Krebs von den Lungen-6 levels at admission predicts exercise-induced hypoxemia before and after discharge in patients with COVID-19.

BACKGROUND: There are no reports of exercise-induced hypoxemia in patients with coronavirus disease 2019 (COVID-19). Additionally, the predictive factors and prevalence of exercise-induced hypoxemia are unknown. This study investigated the incidence and predictive factors of exercise-induced hypoxemia before and after discharge in patients with COVID-19. METHODS: We enrolled 77 patients diagnosed with COVID-19 who were hospitalized between November 2020 and October 2021 and who underwent a 6-min walk test before and after discharge. Based on the test results, we classified patients into exercise-induced and non-exercise-induced hypoxemia groups and investigated the predictive factors of exercise-induced hypoxemia using logistic regression analysis. RESULTS: The incidences of exercise-induced hypoxemia in patients with COVID-19 were 37.7% and 19.5% before and after discharge, respectively. At admission, the Krebs von den Lungen-6 levels was the associated factor for exercise-induced hypoxemia in patients with COVID-19 before and after discharge, with cut-off values of 314 U/mL and 367 U/mL, respectively. Age and lactate dehydrogenase levels were the associated factors for exercise-induced hypoxemia in patients with COVID-19 before discharge, with cut-off values of 61 years and 492 U/L, respectively. CONCLUSIONS: Some patients with COVID-19 may continue to experience exercise-induced hypoxemia after discharge. Age, lactate dehydrogenase, and Krebs von den Lungen-6 levels at admission could serve as predictive markers of exercise-induced hypoxemia before and after discharge in these patients.

Cryptogenic organizing pneumonia after withdrawal of systemic corticosteroids for chronic eosinophilic pneumonia and severe asthma under benralizumab treatment.

A 79-year-old woman with severe asthma developed chronic eosinophilic pneumonia (CEP). After CEP resolved with oral prednisolone at 30 mg/day, prednisolone was tapered and discontinued under introduction of benralizumab for her severe asthma. However, 8 weeks later, symptoms and bilateral patchy infiltrates on chest radiography appeared. Lymphocytosis without eosinophilia was seen in bronchoalveolar lavage fluids, and transbronchial biopsy indicated organizing pneumonia. Cryptogenic organizing pneumonia (COP) was diagnosed and resolved with prednisolone at 30 mg/day. Prednisolone was tapered to 3 mg/day without relapse of CEP or COP. This case suggests the overlap and similar pathogenesis of CEP and COP.

Idiopathic Fibrotic Nonspecific Interstitial Pneumonia with Cicatricial Organizing Pneumonia and Intraluminal Pulmonary Ossification Containing Bone Marrow.

A 72-year-old man presented with bilateral ground-glass opacities in the lower lung fields on chest radiography. Computed chest tomography showed ground-glass opacities and micronodules in both lower lungs. A video-assisted thoracoscopic biopsy of the right lower lung showed homogeneous thickening of the alveolar septa with fibrosis and inflammatory cell infiltration consistent with fibrotic non-specific interstitial pneumonia (fNSIP). Cicatricial organizing pneumonia and intraluminal pulmonary ossification containing bone marrow that was considered to represent dendriform pulmonary ossification. Idiopathic fNSIP was diagnosed. The patient remains stable under antifibrotic treatment.

The Prognostic Nutritional Index before durvalumab after chemoradiation predict the overall survival in patients with stage III non-small cell lung cancer.

BACKGROUND: Adjuvant durvalumab after chemoradiation has become the standard of care for patients with stage III NSCLC, according to the PACIFIC trial. Whether biomarkers before durvalumab for patients with stage III NSCLC showed predictive and prognostic effects remains unknown. METHODS: This is a retrospective study in the Fujieda Municipal General Hospital between October 2018 and March 2022. We assessed the predictive value of the Prognostic Nutritional Index (PNI) in stage III non-small cell lung cancer (NSCLC) patients treated with durvalumab after chemoradiation. RESULTS: After applying the inclusion and exclusion criteria, the study included 56 patients for further analysis. The median follow-up period was 17.6 months (range, 3.0-45.4 months). According to receiver operating characteristic curve results, the PNI cutoff value to predict overall survival (OS) was 37.9, with sensitivity and specificity at 67.9% and 67.9%. Accordingly, the patients were divided into low- and high-PNI groups. Patients with the low-PNI group had a significantly shorter progression-free survival compared to the high-PNI group (median, 9.1 vs. 21.3 months, p = 0.032). OS was also shorter in the low-PNI group (median, 19.0 months vs. not reached, p < 0.001). In the multivariate Cox hazards regression analyses, the high-PNI was an independent prognostic factor for OS (hazard ratio, 0.187; 95% confidence interval, 0.046-0.760; p = 0.019).It seems that PNI could be used as a predictor for OS in patients with stage III NSCLC treated with durvalumab after chemoradiation.KEY MESSAGESInadequate immunocompetence and nutritional status after chemoradiation therapy may result in poor antitumor efficacy of ICIs.Pretreatment immune and nutritional assessment using PNI could be considered an independent predictor for the survival of stage III NSCLC patients treated with durvalumab after chemoradiation therapy.

An autopsy case of disseminated Cunninghamella bertholletiae infection in an immunocompetent patient: a case report.

BACKGROUND: Recently, deaths due to mucormycosis in immunocompromised hosts have increased; however, the clinical and pathological features of mucormycosis are not fully understood, especially in view of the associated high mortality and rare incidence in immunocompetent patients. CASE PRESENTATION: We have described a rare autopsy case of a 67-year-old Japanese man with chronic obstructive pulmonary disease who contracted mucormycosis. He had not been on any immunosuppressants, and his immune functions were intact. Since 3 days prior to admission to our hospital, he had experienced progressive dyspnea, productive cough, and fever. Chest computed tomography revealed pleural effusion in the left lower hemithorax and consolidation in the right lung field. Although he was administered with tazobactam-piperacillin hydrate (13.5 g/day), renal dysfunction occurred on the ninth disease day. Therefore, it was switched to cefepime (2 g/day). However, his general condition and lung-field abnormality worsened gradually. Cytological analysis of the sputum sample at admission mainly revealed sporangiophores and unicellular sporangioles, while repeated sputum culture yielded Cunninghamella species. Therefore, he was diagnosed with pulmonary mucormycosis. Liposomal amphotericin B (5 mg/kg/day) was initiated on the 28th disease day. However, chest radiography and electrocardiography detected cardiomegaly and atrial fibrillation, respectively, and he died on the 37th disease day. A postmortem examination revealed clusters of fungal hyphae within the arteries of the right pulmonary cavity wall, the subpericardial artery, intramyocardial capillary blood vessels, and the esophageal subserosa vein. Direct sequencing revealed that all fungal culture samples were positive for Cunninghamella bertholletiae. CONCLUSIONS: Cunninghamella bertholletiae could rapidly progress from colonizing the bronchi to infecting the surrounding organs via vascular invasion even in immunocompetent patients.

The Geriatric Nutritional Risk Index and Prognostic Nutritional Index Predict the Overall Survival of Advanced Non-Small Cell Lung Cancer Patients.

We aimed to assess the prognostic and predictive significance of pretreatment Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) measurements on advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Patients with advanced NSCLC treated between February 2014 and August 2020 were retrospectively analyzed. The optimal cutoff points for GNRI and PNI were measured with receiver operating characteristic (ROC) curve analysis according to overall survival (OS). The predictive factors for progression-free survival (PFS) and OS were evaluated with univariate and multivariate analyses via the Cox hazards regression. A total of 160 patients were included in the study. Significant differences between the low and high-GNRI or PNI groups were found regarding ECOG-PS. The low-GNRI and low-PNI groups had significantly shorter PFS and OS than the high-GNRI and high-PNI groups. A multivariate analysis using a Cox regression model revealed that the high-GNRI group was an independent prognostic factor of OS and PFS, and the PNI group was an independent prognostic factor of OS. Pretreatment GNRI and PNI may therefore be a potential effective predictor of the survival of advanced NSCLC patients undergoing first-line treatment.

Association between Cerebral Infarction Risk and Medication Adherence in Atrial Fibrillation Patients Taking Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) are available for nonvalvular atrial fibrillation patients. The advantage of DOACs is that regular anticoagulation monitoring is not required. However, adherence to the recommended regimen is essential. We investigated the association between medication adherence and the risk of cerebral infarction in patients taking DOACs. Patients admitted to any of the participating hospitals for cerebral infarction from September 2018 to February 2020 and prescribed DOACs before admission were defined as the case group, and patients hospitalized for diseases other than cerebral infarction, except for bleeding disorders, and prescribed DOACs before admission were defined as the control group. A nested case-control study was adapted, and 58 and 232 patients were included in the case and control groups, respectively. Medication adherence was assessed by the pharmacists through standardized interviewing. The adjusted odds ratio for the risk of cerebral infarction for low-adherence patients (<80% adherence rate) against good-adherence patients (100% adherence rate) was 9.69 (95% confidence interval, 3.86-24.3; p < 0.001). The patients' age and other background characteristics were not found to be risk factors for cerebral infarction. In conclusion, low adherence is a risk factor for cerebral infarction in patients taking DOACs. Pharmacists should focus on maintaining ≥80% adherence to DOAC therapy to prevent cerebral infarction.

Argon plasma coagulation with atezolizumab and chemoradiation in lung pleomorphic cancer showed a remarkable response: Case report.

RATIONALE: Lung pleomorphic carcinoma (LPC) is generally resistant to chemotherapy or radiotherapy. However, a combination of immune checkpoint inhibitors and radiotherapy has a remarkable efficacy against LPC. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of a 50-year old man diagnosed with progressive LPC. The tumor invaded the carina and predominantly obstructed the right main bronchus; therefore, a combination of palliative chemoradiotherapy and atezolizumab was initiated. However the trachea was gradually obstructed. INTERVENTION AND OUTCOME: Argon plasma coagulation (APC) was performed to prevent tumor invasion. After three APC sessions, the tumor showed a necrotic change and was easily excised using biopsy forceps. LESSONS: A combination of chemoradiotherapy, atezolizumab, and APC showed a good efficacy, and the patient had a good response to atezolizumab maintenance therapy. Multidisciplinary treatments, such as a combination of immune checkpoint inhibitors and APC, could have synergistic efficacy in lung cancer.

Prediction of Postoperative Delirium after Gastrointestinal Surgery Using the Mie Constructional Apraxia Scale.

BACKGROUND: Postoperative delirium (POD) is a transient postoperative complication that occurs after surgical procedures. Risk factors reported for POD include dementia and cognitive decline. The purpose of this study was to identify predictors of POD by examining the use of preoperative neuropsychological tests, including the Mie Constructional Apraxia Scale (MCAS), and patient background factors. METHOD: The study was performed as a retrospective cohort study. The subjects were 33 patients (mean age, 75.8 ± 10.9 years; male:female ratio, 26:7) who underwent gastrointestinal surgery at Matsusaka City Hospital between December 2019 and April 2021. Data were collected retrospectively from medical records. The study was started after receiving approval from the institution's ethics committee. The survey items included general patient information, nutritional assessment, surgical information, and neuropsychological tests. Subjects were classified into 2 groups according to the presence or absence of POD. If a significant difference was observed between the 2 groups, the sensitivity, specificity, and area under the curve were calculated using a receiver operating characteristic (ROC) curve. RESULT: There were 10 patients in the POD group (male:female ratio, 6:4) and 23 patients in the non-POD group (20:3). The POD group had a shorter education history (p = 0.047) and significantly higher MCAS scores (p = 0.007) than the non-POD group. The ROC curve showed a sensitivity of 90%, a specificity of 69%, and an area under the curve of 0.798 when the MCAS cutoff value was set at 3 points. CONCLUSION: Preoperative MCAS results were capable of predicting the occurrence of POD after gastrointestinal surgery. In addition, a relatively short education background was also considered a risk factor for POD.

Difference in Local Lung Movement During Tidal Breathing Between COPD Patients and Asthma Patients Assessed by Four-dimensional Dynamic-ventilation CT Scan.

Background: The validity of four-dimensional dynamic-ventilation CT scan for distinguishing COPD from asthma has not been established. Purpose: To assess whether four-dimensional dynamic-ventilation CT scan can aid in the diagnosis of COPD by comparing local lung movement during tidal breathing between COPD and asthma. Patients and Methods: Thirty-three COPD patients (30 males and three females; median age 74; range 44-89 years) and 11 asthma patients (five males and six females; median age 55; range: 32-75 years) underwent whole-lung dynamic-ventilation CT scan. CT data were reconstructed, one respiratory cycle to 10 phases, and in addtion we reconstructed threefold new phase data sets. We then analyzed local lung movement during tidal breathing using unpaired t-tests and chi-squared tests. Results: The local lung movement in COPD patients was significantly smaller than in asthma patients, especially in the ventral part of the lung. This was so even in patients who had mild emphysema (Goddard score <8). Conclusion: Quantitative evaluation using four-dimensional dynamic-ventilation CT scan demonstrated that local lung movement during tidal breathing, particularly in the ventral lung, was smaller in COPD than in asthma patients, which may help distinguish COPD from asthma.

Good response with durvalumab after chemoradiotherapy for epidermal growth factor receptor exon 20 insertion adenocarcinoma: A case report.

Epidermal growth factor receptor (EGFR) exon 20 insertion is not associated with sensitivity to EGFR tyrosine kinase inhibitors and chemotherapy. Here, we report the case of a 41-year-old man who presented a right lower lobe nodule and mediastinal lymph node enlargement diagnosed as EGFR exon 20 insertion adenocarcinoma with high-expression programmed cell death ligand 1 (PD-L1). He showed stable disease to chemoradiation treatment at the primary tumor site. However, durvalumab treatment has good response. Non-small cell lung cancer with EGFR exon 20 insertion and high PD-L1 expression may be treated with immunotherapy exposure.

A Prediction Equation to Assess Resting Energy Expenditure in Japanese Patients with COPD.

BACKGROUND: Medical nutrition therapy is important in the management of chronic obstructive pulmonary disease (COPD) patients. Determination of resting energy expenditure is essential to define therapeutic goals for medical nutrition. Previous studies proposed the use of equations to predict resting energy expenditure. No prediction equation is currently available for the Japanese population. The objective of this study was to develop an equation to predict resting energy expenditure in Japanese chronic obstructive pulmonary disease patients. To this end, we investigated clinical variables that correlate with the resting energy expenditure. METHODS: This study included 102 COPD patients admitted at the Matsusaka Municipal Hospital Respiratory Center. We measured resting energy expenditure by indirect calorimetry and explored the relationship of resting energy expenditure with clinical variables by univariate and stepwise linear regression analysis. RESULTS: The resting energy expenditure by indirect calorimetry was significantly correlated with fat-free mass, body weight, body mass index, height, gender, and pulmonary function test by univariate analysis. In the stepwise linear regression analysis, the fat-free mass, body weight, and age remained significantly correlated with indirect calorimetry's resting energy expenditure. The fat-free mass, body weight, and age explained 50.5% of the resting energy expenditure variation. CONCLUSION: Fat-free mass, body weight, and age were significantly correlated with resting energy expenditure by stepwise linear regression analysis, and they were used to define a predictive equation for Japanese COPD patients.

SURGICAL OUTCOMES OF 27-GAUGE VITRECTOMY FOR A CONSECUTIVE SERIES OF 163 EYES WITH VARIOUS VITREOUS DISEASES.

PURPOSE: To evaluate the safety and efficacy of 27-gauge vitrectomy for various vitreoretinal disorders. METHODS: In this retrospective comparative study, 163 consecutive eyes with various diseases that underwent 27-gauge pars plana vitrectomy with or without ultraspeed transformer by a single surgeon from June 2012 through December 2014 were analyzed in regard to best-corrected visual acuity, intraocular pressure, intraoperative and postoperative complications, and surgery time. RESULTS: In 2 eyes (1.2%), peripheral retina breaks were encountered intraoperatively, yet no other complications were found in those eyes. No cases required larger-gauge vitrectomy. Mean best-corrected visual acuity improved from 20/58 (logarithm of the minimum angle of resolution, 0.46 ± 0.64) preoperatively to 20/32 (logarithm of the minimum angle of resolution, 0.20 ± 0.40) postoperatively (P < 0.001). Mean follow-up was 16.7 months (range, 6-33 months). Intraocular pressure remained stable throughout the postoperative course. Hypotony was seen in 15 eyes (9.2%) at 1-day postoperative, yet that spontaneously improved within 1 week. No case of retinal detachment or endophthalmitis was recorded. In macular surgeries, such as idiopathic epiretinal membrane and macular hole combined with cataract surgery, the mean surgery time was 32.1 ± 6.9 minutes with ultraspeed transformer (n = 38) and 37.1 ± 7.7 minutes without ultraspeed transformer (n = 40) (P = 0.004). CONCLUSION: The 27-gauge pars plana vitrectomy was found to be safe and effective for treating various vitreoretinal disorders.

[Indication and Efficacy of Amniotic Membrane Transplantation Performed under Advanced Medical Healthcare].

PURPOSE: To survey indications and outcomes of amniotic membrane transplantation (AMT) performed under Advanced Medical Healthcare (AMH) in Japan. METHODS: Questionnaires were sent to 21 facilities performing AMT under AMH from 2010-2012. Diagnosis, effectiveness, and final outcomes were surveyed. Moreover, we retrospectively examined the diagnosis, treatment effectiveness, and final outcomes in all AMTs performed under AMH at Kyoto Prefectural University of Medicine (KPUM) from April 2009 through June 2013. RESULTS: Clinical data of 311 eyes that underwent AMT under AMH was obtained. Of those, diagnoses included pterygium (n = 148), corneal ulcer/epithelial defect (n = 60), corneal perforation (n = 28), intractable glaucoma (n = 24), and others (n = 51). The surgical outcome was completely or partially successful in 287 eyes (92.3%). The final outcome was effective in 281 eyes (90.4%). A total of 45 eyes of 37 patients underwent AMT under AMH at KPUM. Of those, diagnoses included pterygium (n = 15), recurrence of pterygium (n = 27), and symblepharon (n = 3). The surgical outcome was completely successful in 98% and partially successful in 2%. The final outcome was effective in all cases. CONCLUSION: AMT performed under AMH in Japan was most common in eyes with pterygium, and was highly effective in these cases, as well as corneal ulcer/epithelial defect, corneal perforation, and intractable glaucoma.

Autophagy is activated for cell survival after endoplasmic reticulum stress.

Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. Treatment of SK-N-SH neuroblastoma cells with ER stressors markedly induced the formation of autophagosomes, which were recognized at the ultrastructural level. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"), representing autophagosomes, was extensively induced in cells exposed to ER stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. Disturbance of autophagy rendered cells vulnerable to ER stress, suggesting that autophagy plays important roles in cell survival after ER stress.

Identification of regulatory cis-acting elements for alternative splicing of presenilin 2 exon 5 under hypoxic stress conditions.

An alternatively spliced form of the presenilin 2 (PS2) gene lacking exon 5 (PS2V) was found in human brains with sporadic Alzheimer's disease. PS2V was induced by hypoxic stress in human neuroblastoma SK-N-SH cells, indicating that hypoxic stress affects the splicing machineries for PS2 exon 5. Here, we identified the critical cis-acting element (sec 2) on the PS2 pre-mRNA responsible for the aberrant splicing of PS2 exon 5 under hypoxic stress conditions. The element was composed of 23 nucleotides in exon 5 and RNA structural analyses showed a stem-loop structure in this sequence. Treatment with an antisense oligonucleotide directed toward the cis-acting element caused an increase in exon 5 inclusion. These results indicate that the sec 2 identified in this study is a novel regulatory element for exon 5 splicing under stress conditions and that trans-acting factors could specifically bind to the element to skip exon 5 of PS2.