1 plus oxaliplatin for 1 year, which was ceased thereafter to enhance her quality of life. The patient survived more than 5 years without relapse after gastrectomy. CONCLUSIONS: Stage IV GACED, determined by positive spalt-like transcription factor 4, can be successfully treated with surgery and chemotherapy.

The appearance of anti-spike receptor binding domain immunoglobulin G4 responses after repetitive immunization with messenger RNA-based COVID-19 vaccines.

OBJECTIVES: It is crucial to analyze the consequences of repeated messenger RNA (mRNA)-based COVID-19 vaccinations on SARS-CoV-2 spike receptor binding domain (RBD)-specific immunoglobulin (Ig)G subclass and the possible causal relationship with breakthrough infection. METHODS: We examined the longitudinal kinetics of RBD-specific IgG subclass antibodies in sera after receiving the second, third, and fourth doses of mRNA-based COVID-19 vaccines in Japanese healthcare workers. Anti-RBD IgG subclass in sera of patients with COVID-19-infected who had not received the COVID-19 vaccine were also examined. We compared anti-RBD IgG subclass antibody titers in the serum of pre-breakthrough-infected vaccinees and non-infected vaccinees. RESULTS: The seropositivity of anti-RBD IgG4 after the vaccination was 6.76% at 1 month after the second dose, gradually increased to 50.5% at 6 months after the second dose, and reached 97.2% at 1 month after the third dose. The seropositivity and titers of anti-RBD IgG1/IgG3 quickly reached the maximum at 1 month after the second dose and declined afterward. The elevated anti-RBD IgG4 Ab levels observed after repeated vaccinations were unlikely to increase the risk of breakthrough infection. CONCLUSIONS: Repeated vaccinations induce delayed but drastic increases in anti-RBD IgG4 responses. Further functional investigations are needed to reveal the magnitude of the high contribution of spike-specific IgG4 subclasses after repeated mRNA-based COVID-19 vaccinations.

Insufficient anti-spike RBD IgA responses after triple vaccination with intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2.

Objectives: This study aims to examine whether the parenterally administered mRNA-based COVID-19 vaccines can induce sufficient mucosal-type IgA responses to prevent SARS-CoV-2 transmission. Methods: We examined the longitudinal kinetics of SARS-CoV-2 spike RBD-specific IgA and IgG responses in sera of Japanese healthcare workers (HCWs) after receiving two doses and the third dose of BNT162b2 mRNA vaccines. During the prospective cohort study, Omicron breakthrough infections occurred in 62 participants among 370 HCWs who had received triple doses of the vaccine. Pre-breakthrough sera of infected HCWs and non-infected HCWs were examined for the levels of anti-RBD IgA and IgG titers. Results: The seropositivity of anti-RBD IgA at 1 M after the second vaccine (2D-1M) and after the third dose (3D-1M) was 65.4% and 87.4%, respectively, and wanes quickly. The boosting effect on anti-RBD Ab titers following breakthrough infections was more notable for anti-RBD IgA than for IgG. There were partial cause-relationships between the lower anti-RBD IgA or IgG at pre-breakthrough sera and the breakthrough infection. Conclusions: Parenterally administered COVID-19 vaccines do not generate sufficient mucosal-type IgA responses despite strong systemic IgG responses to SARS-CoV-2. These results demonstrate the necessity and importance of reevaluating vaccine design and scheduling to efficiently increase oral or respiratory mucosal immunity against SARS-CoV-2.

[Synchronous multiple primary lung and colon cancers].

We report a rare surgical case of synchronous multiple primary lung cancers with synchronous multiple colon cancers. A 74-year-old woman was incidentally pointed out abnormal chest shadows. Chest computed tomography revealed 2 nodules in the right upper and middle lobe. Transbronchilal lung biopsy (TBLB) was done, and the tumor in the middle lobe was diagnosed as adenocarcinoma. In addition, positron emission tomography pointed out colon cancer. Colon fiber revealed multiple colon polyps and colon cancers. Immunostaining with thyroid transcription factor (TTF)-1 and Napsin-A for TBLB specimen was done to distinguish their association. With the diagnosis as primary lung cancer, we performed right upper and middle lobectomy with lymph node dissection. These tumors were pathologically diagnosed as synchronous multiple primary lung cancers with adenocarcinoma and squamous cell carcinoma. Several months later, colon regions were resected through colonoscopic endometric mucosal resection and left hemicolectomy.

Clinicopathological features of endoscopically treated early gastric cancer with lymphovascular infiltration.

PURPOSE: Lymphovascular infiltration (LVI) may play a critical role in radicality and prognostic assessment of early gastric cancer (EGC). However, risk factors for LVI in endoscopically resected EGC remain unknown. This study evaluated the clinicopathological characteristics and prognoses of patients who underwent endoscopic resection of EGC to identify potential risk factors of LVI. METHODS: A cross-sectional study of patients who received gastric endoscopic submucosal dissection between February 1, 2012, and December 31, 2019, at two institutions was conducted. Among 1,462 lesions, 943 met the criteria for radical treatment considering features other than LVI and were included. The lesions were classified based on the presence of LVI. The clinicopathological characteristics of the two groups were compared. RESULTS: LVI was detected in 17 lesions (1.8%). The positivity rates of LVI were 0.7% (7/903) for intramucosal cancer and 25% (10/40) for submucosally invasive cancer. The LVI positivity rate was significantly higher for mixed-type cancer (lesions containing differentiated and undifferentiated-type carcinoma) than for non-mixed-type cancer (35.3 vs. 2.8%; P < 0.001) and for submucosally invasive cancer than for intramucosal cancer (58.8 vs. 3.2%; P < 0.001). In the multivariate logistic regression analysis, independent risk factors for LVI were mixed-type cancer (odds ratio; 95% confidence interval: 23.9; 5.0-115; P < 0.001) and submucosal invasion (58.7; 16.0-215; P < 0.001). CONCLUSIONS: Mixed-type cancer and submucosal invasion were risk factors for LVI in endoscopically resected EGC. These factors may play a critical role in the radicality and prognostic assessment of EGC.

Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

New terminology for intrauterine endometrial samples: a group study by the Japanese Society of Clinical Cytology.

OBJECTIVE: To evaluate the sensitivity and specificity of endometrial cytology obtained by intrauterine sample using a descriptive reporting format for endometrial cytological diagnosis. STUDY DESIGN: 10,152 consecutive endometrial scrapings obtained in 13 different Japanese hospitals were analyzed. Cytological results were classified as 'negative for malignancy', 'atypical endometrial cells' (ATEC), 'endometrial hyperplasia', 'atypical endometrial hyperplasia' or 'malignant tumor'. ATEC was subclassified as 'ATEC, of undetermined significance' (ATEC-US) and 'ATEC, cannot exclude atypical endometrial hyperplasia or more' (ATEC-A). Cytological results were compared with the histological diagnosis as a gold standard. When the cytological result was 'negative for malignancy' and there was no subsequent histological examination, the case was considered a true negative when the endometrium was assessed as normal on transvaginal ultrasonography and there was no abnormal uterine bleeding. RESULTS: 1,083 cases in which histology was not performed, 557 cases of 'unsatisfactory specimen' and 76 cases of ATEC-US were excluded. In the remaining 8,436 cases, the sensitivity and specificity, positive predictive value and negative predictive value for detecting atypical endometrial hyperplasia or malignant tumors were 79.0 and 99.7, 92.9 and 98.9%, respectively. CONCLUSION: The current diagnostic standards for endometrial cytology in Japan were established. Specificity is satisfactory for excluding cancer or precancerous diseases.

Longitudinal Dynamics of SARS-CoV-2 IgG Antibody Responses after the Two-Dose Regimen of BNT162b2 Vaccination and the Effect of a Third Dose on Healthcare Workers in Japan.

Analysis of longitudinal dynamics of humoral immune responses to the BNT162b2 COVID-19 vaccine might provide useful information to predict the effectiveness of BNT162b2 in preventing SARS-CoV-2 infection. Herein, we measure anti-RBD IgG at 1, 3 and 6 months (M) after the second dose of BNT162b2, and at 1 M after a third dose of BNT162b2 vaccination in 431 COVID-19-naïve healthcare workers (HCWs) in Japan. All HCWs mounted high-anti-RBD IgG responses after the two-dose regimen of BNT162b2 vaccinations. Older persons and males presented lower anti-RBD IgG responses than younger adults and females, respectively. The decay in anti-RBD IgG started from 1 M after the second dose of BNT162b2 and anti-RBD IgG titers dropped to nearly one-tenth at 6 M after the second vaccination. Subsequently, the participants received a third dose of BNT162b2 at 8 M after the second dose of BNT162b2 vaccine. Anti-RBD antibody titers 1 M after the third dose of BNT162b2 increased seventeen times that of 6 M after the second dose, and was twice higher than the peak antibody titers at 1 M after the second dose of vaccination. The negative effect of age for the male gender on anti-RBD IgG antibody titers was not observed at 1 M after the third dose of BNT162b2 vaccine. There were no notable adverse events reported, which required hospitalization in these participants. These results suggest that the third dose of BNT162b2 safely improves humoral immunity against SARS-CoV-2 with no major adverse events.

Ephedrae Herba and Cinnamomi Cortex interactions with G glycoprotein inhibit respiratory syncytial virus infectivity.

Although respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in children, no effective therapies are available. Recently, RSV G, the attachment glycoprotein, has become a major focus in the development of therapeutic strategies against RSV infection. Treatment of RSV-infected cultured cells with maoto, a traditional herbal medicine for acute febrile diseases, significantly reduced the viral RNA and titers. RSV attachment to the cell surface was inhibited both in the presence of maoto and when RSV particles were pre-treated with maoto. We demonstrated that maoto components, Ephedrae Herba (EH) and Cinnamomi Cortex (CC), specifically interacted with the central conserved domain (CCD) of G protein, and also found that this interaction blocked viral attachment to the cellular receptor CX3CR1. Genetic mutation of CX3C motif on the CCD, the epitope for CX3CR1, decreased the binding capacity to EH and CC, suggesting that CX3C motif was the target for EH and CC. Finally, oral administration of maoto for five days to RSV-infected mice significantly reduced the lung viral titers. These experiments clearly showed the anti-RSV activity of EH and CC mixed in maoto. Taken together, this study provides insights for the rational design of therapies against RSV infection.

Whole-body MRI: detecting bone metastases from prostate cancer.

Whole-body magnetic resonance imaging (WB-MRI) is currently used worldwide for detecting bone metastases from prostate cancer. The 5-year survival rate for prostate cancer is > 95%. However, an increase in survival time may increase the incidence of bone metastasis. Therefore, detecting bone metastases is of great clinical interest. Bone metastases are commonly located in the spine, pelvis, shoulder, and distal femur. Bone metastases from prostate cancer are well-known representatives of osteoblastic metastases. However, other types of bone metastases, such as mixed or inter-trabecular type, have also been detected using MRI. MRI does not involve radiation exposure and has good sensitivity and specificity for detecting bone metastases. WB-MRI has undergone gradual developments since the last century, and in 2004, Takahara et al., developed diffusion-weighted Imaging (DWI) with background body signal suppression (DWIBS). Since then, WB-MRI, including DWI, has continued to play an important role in detecting bone metastases and monitoring therapeutic effects. An imaging protocol that allows complete examination within approximately 30 min has been established. This review focuses on WB-MRI standardization and the automatic calculation of tumor total diffusion volume (tDV) and mean apparent diffusion coefficient (ADC) value. In the future, artificial intelligence (AI) will enable shorter imaging times and easier automatic segmentation.