Incidence of air leaks in patients undergoing robotic thoracic surgery and video-assisted thoracic surgery.

Postoperative air leakage is the most common complication in surgery for malignant lung tumors, leading to extended hospital stays and substantial medical expenses. This study aimed to identify the incidence and characteristics of intraoperative and postoperative air leaks in both robotic-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS), as well as the causes of persistent air leakage following RATS. We conducted a retrospective analysis of patients who underwent lung resection for malignant lung tumors at our institution from October 2018 to August 2022. We compared the incidence rates of intraoperative air leak, postoperative air leak, and persistent air leak between patients who underwent RATS and those who underwent VATS. Background factors were adjusted using propensity score matching. A subanalysis was performed to compare unexpected air leaks, defined as air leaks not observed intraoperatively but confirmed postoperatively. The study included 295 cases of RATS and 227 cases of VATS. In both the overall population and the matched group (187 cases each for RATS and VATS), RATS demonstrated a significantly higher incidence of persistent air leaks compared to VATS (11% vs 3%, p < 0.01; 9% vs 3%, p = 0.02, respectively). RATS also had a significantly higher incidence of unexpected air leaks compared with VATS (29% vs 18%, p = 0.05). Although there was no statistically significant difference in hospital stays, RATS showed a higher incidence of postoperative persistent air leaks and unexpected postoperative air leaks than VATS.

Transcriptomic profiling of a late recurrent nuclear protein in testis carcinoma of the lung 14 years after the initial operation: a case report.

Background: Nuclear protein in testis (NUT) carcinoma (NC) of the lung is a rare cancer that occurs mainly in young adolescents and adults. NC is genetically characterized by NUTM1 rearrangements, which usually take the form of BRD4-NUT fusions. The prognosis for NC is dismal, and treatment with conventional chemotherapeutic regimens is ineffective. Case Description: We herein describe the case of a 53-year-old woman with recurrent NC of the lung 14 years after surgery for nasal cavity cancer. Chest computed tomography revealed a 5.5-cm tumor in the lower lobe of the left lung. We completely resected the recurrent lung NC via thoracotomy. Immunohistochemistry (IHC) of the lung and nasal cavity cancers showed diffuse strong expression of NUT. RNA-seq of the lung NC revealed NUTM1 rearrangement, with a fusion of BRD4 exon 10 to NUTM1 exon 4. This breakpoint has never been reported before. In addition, IHC revealed elevated expression of parathyroid hormone-like hormone in the lung NC but not in the nasal cavity NC, indicating that the lung and nasal cavity NCs were metachronous multiple primary cancers. Conclusions: We experienced a rare recurrence of lung NC 14 years after the initial surgery. The BRD4-NUT fusion consisted of a new breakpoint. Furthermore, the expression pattern of parathyroid hormone-like hormone (PTHLH) suggested that the NCs in the nasal cavity and lung may be metachronous multiple lung cancers. This extremely rare case highlighted the possibility of identifying less malignant NCs in patients with poorly differentiated tumors via fusion gene analysis and the need to develop more effective treatment strategies for this malignancy.

Efficacy of Immune Checkpoint Inhibitors in Postoperative Recurrence of Wild-type EGFR Non-Small Cell Lung Cancer.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC), but specific outcomes of ICIs treatment among patients with postoperative recurrence of NSCLC remain unclear. The objective of the study was to compare the efficacy of ICIs and chemotherapy with conventional chemotherapy only in patients with postoperative recurrence of epidermal growth factor receptor (EGFR) wild-type NSCLC. PATIENTS AND METHODS: A retrospective analysis was performed on patients who underwent anatomical lung resection at the Nagoya University Hospital and were treated for postoperative recurrence of wild-type EGFR NSCLC. This study evaluated the prognosis for postoperative recurrence, including ICIs treatment and other clinicopathological factors. RESULTS: Of the 83 patients included in the analysis, 20 patients underwent chemotherapy and 63 patients underwent chemotherapy combined with ICIs. The combination of ICIs and chemotherapy significantly prolonged survival after recurrence (median survival: 33.1 months vs. 22.0 months, p=0.01). In the ICIs group, no significant differences in survival were detected between patients with different programmed death ligand 1 (PD-L1) status (Tumor Proportion Scores: <1%, 1%-49%, ≥50%, p=0.27). Multivariate analysis revealed that postoperative distant recurrence was a significant poor prognostic factor for survival after recurrence (HR=1.85, 95% CI=1.06-3.25, p=0.03), and combining ICIs with chemotherapy significantly improved survival after recurrence (HR=0.43, 95% CI=0.24-0.78, p<0.01). CONCLUSION: Combination of ICIs with chemotherapy significantly prolonged survival of postoperative recurrence with wild-type EGFR NSCLC regardless of PD-L1 status.

Multidisciplinary treatment of giant thymoma, paving the way to complete surgical resection: a case report.

BACKGROUND: A multidisciplinary treatment approach is recommended for patients with extensive, advanced, or recurrent thymomas. However, detailed treatment strategies, such as chemotherapy regimens and optimal surgical procedures, are still under debate. CASE PRESENTATION: We report a case of gigantic locally advanced thymoma. A 70-year-old male was referred to our hospital following the detection of abnormal chest shadows. Chest X-ray and computed tomography (CT) scans revealed a 21-cm mass in the anterior mediastinum, encircling the pulmonary hilum and extending into the left thoracic cavity. PET/CT showed increased 18F-fluorodeoxyglucose uptake at the tumor site. Based on a trans-percutaneous CT-guided needle biopsy, the tumor was diagnosed as a Type B2 thymoma at the clinical IIIA stage. The patient underwent four cycles of preoperative induction chemotherapy, including cisplatin, doxorubicin, and methylprednisolone (CAMP), resulting in a partial response; the tumor shrank to 12 cm and FDG uptake decreased. Considering the patient's age and comorbidities, we performed total thymectomy, along with partial resections of the parietal, mediastinal and visceral pleura, pericardium, and left upper lobectomy. This approach achieved complete histological resection, mitigating the risk of recurrence. Pathological analysis confirmed a thymoma, ypT3 (lung) N0M0 stage IIIA, with no malignancy in the pericardial or pleural effusions. No recurrence was detected 9 months post-surgery. CONCLUSIONS: We report a case of giant thymoma successfully treated with multidisciplinary strategy. Surgical treatment alone may not have achieved complete resection, but after inducing significant tumor shrinkage with preoperative CAMP therapy, we were able to achieve complete resection. This treatment strategy may be effective in large thymoma cases.

Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer.

BACKGROUND: The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. METHODS: We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results. RESULTS: Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). CONCLUSION: Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

The role of SLC26A4 in bony labyrinth development and otoconial mineralization in mouse models.

Inner ear malformations are predominantly attributed to developmental arrest during the embryonic stage of membranous labyrinth development. Due to the inherent difficulty in clinically assessing the status of the membranous labyrinth, these malformations are diagnosed with radiographic imaging, based on the morphological characteristics of the bony labyrinth. While extensive research has elucidated the intricacies of membranous labyrinth development in mouse models, comprehensive investigations into the developmental trajectory of the bony labyrinth, especially about its calcification process, have been notably lacking. One of the most prominent types of inner ear malformations is known as incomplete partition (IP), characterized by nearly normal external cochlear appearance but pronounced irregularities in the morphology of the modiolus and inter-scalar septa. IP type II (IP-II), also known as Mondini dysplasia, is generally accompanied by an enlargement of the vestibular aqueduct and is primarily attributed to mutations in the SLC26A4 gene. In the case of IP-II, the modiolus and inter-scalar septa of the cochlear apex are underdeveloped or missing, resulting in the manifestation of a cystic structure on radiographic imaging. In this overview, we not only explore the normal development of the bony labyrinth in mice but also present our observations on otolith mineralization. Furthermore, we investigated the specifics of bony labyrinth and otolith mineralization in Slc26a4-deficient mice, which served as an animal model for IP-II. We ensured that these findings promise to provide valuable insights for the establishment of therapeutic interventions, optimal timing, targeted sites, and preventive measures when considering the management of this condition.

A Case of Incidentally Discovered Congenital Complete Pericardial Defect during Lobectomy for Lung Cancer: A Case Report and Literature Review.

An 82-year-old male patient underwent a left upper lobectomy with anterolateral thoracotomy for lung cancer. Although a complete left-pericardial defect was observed during surgery, the pericardial repair was not performed because the left lower lobe remained and the heart was considered stable. Postoperative pathological examination revealed primary synchronous double-lung squamous-cell carcinoma (pathological stage pT2a(2)N0M0 stage IB). He was discharged without complications on postoperative day 8. Leftward displacement of the heart and left diaphragmatic elevation, suspected of phrenic-nerve paralysis, were found in the chest X-ray after discharge. However, the patient's overall condition remained unaffected at the 5-month postoperative follow-up. To assess the need for pericardial repair, we compared cases of complete pericardial defects observed during lobectomy or pneumonectomy reported in the literature. Only one of 12 cases occurred postoperative death despite pericardial repair, and that case combined pectus excavatum and pericardial defects. Our assessment indicated that pericardial repair might not be necessary, excluding complex cases.

Lung cancer after kidney transplantation: a 50-year experience at a single institution.

PURPOSE: To investigate the clinical characteristics of lung cancer that develops after kidney transplantation. METHODS: The clinical data of patients with lung cancer diagnosed after kidney transplantation were collected retrospectively. The medical records were extracted from our database. All patients underwent routine chest examination after kidney transplantation. RESULTS: In total, 17 lung tumors were detected in 15 (0.6%) of 2593 patients who underwent kidney transplantation at our institution. Eleven lung tumors were completely resected from a collective 10 patients (surgical group). The remaining five patients did not receive surgical treatment (nonsurgical group). The surgical group underwent wedge resection (n = 5), segmentectomy (n = 1), lobectomy (n = 3), and bilobectomy (n = 1). The pathological stages were 0 (n = 1), IA1 (n = 2), IA2 (n = 4), IA3 (n = 2), and IB (n = 1). The surgical group had a significantly better prognosis than the nonsurgical group. There were no perioperative complications related to kidney transplantation in either group. CONCLUSIONS: Routine chest examination would be useful for the early diagnosis and treatment of lung cancer after kidney transplantation. Moreover, surgical resection for early-stage lung cancer was associated with a better prognosis for kidney transplantation patients.

CHST4 Gene as a Potential Predictor of Clinical Outcome in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) develops primarily from asbestos exposures and has a poor prognosis. In this study, The Cancer Genome Atlas was used to perform a comprehensive survival analysis, which identified the CHST4 gene as a potential predictor of favorable overall survival for patients with MPM. An enrichment analysis of favorable prognostic genes, including CHST4, showed immune-related ontological terms, whereas an analysis of unfavorable prognostic genes indicated cell-cycle-related terms. CHST4 mRNA expression in MPM was significantly correlated with Bindea immune-gene signatures. To validate the relationship between CHST4 expression and prognosis, we performed an immunohistochemical analysis of CHST4 protein expression in 23 surgical specimens from surgically treated patients with MPM who achieved macroscopic complete resection. The score calculated from the proportion and intensity staining was used to compare the intensity of CHST4 gene expression, which showed that CHST4 expression was stronger in patients with a better postoperative prognosis. The median overall postoperative survival was 107.8 months in the high-expression-score group and 38.0 months in the low-score group (p = 0.044, log-rank test). Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

Thoracoscopic Wedge Resection for Low-Grade Fibromyxoid Sarcoma (Evans Tumor) with Massive Calcification and Originating from the Lung: A Rare Case in an Unexpected Location.

We encountered a rare case of low-grade fibromyxoid sarcoma, which is generally known as Evans tumor, with massive calcification originating from the lung. The patient was a 22-year-old man with Duchenne muscular dystrophy who was referred for a detailed investigation of an intrathoracic tumor with massive calcification. Although our preoperative diagnosis was a solitary fibrous tumor originating from the mediastinum or diaphragm, intraoperative thoracoscopy revealed the tumor arising from the left lower lobe without adhesion to the other organs. Considering his medical history, we aimed to preserve lung function and chose wedge resection, which completely removed the tumor. Based on the pathological findings, the tumor was diagnosed as low-grade fibromyxoid sarcoma with massive calcification originating from the lung. Although extremely rare, this tumor should be considered as a differential diagnosis for a solitary lung mass with massive calcification in young adults.

Transbronchial cryobiopsy for small peripheral pulmonary lesions using endobronchial ultrasonography and an ultrathin bronchoscope.

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.

Immunosuppressive treatment for myasthenia gravis crises improve the taste disorder in patients with thymoma: two case reports.

Background: Taste disorders in patients with thymoma accompanied by myasthenia gravis (MG) is rare. Case Description: The first case was a male in his 50s who underwent surgery for Masaoka stage III type B3 thymoma. He experienced a loss of taste before surgery, which showed no improvement after surgery. Due to a MG crisis 44 days after surgery, the patient underwent intensive treatment with mechanical ventilation, steroid pulse therapy, and intravenous immunoglobulin (IVIG) therapy. The patient recovered taste when he started oral food intake after the treatment for the MG crisis (about 3 months after surgery). Despite the recovery of taste after steroid pulse therapy and IVIG therapy, taste disorder gradually worsened about 1 year and 9 months after surgery, resulting in an almost complete loss of sweet taste 2 years after surgery. The second case was a male in his 60s who underwent surgery for Masaoka stage II type B1 thymoma. He experienced loss of taste before surgery, which showed no improvement after surgery. Five years and two months after surgery, the patient was diagnosed with a MG crisis and underwent steroid pulse therapy. Along with improvements in MG symptoms, taste disorders gradually improved. After 6 years and 10 months of surgery, the patient is still alive without MG symptoms (only pyridostigmine, 180 mg/body/day), taste disorder, and thymoma recurrence. Conclusions: The autoimmune mechanism may contribute to taste disorders in patients with thymoma, which can be recovered by immunosuppressive treatment in our cases.

Influencing Factors on Intersegmental Identification Adequacy in Segmentectomy with Intraoperative Indocyanine Green (ICG) Intravenous Administration.

Accurate identification of the intersegmental plane is essential in segmentectomy, and Indocyanine Green (ICG) assists in visualizing lung segments. Various factors, including patient-related, intraoperative, and technical issues, can influence boundary delineation. This study aims to assess the rate of unsuccessful intersegmental identification and identify the contributing factors. We analyzed cases of lung segmentectomy from April 2020 to March 2023, where intraoperative ICG was intravenously administered during robot-assisted or video-assisted thoracoscopic surgery. Cases where fluorescence extended beyond expected boundaries within 30 s were classified as the "unclear boundary group". This group was then compared to the "clear boundary group". The study encompassed 111 cases, 104 (94%) of which were classified under the "clear boundary group" and 7 (6%) under the "unclear boundary group". The "unclear boundary group" had a significantly lower DLCO (15.7 vs. 11.8, p = 0.03) and DLCO/VA (4.3 vs. 3.0, p = 0.01) compared to the "clear boundary group". All cases in the "unclear boundary group" underwent lower lobe segmentectomy. ICG administration effectively outlines pulmonary segments. Challenges in segment demarcation may occur in cases with low DLCO and DLCO/VA values, particularly during lower lobe segmentectomy.

Paraneoplastic Neuromyelitis Optica Spectrum Disorder: A Rare Case of Advanced Breast Cancer with Intractable Nausea and Vomiting.

BACKGROUND Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating disease of the central nervous system that includes the triad of transverse myelitis, optic neuritis, and area postrema syndrome (APS), characterized by intractable nausea and vomiting. NMOSD can be part of a paraneoplastic syndrome and is associated with seropositivity to aquaporin-4 (AQP-4). We present a patient with uncontrollable nausea and vomiting who developed herpes zoster and acute myelitis and was finally diagnosed with paraneoplastic NMOSD due to breast cancer. CASE REPORT A 51-year-old woman was hospitalized due to 2 weeks of intractable nausea and vomiting. Although contrast-enhanced thoracoabdominal computed tomography (CT) on day 4 suggested breast cancer in her left breast, the etiology of her symptoms remained unknown. On day 13, she developed herpes zoster, followed by acute myelitis on day 25. Magnetic resonance imaging (MRI) showing longitudinal extensive transverse myelitis and an elevated serum AQP-4 antibody level led to the diagnosis of NMOSD. Brain MRI detected a small lesion in the dorsal medulla oblongata, which explained the preceding APS. After starting intravenous methylprednisolone pulse therapy, her nausea and vomiting rapidly subsided. Breast cancer was resected on day 63, and immunohistochemical staining revealed overexpression of AQP-4 in the tumor cells, suggesting paraneoplastic NMOSD. CONCLUSIONS This report has highlighted the presentation and diagnosis of NMOSD and supports the possibility that this can present as part of a paraneoplastic syndrome. In addition, diagnosis of NMOSD preceded by APS requires meticulous history taking and careful interpretation of MRI in the dorsal medulla oblongata.

Feasibility and Efficacy of the Newly Developed Robotic Hybrid Assistive Limb Shoulder Exercises in Patients with C5 Palsy during the Acute Postoperative Phase.

Background and Objectives: Although postoperative C5 palsy is a frequent complication of cervical spine surgery, no effective therapeutic rehabilitation approach has been established for postoperative C5 palsy. The purpose of this study was to find evidence confirming the effectiveness and feasibility of robotic Hybrid Assistive Limb (HAL) shoulder exercises for C5 palsy. Materials and Methods: In this before-after, uncontrolled case series clinical study, we performed a mean of 11.7 shoulder training sessions using a shoulder HAL immediately after the onset of C5 palsy in seven shoulders of six patients who developed postoperative C5 palsy and had difficulty raising their shoulder during the acute postoperative phase of cervical spine surgery. Shoulder HAL training was introduced as early as possible after evaluating the general condition of all inpatients who developed C5 palsy. Patients underwent shoulder abduction training using shoulder HAL on an inpatient and outpatient basis at 2-week or 1-month intervals. Adverse events associated with shoulder HAL training were investigated. The shoulder abduction angle and power without the shoulder HAL were evaluated before shoulder HAL usage, at every subsequent session, and upon completion of all sessions. Results: Severe adverse events due to shoulder HAL training were not reported. After completion of all shoulder HAL sessions, all patients showed improved shoulder elevation, while shoulder abduction angle and power improved over time. Conclusions: Shoulder elevation training with HAL in patients in the acute stage of postoperative C5 palsy has the potential to demonstrate improvement in shoulder joint function with a low risk of developing severe adverse events.

Pneumocystis Pneumonia Infection Following the Initiation of Pembrolizumab Therapy for Lung Adenocarcinoma.

Pneumocystis pneumonia (PCP) is an opportunistic infection that presents a ground-glass appearance in the lungs on chest radiography. Interstitial lung disease is a commonly reported adverse effect of immune checkpoint inhibitor (ICI) treatment; however, there are few reports of ICI treatment-associated PCP infection. A 77-year-old man with lung adenocarcinoma was administered pembrolizumab and hospitalized for dyspnea 2 weeks after treatment. Chest computed tomography showed bilateral ground-glass opacities in all lung lobes. PCP was therefore diagnosed, and steroids and sulfamethoxazole-trimethoprim were initiated. Following treatment, the patient's condition improved promptly. This report suggests that ICI treatment can cause PCP infection.

Effects of short-term treatment with vibegron for refractory nocturnal enuresis.

BACKGROUND: Long-term nocturnal enuresis treatment leads to stress and lowered self-esteem for children and their parents. This study evaluated the short-term effectiveness and safety of vibegron (50 mg) for children with refractory nocturnal enuresis. METHODS: A retrospective cohort study of children with therapy-resistant enuresis was conducted using data for July to December 2019. Enuresis frequency was recorded during 30 days before and after additional vibegron administration with prior treatment. We assessed the treatment effectiveness based on enuresis frequencies between before and after treatment with vibegron 50 mg. Statistical evaluation was performed using a paired t-test. RESULTS: Among 29 children receiving vibegron, 14 (48.3%) exhibited a partial or complete response to the drug. Enuresis frequencies (mean ± standard deviation [SD]) were, respectively, 15.8 ± 9.2 and 9.5 ± 9.6 before and after treatment with vibegron during the observed 30 days. A statistically significant reduction in enuresis frequency was found (p < 0.001). Moreover, maximum mean±SD morning urine of 200 ± 62.9 mL before treatment with vibegron changed to 232 ± 76.6 mL after treatment. A significant increase in voiding volume in the early morning was found (p < 0.05). No drug-related severe adverse event was found. CONCLUSION: Short-term treatment with vibegron is safe and effective for children with refractory enuresis.

Sex Differences in Clinical Outcomes After Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of studies comparing the clinical outcomes after percutaneous coronary intervention (PCI) for women and men stratified by the presentation of acute coronary syndromes (ACS) or stable coronary artery disease (CAD).Methods and Results: The study population included 26,316 patients who underwent PCI (ACS: n=11,119, stable CAD: n=15,197) from the CREDO-Kyoto PCI/CABG registry Cohort-2 and Cohort-3. The primary outcome was all-cause death. Among patients with ACS, women as compared with men were much older. Among patients with stable CAD, women were also older than men, but with smaller difference. The cumulative 5-year incidence of all-cause death was significantly higher in women than in men in the ACS group (26.2% and 17.9%, log rank P<0.001). In contrast, it was significantly lower in women than in men in the stable CAD group (14.2% and 15.8%, log rank P=0.005). After adjusting confounders, women as compared with men were associated with significantly lower long-term mortality risk with stable CAD but not with ACS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.69-0.82, P<0.001, and HR: 0.92, 95% CI: 0.84-1.01, P=0.07, respectively). There was a significant interaction between the clinical presentation and the mortality risk of women relative to men (interaction P=0.002). CONCLUSIONS: Compared with men, women had significantly lower adjusted mortality risk after PCI among patients with stable CAD, but not among those with ACS.

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer.

Pembrolizumab treatment is associated with a favorable prognosis in patients with non-small-cell lung cancer (NSCLC). Here, we investigated the associations among pre-treatment clinical factors, baseline overall tumor burden, and development of severe immune-related adverse events (irAEs; grade ≥ 3) after pembrolizumab treatment with or without chemotherapy. We retrospectively examined consecutive patients with advanced NSCLC who received pembrolizumab with or without chemotherapy at Hakodate Goryoukaku Hospital from March 2017 to February 2021. The baseline overall tumor burden was measured as the sum of the unidimensional diameters of up to five target lesions. We defined irAEs as toxicities related to immune checkpoint inhibitors based on the Common Terminology Criteria for Adverse Events, version 5.0. Tumor burden differed significantly between patients with and without severe irAEs (85 vs. 65 mm, p = 0.0367). The cutoff value for overall tumor burden was set to 80 mm. Good performance status (PS = 0) and PD-L1 expression > 80%, but not overall tumor burden, were correlated with severe irAEs, regardless of complementary chemotherapy. The multivariate odds ratios of good PS and high PD-L1 expression for severe irAEs were 3.27 (95% confidence interval [CI]: 1.22-8.77, p = 0.019) and 4.44 (95% CI: 1.59-12.42, p = 0.0044), respectively. Baseline overall tumor burden, good PS, and high PD-L1 expression were associated with severe irAEs in patients with NSCLC treated with first-line pembrolizumab with or without chemotherapy. Patients with these factors should be carefully monitored to prevent irAEs.

Cytokine release syndrome in a patient with non-small cell lung cancer on ipilimumab and nivolumab maintenance therapy after vaccination with the mRNA-1273 vaccine: a case report.

Background: Cytokine release syndrome (CRS) is caused by the release of inflammatory cytokines that appear during or immediately after administration of a therapeutic antibody and can cause a variety of symptoms. COVID-19 vaccination is effective in cancer patients and prevents breakthrough infections. The safety of vaccines during immune checkpoint inhibitor (ICI) therapy has been reported; however, multiple vaccinations have been developed in recent years, and it is unclear whether repeated vaccinations play a role in the development of CRS in patients receiving ICI. Case Description: A 55-year-old man with stage IV non-small cell lung cancer received ipilimumab and nivolumab maintenance therapy; adverse reactions during the first and second COVID-19 vaccinations (BNT162b2) included injection site pain and slight fever; however, the day after the third COVID-19 vaccination (mRNA-1273), he developed a high fever and lost consciousness. Brain MRI showed parietal meningitis. Cytokine levels (IL-6, sIL-2R, IL-10, IFN-γ) were elevated and Grade 2 liver and renal dysfunction were also observed. As various tests ruled out infection and a PCR test for SARS-CoV-2 was negative, a diagnosis of CRS due to COVID-19 vaccination was made. After steroid therapy, his symptoms improved dramatically. Conclusions: In this case, there was a close association between the time course after vaccination and clinical symptoms of high fever and lost consciousness. Clinicians should be aware of the possibility of vaccine-induced adverse effects such as CRS.