Increased SLAMF7high monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab.

Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7high monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored JAK2V617F had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7high monocyte percentage and JAK2V617F allele burden. These findings suggest that both SLAMF7high monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the JAK2V617F allele burden of SLAMF7high monocytes was significantly higher than that of SLAMF7low monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7high monocytes with higher JAK2V617F allele burden was associated with the onset of MF in MPN patients harboring JAK2V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor JAK2V617F.

Medical costs of Japanese lung cancer patients during end-of-life care.

OBJECTIVE: The medical costs associated with cancer treatment have increased rapidly in Japan; however, little data exist on actual costs, especially for end-of-life care. Therefore, this study aimed to examine the medical costs of lung cancer patients during the last 3 months before death and to compare the costs with those of initial anticancer treatment. METHODS: We retrospectively evaluated all patients who died from lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 August 2019. Patients were classified into three cohorts (2008-2011, 2012-2015 and 2016-2019) according to the year of death; the medical costs were evaluated for each cohort. Costs were then divided into outpatient and inpatient costs and calculated per month. RESULTS: Seventy-nine small cell lung cancer and 213 non-small cell lung cancer patients were included. For small cell lung cancer and non-small cell lung cancer patients, most end-of-life medical costs were inpatient costs across all cohorts. The median monthly medical costs for the last 3 months among both small cell lung cancer and non-small cell lung cancer patients did not differ significantly among the cohorts, but the mean monthly costs for non-small cell lung cancer tended to increase. The monthly medical costs for the last 3 months were significantly higher than those for the first year in SCLC (P = 0.013) and non-small cell lung cancer (P < 0.001) patients and those for the first 3 months in non-small cell lung cancer patients (P = 0.005). CONCLUSIONS: The medical costs during the end-of-life period for lung cancer were high and surpassed those for initial treatment.

Medical costs of lung cancer care in Japan during the first one or two years after initial diagnosis.

OBJECTIVES: Japan's healthcare expenditures, especially on oncology, are rapidly growing; however, there are scant data on actual costs and cost-effectiveness in the real world. The aim was to assess the medical costs and outcomes of patients with advanced lung cancer. METHODS: We retrospectively investigated all patients who were diagnosed with advanced lung cancer at the Japanese Red Cross Medical Center between 1 January 2008 and 31 December 2018. Patients were classified into three cohorts according to the year of diagnosis-Cohort 1: 2008-2010, Cohort 2: 2011-2014 and Cohort 3: 2015-2018-and assessed for medical costs and outcome. Medical costs were divided into outpatient and inpatient costs and were calculated on a monthly basis. RESULTS: Ninety-five patients with small cell lung cancer (SCLC) and 330 with nonsmall cell lung cancer (NSCLC) were included. There was a trend toward increased costs during the first two years after diagnosis in NSCLC patients, without changes in monthly costs, reflecting improved survival. Compared to Cohort 1, Cohort 3 patients with NSCLC had longer survival (median: 24 versus 12 months, P < 0.001), with a median incremental cost of Japanese Yen 6 million during the initial two years. The proportion of outpatient costs increased over time, especially for NSCLC patients (P < 0.001). No changes in costs or survival were observed in SCLC patients. CONCLUSIONS: In NSCLC patients, medical costs increased with prolonged survival during the last decade. The costs on a monthly basis did not change. The proportion of outpatient costs increased.

Drug-induced hypersensitivity syndrome caused by minodronic acid hydrate.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings. CASE PRESENTATION: An 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test. CONCLUSIONS: We described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

[Spontaneous resolution of refractory ascites in the late phase after cord blood transplantation in acute myeloid leukemia].

Patients with refractory ascites that develops >3 months after allogenic stem cell transplantation typically have a poor prognosis. We present the case of a 61-year-old man who developed refractory massive ascites approximately 3 months after cord blood transplantation (CBT) and showed complete and spontaneous remission from ascites after 18 months. The patient complained of severe bloating and needed weekly paracentesis to manage the fluid levels. Laboratory tests indicated that the ascites was caused by liver fibrosis. After the patient underwent Keisuke-Matsusaki cell-free and concentrated ascites reinfusion therapy (KM-CART), we were able to decrease the frequency of paracentesis treatments. We planned a transjugular liver biopsy, but the patient contracted pneumocystis pneumonia before the procedure could be performed. Although the pneumonia improved, the ascites worsened again. However, weekly paracentesis spontaneously stopped the progression of ascites and eventually resolved it completely, resulting in the patient's survival.

Prehospital Epinephrine as a Potential Factor Associated with Prehospital Rearrest.

Objective: To investigate the impact of epinephrine on prehospital rearrest and re-attainment of prehospital return of spontaneous circulation (ROSC). Methods: Data for 9,292 (≥ 8 years) out-of-hospital cardiac arrest (OHCA) patients transported to hospitals by emergency medical services were collected in Ishikawa Prefecture, Japan during 2010-2018. Univariate and multivariable analyses were retrospectively performed for 1,163 patients with prehospital ROSC. Results: Of 1,163 patients, rearrest occurred in 272 (23.4%) but not in 891 (76.6%). Both single and multiple doses of epinephrine administered before prehospital ROSC (adjusted odds ratio (OR): 3.62, 95% confidence interval (CI): 2.42-5.46 for 1 mg, and 4.27, 2.58-6.79 for ≥ 2 mg) were main factors associated with rearrest. The association between initial and rearrest rhythms was significantly associated with epinephrine administration (p = 0.02). However, the rearrest rhythm was primarily associated with the initial rhythm (p < 0.01). The majority of patients with the non-shockable initial rhythm had pulseless electrical activity (PEA) as the rearrest rhythm, regardless of epinephrine administration (80.4% for administration, 81.6% for no administration). When the initial rhythm was shockable, the primary rearrest rhythms in patients with and without epinephrine administration before prehospital ROSC were PEA (52.2%) and ventricular fibrillation/pulseless ventricular tachycardia (56.8%), respectively. Only epinephrine administration after rearrest was associated with prehospital re-attainment of ROSC (adjusted OR: 2.49, 95% CI: 1.20-5.19). Stepwise multivariable logistic regression analyses revealed that neurologically favorable outcome was poorer in patients with rearrest than those without rearrest (9.9% vs. 25.0%, adjusted OR: 0.42, 95% CI: 0.23-0.73). The total prehospital doses of epinephrine were associated with poorer neurological outcome in a dose-dependent manner (adjusted OR: 0.22, 95% CI: 0.13-0.36 for 1 mg; 0.09, 0.04-0.19 for 2 mg; 0.03, 0.01-0.09 for ≥ 3 mg, no epinephrine as a reference). Transportation to hospitals with a unit for post-resuscitation care was associated with better neurological outcome (adjusted OR: 1.53, 95% CI: 1.02-2.32). Conclusions: The requirement for epinephrine administration before prehospital ROSC was associated with subsequent rearrest. Routine epinephrine administrations and rearrest were associated with poorer neurological outcome of OHCA patients with prehospital ROSC.

[Bendamustine and rituximab combination therapy for recurrent indolent B-cell lymphomas: a retrospective single-institution study].

This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.

[VEGF secretion from Epstein-Barr virus-infected cells as a cause of severe anasarca in a patient with angioimmunoblastic T-cell lymphoma].

A 69-year-old woman presented to National Defense Medical College hospital for suspected nephrotic syndrome due to weight gain of 30 kg in 3 weeks and bilateral lower leg edema. However, her urinalysis showed microproteinuria, which excluded nephrotic syndrome. Computed tomography revealed severe systemic edema, pleural effusion, ascites, and enlarged cervical and axillary lymph nodes. Histological examination of axillary lymph node specimen showed a typical architecture of angioimmunoblastic T-cell lymphoma. One course of CHOP chemotherapy regimen was administered which improved the lymph nodes and systemic edema. The patient achieved complete remission after 6 courses of CHOP. Because serum vascular endothelial growth factor (VEGF) level was elevated before the treatment and normalized after the treatment, increased vascular permeability mediated by VEGF was hypothesized to have caused the systemic edema. In addition, VEGF secretion from Epstein-Barr virus (EBV)-infected cells was likely associated with the patient's clinical condition because B lymphocytes stained with CD20 were positive for Epstein-Barr virus-encoded small RNAs (EBERs) and VEGF.

Temporary umbilical loop colostomy for anorectal malformations.

Transumbilical surgical procedures have been reported to be a feasible, safe, and cosmetically excellent procedure for various pediatric surgical diseases. Umbilical loop colostomies have previously been created in patients with Hirschsprung's disease, but not in patients with anorectal malformations (ARMs). We assessed the feasibility and cosmetic results of temporal umbilical loop colostomy (TULC) in patients with ARMs. A circumferential skin incision was made at the base of the umbilical cord under general anesthesia. The skin, subcutaneous tissue, and fascia were cored out vertically, and the umbilical vessels and urachal remnant were individually ligated apart from the opening in the fascia. A loop colostomy was created in double-barreled fashion with a high chimney more than 2 cm above the level of the skin. The final size of the opening in the skin and fascia was modified according to the size of the bowel. The bowel wall was fixed separately to the peritoneum and fascia with interrupted 5-0 absorbable sutures. The bowel was opened longitudinally and everted without suturing to the skin. The loop was divided 7 days postoperatively, and diversion of the oral bowel was completed. The colostomy was closed 2-3 months after posterior saggital anorectoplasty through a peristomal skin incision followed by end-to-end anastomosis. Final wound closure was performed in a semi-opened fashion to create a deep umbilicus. TULCs were successfully created in seven infants with rectourethral bulbar fistula or rectovestibular fistula. Postoperative complications included mucosal prolapse in one case. No wound infection or spontaneous umbilical ring narrowing was observed. Skin problems were minimal, and stoma care could easily be performed by attaching stoma bag. Healing of umbilical wounds after TULC closure was excellent. The umbilicus may be an alternative stoma site for temporary loop colostomy in infants with intermediate-type anorectal malformations, who undergo radical anorectoplasty via a non-abdominal approach.

Time point for transport initiation in out-of-hospital cardiac arrest cases with ongoing cardiopulmonary resuscitation: a nationwide cohort study in Japan.

Aim: This study aimed to investigate the time point of the decision to initiate transport with ongoing cardiopulmonary resuscitation (CPR) in Japan. Methods: We analyzed adult out-of-hospital cardiac arrest (OHCA) cases that achieved return of spontaneous circulation (ROSC) before hospital arrival from the All-Japan Utstein Registry during 2015-2017. We constructed receiver operating characteristics (ROC) curves to illustrate the ability of achieving ROSC as a predictor of neurologically favorable outcomes as a function of increasing time points of resuscitation before ROSC. Furthermore, a multivariable logistic regression analysis was carried out to identify factors associated with outcomes. Results: Of 373,993 OHCA patients with attempted resuscitation during 2015-2017, 22,067 patients with prehospital ROSC were included in our study. Patients were divided into the shockable initial rhythm (n = 5,580) and nonshockable initial rhythm (n = 16,487) cohorts. The ROC curves showed 10 min was the best test performance time point for a neurologically favorable outcome for shockable initial rhythm patients (sensitivity, 0.78; specificity, 0.53; area under the ROC curve [AUC], 0.70) and 8 min for nonshockable initial rhythm patients (sensitivity, 0.74; specificity, 0.77; AUC, 0.83). Multivariable logistic regression analyses revealed that CPR durations using the cut-off value were independently associated with better outcomes for both shockable initial rhythm patients (odds ratio, 2.09; 95% confidence interval, 1.81-2.42) and nonshockable initial rhythm patients (odds ratio, 3.34; 95% confidence interval, 2.92-3.82). Conclusion: When Japanese emergency medical service (EMS) providers attend OHCA cases, the decision to initiate transport with ongoing CPR should be made at approximately 10 min after EMS providers initiate CPR for shockable initial rhythm patients and at approximately 8 min for nonshockable initial rhythm patients.

Feasibility of the modified balloon occlusion method using a 6-Fr balloon catheter in transbronchial lung cryobiopsy.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is useful for diagnosing diffuse parenchymal lung diseases (DPLD). To prevent bleeding during TBLC, the balloon occlusion method has been recommended. However, displacement can occur occasionally, especially with a 4-Fr balloon. We aimed to investigate whether the use of a 6-Fr balloon would allow tamponade at a more proximal position and decrease balloon displacement in TBLC under flexible bronchoscopy. METHODS: We retrospectively reviewed 20 patients with DPLD who underwent TBLC using the modified balloon occlusion method between June 2019 and May 2021. RESULTS: The median number of TBLCs was three (range, 2-5). The most common balloon placement site was the right basal bronchus (14 patients). Mild and moderate bleeding was seen in 10 patients each. Successful balloon occlusion was achieved in all patients without dislocation. CONCLUSION: The modified balloon occlusion method in TBLC under flexible bronchoscopy might be a reasonable option for bleeding prevention.

Effect of large-scale disasters on bystander-initiated cardiopulmonary resuscitation in family-witnessed, friend-witnessed and colleague-witnessed out-of-hospital cardiac arrest: a retrospective analysis of prospectively collected, nationwide, population-based data.

IMPORTANCE: The effect of large-scale disasters on bystander cardiopulmonary resuscitation (BCPR) performance is unknown. OBJECTIVE: To investigate whether and how large-scale earthquake and tsunami as well as subsequent nuclear pollution influenced BCPR performance for out-of-hospital cardiac arrest (OHCA) witnessed by family and friends/colleagues. DESIGN AND SETTING: Retrospective analysis of prospectively collected, nationwide, population-based data for OHCA cases. PARTICIPANTS: From the nationwide OHCA registry recorded between 11 March 2010 and 1 March 2013, we extracted 74 684 family-witnessed and friend/colleague-witnessed OHCA cases without prehospital physician involvement. EXPOSURE: Earthquake and tsunamis that were followed by nuclear pollution and largely affected the social life of citizens for at least 24 weeks. MAIN OUTCOME AND MEASURE: Neurologically favourable outcome after 1 month, 1-month survival and BCPR. METHODS: We analysed the 4-week average trend of BCPR rates in the years affected and before and after the disaster. We used univariate and multivariate logistic regression analyses to investigate whether these disasters affected BCPR and OHCA results. RESULTS: Multivariable logistic regression for tsunami-affected prefectures revealed that the BCPR rate during the impact phase in 2011 was significantly lower than that in 2010/2012 (42.5% vs 48.2%; adjusted OR; 95% CI 0.82; 0.68 to 0.99). A lower level of bystander compliance with dispatcher-assisted CPR instructions (62.1% vs 69.5%, 0.72; 95% CI 0.57 to 0.92) in the presence of a preserved level of voluntary BCPR performance (23.6% vs 23.8%) was also observed. Both 1-month survival and neurologically favourable outcome rates during the impact phase in 2011 were significantly poorer than those in 2010/2012 (8.5% vs 10.7%, 0.72; 95% CI 0.52 to 0.99, 4.0% vs 5.2%, 0.62; 95% CI 0.38 to 0.98, respectively). CONCLUSION AND RELEVANCE: A large-scale disaster with nuclear pollution influences BCPR performance and clinical outcomes of OHCA witnessed by family and friends/colleagues. Basic life-support training leading to voluntary-initiated BCPR might serve as preparedness for disaster and major accidents.

Efficacy and safety of sotrovimab for vaccinated or unvaccinated patients with mild-to-moderate COVID-19 in the omicron era.

Although sotrovimab, one of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies has been shown to be effective in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) with risk factors, their efficacy in mRNA COVID-19 vaccinated patients in omicron era is unknown. To evaluate the effectiveness of sotrovimab clinical data from both COVID-19 vaccinated and unvaccinated patients who were hospitalized and receiving sotrovimab at the Japanese Red Cross Medical Center were compared. The efficacy and adverse events were evaluated. Of the total 60 patients enrolled in this study, 45 had received the mRNA COVID-19 vaccine and 15 were unvaccinated. The clinical progression with low nasal cannula or face mask was not significantly different between groups (occurring in one patient in each group; p = 0.44), with no further progression in both groups. The duration of hospitalization was eight days for both groups (p = 0.90). Two patients in each group experienced adverse events (7%, p = 0.26). The results suggested that the efficacy and safety of sotrovimab against mild-to-moderate COVID-19 with risk factors in the omicron era might not be different regardless of the vaccination status. The results of the present study are encouraging; however, further randomized clinical studies are needed.

An autopsy case of idiopathic pulmonary fibrosis with remarkable honeycomb cyst expansion.

Herein, we report an autopsy case of idiopathic pulmonary fibrosis (IPF) in which remarkable honeycomb cyst expansion appeared in the clinical course. Radiological findings initially showed subpleural predominant reticulation that had progressed to usual interstitial pneumonia with honeycomb cysts, along with a restrictive pattern in the pulmonary function tests. The diameter of honeycomb cysts had gradually increased, and some cysts had abruptly expanded at the end stage. Based on pathological findings of autopsy specimens, bronchiectasis, alveolar collapse due to inflammation, and check-valve mechanism caused by a slit-like orifice of the cysts could have contributed to honeycomb cyst expansion.

Comparison of Mental Health among Japanese Healthcare Workers at Two Points during the COVID-19 Pandemic.

BACKGROUND: The prolonged pandemic of coronavirus disease 2019 (COVID-19) has resulted in mental burden among healthcare workers (HCWs). This study aimed to conduct a repeated study to assess changes in psychological concerns among Japanese HCWs. METHODS: This study is the second survey involving HCWs at the Japanese Red Cross Medical Center conducted between November 20, 2020 and December 4, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale, Center for Epidemiologic Studies Depression Scale, and 10-item Connor-Davidson Resilience Scale, respectively. RESULTS: The survey included 594 HCWs, comprising 95 physicians, 261 nurses, 150 other co-medical staff, and 88 office workers. Among them, 46 (7.7%) and 152 (25.6%) developed moderate-to-severe symptoms of anxiety and depression, respectively. Compared with those in the initial survey conducted 6 months earlier, the resilience score did not change, whereas the anxiety and depression scores improved significantly (P < 0.001, P = 0.033, respectively). However, the frequency of HCWs developing moderate-to-severe symptoms of anxiety or depression did not significantly improve. Multivariable logistic regression analysis showed that having higher anxiety symptoms was a risk factor for depression symptoms, while older HCWs and those with higher resilience were less likely to develop depression symptoms. CONCLUSIONS: Many HCWs still suffer from psychological concerns during the COVID-19 pandemic.

Seizure-like activity at the onset of emergency medical service-witnessed out-of-hospital cardiac arrest: An observational study.

AIMS: Emergency medical service (EMS) may detect seizure-like activity in addition to agonal breathing in out-of-hospital cardiac arrest (OHCA). This study investigates the incidence and predictors of seizure-like activity in nontraumatic, EMS-witnessed OHCA and their association with clinical outcomes. METHODS: This prospective study explored EMS-recorded concomitant signs/symptoms that lead to the requirement of advanced life support in patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity includes abnormal/tonic movements and eyeball deviation. Sudden OHCA was defined by the absence of signs/symptoms of impending cardiac arrest at EMS contact or progressive circulatory/respiratory depressions after the EMS contact. Neurologically favorable outcomes were defined as the cerebral performance category score of 1 or 2 at discharge. RESULTS: From April 2012 to March 2020, 465 patients were studied. The incidence of seizure-like activity at cardiac arrest onset was 12.7% (59/465) in all patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity was common during shockable initial rhythm; in patients with "sudden" OHCA; and in patients who were younger, male, or had a presumed cardiac etiology. In a boosting tree, shockable initial rhythm, "sudden" OHCA, and presumed cardiac etiology were major factors that predicted the incidence of seizure-like activity. Multivariate logistic regression models including and excluding OHCA characteristics revealed that both seizure-like activity and agonal breathing recorded during EMS-witnessed OHCA were associated with favorable outcomes. CONCLUSIONS: Seizure-like activity is a major sign/symptom of the onset of "sudden" cardiac arrest of presumed cardiac etiology, particularly in patients with shockable initial rhythms. Such activity were significantly associated with neurologically favorable outcomes.

Predictive model for the development of critical coronavirus disease 2019 and its risk factors among patients in Japan.

BACKGROUND: This study aimed to examine risk factors associated with critical coronavirus disease 19 (COVID-19) and to establish a risk predictive model for Japanese patients. METHODS: We retrospectively assessed adult Japanese patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center, Tokyo, Japan between February 1, 2020 and March 10, 2021. The patients were divided into critical and non-critical groups based on their condition during the clinical courses. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between clinical characteristics and critical illness. Based on the results, we established a predictive model for the development of critical COVID-19. RESULTS: In total, 300 patients were enrolled in this study. Among them, 86 were included in the critical group. Analyses revealed that age ≥65 y, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL were independently associated with the development of critical COVID-19. Next, a predictive model for the development of critical COVID-19 was created, and this included the following variables: age ≥65 y, male sex, diabetes, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL. The area under the receiver operating characteristic curve of the model was 0.86 (95% confidence interval, 0.81-0.90). Using a cutoff score of 12, the positive and negative predictive values of 74.0% and 80.4% were obtained, respectively. CONCLUSIONS: Upon diagnosis, the predictive model can be used to identify adult Japanese patients with COVID-19 who will require intensive treatment.

Comparison of adequacy between transbronchial lung cryobiopsy samples and endobronchial ultrasound-guided transbronchial needle aspiration samples for next-generation sequencing analysis.

BACKGROUND: Most lung cancer patients present with lesions in both lung fields and lymphadenopathy. Thus, transbronchial lung cryobiopsy (TBLC) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are commonly performed for diagnosing lung cancer. However, the adequacy of these samples for next-generation sequencing (NGS) analysis remains unclear. This study aimed to compare the adequacy between TBLC and EBUS-TBNA samples for NGS analysis. METHODS: This retrospective cohort study included patients whose lung samples were collected via TBLC or EBUS-TBNA and analyzed using NGS. Out of 46 genes, the number of genes in TBNA and TBLC samples that could not be assessed via NGS analysis was mainly evaluated. RESULTS: A total of 37 patients were included and classified into two groups (TBLC group, n = 18 and TBNA group, n = 19). The mean number of genes that could not be evaluated via NGS analysis was significantly lower in the TBLC group than in the TBNA group (0.9 vs. 10.3, P = 0.024). The median total area of tumor cells in TBLC samples was significantly greater than that in TBNA samples (6.3 [1.6-4.2] vs. 2.6 [0.2-17.3] mm2 , P < 0.01). In the TBNA group, there were two fully inadequate samples for NGS analysis with a high degree of cell crush or low tumor content, while there was no fully inadequate sample in the TBLC group. CONCLUSIONS: TBLC is more effective in obtaining adequate samples for NGS analysis than EBUS-TBNA. TBLC should be performed to obtain adequate samples for NGS analysis in lung cancer patients with target lesions in lung fields, even if they have lymphadenopathy. KEY POINTS: Significant findings of the study The mean number of genes that could not be evaluated was significantly lower in TBLC samples than in EBUS-TBNA samples (0.9 vs. 10.3, P = 0.024). TBLC could obtain adequate samples with a high concentration of uncrushed tumor cells for NGS. What this study adds To obtain samples for NGS analysis, the use of TBLC should be aggressively considered in lung-cancer patients with target lesions located in lung fields, even if they have lymphadenopathy.

A case of pulmonary sclerosing pneumocytoma diagnosed preoperatively using transbronchial cryobiopsy.

BACKGROUND: The preoperative diagnosis of pulmonary sclerosing pneumocytoma (PSP) is complicated since PSP has several histological structural patterns in the same neoplasm; hence, it is sometimes pathologically misdiagnosed as adenocarcinoma or carcinoid. In recent years, with the prevalence of transbronchial cryobiopsy (TBLC), we are able to obtain larger specimens than previously. However, to date, there have been no reports describing PSP diagnosed using TBLC. CASE REPORTS: A 43-year-old man was referred to our hospital for an abnormal lesion in the left lung discovered on routine health examination. A computed tomography scan of the chest revealed a 14-mm heterogeneous round nodule with surrounding ground-glass opacity in the left lower lobe. The tumor size increased to 18 mm in three weeks, and he developed bloody sputum. TBLC was performed using radial endobronchial ultrasonography and fluoroscopy. An occlusion balloon and prophylactic epinephrine were used to prevent severe bleeding. Histologically, epithelioid cells with solid proliferation, various papillary lesions, and hemosiderin-laden histiocytes were observed. Immunohistochemical staining revealed the histiocytes positive for thyroid transcription factor-1 and vimentin, and the type II pneumocyte-like-cells positive for cytokeratin 7. The tumor was preoperatively diagnosed as a PSP; the patient underwent left basal segmentectomy and consequently, a final diagnosed of PSP was formulated. CONCLUSION: We report the first case of PSP preoperatively diagnosed using TBLC. Therefore, cryobiopsy could be beneficial in the preoperative diagnosis of PSP.

Side effects and antibody titer transition of the BNT162b2 messenger ribonucleic acid coronavirus disease 2019 vaccine in Japan.

BACKGROUND: The coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear. METHODS: The side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition. RESULTS: In this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p < 0.001). Side effects occurred after the second dose in 571 female (92.1%) and 178 male participants (80.1%). Female participants had a higher incidence of side effects than the male participants (p < 0.001). A comparison among the age groups showed significant differences (p = 0.018), and the frequency of side effects decreased with age. Twenty-three individuals participated in the survey of antibody titer transition. After the second vaccine dose, the median antibody titers for IgG and IgM were 3.76 and 0.07 AU/mL, respectively. Both IgG and IgM titers showed a significant increase over the study period (p < 0.001). CONCLUSIONS: The BNT162b2 mRNA COVID-19 vaccine might be safe for Japanese people, and the antibody titer increased with two doses of vaccination. Larger nationwide studies are warranted to verify these findings.