Deleterious impact of trivial to severe interstitial pneumonia and emphysema on mortality and acute exacerbation of interstitial pneumonia in patients with lung cancer: a retrospective cohort study.

BACKGROUND: Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer. METHODS: This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates. RESULTS: Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18-1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39-2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63-3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01-1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP. CONCLUSION: Our results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones.

Long-term psychiatric disorders in families of severe COVID-19 patients.

Aim: The present study aimed to describe in detail the changes to and assess the risk factors for poor long-term outcomes of psychiatric disorders in families of COVID-19 patients. Methods: A single-center, retrospective study using questionnaires. Family members of patients admitted to the intensive care unit (ICU) with severe COVID-19 participated. Psychiatric disorders refer to the psychological distress such as anxiety, depression, and posttraumatic stress disorder (PTSD) experienced by the patient's family. Results: Forty-six family members completed the survey and were analyzed. Anxiety, depression, and PTSD occurred in 24%, 33%, and 2% of family members, respectively, and psychiatric disorders occurred in 39%. On multivariable analysis, living in the same house with the patient was independently associated with a lower risk of psychiatric disorders in families of COVID-19 patients (OR, 0.180; 95% CI, 0.036-0.908; p = 0.038). Furthermore, four family members overcame psychiatric disorders, and six family members newly developed psychiatric disorders during the one-year follow-up period. Conclusion: Approximately 40% of family members had long-term psychiatric disorders, and some of them overcame the psychiatric disorders, and some newly developed psychiatric disorders over the one-year follow-up. Living in the same house with the patient was possibly significantly associated with the reduction of long-term symptoms of psychiatric disorders, but this result must be interpreted with care. Further large studies are needed to examine the factors associated with the long-term mental status of family members.

An Ionizable Lipid Material with a Vitamin E Scaffold as an mRNA Vaccine Platform for Efficient Cytotoxic T Cell Responses.

RNA vaccines based on lipid nanoparticles (LNPs) with in vitro transcribed mRNA (IVT-mRNA) encapsulated are now a currently successful but still evolving modality of vaccines. One of the advantages of RNA vaccines is their ability to induce CD8+ T-cell-mediated cellular immunity that is indispensable for excluding pathogen-infected cells or cancer cells from the body. In this study, we report on the development of LNPs with an enhanced capability for inducing cellular immunity by using an ionizable lipid with a vitamin E scaffold. An RNA vaccine that contained this ionizable lipid and an IVT-mRNA encoding a model antigen ovalbumin (OVA) induced OVA-specific cytotoxic T cell responses and showed an antitumor effect against an E.G7-OVA tumor model. Vaccination with the LNPs conferred protection against lethal infection by Toxoplasma gondii using its antigen TgPF. The vitamin E scaffold-dependent type I interferon response was important for effector CD8+ T cell differentiation induced by the mRNA-LNPs. Our findings also revealed that conventional dendritic cells (cDCs) were essential for achieving CD8+ T cell responses induced by the mRNA-LNPs, while the XCR1-positive subset of cDCs, cDC1 specialized for antigen cross-presentation, was not required. Consistently, the mRNA-LNPs were found to selectively transfect another subset of cDCs, cDC2 that had migrated from the skin to lymph nodes, where they could make vaccine-antigen-dependent contacts with CD8+ T cells. The findings indicate that the activation of innate immune signaling by the adjuvant activity of the vitamin E scaffold and the expression of antigens in cDC2 are important for subsequent antigen presentation and the establishment of antigen-specific immune responses.

Successful treatment with atezolizumab in a haemodialysis patient with large cell neuroendocrine carcinoma.

In this report, a modified regimen based on IMpower 133 (carboplatin + etoposide + atezolizumab) was administered to a patient diagnosed with large cell neuroendocrine carcinoma (LCNEC) who was concurrently undergoing haemodialysis. Adverse events led to the discontinuation of carboplatin and etoposide after the first course. Nevertheless, the patient exhibited reduction in pulmonary nodule and adrenal metastasis while receiving atezolizumab, indicating its sustained efficacy for a duration of 7 months. To the best of our knowledge, this is the first documented case demonstrating successful treatment with atezolizumab in LCNEC patients undergoing haemodialysis. Atezolizumab can be administered safely in patients undergoing dialysis and is a promising therapeutic option for dialysis patients with LCNEC.

Investigating Viral Involvement in Immunocompromised Patients Using Comprehensive Infectious Disease Testing Including FilmArray Respiratory Panel 2.1 on Bronchoscopy: A Retrospective Study.

Introduction Reports are rare on the usefulness of the FilmArray Respiratory Panel 2.1 (FARP) using lower respiratory tract specimens. This retrospective study assessed its use, as part of a comprehensive infectious disease panel, to detect the viral causes of pneumonia using bronchoalveolar lavage samples from immunosuppressed patients. Methods This study included immunocompromised patients who underwent bronchoalveolar lavage or bronchial washing by bronchoscopy between April 1, 2021, and April 30, 2022. The collected samples were submitted for comprehensive testing, including FARP test; reverse transcription polymerase chain reaction (RT-PCR) for cytomegalovirus, varicella-zoster virus DNA, and herpes simplex virus; PCR for Pneumocystis jirovecii DNA; antigen testing for Aspergillus and Cryptococcus neoformans; and loop-mediated isothermal amplification method for Legionella. Results Out of 23 patients, 16 (70%) showed bilateral infiltrative shadows on computed tomography and three (13%) were intubated. The most common causes of immunosuppression were anticancer drug use (n=12, 52%) and hematologic tumors (n=11, 48%). Only two (9%) patients tested positive for severe acute respiratory syndrome coronavirus 2 and adenovirus by FARP. Four patients (17%) tested positive for cytomegalovirus by RT-PCR, but no inclusion bodies were identified cytologically. Nine (39%) patients tested positive for Pneumocystis jirovecii by PCR, but cytology confirmed the organism in only one case. Conclusions Comprehensive infectious disease testing, performed using bronchoalveolar lavage samples collected from lung lesions in immunosuppressed patients, showed low positive detection by FARP. The viruses currently detectable by FARP may be less involved in viral pneumonia diagnosed in immunocompromised patients.

Sarcoidosis or sarcoid-like reaction with mediastinal lymphadenopathy in patients after breast cancer surgery.

BACKGROUND: Patients with breast cancer present with lymphadenopathy involving non-caseating epithelioid cell granulomas in the mediastinum or axilla, referred to as sarcoidosis or sarcoid-like reactions (SLRs). However, sarcoidosis/SLRs prevalence and clinical presentation remain unclear. This study aimed to determine the frequency and clinical presentation of sarcoidosis/SLRs among postoperative patients with breast cancer. METHODS: Among all patients who underwent surgery for early-stage breast cancer at St. Luke's International Hospital in Japan between 2010 and 2021, those who subsequently developed enlarged mediastinal lymph nodes and underwent bronchoscopy for suspected breast cancer recurrence were included. Patients were classified into sarcoidosis/SLR or metastatic breast cancer groups, and the clinical characteristics were compared. RESULTS: A total of 9,559 patients underwent breast cancer surgery; bronchoscopy was performed to diagnose enlarged mediastinal lymph nodes in 29 cases. Breast cancer recurrence was observed in 20 patients. Eight women with a median age of 49 years (range 38-75) and a median time from surgery to diagnosis of 4.0 years (range 0.2-10.8) were diagnosed with sarcoidosis/SLRs. Four of the eight patients underwent mammoplasty with silicone breast implants (SBIs), and two experienced postoperative recurrences of breast cancer before or after lymphadenopathy, which was considered inciting factors for SLRs. The remaining two cases could have developed sarcoidosis after breast cancer surgery with no underlying causes for SLR. CONCLUSIONS: Postoperative sarcoidosis/SLRs rarely occur in patients with breast cancer. An adjuvant action of SBI likely contributed to the progression of SLRs; few cases exhibited a causal relationship with breast cancer recurrence.

Intravascular large B-cell lymphoma appearance on dual-energy computed tomography: a case report.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is the proliferation of neoplastic B lymphocytes in the vascular space. Since conventional computed tomography (CT) shows nonspecific findings, differentiation between IVLBCL and other lung diseases, such as diffuse interstitial lung disease, is difficult. CASE PRESENTATION: A 73-year-old man presented with dyspnea and hypoxemia. Laboratory findings showed an increased lactate dehydrogenase level of 1690 U/L (normal: 130-235 U/L) and soluble interleukin-2 receptor level of 1140 U/mL (normal: 157-474U/mL). Dual-energy CT iodine mapping showed a significant symmetrical decrease in iodine distribution in the upper lungs, suggesting an unusual distribution of pulmonary hypoperfusion. Therefore, IVLBCL was suspected. A random skin biopsy confirmed the diagnosis of IVLBCL. Due to the severity of the disease, lung biopsy was averted. After admission to the hospital, high-dose methotrexate was administered for central nervous system involvement, due to findings of suspected intracranial infiltration on a brain magnetic resonance imaging and elevated cell counts on lumbar puncture. Subsequently, oxygen demand improved, and rituximab along with cyclophosphamide, doxorubicin, vincristine, and prednisone was added to the patient's regime. Eventually, oxygen administration was terminated, the patient's general condition improved, and the patient was discharged after 47 days of hospitalization. CONCLUSIONS: Since the diagnosis of IVLBCL depends on whether it is possible to suspect IVLBCL, the finding of decreased iodine perfusion demonstrated on dual-energy CT is considered important information for diagnosis. An immediate diagnosis of IVLBCL is needed to avoid rapid disease progression and introduce early treatment for a favorable prognosis. In this case, unique pulmonary hypoperfusion demonstrated by dual-energy CT promoted early diagnosis of IVLBCL.

The location of unilateral axillary lymphadenopathy after COVID-19 vaccination compared with that of metastasis from breast cancer without vaccination.

PURPOSE: Unilateral axillary lymphadenopathy is known to occur after coronavirus disease (COVID-19) vaccination. Post-vaccination lymphadenopathy may mimic the metastatic lymph nodes in breast cancer, and it is challenging to distinguish between them. This study investigated whether the localization of axillary lymphadenopathy on magnetic resonance imaging (MRI) could be used to distinguish reactive lymphadenopathy after COVID-19 vaccines from metastatic nodes. MATERIALS AND METHODS: We retrospectively examined preoperative MRI images of 684 axillae in 342 patients who underwent breast cancer surgery from June to October 2021. Lymphadenopathy was defined as cortical thickening or short axis ≥ 5 mm. The axilla was divided into ventral and dorsal parts on the axial plane using a perpendicular line extending from the most anterior margin of the muscle group, including the deltoid, latissimus dorsi, or teres major muscles, relative to a line along the lateral chest wall. We recorded the presence or absence of axillary lymphadenopathy in each area and the number of visible lymph nodes. RESULTS: Of 80 axillae, 41 and 39 were included in the vaccine and metastasis groups, respectively. The median time from the last vaccination to MRI was 19 days in the vaccine group. The number of visible axillary lymph nodes was significantly higher in the vaccine group (median, 15 nodes) than in the metastasis group (7 nodes) (P < 0.001). Dorsal lymphadenopathy was observed in 16 (39.0%) and two (5.1%) axillae in the vaccine and metastasis groups, respectively (P < 0.001). If the presence of both ventral and dorsal lymphadenopathy is considered indicative of vaccine-induced reaction, this finding has a sensitivity of 34.1%, specificity of 97.4%, and positive and negative predictive values of 93.3％ and 58.5%, respectively. CONCLUSION: The presence of deep axillary lymphadenopathy may be an important factor for distinguishing post-vaccination lymphadenopathy from metastasis. The number of axillary lymph nodes may also help.

Clinical characteristics and outcomes after extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients with an initial asystole rhythm.

AIM: This study aimed to describe the characteristics of cases of out-of-hospital cardiac arrest (OHCA) with an initial asystole rhythm in which extracorporeal cardiopulmonary resuscitation (ECPR) was introduced and discuss the clinical indications for ECPR in such patients. METHODS: This was a secondary analysis of the SAVE-J II study, a retrospective, multicentre, registry study involving 36 participating institutions in Japan. Patients with an initial asystole rhythm were selected. Favourable neurological outcomes (cerebral performance categories 1-2) constituted the primary outcome. RESULTS: In total, 202 patients met the inclusion criteria, with favourable neurological outcomes at hospital discharge in 12 patients (5.9%). Causes of cardiac arrest with favourable neurological outcomes were hypothermia (7 cases), acute coronary syndrome (2 cases), arrhythmia (2 cases), and pulmonary embolism (1 case). Among patients with non-hypothermia (temperature ≥32 °C) on hospital arrival with the cardiac rhythm of asystole or pulseless electrical activity (PEA) on arrival, all 107 patients (66 asystole, 41 PEA) who lacked one or more of the requirements (witness; bystander CPR; signs of life or pupil < 5 mm) had unfavourable neurological outcomes. All 5 cases with favourable neurological outcomes, except for 1 case with a short duration of no-flow time that was highly suspected based on the patient's history, met all the requirements on hospital arrival. CONCLUSIONS: A total of 202 ECPR cases with an initial asystole rhythm, including 12 patients with favourable neurological outcomes, were described. Even if the initial cardiac rhythm is asystole, ECPR could be considered if certain conditions are met.

A case of a thoracic mass negative on thoracentesis diagnosed by cryobiopsy from the visceral pleura.

Thoracoscopy under local anaesthesia is recommended for malignant tumours with negative pleural effusion cytology. Cryobiopsy from the visceral pleura by thoracoscopy under local anaesthesia can provide more diagnostic options for patients with thoracentesis-negative malignant effusions. Here we present the first case in which this technique was used. The patient had a pleural metastasis that could not be diagnosed even with rapid cytology of the parietal pleura biopsy. Indications, technical pitfalls, and safety tips are discussed.

The Tumor Immune Microenvironment and Frameshift Neoantigen Load Determine Response to PD-L1 Blockade in Extensive-Stage SCLC.

Introduction: Despite a considerable benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy for patients with extensive-stage SCLC (ES-SCLC), a durable response to ICIs occurs in only a small minority of such patients. Methods: A total of 135 patients with ES-SCLC treated with chemotherapy either alone (chemo-cohort, n = 71) or together with an ICI (ICI combo-cohort, n = 64) was included in this retrospective study. Tumors were classified pathologically as inflamed or noninflamed on the basis of programmed death-ligand 1 expression and CD8+ tumor-infiltrating lymphocyte density. Immune-related gene expression profiling was performed, and predicted neoantigen load was determined by whole-exome sequencing. Results: Among patients in the ICI combo-cohort, median progression-free survival was 10.8 and 5.1 months for those with inflamed (n = 7) or noninflamed (n = 56) tumors, respectively (log-rank test p = 0.002; hazard ratio of 0.26). Among the 89 patients with immune-related gene expression profiling data available, inflamed tumors had a higher T cell-inflamed GEP score than did noninflamed tumors (-0.18 versus -0.58, p < 0.001). The 12-month progression-free survival rate was 16.1% and 0% for patients in the ICI combo-cohort harboring tumors with a high (n = 26) or low (n = 18) frameshift neoantigen load, respectively. A high-frameshift neoantigen load was associated with up-regulation of gene signatures related to antigen presentation and costimulatory signaling. A durable clinical benefit of ICI therapy was observed only in patients with inflamed tumors and a high-frameshift neoantigen load. Conclusions: Expression of programmed death-ligand 1, CD8+ T cell infiltration, and a high-frameshift neoantigen load are associated with clinical benefit of ICI therapy in ES-SCLC. Clinical trial registration: UMIN000041056.

Elevated plasma levels of Krebs von den Lungen-6 and geographic appearance on high-resolution computed tomography are associated with diffuse alveolar damage in autopsy cases of acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Although diffuse alveolar damage (DAD) is a histopathological hallmark of acute respiratory distress syndrome (ARDS), its detection without lung biopsy is challenging. In patients with ARDS, the specificity of the Berlin definition to diagnose DAD as a reference standard is not adequately high, making it difficult to adequately diagnose DAD. The purpose of this study was to investigate the relationship between DAD and clinical findings, including KL-6 and geographic appearance, in ARDS patients and to identify more specific diagnostic criteria for DAD. METHODS: Among all adult autopsy cases at a tertiary hospital in Japan between January 2006 and March 2021, patients with ARDS who met the Berlin definition criteria were included. The patients' conditions were classified according to histopathological patterns as DAD or non-DAD, and clinical characteristics, laboratory data, and high-resolution computed tomography (HRCT) findings were compared between the two groups. RESULTS: During the study period, 27 met the Berlin definition (median age: 79 years, 19 men), of whom 18 (67%) had DAD and 9 (33%) did not. In the non-DAD group, histopathologic findings revealed organizing pneumonia in seven patients and pulmonary hemorrhage in two patients. On HRCT at onset, patients with DAD had more geographic appearance than those without DAD (89% vs. 44%). In patients with geographic appearance and elevated KL-6 (> 500 U/mL), the sensitivity and specificity for DAD diagnosis were 56% and 100%, respectively. All three patients with no geographic appearance and normal KL-6 did not have DAD. CONCLUSIONS: Geographic appearance on HRCT combined with KL-6 levels may predict the presence of DAD in patients with ARDS.

Findings of virtual bronchoscopic navigation can predict the diagnostic rate of primary lung cancer by bronchoscopy in patients with peripheral lung lesions.

BACKGROUND: Despite being minimally invasive, bronchoscopy does not always result in pathological specimens being obtained. Therefore, we investigated whether virtual bronchoscopic navigation (VBN) findings were associated with the rate of diagnosis of primary lung cancer by bronchoscopy in patients with peripheral lung lesions. METHODS: This study included patients with suspected malignant peripheral lung lesions who underwent bronchoscopy at St. Luke's International Hospital between October 2013 and March 2020. Patients diagnosed with primary lung cancer were grouped according to whether their pathology could be diagnosed by bronchoscopy, and their clinical factors were compared. In addition, the distance between the edge of the lesion and the nearest branch ("distance by VBN") was calculated. The distance by VBN and various clinical factors were compared with the diagnostic rates of primary lung cancer. RESULTS: The study included 523 patients with 578 lesions. After excluding 55 patients who underwent multiple bronchoscopies, 381 patients were diagnosed with primary lung cancer. The diagnostic rate by bronchoscopy was 71.1% (271/381). Multivariate analysis revealed that the lesion diameter (odds ratio [OR] 1.107), distance by VBN (OR 0.94) and lesion structure (solid lesion or ground-glass nodule; OR 2.988) influenced the risk of a lung cancer diagnosis. The area under the receiver operating characteristic curve for diagnosis based on lesion diameter and distance by VBN was 0.810. CONCLUSION: The distance by VBN and lesion diameter were predictive of the diagnostic rates of primary lung cancer by bronchoscopy in patients with peripheral lung lesions.

Combined treatment with endobronchial Watanabe spigot and N-butyl-2-cyanoacrylate for refractory pneumothorax in COVID-19.

Coronavirus disease 2019 (COVID-19) causes pneumothorax or mediastinal emphysema in approximately 1% of patients. According to the British Thoracic Society guidelines, the next treatment option for patients with persistent pneumothorax despite chest drainage is pleurodesis or surgery. In fact, there are reports of autologous blood pleurodesis or surgery for the treatment of pneumothorax caused by COVID-19. However, elderly patients or patients in poor general condition may not be able to tolerate surgical invasion. In this report, we present two patients who did not respond to chest drainage or pleurodesis and who were not suitable for surgery because of their poor general condition. These patients were successfully treated with an endobronchial Watanabe spigot and N-butyl-2-cyanoacrylate. This method may be an option for the treatment of refractory pneumothorax in COVID-19.

Progressive pulmonary fibrosis due to diffuse alveolar damage in a COVID-19-infected autopsy case.

We encountered a patient with severe coronavirus disease 2019 (COVID-19)-related pneumonia, who died of progressive respiratory acidosis after 2 months of treatment with mechanical ventilation. The autopsy revealed diffuse alveolar damage (DAD) without any active signs of fungal or bacterial infections, suggesting prolonged and over-activated immune responses against COVID-19 infection. When COVID-19 patients develop acute respiratory distress syndrome, it is essential to remember that the infection can progress to DAD a few months after the disease onset.

Visual classification of three computed tomography lung patterns to predict prognosis of COVID-19: a retrospective study.

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.

A Case of Nonsmall-Cell Lung Cancer with Anaphylaxis after 41 Courses of Pembrolizumab along with Adrenal Insufficiency as an Immune-Related Adverse Event.

In this report, we present a case of nonsmall-cell lung cancer with anaphylaxis after 41 courses of pembrolizumab along with adrenal insufficiency as an immune-related adverse event (irAE). A 73-year-old man with no allergic disease started pembrolizumab for postoperative recurrence of lung cancer. After four courses, tumor shrinkage was observed and maintained thereafter. After the 39th course, his serum sodium level and random serum cortisol level decreased. Adrenal insufficiency was considered; however, the patient was asymptomatic. Furthermore, his serum sodium level improved spontaneously; therefore, he was followed up. At the end of the 40th course, rhinorrhea and pharyngeal discomfort were noted; however, they were mild and resolved spontaneously. Immediately after administration of the 41st course, he developed pembrolizumab-induced anaphylaxis with percutaneous oxygen saturation decreased. The symptoms quickly improved after intramuscular adrenaline were administered and did not recur. Three months after discharge, the patient was urgently examined for vomiting and anorexia. His serum sodium levels decreased to 119 mEq/L, and an adrenocorticotropic hormone stimulation test was performed. It showed a low response, and the patient was diagnosed with secondary adrenal insufficiency as an irAE of pembrolizumab and treated with hydrocortisone, which quickly improved his serum sodium levels and symptoms. When adrenal insufficiency develops due to irAEs, patients may be susceptible to allergic reactions.

Bereaved Family Members' Perceived Care at the End of Life for Patients with Noncancerous Respiratory Diseases.

Background: Data regarding the quality of end-of-life care for patients with noncancerous illnesses are lacking. Objective: This study aimed to evaluate end-of-life care for patients with noncancerous respiratory disease from the perspective of bereaved family members and explore the factors associated with the quality of patient death and care. Design: This cross-sectional study included patients who had died of noncancerous respiratory disease in general wards of pulmonary department in Japan between 2014 and 2016 and conducted an anonymous self-report questionnaire survey for the patients' bereaved family members. Measurements: We evaluated overall satisfaction with care and the quality of death and end-of-life care using the Good Death Inventory (GDI) and Care Evaluation Scale (CES), respectively. A multiple linear regression analysis was performed to explore the factors associated with these outcomes. Results: In total, 130 questionnaires were distributed, and the effective response rate was 38% and 50 patients were included (median age: 82 [range 58-101] years; 37 men [74%]). Primary diagnoses at death included 29 cases of pneumonia (58%), 15 interstitial lung disease (30%), and 3 chronic obstructive pulmonary disease (6%). Of the bereaved family members, 26 (52%) were spouses, and 19 (38%) were children (median age [range]: 68 [33-102] years, 15 men [30%]). The overall CES and GDI scores (mean ± standard deviation) were 77 ± 15 and 79 ± 15, respectively. The presence of dementia was an independent factor associated with high CES and GDI scores in the multiple linear regression analysis. Conclusions: In patients who died of noncancerous respiratory disease, the presence of dementia could be associated with the higher quality of patient death and care. In dementia, an understanding of the terminal nature of this condition may lead to an appropriate end-of-life care.

Protocol for a systematic review and meta-analysis of studies on the use of brain natriuretic peptide and N-terminal brain natriuretic peptide levels in the diagnosis of cardiopulmonary edema in acute respiratory failure.

BACKGROUND: Dyspnea with bilateral pulmonary edema is common among patients in emergency departments (EDs) or intensive care units (ICUs). For the initial management of patients with this condition, cardiopulmonary edema (CPE) must be differentiated from acute respiratory distress syndrome (ARDS) in clinical settings. Brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) are useful in distinguishing these conditions. However, current data about the use of these indexes are limited. Hence, we planned to perform a systematic review and meta-analysis to determine the accuracy of the two indexes for the diagnosis of CPE. METHODS: We designed and registered a study protocol for a systematic review and meta-analysis. This study aims to determine the diagnostic accuracy of BNP and NT-proBNP based on the standards of the methodology of the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies in reporting the findings of this review. We will search PubMed (MEDLINE), Cochrane Library, Embase, www.ClinicalTrials.gov , International Clinical Trials Registry Platform, and Google Scholar. Randomized controlled trials, cross-sectional studies, and observational cohort studies reporting the accuracy in diagnosing CPE among adult patients with dyspnea and bilateral pulmonary edema will be included in the analysis. There will be no limits regarding language and publication date for this review. Two reviewers will independently screen articles, extract data, evaluate for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), and use Grading of Recommendations Assessment, Development and Evaluation to summarize the strength of body of evidence. Then, a meta-analysis will be performed, and different statistical methods will be used to investigate heterogeneity among studies. A subgroup analysis of elderly patients with left ventricular dysfunction or chronic renal dysfunction will be performed. In the meta-analysis, a hierarchical summary receiver operating characteristic model or a bivariate model will be used in each index test, as appropriate. DISCUSSION: A systematic review and meta-analysis of the accuracy of BNP and NT-proBNP for the diagnosis of CPE will be conducted. The result of this study can help clinicians to identify an appropriate initial treatment for patients with acute respiratory failure, including those with ARDS and CPE. To the best of our knowledge, this will be the first comprehensive systematic review focusing on ARDS management in a specific population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42020201576.

Pectoralis Muscle Mass on Chest CT at Admission Predicts Prognosis in Patients with Pneumonia.

Methods: A retrospective cohort study was performed in patients aged 18 years or older with pneumonia who underwent chest CT within 24 hours of admission between April 2014 and March 2019. We measured the thickness, area, and volume of the pectoralis major and minor muscles at the level of the aortic arch. Factors associated with mortality were examined using logistic regression analysis. Results: A total of 483 patients (mean age 77 ± 14 years, 300 men (62%)) were included, and fifty-one patients (11%) died during admission. In univariate analysis, decreased thickness, area, and volume of the pectoralis major and minor muscles were associated with higher in-hospital mortality. Multivariate analysis with adjustment for age, gender, serum albumin, and A-DROP revealed that thinner pectoralis major and minor muscles were independent factors of poor prognosis (odds ratio: 0.878, 95% confidence interval (CI): 0.783-0.985, P=0.026 and odds ratio: 0.842, 95% CI: 0.733-0.968, P=0.016, respectively). Approximately 25% of the patients died when the pectoralis minor muscle thickness was 5 mm or less, and no patients died when it was 15 mm or more. Conclusion: The pectoralis muscle mass may be an independent prognostic factor in hospitalized patients with pneumonia.