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Macrophages contribute to post-transplant lung rejection. Disulfiram (DSF), an anti-alcoholic drug, has an anti-inflammatory effect and regulates macrophage chemotactic activity. Here, we investigated DSF efficacy in suppressing acute rejection post-lung transplantation. Male Lewis rats (280–300 g) received orthotopic left lung transplants from Fisher 344 rats (minor histocompatibility antigen-mismatched transplantation). DSF (0.75 mg/h) monotherapy or co-solvent only (50% hydroxypropyl-β-cyclodextrin) as control was subcutaneously administered for 7 days (n = 10/group). No post-transplant immunosuppressant was administered. Grades of acute rejection, infiltration of immune cells positive for CD68, CD3, or CD79a, and gene expression of monocyte chemoattractant protein and pro-inflammatory cytokines in the grafts were assessed 7 days post-transplantation. The DSF-treated group had significantly milder lymphocytic bronchiolitis than the control group. The infiltration levels of CD68+ or CD3+ cells to the peribronchial area were significantly lower in the DSF than in the control groups. The normalized expression of chemokine ligand 2 and interleukin-6 mRNA in allografts was lower in the DSF than in the control groups. Validation assay revealed interleukin-6 expression to be significantly lower in the DSF than in the control groups. DSF can alleviate acute rejection post-lung transplantation by reducing macrophage accumulation around peripheral bronchi and suppressing pro-inflammatory cytokine expression.

Abstract Background Pulmonary segmentectomy for a lung with an incomplete interlobar fissure may complicate persistent air leakage. The fissureless technique is often used in lobectomy to prevent persistent air leakage. We herein describe successful use of the fissureless technique for segmentectomy with the aid of a robotic surgical system. Case presentation A 63-year-old man was clinically diagnosed with early-stage lung cancer for which lingular segmentectomy was indicated. A preoperative image revealed a lung with an incomplete fissure. Based on three-dimensional reconstruction imaging, we planned to divide the hilum structures in the order of the pulmonary vein, bronchus, and pulmonary artery and finally resect the lung parenchyma by dividing the intersegmental plane and interlobar fissure. This fissureless technique was successfully conducted using a robotic surgical system. The patient did not develop persistent air leakage and was alive without recurrence 1 year after segmentectomy. Conclusions The fissureless technique may be a useful option in segmentectomy for a lung with an incomplete interlobar fissure.

Living-donor lobar lung transplantation (LDLLT) is a well-established surgical procedure with favorable outcomes; however, the frequency of readmission and costs in LDLLT are poorly understood. Here, we aimed to compare health care costs and readmissions at 90 days and 1 year after the index discharge in LDLLT and cadaveric lung transplantation (CLT) and evaluate the reasons for readmission and in-hospital mortality. In this retrospective cohort study, we used the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan to obtain initial lung transplantation data for all patients from July 2010 to March 2020. Multivariable Poisson or multiple regression analyses after multiple imputation was performed to compare the cumulative number of readmissions and costs between patients receiving LDLLT and CLT. Among 514 recipients, 115 (22%) underwent LDLLT and 399 (78%) received CLT. Overall, in-hospital mortality after transplantation was 4.5%. The LDLLT group showed a significantly lower crude readmission rate (90 days, 22% vs 37%, p = 0.004; 1 year, 48% vs 62%, p = 0.031) and median readmission cost (90 days, United States dollar (USD) 0 vs 0, p = 0.003; 1 year, USD 1178 vs 4714, p = 0.005) than the CLT group. Multivariable regression analyses showed that the LDLLT group had a lower risk of readmission (incidence rate ratio, 0.59; 95% confidence interval, 0.38-0.92; p = 0.020) and lower costs at 90 days (difference, USD −11,629; 95% confidence interval, −5682 to −17,462; p

Objective: There is little evidence of the outcome of pulmonary metastasectomy for uterine tumors when comparing different histologies. This study aimed to delineate the primary histology that leads to more favorable outcomes after pulmonary metastasectomy. Methods: The database of the Metastatic Lung Tumor Study Group of Japan for 1984 to 2016 was used to analyze the outcomes of patients with gynecologic malignancies who underwent pulmonary metastasectomy. Prognostic factors and long-term outcomes were compared according to the histology of the primary uterine tumors, specifically adenocarcinoma, squamous cell carcinoma, and sarcoma. The adjusted hazard risks according to disease-free intervals (DFIs) and the number and maximum size of resected tumors were also analyzed to delineate the pattern of risk trends. Results: A total of 319 patients were included in the analysis (122 with adenocarcinomas, 113 with squamous cell carcinomas, 46 with sarcomas, and 38 with other types). The 5-year survival rate was 66.5% for the entire cohort, 71.6% for the patients with adenocarcinoma, 61.3% for those with squamous cell carcinoma, and 55.4% for those with sarcoma. Multivariate analyses identified the positive prognostic factors as DFI ≥12 months in adenocarcinoma and sarcoma and the primary site (corpus) of uterine tumors in adenocarcinoma. The nonlinear adjusted hazard risks indicated that a shorter DFI was associated with an elevated risk of death in patients with adenocarcinoma and sarcoma. Conclusions: The survival outcome after pulmonary metastasectomy varies according to primary tumor histology, and the prognostic factors differ among histologic subtypes. Surgical indications should be determined based on the prognostic factors for each histology.

Abstract Lung transplantation (LT) is the only option for patients with pulmonary arterial hypertension (PAH) refractory to maximal medical therapy. However, some patients referred for LT could survive without LT, and its determinants remain unclear. This study aimed to elucidate prognostic factors of severe PAH at the referral time. We retrospectively analyzed 34 patients referred for LT evaluation. The primary outcome was a composite of death or LT. Over a median follow-up period of 2.56 years, eight patients received LT and eight died. Compared with LT-free survival group, pulmonary arterial systolic pressure (PASP) was higher (p = 0.042), and the ratio of tricuspid annular plane systolic excursion (TAPSE) to PASP (TAPSE/PASP) was lower (p = 0.01) in LT or death group. In receiver operating characteristic analysis, the area under the curve was 0.759 (95% confidence interval 0.589–0.929) for TAPSE/PASP to predict primary outcome, and the optimal cut-off value was 0.30 mm/mmHg (sensitivity 0.875 and specificity 0.667). In a multivariate analysis, TAPSE/PASP was independently associated with death or LT. Kaplan–Meier analysis showed a better LT-free survival in patients with TAPSE/PASP ≧0.30 mm/mmHg than in those with

Abstract In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial thymectomy, the prognosis is greatly improved by ensuring a sufficient margin from the tumor, and therefore intraoperative fluorescent imaging of the tumor is especially valuable in thoracoscopic and robotic surgery, where tactile information is not available. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been applied for fluorescence imaging of some types of tumors in the resected tissues, and here we aimed to examine its validity for the imaging of thymoma and thymic carcinoma. 22 patients with thymoma or thymic carcinoma who underwent surgery between February 2013 and January 2021 were included in the study. Ex vivo imaging of specimens was performed, and the sensitivity and specificity of gGlu-HMRG were 77.3% and 100%, respectively. Immunohistochemistry (IHC) staining was performed to confirm expression of gGlu-HMRG's target enzyme, γ-glutamyltranspeptidase (GGT). IHC revealed high GGT expression in thymoma and thymic carcinoma in contrast to absent or low expression in normal thymic parenchyma and fat tissue. These results suggest the utility of gGlu-HMRG as a fluorescence probe for intraoperative visualization of thymomas and thymic carcinomas.

Pulmonary artery aneurysms (PAAs) occurring in the distal branch of the pulmonary artery are rare, and there are only a few reports of transcatheter embolization of unruptured idiopathic peripheral PAAs. We report a case of a 66-year-old woman with a history of surgery for pulmonary arteriovenous malformations who presented with an idiopathic peripheral PAA of A10 confirmed by contrast-enhanced computed tomography and pulmonary artery angiography. Transcatheter embolization was performed to prevent rupture, and the aneurysm was successfully embolized. Although there is no consensus on the indications and treatment for unruptured idiopathic peripheral PAAs, transcatheter embolization may be a favorable treatment option.

Acupuncture is an alternative treatment for a variety of diseases, and serious complications are rare. We report a case of transcatheter arterial embolization performed in a patient with a massive hemothorax after acupuncture treatment.A 36-year-old woman with no previous medical history was admitted to our hospital with left back pain and respiratory distress after acupuncture treatment. Contrast-enhanced computed tomography showed a left hemothorax and leakage of contrast medium, which was considered to result from an injury to the second intercostal artery, caused by acupuncture treatment. Transcatheter arterial embolization successfully stopped the bleeding, and the hematoma was thoracoscopically removed. No rebleeding was observed 6 months after treatment.

Abstract Background Thrombotic microangiopathy is a syndrome characterized by microangiopathic hemolytic anemia and platelet aggregation, which is caused by endothelial injury, microcirculation thrombosis, and fibrin deposition. Transplant-associated thrombotic microangiopathy rarely occurs after lung transplantation and the onset is generally later than that after bone marrow or other solid organ transplantation. The treatment is to stop administration of the causal agent, which is often a calcineurin inhibitor, such as tacrolimus and cyclosporine. We herein report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation treated by introducing basiliximab and temporarily stopping any calcineurin inhibitors until resuming treatment with an alternative calcineurin inhibitor. Case presentation A 58-year-old Asian woman underwent bilateral lung transplantation for hypersensitivity pneumonitis caused by an avian antigen, or bird fancier’s lung disease. Postoperatively, she was started on triple immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and steroids. On postoperative day 6, she developed thrombocytopenia followed by fever, hemolytic anemia, renal dysfunction, and purpura on her limbs and abdomen. She was diagnosed with transplant-associated thrombotic microangiopathy, and tacrolimus was thought to be the causal agent. We stopped tacrolimus and administered basiliximab. Then, she developed oliguria and needed continuous hemodiafiltration. On postoperative day 14, the platelet count recovered and she was switched from basiliximab to cyclosporine. Using this protocol, worsening thrombotic microangiopathy and acute rejection were avoided. Conclusions We report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation that was treated with basiliximab. Switching from calcineurin inhibitors using basiliximab may be an option for treating thrombotic microangiopathy without increasing the risk of acute rejection.

Abstract Background Thymic epithelial tumors (TETs) exhibit irregular shapes reflective of the heterogeneity in tumor growth and invasive properties. We aimed to identify the prognostic value of the pathological tumor long‐to‐short axis (L/S) ratio in TETs. Methods A retrospective study was performed on patients with TETs who underwent extended thymectomy between January 1999 and December 2019 in our institute. Patients were divided into two groups according to the threshold of the L/S ratio. Overall survival (OS) and progression‐free survival (PFS) were evaluated by Kaplan‐Meier analysis. The independent prognostic factors of TETs were identified by multivariate analysis. The performance of prediction models for the above survival outcomes with and without the L/S ratio was evaluated using an integrated time‐dependent area under the curve (iAUC). Results Eligible patients were divided into two groups based on higher (n = 42) and lower (n = 94) L/S ratios according to a threshold value of 1.39. A significant difference was found between the two groups only in disease progression (p = 0.001). Poorer survival outcomes were found from Kaplan‐Meier curves in the higher L/S ratio group (p 1.39 is associated with worse survival outcomes.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Abstract Objectives Distally located small common bile duct stones are often difficult to treat or grasp endoscopically. Therefore, multiple devices, such as baskets or balloon catheters, are frequently used in such cases. However, it is desirable to use a single device for stone extraction from the perspective of cost‐effectiveness. In this multicenter study, we evaluated the efficacy of a new eight‐wire basket catheter for extracting small (≤10 mm) common bile duct stones. Methods We retrospectively analyzed the records of 144 patients who underwent stone extraction using the eight‐wire basket catheter for common bile duct stones ≤10 mm. The success rate of complete stone extraction and the risk factors for the difficulty in stone extraction with the eight‐wire catheter alone were mainly evaluated. Results The success rate of stone extraction with the eight‐wire catheter alone was 86.1%. The final rate of complete stone extraction was 98.0%. The mean of the maximum diameter of the common bile duct and the largest stone dimension were 10.5 ± 3.5, and 5.1 ± 2.1 mm, respectively. Common bile duct diameter ≥12 mm and stone diameter ≥6 mm were identified as independent risk factors for the difficulty in stone extraction with the eight‐wire catheter alone. Conclusions The success rate of the new eight‐wire basket for small common bile duct stone extraction was acceptable. The device is beneficial and could be used from the start for the extraction of small stones

Background: Blunt chest trauma is a common presentation in emergency departments. The relationship between bone fractures and organ injuries has not been studied in detail. The purpose of this study was to examine the degree of external force represented by the number of rib fractures that causes lung injury in blunt chest trauma. Patients and methods: This study was performed retrospectively using trauma patients who received medical examinations in a single university hospital emergency center between April 2015 and March 2020. We examined the association between the number of rib fractures and pulmonary damage using multivariable regression analysis and considered the relationship between rib fracture location and each type of lung injury. Results: A total of 317 patients were included. The mean age was 63.1 years, 65.0% were male, and traffic accidents were the most common mechanism of injury (55.8%). The number of mean rib fractures was 4.0, and the mean Injury Severity Score was 11.3. The number of rib fractures was associated with an increased risk of pulmonary injuries: pulmonary contusion (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.14–1.48, p

Abstract Rapid identification of lung-cancer micro-lesions is becoming increasingly important to improve the outcome of surgery by accurately defining the tumor/normal tissue margins and detecting tiny tumors, especially for patients with low lung function and early-stage cancer. The purpose of this study is to select and validate the best red fluorescent probe for rapid diagnosis of lung cancer by screening a library of 400 red fluorescent probes based on 2-methyl silicon rhodamine (2MeSiR) as the fluorescent scaffold, as well as to identify the target enzymes that activate the selected probe, and to confirm their expression in cancer cells. The selected probe, glutamine-alanine-2-methyl silicon rhodamine (QA-2MeSiR), showed 96.3% sensitivity and 85.2% specificity for visualization of lung cancer in surgically resected specimens within 10 min. In order to further reduce the background fluorescence while retaining the same side-chain structure, we modified QA-2MeSiR to obtain glutamine-alanine-2-methoxy silicon rhodamine (QA-2OMeSiR). This probe rapidly visualized even borderline lesions. Dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase were identified as enzymes mediating the cleavage and consequent fluorescence activation of QA-2OMeSiR, and it was confirmed that both enzymes are expressed in lung cancer. QA-2OMeSiR is a promising candidate for clinical application.

Abstract Background Sublineage BA.5 of the SARS‐CoV‐2 Omicron variant rapidly spread and replaced BA.2 in July 2022 in Tokyo. A high viral load can be a possible cause of high transmissibility. Methods and Results The copy numbers of SARS‐CoV‐2 in nasopharyngeal swab samples obtained from all patients visiting the hospital where this research was conducted were measured using reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Viral genotypes were determined using PCR‐based melting curve analysis. Next, whole‐genome sequencing was performed using approximately one fifth of the samples to verify the viral genotypes determined using PCR. Then, the copy numbers of the BA.1, BA.2, and BA.5 cases were compared. Contrary to expectations, the copy numbers of the BA.5 cases (median 4.7 × 104 copies/μL, n = 291) were significantly (p = .001) lower than those of BA.2 cases (median 1.1 × 105 copies/μL, n = 184). There was no significant difference (p = .44) between the BA.5 and BA.1 cases (median, 3.3 × 104 copies/μL; n = 215). Conclusion: The results presented here suggest that the increased infectivity of BA.5 is not caused by higher viral loads, but presumably by other factors such as increased affinity to human cell receptors or immune escape due to its L452R mutation.

A 16-year-old girl with a genetic diagnosis of cystic fibrosis was referred to us for consideration of lung transplantation. She had been hospitalized repeatedly for pneumonia and pneumothoraxes and her respiratory function had worsened progressively. Although she also had liver cirrhosis, she was considered a candidate for lung transplantation because her liver disease was compensated and only slowly progressive. After bilateral lung transplantation from a brain-dead donor, she developed ascites that was well controlled with diuretics. Otherwise, her post-operative course was uneventful and she was transferred to another hospital for rehabilitation 39 days after lung transplantation.

Elimination of regulatory T cells via the anti-CCR4 monoclonal antibody, mogamulizumab, is expected to augment anti-tumour immune response. Authors show here that although regulatory T cell targeting is successful, clinical improvement remains minimal in patients with solid tumours due to concomitant and unintended depletion of central memory CD8+ T cells.

Introduction: Lung cancer presenting as ground-glass nodules (GGNs) with little consolidation is often diagnosed as noninvasive carcinoma. Increasing evidence suggests that sublobar lung resection, such as wedge resection, provides satisfactory long-term outcomes equivalent to those of lobectomy. Spread through alveolar spaces (STAS) is a reported risk factor for recurrence, especially when sublobar lung resection is applied. We herein report a rare case of a pure GGN that was histologically confirmed to be adenocarcinoma in situ (AIS) and associated STAS after limited resection. Case presentation: A 67-year-old woman presented with an 8-mm pure GGN in S2 of the right upper lobe and a part-solid GGN in S8 of the right lower lobe. The clinical stages of these GGNs were TisN0M0 stage 0 and T1aN0M0 stage IA1, respectively. The patient underwent video-assisted thoracoscopic segmentectomies of S2 and S8. Histopathological examination of the resected specimens revealed minimally invasive adenocarcinoma in S8 and AIS in S2. Stromal invasion was not observed in the tumor located in S2, but a tumor cell cluster was found in the air space located away from the AIS lesion. Thus, the lesion was positive for STAS. Conclusion: We have reported a rare case of a pure GGN that was histologically STAS-positive, otherwise diagnosed as AIS after limited resection.

Abstract Background Although the number of patients who undergo extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is increasing worldwide, there are few reports on lung transplantation after long-term ECMO (more than 1 month). We report a rare case of successful bilateral lung transplantation in a Japanese patient after 5 months of veno-venous (VV)-ECMO support. Case presentation A 27-year-old man who underwent bone marrow transplantation (BMTx) with fully matched human leukocyte antigen typing was diagnosed with bronchiolitis obliterans caused by chronic graft-versus-host disease 3 years after the BMTx. One year later, his respiratory condition had exacerbated, with carbon dioxide retention that required conventional mechanical ventilation. He was then deemed a suitable candidate for lung transplantation by a multidisciplinary transplantation selection committee. While waiting for donor lungs, his hypercapnia and acidosis became barely manageable under care with mechanical ventilation and ultimately he was switched to VV-ECMO. He remained on VV-ECMO for the next 5 months, during which period the circuit was switched nine times. In addition, sophisticated intensive care was required to manage multiple episodes of sepsis and coagulopathy. A suitable donor was identified 5 months later, and bilateral lung transplantation was initiated with continuous VV-ECMO. The procedure itself was extremely challenging owing to severe adhesions resulting from previous thoracotomy, inflammation, infection, and intrapulmonary hemorrhage. The operative time for the transplantation was about 19 h. Currently, at 2 years 8 months postoperatively, the patient is alive and well. Conclusion Transplant surgery in this patient was extremely challenging because of the presence of severe pleural adhesions and stiff native lungs secondary to hemorrhagic complications due to the prolonged ECMO support. Surgeons must recognize that lung transplantation after long-term ECMO bridging can be technically more complicated and challenging than shorter-term ECMO.

Abstract Information regarding the molecular features of pulmonary pleomorphic carcinoma (PPC) is insufficient. Here, we performed next-generation sequencing to determine the genomic and transcriptomic profiles of PPC. We sequenced the DNAs and RNAs of 78 specimens from 52 patients with PPC. We analyzed 15 PPC cases to identify intratumoral differences in gene alterations, tumor mutation burden (TMB), RNA expression, and PD-L1 expression between epithelial and sarcomatoid components. The genomic alterations of six cases of primary tumors and corresponding metastatic tumors were analyzed. KRAS mutations (27%) were the most common driver mutations, followed by EGFR (8%), and MET (8%) mutations. Epithelial and sarcomatoid components shared activating driver mutations, and there were no significant differences in CD274 expression or TMB between the two components. However, PD-L1 was highly expressed in the sarcomatoid component of several cases compared with the epithelial component. Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.

Abstract Background A bronchial fistula is a relatively rare and potentially fatal complication after lung transplantation. Thoracic surgeons and pulmonologists often face challenges when selecting treatment options. We herein report an exceptional case of intrabronchial migration of a nonabsorbable hemostatic agent, which had been placed around the pulmonary artery at the time of lung transplantation, through a bronchial fistula. Case presentation A 61-year-old man developed respiratory distress 1 year after left single-lung transplantation for idiopathic interstitial pneumonia. Bronchoscopic examination revealed an apparent foreign body protruding from the mediastinum into the distal site of the bronchial anastomosis. The foreign body was easily removed bronchoscopically and appeared to be a hemostatic agent that had been placed during the previous lung transplantation. The patient developed a similar clinical episode and finally developed hemoptysis. Computed tomography revealed a foreign body located between the bronchus and pulmonary artery, partially protruding into the bronchial lumen. Given the possibility of a bronchopulmonary arterial fistula, surgical treatment was performed. The foreign body was located between the bronchus and left pulmonary artery and was easily removed. Multiple bronchial fistulas were found, and all were closed with direct sutures. Bypass grafting of the left pulmonary artery was then performed, initially with a homograft but eventually with an extended polytetrafluoroethylene graft. The patient was finally discharged 5 months after the surgery. Conclusion We experienced an extremely rare case of intrabronchial migration of hemostatic agents used during the previous lung transplantation through a bronchial fistula, which were successfully managed by direct bronchial closure and bypass grafting of the left pulmonary artery.

Abstract Background Bronchial necrosis is a rare but fatal complication after radiation therapy. Because of the anatomical complexity and rarity of this condition, determining the most appropriate management for individual patients is extremely challenging. Lung autotransplantation is a surgical technique that has been applied to hilar neoplastic lesions to preserve pulmonary function and avoid pneumonectomy. We herein report a case of bronchial necrosis secondary to radiotherapy that was treated with lung autotransplantation. Case presentation A 46-year-old man developed broad necrosis and infection of the right bronchus secondary to previous stereotactic body-radiation therapy. This treatment was supplied close to a right hilar metastatic pulmonary tumor derived from a mediastinal malignant germ cell tumor that had been surgically resected with the left phrenic nerve. The bronchial necrosis accompanied by infection with Aspergillus fumigatus was progressive despite antibiotics and repetitive bronchoscopic debridement. Because of the patient’s critical condition and limited pulmonary function, right lung autotransplantation with preservation of the right basal segment was selected. An omental flap was placed around the bronchial anastomosis to prevent later complications. The postoperative course involved multiple complications including contralateral pneumonia and delayed wound healing at the bronchial anastomosis with resultant stenosis, the latter of which was overcome by placement of a silicone stent. The patient was discharged 5 months postoperatively. Three months after discharge, however, the patient developed hemoptysis and died of bronchopulmonary arterial fistula formation. Conclusions We experienced an extremely challenging case of bronchial necrosis secondary to radiotherapy. The condition was managed with lung autotransplantation and omental wrapping; however, the treatment success was temporary and the patient eventually died of bronchopulmonary arterial fistula formation. This technique seems to be a feasible option for locally advanced refractory bronchial necrosis, although later complications can still be fatal.

ABSTRACT Neisseria meningitidis causes a life-threatening invasive meningococcal disease (IMD). Isolates resistant to antibiotics, such as penicillin, ceftriaxone, and ciprofloxacin that are recommended for the treatment of IMD patients and their close contacts have been serious public health concerns globally. However, susceptibility profiles to critically important antibiotics and the genetic characteristics of isolates possessing antibiotic resistance are extremely limited as IMD incidence is low in Japan. We assessed the susceptibility profiles of 87 randomly selected, sterile site-derived N. meningitidis strains isolated from hospitals nationwide, recovered between April 1998 and March 2018 in Japan, to seven antibiotics. As a result, we demonstrated, for the first time, that the isolates remained highly susceptible to ceftriaxone, meropenem, azithromycin, ciprofloxacin, chloramphenicol, and rifampin, but not to penicillin. We then characterized the genetic relatedness of six penicillin- and/or ciprofloxacin-resistant isolates obtained in this study with global 112 genomes using core-genome phylogenetic analysis. These results provide the first evidence that invasive lineages such as a penicillin-resistant serogroup W, sequence type (ST)-11 clonal complex (CC), and a ciprofloxacin-resistant serogroup B/C, ST-4821 CC that is considered as a global threat, have been sporadically identified in Japan. Our findings highlight the need to monitor antibiotic resistance in clinical isolates of N. meningitidis, thereby preventing the spread of antibiotic-resistant invasive lineages and maintaining effective treatment for IMD patients and their close contacts. IMPORTANCE Although antibiotics such as penicillin and ceftriaxone can treat invasive meningococcal disease (IMD), the emergence and spread of antibiotic-resistant Neisseria meningitidis have become a global concern. To provide effective treatment, including chemoprophylaxis to IMD patients and their close contacts, we highlighted the importance of recognizing the antibiotic resistance and genetic features of N. meningitidis isolates.

We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each component suggested that mutations in RB1, TP53, and SMAD4 and apparent loss of heterozygosity of TP53 and SMAD4 accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including PTEN, MST1R, and PIK3CA were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma. Combined DNA and RNA analysis using Todai OncoPanel revealed that transdifferentiation to different pathologic subtypes occurred in a single tumor through the accumulation of gene mutations.

Aim: This study evaluated whether the prehospital administered dosage of epinephrine (Ep) influences the plasma levels of catecholamines in patients with out-of-hospital cardiac arrest (OHCA). Methods: This was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were analyzed. The plasma levels of catecholamines were measured using blood samples obtained immediately upon arrival at the hospital and before the administration of Ep. Patients were divided into three groups based on the prehospital administered dosage of Ep: no prehospital administration (group Z); 1 mg of Ep (group O); and 2 mg of Ep (group T). The levels of catecholamines, as well as the conditions of resuscitation prior to and after arrival at the hospital were compared between the three groups. Results: We analyzed 145 patients with OHCA (96, 38, and 11 patients in groups Z, O, and T, respectively). Group T exhibited the highest plasma levels of Ep with a statistically significant difference, however, there were no significant differences in the plasma levels of norepinephrine (Nep), dopamine (DOA) and vasopressin (ADH) among the three groups. Conclusion: The prehospital administered dosage of Ep influences the plasma levels of Ep; however, it does not contribute to the plasma levels of Nep, DOA and ADH in patients with OHCA.

Abstract Background Clostridioides difficile ribotype (RT) 019/sequence type (ST) 67 strains belong to a hypervirulent lineage closely related to RT027/ST1; however, limited data are available for hypervirulent clade 2 lineages in Japan. Herein, we report the draft genome of a C. difficile strain B18-123 belonging to clade 2, RT019/ST67 for the first time in Japan. Results The pathogenicity locus carried by B18-123 (19.6 kb) showed higher homology (97.29% nucleotide identity) with strain R20291 (RT027/ST1) than the reference strain 630 (RT012/ST54), and B18-123 harbored 8-nucleotide substitutions in tcdC. However, it did not contain an 18-base pair (bp) deletion or a single-bp deletion at position 117 in tcdC, which was identified in the previous strain R20291. A cytotoxicity assay revealed similar cytotoxicity levels between strains B18-123 and ATCC BAA-1870 (RT027/ST1). The B18-123 strain was found to be susceptible to metronidazole and vancomycin. Conclusion Our findings contribute to the further understanding of the characteristics of hypervirulent clade 2 including RT019/ST67 lineages.

Background The current staging systems do not consider the tumor location of thymomas, and its clinical relevance is poorly understood. This study aimed to evaluate the impact of tumor location on the clinicopathological features and prognosis of thymomas. Methods We performed a retrospective review of patients at our institution who underwent an extended thymectomy for a thymoma from 1976 to 2015. The tumor location was classified as either the superior or inferior mediastinum based on the maximum tumor diameter. The clinicopathological characteristics of the thymoma were also evaluated. Kaplan‐Meier estimates and Cox proportional hazards models were used to analyze the survival outcomes and risk factors for recurrence. Results A total of 194 patients with thymoma were eligible for this study. Compared with the inferior mediastinum group (n = 167), the superior mediastinum group (n = 27) had a higher frequency of myasthenia gravis (MG), advanced Masaoka‐Koga staging, disease progression and recurrence (P

Objectives: We evaluated the impact of age in septic patients admitted through the ER on clinical outcome and cost. Methods: Patients with sepsis admitted to the intensive care unit (ICU) through the emergency room in our hospital between January 2013 and December 2018 were analyzed. They were divided into three groups according to their age:

Background The thyroid ima artery (ThIA) is a rare anatomical anomaly, commonly branching from the brachiocephalic artery. Thyroid ima artery injury can cause severe mediastinal hematoma because its descending branch extends into the mediastinum. Case presentation A 91‐year‐old man presented with syncope after a motor vehicle accident. A bruise on the chest was evident. Contrast‐enhanced computed tomography revealed a massive mediastinal hematoma with signs of active hemorrhage. Injury to a descending branch of the ThIA was indicated. Transcatheter arterial embolization (TAE) was successful in stopping the bleeding. Conclusions Although a ThIA injury is rare, it can cause serious mediastinal hematoma. Thyroid ima artery injury should be considered as a cause of traumatic mediastinal hematoma. Transcatheter arterial embolization for traumatic ThIA injury is considered a safe and effective treatment.

Purpose. The dynamic state of epinephrine (Ep) in the plasma of patients with out-of-hospital cardiac arrest (OHCA) remains unclear. The purpose of this study was to evaluate the relationship between the plasma levels of catecholamines (such as epinephrine (Ep), norepinephrine (Nep), and dopamine) and vasopressin (antidiuretic hormone (ADH)) and the acquisition of return of spontaneous circulation (ROSC) in OHCA patients. Methods. This was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were enrolled. The levels of catecholamines and ADH in the plasma were measured using blood samples immediately obtained on arrival at our hospital and before the administration of Ep. Patients in whom Ep was already administered prior to obtaining blood samples were excluded. Patients were divided into two groups: with and without ROSC, that is, ROSC (+) and ROSC (−) groups, respectively. The plasma levels of these agents and the conditions of resuscitation were compared between the two groups. Results. A total of 96 patients with OHCA were analyzed. The ROSC (+) and ROSC (−) groups included 34 and 62 patients, respectively. There were no significant differences observed between the two groups in age, cause of cardiopulmonary arrest, and prehospital resuscitation time. The plasma levels of Ep and Nep were significantly lower in the ROSC (+) group than in the ROSC (−) group. However, there were no significant differences in the plasma levels of dopamine and ADH between the two groups. Conclusion. Increased levels of Ep in the plasma may not be associated with the acquisition of ROSC in patients with OHCA.

Background Not all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed. Here, we report the results of a phase 2 clinical trial of adoptive cell therapy using zoledronate-expanded autologous Vγ9Vδ2 T-cells for treatment-refractory NSCLC.Methods NSCLC patients who had undergone at least two regimens of standard chemotherapy for unresectable disease or had had at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase 2 study. After preliminary testing of Vγ9Vδ2 T-cell proliferation, autologous peripheral blood mononuclear cells were cultured with zoledronate and IL-2 to expand the Vγ9Vδ2 T-cells. Cultured cells (>1×109) were intravenously administered every 2 weeks for six injections. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), safety and immunomonitoring. Clinical efficacy was defined as median PFS significantly >4 months.Results Twenty-five patients (20 adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma) were enrolled. Autologous Vγ9Vδ2 T-cell therapy was administered to all 25 patients, of which 16 completed the foreseen course of 6 injections of cultured cells. Median PFS was 95.0 days (95% CI 73.0 to 132.0 days); median OS was 418.0 days (179.0–479.0 days), and best overall responses were 1 partial response, 16 stable disease (SD) and 8 progressive disease. ORR and DCR were 4.0% (0.1%–20.4%) and 68.0% (46.5%–85.1%), respectively. Severe adverse events developed in nine patients, mostly associated with disease progression. In one patient, pneumonitis and inflammatory responses resulted from Vγ9Vδ2 T-cell infusions, together with the disappearance of a massive tumor.Conclusions Although autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint.Trial registration number UMIN000006128

Neuroleptic malignant syndrome is a rare but life-threatening disorder associated with the use of neuroleptic drugs, and is characterized by fever, altered mental status, muscle rigidity, autonomic instability, myoclonus, elevated creatine kinase levels, rhabdomyolysis, and leukocytosis. Previous reports have shown that most patients with neuroleptic malignant syndrome recover without neurologic sequelae. Some patients with neuroleptic malignant syndrome show reversible magnetic resonance imaging (changes in the brain. The severe neurological impairments do not persist in neuroleptic malignant syndrome patients with reversible lesions. Here, we describe a 66-year-old Japanese woman who was diagnosed with septic shock secondary to obstructive pyelonephritis. She was administered haloperidol for delirium and developed neuroleptic malignant syndrome. Magnetic resonance imaging of the brain showed diffuse hyperintense signals in the cerebellar cortex, cerebellar dentate nucleus, superior cerebellar peduncle, and thalamus on T2-weighted imaging or fluid-attenuated inversion recovery, and in the bilateral substantia nigra and bilateral globus pallidus on diffusion-weighted imaging. Subsequently, the signal intensities of the cerebellar and thalamic lesions diminished and the basal ganglia lesions disappeared, but the severe neurologic sequelae remained. The cerebellum is reportedly particularly sensitive to thermal damage because Purkinje cells are believed to be vulnerable to heat. Although brain imaging studies revealed reversible changes, her disturbance of consciousness was prolonged. Therefore, brain magnetic resonance imaging findings might not reflect the neurologic prognosis in patients with neuroleptic malignant syndrome.

Background: Catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) is an effective treatment. However, the frequency of asymptomatic AF recurrence after CA in patients with PAF and sick sinus syndrome (SSS) is not clear. The aim of this study was to elucidate the real AF recurrence after CA in patients with PAF and a pacemaker for SSS. Methods and results: Fifty-one consecutive patients (mean age 66.6 ± 7.0 years, male 34) with PAF and SSS and pacemakers underwent CA. All patients were followed at 1, 3, 6, 9, and 12 months after the CA using a 12-lead ECG, Holter-ECG, and 1-month event recorder as a conventional follow-up. In addition, the pacemakers were interrogated every 12 months. During a 5-year follow-up after the final CA procedure, AF recurrences were observed in 7 patients (13.7%) with a conventional follow-up, including 1 (2.0%) asymptomatic patient. Pacemaker-interrogation revealed another 10 patients (19.6%) with asymptomatic AF recurrences. Ultimately, the conventional follow-up plus pacemaker-interrogation provided a higher incidence of AF recurrences (P = 0.009). Multiple CA procedures contributed to a significant increase in the AF-free survival rate at 5 years: 58.6% after a single CA and 86.0% after multiple CA procedures with a conventional follow-up, but which decreased to 40.6% and 60.9% with a conventional follow-up plus a pacemaker interrogation, respectively. Conclusions: One-third of PAF patients with SSS and pacemakers recurred after multiple CA sessions. However, 65% of them were asymptomatic and difficult to be identified with conventional follow-up. Pacemaker interrogation significantly increased the detection rate of AF-recurrence.

Abstract Background Adenocarcinoma with lepidic growth pattern presents as a ground glass nodule (GGN) on high resolution computed tomography (CT), whereas peripheral pulmonary squamous cell carcinoma (SCC) usually presents as a solid nodule. We herein report a rare case of pulmonary SCC extending along the alveolar lumen representing as a GGN on a CT scan in a patient with pneumoconiosis. Case presentation A 77-year-old man with pneumoconiosis was found to have a gradually enlarging GGN in the right lower lobe of the lung on CT. An adenocarcinoma of the lung was suspected. The GGN was successfully resected by thoracoscopic segmentectomy. Pathological examination of the resected specimen was pathologically diagnosed as a stage IA SCC extending along the alveolar lumen. The patient had no evidence of recurrence 19 months after surgery. Conclusions SCC should be included in the differential diagnosis of peripherally located GGNs, especially in patients at high risk of SCC of the lung such as those with pneumoconiosis.

Abstract Background Virtual-assisted lung mapping (VAL-MAP) has been used not only in wedge resection but also in segmentectomy for hardly palpable lung nodules. We herein report a case of bilateral segmentectomy using VAL-MAP with chronological change of pulmonary function test results. Case presentation A 50-year-old female was found to have a colorectal cancer with pulmonary nodules in both sides of the lungs considered as synchronous lung metastases. After sigmoidectomy for primary cancer and chemotherapy, treatments for small nodules in both sides of the lungs were planned. Most nodules were small and supposed to be impalpable. We performed thoracoscopic segmentectomy of right S8 with the aid of VAL-MAP and, after 2 months, combined subsegmentectomy of left S8a and 9a and wide wedge resection of left S8b with the aid of VAL-MAP. All nodules suspected of lung metastases were successfully resected with adequate margins, and the decrease in pulmonary function was minimal compared with predicted postoperative forced vital capacity (FVC) and forced expiratory volume (FEV) 1.0 calculated by the numbers of subsegments. Conclusions Bilateral segmentectomies of small impalpable metastatic tumors were performed successfully with the aid of VAL-MAP.

Background: The present study aimed to elucidate the safety and effectiveness of a noble and unique airway management technique in which a pediatric intubation tube is used in adult patients with atrial fibrillation (AF) undergoing catheter ablation (CA) under continuous deep sedation. Methods: In total, 246 consecutive patients with AF (mean age, 65±10 years; 60 women) underwent CA under dexmedetomidine-based continuous deep sedation. A 4-mm pediatric intubation tube guided by a 10-French intratracheal suction tube was inserted smoothly, and the tip of the tube was located at the base of the epiglottis. The maximum shifting distance of the heart (MSDH) was measured with the 3D mapping system (Ensite NavX system) before and after inserting the pediatric intubation tube. Results: At baseline, the MSDH of patients under continuous deep sedation was 23±14 mm. The pediatric intubation tube reduced the MSDH to 13±6 mm (mean reduction from baseline, 38.4±21.7%; P

Abstract Background Virtual-assisted lung mapping is a novel bronchoscopic lung marking technique that uses virtual images to perform multiple concurrent dye marking of barely palpable pulmonary tumors. Subsequent chest computed tomography is required to confirm the locations marked. We here report a patient in whom computed tomography after virtual-assisted lung mapping unexpectedly revealed additional tiny pulmonary nodules. Case presentation A 64-year-old woman with a history of renal cell carcinoma presented with two pulmonary nodules suspicious of metastases from renal cell carcinoma. Because we anticipated that the nodules would be difficult to palpate intraoperatively, we performed virtual-assisted lung mapping prior to attempting to resect them. Computed tomography after mapping unexpectedly detected two additional nodules. Although the existing markings did not relate to the newly found nodules, we used imaginary auxiliary lines and anatomical landmarks to extend the lung map to incorporate the unexpected nodules. The additional nodules were successfully resected by thoracoscopic wedge resection. Pathologic examination identified all nodules as metastases from renal cell carcinoma, and the surgical margins were negative. Conclusions Imaginary auxiliary lines and anatomical landmarks extended the existing lung map of virtual-assisted lung mapping, enabling resection of unexpected pulmonary nodules found in post-mapping computed tomography images.

Background: Adjuvant chemotherapy (AC) is known to be beneficial for stage III colorectal cancer (CRC). In contrast, only a few studies have reported the survival benefits of AC for stage IV CRC after curative surgery. Methods: We identified 155 CRC patients with various organ metastases who underwent curative surgery in our hospital between 2003 and 2017. Clinicopathological parameters and postoperative AC were reviewed. Multivariate analyses were performed to identify prognostic factors. Moreover, the effects of AC on recurrence-free survival (RFS) and overall survival (OS) were analyzed using inverse probability of treatment weighting. Results: The cohort comprised 94 males and 61 females, with a mean age of 63 years. AC was administered to 57% of patients who underwent surgery between 2003 and 2010 and 76% between 2011 and 2017 ( p = 0.015). AC was more likely administered to patients with a good performance status, high preoperative albumin level, regional node and peritoneal metastases, and no intraoperative blood transfusion. Multivariate analyses identified AC as a significant prognostic factors for RFS and OS [hazard ratio (HR): 1.86, p = 0.003, and 2.66, p = 0.002, respectively]. After adjusting for different backgrounds, 5-year RFS and OS rates were higher in patients receiving AC (27% and 67%) than in those without AC (14% and 46%, p < 0.0001 and p = 0.0005). Subgroup analyses showed that AC significantly improved RFS in node-negative patients (HR: 2.16, p = 0.029), and RFS and OS in node-positive patients (HR: 2.03, p < 0.0001, and 2.02, p = 0.001, respectively). Conclusion: AC can be discussed with resectable stage IV CRC patients because of its significant survival-improving effects.

BACKGROUND: We set out to examine the activity of γ-glutamyltranspeptidase (GGT) in lung cancer and the validity of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) for intraoperative imaging of primary lung cancer. METHODS: GGT activities and mRNA expression levels of GGT1 (one of the GGT subtypes) in five human lung cancer cell lines were examined by fluorescence imaging and quantitative reverse transcription polymerase chain reaction. In vivo imaging of an orthotopic A549 xenograft model in nude mice was performed to confirm its applicability to intraoperative imaging. Furthermore, ex vivo imaging of 73 specimens from lung cancer patients were performed and analyzed to calculate the sensitivity/specificity of gGlu-HMRG for lung cancer diagnosis. RESULTS: GGT activities and mRNA expression levels of GGT1 are diverse depending on cell type; A549, H441, and H460 showed relatively high GGT activities and expression levels, whereas H82 and H226 showed lower values. In the in vivo mouse model study, tiny pleural dissemination and hilar/mediastinal lymph node metastasis (less than 1 mm in diameter) were clearly detected 15 minutes after topical application of gGlu-HMRG. In the ex vivo study of specimens from patients, the sensitivity and specificity of gGlu-HMRG were calculated to be 43.8% (32/73) and 84.9% (62/73), respectively. When limited to female patients, never smokers, and adenocarcinomas, these values were 78.9% (15/19) and 73.7% (14/19), respectively. CONCLUSIONS: Although GGT activity of lung cancer cells vary, gGlu-HMRG can serve as an intraoperative imaging tool to detect small foci of lung cancer when such cells have sufficient GGT activity.

Equestrianism is associated with a risk of severe trauma due to falls and/or direct injury from the horse, depending on the mechanism of injury. This article presents four cases of equestrian injury treated in Gunma University Hospital: Case 1: hepatic injury (fall and kick by the horse); Case 2: left hemopneumothorax and pulmonary contusion with multiple rib fractures (fall and trampling by the horse); Case 3: lumbar compression fracture (fall); and Case 4: scrotum injury (horse bite). Equestrian injuries may be high-energy traumas. Therefore, adhering to relevant primary care guidelines may prevent mortality by trauma.

BackgroundAlthough several studies have reported an association between atrial fibrillation (AF) and alcohol, the impact of alcohol consumption on the outcome after catheter ablation (CA) for AF has not been discussed. We aimed to elucidate the effect of alcohol consumption on the outcome of CA for paroxysmal AF. Methods and ResultsWe examined 1361 consecutive patients with paroxysmal AF (mean age, 61±11 years, 334 women) who underwent CA, including 623 (45.8%) patients who consumed alcohol. The clinical characteristics and outcomes of CA were compared between patients who did and did not consume alcohol. No significant differences were seen in the left atrial size, duration of AF history, and incidence of nonpulmonary vein foci between 2 groups (P=NS). Although the AF recurrence‐free rate after the initial CA was higher in patients who did not consume alcohol (261/623 [41.9%] versus 252/738 [34.1%]; mean follow‐up, 44.4±30.7 months; P=0.003), the outcome after the final CA was similar between 2 groups (patients who consumed alcohol: 111/628 [17.7%] versus patients who did not consume alcohol: 138/738 [18.7%]; mean follow‐up, 53.1±25.8 months; P=0.67). The frequency (hazard ratio 1.07 per 1 day/week increase, CI 1.00–1.15, P=0.04) of alcohol consumption was significantly associated with AF recurrence after CA. ConclusionsThe frequency of alcohol consumption may be associated with AF recurrence after the initial CA for paroxysmal AF, but it may not affect the outcome after the final CA.

Miriplatin, a cisplatin derivative with a high affinity for iodized ethyl esters of fatty acids from poppy seed oil, is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma (HCC). Here, we describe transcatheter arterial infusion (TAI) using miriplatin to treat a case of advanced HCC with portal vein tumor thrombus (PVTT) refractory to TAI with epirubicin. A 66-year-old man with advanced hepatitis C virus-related HCC with PVTT in the right lobe of the liver was treated with TAI with epirubicin suspended in iodized oil; however, tumor marker levels (alpha-fetoprotein and des-gamma-carboxy protein) did not decrease. Next, he was treated twice with TAI with miriplatin suspended in iodized oil. The tumor marker levels markedly decreased to a nearly normal range and the size of the main tumor was markedly reduced according to dynamic computed tomography. No serious adverse events occurred during the course of treatment with TAI and miriplatin. Therefore, we suggest that TAI with miriplatin is a safe and effective treatment option for advanced HCCs refractory to TAI with epirubicin.

Comprehensive immunological evaluation is crucial for monitoring patients undergoing antigen-specific cancer immunotherapy. The identification and quantification of T cell responses is most important for the further development of such therapies. Using well-characterized clinical samples from a high responder patient (TK-f01) in an NY-ESO-1f peptide vaccine study, we performed high-throughput T cell receptor β-chain (TCRB) gene next generation sequencing (NGS) to monitor the frequency of NY-ESO-1-specific CD8+ T cells. We compared these results with those of conventional immunological assays, such as IFN-γ capture, tetramer binding and limiting dilution clonality assays. We sequenced human TCRB complementarity-determining region 3 (CDR3) rearrangements of two NY-ESO-1f-specific CD8+ T cell clones, 6-8L and 2F6, as well as PBMCs over the course of peptide vaccination. Clone 6-8L possessed the TCRB CDR3 gene TCRBV11-03*01 and BJ02-01*01 with amino acid sequence CASSLRGNEQFF, whereas 2F6 possessed TCRBV05-08*01 and BJ02-04*01 (CASSLVGTNIQYF). Using these two sequences as models, we evaluated the frequency of NY-ESO-1-specific CD8+ T cells in PBMCs ex vivo. The 6-8L CDR3 sequence was the second most frequent in PBMC and was present at high frequency (0.7133%) even prior to vaccination, and sustained over the course of vaccination. Despite a marked expansion of NY-ESO-1-specific CD8+ T cells detected from the first through 6th vaccination by tetramer staining and IFN-γ capture assays, as evaluated by CDR3 sequencing the frequency did not increase with increasing rounds of peptide vaccination. By clonal analysis using 12 day in vitro stimulation, the frequency of B*52:01-restricted NY-ESO-1f peptide-specific CD8+ T cells in PBMCs was estimated as only 0.0023%, far below the 0.7133% by NGS sequencing. Thus, assays requiring in vitro stimulation might be underestimating the frequency of clones with lower proliferation potential. High-throughput TCRB sequencing using NGS can potentially better estimate the actual frequency of antigen-specific T cells and thus provide more accurate patient monitoring.

Unicentric Castleman’s disease is a rare, benign lymphoproliferative disorder that is curable with surgical resection. However, significant bleeding often occurs during surgery because of tumor hypervascularity. We herein present a case of hyaline-vascular-type mediastinal unicentric Castleman’s disease, successfully resected using video-assisted thoracoscopic surgery with preoperative embolization. In the present case, tumor hypervascularity and feeding vessels were revealed by computed tomography (CT), which led us to perform preoperative angiography and embolization to the tumor feeding arteries to reduce intraoperative bleeding. Castleman’s disease should be considered in the differential diagnosis of hypervascular mediastinal tumors. Tumor vascularity should be assessed prior to surgery, and preoperative embolization should be considered.

Background: This retrospective observational study aimed to examine whether clinical inflammatory parameters were associated with the requirement dosage of unfractionated heparin (UFH) to maintain the range of ACT in veno-arterial extracorporeal membrane oxygenation (V-A ECMO) during lung transplantation surgery. Methods: Among all patients who underwent lung transplantation using V-A ECMO from January 2021 to May 2022, 27 patients were included. These patients were divided into two groups based on whether the infusion rate of UFH was increased from the initial infusion rate (7-8 units/kg/h) (increased group, n = 10) or the infusion rate was maintained or decreased (non-increased group, n = 17). The infusion rate was adjusted with an activated clotting time (ACT) target of 160-200 s. Results: At 1-2 h after starting ECMO, ACT was significantly lower (179.0 (166.5-188.5) versus 224.0 (193.0-242.0) sec, p = 0.006) and white blood cell (WBC) counts were higher in the increased group (12.6 ± 3.3 versus 9.5 ± 4.0 x 103/lL, p = 0.046). The UFH infusion rates were higher in the increased group during the surgery. The cutoff value of WBC count at 1-2 h after starting ECMO for discriminating the need for increasing the UFH dosage was determined as 10.2 x 103/lL (sensitivity 90.0%, specificity 58.8%, area under the curve 0.712) and discrimination of this cut-off value was confirmed as statistically significant (p = 0.018). Conclusion: These data suggested that WBC count was associated with the requirement of an increase in the UFH infusion rate of V-A ECMO during lung transplantation surgery. Further evaluation is necessary to clarify the role of WBC count in determining the optimal UFH dosage. [ABSTRACT FROM AUTHOR]