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A 69-year-old woman who had undergone renal transplantation and was receiving sulfamethoxazole/trimethoprim (ST) developed pulmonary nocardiosis. To our knowledge, this is the first report of the identification of Nocardia elegans using nanopore sequencing, supported by 16S rDNA capillary sequencing findings. Chest computed tomography performed after ST initiation revealed significant improvement of the pulmonary shadows compared to previous findings. We herein report the value of nanopore sequencing for rapid identification of rare pathogens, such as Nocardia elegans. Furthermore, our findings suggest that Nocardia may infect even patients receiving ST, which is currently the most effective prophylactic drug.

Aim After the hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) around 2018, the importance of HAV vaccination was emphasized, especially for MSM-living with human immunodeficiency virus (MSM-LWHIV). Aimmugen® is licensed and distributed exclusively in Japan. While administration of three doses is recommended, 85% of recipients in the general population were reported to acquire seroprotection after the second dose. In this study, we evaluated the efficacy of two or three vaccine doses along with predictors associated with the response to Aimmugen® in MSM-LWHIV. Methods We retrospectively examined anti-HA-IgG titers of MSM-LWHIV vaccinated with Aimmugen® in our hospital. Patients' data were collected from medical records. Results Between January 2018 and October 2019, 141 subjects whose median age was 46 years old, were examined. All the subjects were on antiretroviral therapy (ART) and the median CD4 count was 615/μL. The acquisition rate of protectable anti-HA-IgG titers after the second and third dose was 71.1% and 98.6%, respectively. In 114 subjects whose anti-HA-IgG titers were tested after the second-dose, factors significantly associated with better response were prolonged ART duration and higher CD4 count. The titers of anti-HA-IgG after the third dose were higher in those who became seropositive after the second-dose than those who did not. Conclusions Three-dose of Aimmugen® for MSM-LWHIV was effective while two-dose was less effective compared to non-HIV-infected people. People-LWHIV with shorter duration of ART and lesser CD4 cell count achieved lower titers of anti-HA-IgG and might require an additional vaccination. This article is protected by copyright. All rights reserved.

HIV-1 escapes by acquiring mutations that differentially influence the course of infection. Unlike HIV-1 structural and enzymatic proteins, it remains elusive what extent the host immune-mediated selection pressure influences the variability of the accessory (Vif, Vpu, Vpr, and Nef) and regulatory (Tat and Rev) proteins. To address this, we analyzed the viral sequences encoding accessory and regulatory proteins from 446 human leukocyte antigen (HLA)-typed, chronically HIV-1 subtype B-infected, and treatment-naive individuals in Japan. We observed that Vpu and Vpr were the most and least polymorphic proteins with the average Shannon entropy scores of 0.63 and 0.38, respectively. Phylogenetically corrected methods identified a total of 161 HLA-associated polymorphisms; whereby Nef and Vpu had the highest (26.6%) and lowest (1.2%) proportion of amino acid sites associated with HLA-class I alleles, respectively. These results add further insight on the role of HLA-mediated selection pressure on HIV-1 sequence polymorphisms of HIV-1 accessory and regulatory proteins.

HIV-1 subtype/circulating recombinant form (CRF) distribution of HIV-1-positive specimens for evaluating HIV in vitro diagnostics (IVDs) were examined and compared with the HIV-1 epidemic in Japan. The nucleotide sequences of the gag-pol region of 173 plasma specimens (84, provided in 2007 and 89 in 2013-2015) were determined. HIV-1 subtype/CRF classification was performed based on the phylogenetic analyses of the sequences. The subtype/CRF distribution resulting in this study was similar to that of a previous epidemiological report. Three CRF02_AG and one unique recombinant form (URF), including subtype G and A regions, were observed in the 2013 and 2014 specimens, except in the 2007 specimens. The reference panel consisting of these specimens was practical for the evaluation of HIV IVDs in Japan.

Adoptive immunotherapy has emerged as a powerful approach to cure cancer and chronic infections. Currently, the generation of a massive number of T cells that provide long-lasting immunity is challenged by exhaustion and differentiation-associated senescence, which inevitably arise during in vitro cloning and expansion. To circumvent these problems, several studies have proposed an induced pluripotent stem cell (iPSC)-mediated rejuvenation strategy to revitalize the exhausted/senescent T cell clones. Because iPSC-derived cytotoxic T lymphocytes (iPSC-CTLs) generated via commonly used monolayer systems have unfavorable, innate-like features such as aberrant natural killer (NK) activity and limited replication potential, we modified the redifferentiation culture to generate CD8αβ(+)CD5(+)CCR7(+)CD45RA(+)CD56(−)-adaptive iPSC-CTLs. The modified iPSC-CTLs exhibited early memory phenotype, including high replicative capacity and the ability to give rise to potent effector cells. In expansion culture with an optimized cytokine cocktail, iPSC-CTLs proliferated more than 10(15)-fold in a feeder-free condition. Our redifferentiation and expansion package of early memory iPSC-CTLs could supply memory and effector T cells for both autologous and allogeneic immunotherapies.

To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan's COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government's role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

Organized hematoma (OH) is benign tumor in the maxillary sinus. The standard treatment for OH is complete surgical resection, however massive bleeding can occur during the procedure, albeit rarely. Some reports have suggested preoperative embolization is useful for reducing the volume of intraoperative bleeding. We report 3 cases of OH in the maxillary performed preoperative embolization. We identified the feeding arteries by angiography or IVR-CT, and we embolized them using Gelatin sponge particles. The embolized artery was the maxillary artery or both the maxillary and the facial artery. There were no major complications as a result of embolization. The mean fluoroscopy time was 35.8 minutes, and the mean fluoroscopy dose was 329.3 mGy. Tumor resection was performed the next day after arterial embolization. The mean bleeding volume for surgery was 383.3 ml, and the mean operative time was 194 minutes. No recurrence was observed in any of the cases over a 4-year follow-up period. We considered that it is possible that preoperative artery embolization is useful for decreasing intraoperative bleeding volume. Although the methods and usefulness of embolization await future reports, it is a technique that should be considered preoperatively because of its potential to prevent massive bleeding.

Introduction Tuberculin skin test (TST) has been used to diagnose tuberculosis (TB) and latent tuberculosis infection (LTBI). However, in Bacillus Calmette-Guerin (BCG) vaccinated patients, TST tends to produce false-positive results. According to the previous vaccination schedule, Japanese people were mandated to receive up to three doses of BCG-vaccine. The vaccination schedule was changed in 2003 and as per the new schedule, only infants are administered a dose of BCG vaccine. Our hypothesis is that this change can lead to a reduction in the cross-reaction to TST. Methods We evaluated the TST results obtained from 1097 recruits from six defense camps and 667 recruits from an air base. These TST data were divided into two groups according to the date of birth: a new group and an old group according to the BCG immunization schedule. We then analyzed positive and negative reaction of TST and erythema sizes. Results We confirmed that the change in BCG-vaccination schedule significantly decreased TST false-positive reaction (Pmeta = 1.4 × 10−18; risk ratio = 0.83; 95% confidence interval: 0.80–0.87) and erythema size (Pmeta = 1.1 × 10−4; mean difference = 6.6 mm; 95% confidence interval: 3.2 mm–9.9 mm). Conclusions We showed the reduction in BCG cross-reaction to TST, in the new BCG vaccination schedule group, compared to the old group, we also have extracted information on the improvement in the specificity of TST for LTBI and TB diagnosis, which resulted from BCG schedule change.

Background The use of intraoral scanners (IOS) has facilitated the use of digital workflows for the fabrication of implant-supported prostheses not only for single missing teeth, but also for multiple missing teeth. However, the clinical application of IOS and computer-aided design/manufacturing (CAD/CAM) in implant-supported prosthodontics remains unclear. This study aimed to compare the accuracy of digital and silicone impressions for single-tooth implants for bounded edentulous spaces and two-unit and three-unit implant-supported fixed dental prostheses for free-end edentulous spaces. Methods This study enrolled 30 patients (n = 10 for each of the three groups) with an average age of 61.9 years. Conventional silicone-based and digital IOS-based impressions were made for all patients, and the implant superstructures were fabricated. We measured the scan-body misfit and compared the accuracy of the impressions for single-unit, two-unit, and three-unit implant prostheses with a bounded edentulous space by superimposing the standard triangulated language (STL) data obtained from IOS over the STL data of the plaster model used for final prosthesis fabrication. The scan bodies of the superimposed single-molar implant, two-unit implant prosthesis without teeth on the mesial side, two-unit implant prosthesis without teeth on the distal side, three-unit implant prosthesis without teeth on the mesial side, and three-unit implant prosthesis without teeth on the distal side were designated as A, B1, B2, C1, and C2, respectively. The misfit for each scan body was calculated and the accuracies were compared using the Tukey–Kramer method. Results The average scan-body misfit for conditions A, B1, B2, C1, and C2 was 40.5 ± 18.9, 45.4 ± 13.4, 56.5 ± 9.6, 50.7 ± 14.9, and 80.3 ± 12.4 μm, respectively. Significant differences were observed between the accuracies of A and B2, A and C2, and C1 and C2 (P Conclusions IOS and CAD/CAM can find clinical applications for implant-supported prostheses of up to three units for a bounded edentulous saddle. The use of IOS could render implant treatment easier, benefiting both the surgeons and patients. Prosthesis maladjustment may lead to peri-implantitis and prosthetic fracture. Therefore, further validation of the accuracy of IOS impressions is required in patients with multiple missing teeth in long-span implant prostheses.

The utility of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for gastric subepithelial lesions (SELs) has been reported. In this study, we examined the optimal number of needle punctures during EUS-FNB for gastric SELs without rapid on-site evaluation (ROSE). The factors that allowed for a single needle puncture to arrive at the correct diagnosis were also analyzed. We conducted a retrospective study of all patients who underwent EUS-FNB to evaluate gastric SELs between April 2015 and September 2020; 51 patients with 57 gastric SELs were enrolled. The optimal number of needle punctures was determined when additional needle passes did not increase diagnostic sensitivity by more than 10%. Factors allowing for only a single needle puncture to arrive at the correct diagnosis were identified by univariate and multivariate logistic regression analyses. EUS-FNB resulted in a definitive final diagnosis in 48 of 57 lesions (84%). Lesions in the gastric body (odds ratio [OR] 6.15, 95% confidence interval [CI] 1.75–21.6; P

Rapid establishment of herd immunity with vaccination is effective to combat emerging infectious diseases. Although the incorporation of adjuvant and intradermal (ID) injection could augment early responses to the vaccine, the current chemical or biological adjuvants are inappropriate for this purpose with their side effects and high reactogenicity in the skin. Recently, a near-infrared (NIR) laser has been shown to augment the immune response to ID vaccination and could be alternatively used for mass vaccination programs. Here, we determined the effect of NIR laser as well as licensed chemical adjuvants on the immunogenicity 1, 2, and 4 weeks after ID influenza vaccination in mice. The NIR laser adjuvant augmented early antibody responses, while the widely used alum adjuvant induced significantly delayed responses. In addition, the oil-in-water and alum adjuvants, but not the NIR laser, elicited escalated TH2 responses with allergenic immunoglobulin E (IgE) responses. The effect of the NIR laser was significantly suppressed in the basic leucine zipper transcription factor ATF-like 3 (Batf3) knockout mice, suggesting a critical role of the cluster of differentiation 103+ (CD103)+ dendritic cells. The current preliminary study suggests that NIR laser adjuvant is an alternative strategy to chemical and biological agents to timely combat emerging infectious diseases. Moreover, its immunomodulatory property could be used to enhance the efficacy of immunotherapy for allergy and cancer.

Background The association between the development of checkpoint inhibitor pneumonitis (CIP) with tumor response and survival has remained unclear so far. The aim of the present study was to evaluate the association between CIP and the clinical efficacy of anti‐programmed cell death‐1 antibody in patients with advanced non‐small cell lung cancer (NSCLC). Methods Between January 2016 and August 2019, 203 advanced NSCLC patients were administered with nivolumab or pembrolizumab. Comparisons were made between patients with and without CIP. We evaluated the time‐to‐treatment failure (TTF), progression‐free survival (PFS), and overall survival (OS). Results CIP was observed in 28 (14%) patients. CIP was associated with a longer PFS (18.9 months [95% confidence interval, CI: 8.7 months–not reached] vs. 3.9 months [95% CI: 3.4–5.1 months, p, This study aimed to evaluate the association between checkpoint inhibitor pneumonitis (CIP) and the clinical efficacy of anti‐programmed cell death‐1 monotherapy in patients with advanced non‐small cell lung cancer (NSCLC). CIP was associated with a longer PFS (18.9 months vs. 3.9 months, p

Despite the growing importance of oxygen-delivery devices worldwide, there are only a few reports of physiological data on various oxygen masks in children. The possibility of carbon dioxide (CO2) rebreathing has been a prevalent concern with the use of oxygen-delivery devices. OxyMask KidTM (Southmedic Inc. Canada; hereafter OxyMask) is expected to reduce CO2 rebreathing even at low oxygen flow rates because of its structural features. Biological data using OxyMask in children have not been well investigated. Measured respiratory parameters of OxyMask with those of a simple oxygen mask in healthy children were compared. Ten subjects were enrolled, with a median age of 5.4 years. All subjects used both OxyMask and a simple oxygen mask. The fraction of inspiratory oxygen (FIO2), partial pressure of inspiratory CO2 (PICO2), and partial pressure of end-tidal CO2 were measured using a sidestream gas-sampling monitor in all subjects. The oxygen flow rate was set at 1, 3, 5, and 10 L/min. FIO2 levels were higher with OxyMask than those with the simple oxygen mask at 3 L/min of oxygen. PICO2 levels were significantly lower with OxyMask than those with the simple oxygen mask (1.5 mmHg vs. 3.7 mmHg at 1 L/min, P = 0.005; 1.0 mmHg vs. 2.7 mmHg at 3 L/min, P = 0.005, respectively), whereas PICO2 levels were higher at low oxygen flow rates with both masks.Conclusion: Our results showed that higher FIO2 and less CO2 rebreathing were achieved with OxyMask than those with a simple oxygen mask at low flow rates of oxygen in healthy children. What is Known: • OxyMask is expected to reduce carbon dioxide rebreathing even at low oxygen flow rates because of its structural features. • Efficacy has been demonstrated in experimental models and adult data, but clinical data on the use of the OxyMask in children are limited. What is New: • Higher fraction of inspiratory oxygen and lesser carbon dioxide rebreathing were achieved with OxyMask than with a simple oxygen mask at low flow rates of oxygen in healthy children.

Background and Objective Patients with position-dependent obstructive sleep apnea have a > 2-fold higher apnea-hypopnea index when sleeping in a supine position compared with a non-supine position. We investigated the effect of body pillow use on sleeping body position and sleep architecture in healthy young adults. Methods In experiment 1, we evaluated the body pressure distribution with or without body pillow use in 8 healthy young adults [age, 36.5 ± 13.0 years; body mass index (BMI); 20.6 ± 1.2 kg/m2]. In experiment 2, we performed a randomized-crossover intervention study to evaluate the effects of body pillow use on sleeping position and sleep architecture in 10 healthy young adults (age, 24.3 ± 7.8 years; BMI, 21.4 ± 1.7 kg/m2). Sleep architecture was characterized by polysomnography, and body positions were monitored using a sensor. Subjective sleep quality was evaluated with the Oguri-Shirakawa-Azumi sleep inventory, middle age and aged version. Results In experiment 1, body pillow use significantly reduced mean body pressure on the shoulder, hip, and whole body. In experiment 2, mean time spent in the supine, lateral, and prone body positions did not differ significantly between the 2 trials. Body pillow use, however, significantly extended the sustained time spent in the lateral body position compared with the control trial. Subjective sleep quality and sleep architecture did not differ significantly between the 2 trials, but body pillow use decreased the number of short (30 s) slow-wave sleep episodes. Conclusions Sleeping with a body pillow effectively extends sustained time in a lateral sleeping position and prevents segmentation of slow-wave sleep episodes.

Hospital-acquired severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection is a healthcare challenge. We hypothesized that polymerase chain reaction testing of symptomatic triaged outpatients and all inpatients before hospitalization in Shinjuku, a coronavirus disease 2019 (COVID-19) epicenter in Tokyo, using the Tokyo Women's Medical University (TMWU) model would be feasible and efficient at preventing COVID-19. This retrospective study enrolled 2981 patients from March to May 2020. The prevalence of SARS-CoV-2 infection was 1.81% (95% credible interval [CI]: 0.95–3.47%) in triaged symptomatic outpatients, 0.04% (95% CI: 0.0002–0.2%) in scheduled asymptomatic inpatients, 3.78% (95% CI: 1.82–7.26%) in emergency inpatients, and 2.4% (95% CI: 1.49–3.82%) in symptomatic patients. There were no cases of hospital-acquired SARS-CoV-2 infection. This shows that the TWMU model could prevent hospital-acquired SARS-CoV-2 infection and is feasible and effective in reducing the impact of SARS-CoV-2 infection in the hospitals.

Residents with limited experience of thoracic surgery have difficulty performing video-assisted thoracoscopic surgery (VATS) lobectomy. However, they can learn early in a stepwise training method to safely manage the pulmonary veins (PVs), which are relatively strong vessels. In this study, we investigated whether the time required to manage the PVs could serve as an indicator of technical skill acquisition in VATS lobectomy. To evaluate the acquisition of residents’ technical skills, we retrospectively assessed the PV management time of 5 residents at our institution who had performed more than 15 VATS lobectomies over an 8-year period (2012–2019). Their PV management time was determined from surgical video. We analyzed whether PV management time was affected by patient characteristics, operative factors, and experience of lobectomy. The 5 residents performed a total of 103 VATS lobectomies during the study period. Median PV management time was 9.6 min. The most frequently resected lobe was the right upper lobe (56.3%). Median PV management time for right middle lobe was 5.2 min, which was shorter than that for other lobes. We categorized the lobectomies according to whether PV management time was ≤10 min or > 10 min. Univariate analysis identified that shorter PV management time (≤10 min) was significantly associated with more right middle lobectomies performed (7.3% vs 0%, p = 0.02) and more lobectomies performed (14 vs 8, p = 0.01). Longer PV management time (>10 min) was significantly associated with lower lobectomies performed (18% vs 35%, p

HLA-A, -C, -B, and -DRB1 genotypes were analyzed in 178 Japanese COVID-19 patients to investigate the association of HLA with severe COVID-19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA-DRB1*09:01 and severe COVID-19 (odds ratio [OR], 3.62; 95% CI, 1.57-8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID-19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID-19.

Introduction Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza. Methods The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system. Results A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67–84), and the patients in the 2015–2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality. Conclusions Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989).

Background In locations where the alveolar bone height is low, such as at the maxillary molars, implant placement can be difficult, or even impossible, without procedures aimed at generating new bone, such as sinus lifts. Various types of bone graft materials are used after a sinus lift. In our study, a three-dimensional image analysis using a volume analyzer was performed to measure and compare the volume of demineralized bovine bone mineral (Bio-Oss®) and carbonate apatite (Cytrans®) after a sinus lift, as well as the amount of bone graft material resorption. Patient data were collected from cone-beam computed tomography images taken before, immediately following, and 6 months after the sinus lift. Using these images, both the volume and amount of resorption of each bone graft material were measured using a three-dimensional image analysis system. Results The amount of bone resorption in the Bio-Oss®-treated group was 25.2%, whereas that of the Cytrans®-treated group was 14.2%. A significant difference was found between the two groups (P < 0.001). Conclusions Our findings indicate that the volume of bone resorption was smaller in the Cytrans®-treated group than in the Bio-Oss®-treated group, suggesting that Cytrans® is more promising for successful implant treatments requiring a sinus lift.

Abstract An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding myeloid cell expansion have been collected in Europe, where the mortality rate by COVID-19 is greater than those in other regions including Japan. Thus, characteristics of COVID-19-induced myeloid cell subsets remain largely unknown in the regions with low mortality rates. Here, we analyzed cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis, using blood samples from Japanese COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, but not other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Contrary to previous studies in Europe, this subset selectively expanded in survivors of severe cases and subsided before discharge, but such transient expansion was not observed in non-survivors in Japanese cohort. Analysis of plasma cytokine/chemokine levels revealed positive correlation of PMN-MDSC frequencies with IL-8 levels, indicating the involvement of IL-8 on recruitment of PMN-MDSCs to peripheral blood following the onset of severe COVID-19. Our data indicate that transient expansion of the PMN-MDSC subset results in improved clinical outcome. Thus, this myeloid cell subset may be a predictor of prognosis in cases of severe COVID-19 in Japan.

We herein report a case of diffuse alveolar hemorrhage (DAH) associated with dilated cardiomyopathy (DCM) and sleep apnea syndrome (SAS) in a 47-year-old man. The patient exhibited recurring dyspnea and bloody sputum. Chest radiography showed bilateral diffuse infiltrative opacities without pleural effusion. A bronchoscopic analysis of bronchoalveolar lavage fluid revealed hemosiderin-laden macrophages. Based on these findings, he was diagnosed with DAH. Laboratory and pathological findings ruled out the possibility of collagen diseases and vasculitis. Overnight polysomnography revealed concomitant severe obstructive SAS. Treatment with continuous positive-pressure ventilation and pharmacological therapy for DCM prevented recurrence of DAH.

Objective: Hypertensive disorders of pregnancy (HDP) are thought to be a multifactorial genetic disease. Myosin light chain phosphorylation, which is involved in the regulation of vascular smooth m...

This study aimed to examine the incidence of hypertensive disorders of pregnancy (HDP) among Japanese women with oocyte donation pregnancy (ODP) aged 40 years or older and estimate whether the women with ODP were more likely to develop HDP than those with autologous oocyte pregnancy (AOP) and spontaneous pregnancy (SP). In our study (N = 1361), the proportions of women who developed HDP were 20.5%, 12.8%, and 7.6% for ODP, AOP, and SP, respectively. After adjustment of covariables, the women with ODP were more likely to develop HDP than those with AOP or SP.

Background Implant treatment using guided surgery is becoming widespread in clinical dental practice. Furthermore, the development of digital technology has enabled the use of intraoral scanners (IOSs) to fabricate surgical guide plates. The objective of this study was to compare the accuracy of guided surgery using the silicone impression method with a three-dimensional (3D) scanner and the digital impression method with IOS for one side of the mandibular free end. In addition, we compared the accuracy of tooth-supported vs tooth/mucosa-supported surgical guide plates. Results The accuracy of the tooth-supported surgical guide plate using the new IOS method instead of the method of obtaining impressions with conventional silicone resulted in better measurements of 3D deviation at the crest, 3D deviation at the apex, and angular deviation. In terms of the accuracy of the tooth/mucosa-supported surgical guide plate, there were no significant differences in all measurements. The surgical guide plate using an IOS and the tooth/mucosa-supported surgical guide plate may enable more accurate guided surgery. Conclusion Tooth/mucosa-supported guided surgery involving preparation with an IOS may result in more accurate implant surgery.

Immunotherapy is considered one of the most important therapeutic strategies for patients with lung adenocarcinoma after the development of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance. However, useful predictors of immunotherapy for these patients has not been examined well, although the status of the tumor immune microenvironment (TIME), including programmed death‐ligand 1 expression and lymphocyte infiltration, has been generally known to provide predictive markers for the efficacy of immunotherapy. This study aimed to clarify novel predictors of immunotherapy following EGFR‐TKI resistance in lung adenocarcinoma, especially regarding micro RNA (miRNA). We evaluated the correlation between EGFR‐TKI resistance and lymphocyte infiltration, before and after acquiring EGFR‐TKI resistance, in 21 cases of lung adenocarcinoma, and further explored this by in vitro studies, using miRNA PCR arrays. Subsequently, we transfected miRNA‐1 (miR‐1), the most variable miRNA in this array, into three kinds of lung cancer cells, and examined the effects of miR‐1 on EGFR‐TKI sensitivity, cytokine expression and lymphocyte migration. Histopathological examination demonstrated that infiltration levels of CD8‐positive T cells were significantly decreased after development of EGFR‐TKI resistance. In vitro studies revealed that miR‐1 significantly inhibited EGFR‐TKI effect and induction of cytokines, such as C‐C motif chemokine ligand 5 and C‐X‐C motif chemokine ligand 10, causing inhibition of monocyte migration. These results indicate that the upregulated miR‐1 might suppress the TIME, following development of EGFR‐TKI resistance. Therefore, miR‐1 could be a clinically useful marker to predict therapeutic efficacy of immunotherapy in lung adenocarcinoma patients with EGFR‐TKI resistance., We firstly revealed that intra‐tumoral CD8‐positive T cells are decreased in lung adenocarcinoma patients acquiring EGFR‐TKI resistance when levels of miR‐1 are raised. In addition, patients with high expression of miR‐1 may be less likely to benefit from subsequent immunotherapy using immune checkpoint inhibitor (ICI). Therefore, an evaluation of serum miR‐1, before treatment and after acquiring EGFR‐TKI resistance, could contribute to predicting therapeutic efficacy of subsequent ICI therapy for the patient.

Acute heart failure (AHF) has become a global public health burden largely because of the associated high morbidity, mortality, and cost. The treatment options for AHF have remained relatively unchanged over the past decades. Historically, clinical congestion alone has been considered the main target for treatment of acute decompensation in patients with AHF; however, this is an oversimplification of the complex pathophysiology. Within the similar clinical presentation of congestion, significant differences in pathophysiological mechanisms exist between the fluid accumulation and redistribution. Tissue hypoperfusion is another vital characteristic of AHF and should be promptly treated with appropriate interventions. In addition, recent clinical trials of novel therapeutic strategies have shown that heart failure management is ‘time sensitive’ and suggested that treatment selection based on individual aetiologies, triggers, and risk factor profiles could lead to better outcomes. In this review, we aim to describe the specifics of the ‘time‐sensitive’ approach by the clinical phenotypes, for example, pulmonary/systemic congestion and tissue hypoperfusion, wherein patients are classified based on pathophysiological conditions. This mechanistic classification, in parallel with the comprehensive risk assessment, has become a cornerstone in the management of patients with AHF and thus supports effective decision making by clinicians. We will also highlight how therapeutic modalities should be individualized according to each clinical phenotype.