Multiple pulmonary nodules with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia and minute pulmonary meningothelial-like nodules.

A 78-year-old woman presented with multiple pulmonary nodules, mixed with solid and ground-glass nodules. We pathologically confirmed that the multiple pulmonary nodules were a combination of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and multiple pulmonary meningothelial-like nodules (MPMNs). This is the first case report of concurrent DIPNECH and MPMNs.

A rare case of tumor-to-tumor metastasis from thymic carcinoma to an ovarian mature teratoma.

Metastasis from one neoplasm to another is referred to as tumor-to-tumor metastasis (TTM). TTM is rarely observed. Here, we present a patient with TTM from a thymic carcinoma to an ovarian mature teratoma. A 25-year-old woman, diagnosed with unresectable thymic carcinoma, presented with a cyst with a solid tumor component in her right ovary. Laparoscopic cystectomy of the right ovary revealed that the solid tumor was a distant metastasis of the thymic carcinoma in an ovarian mature teratoma. The possibility of malignant transformation of the ovarian mature teratoma was ruled out, enabling accurate staging of the thymic carcinoma. This case emphasizes the need for clinicians to consider TTM and the importance of pathological confirmation of TTM when investigating potential distant metastases.

Reliability of the respiratory rate and oxygenation index for successful high-flow nasal cannula support in coronavirus disease pneumonia: a retrospective cohort study.

BACKGROUND: High-flow nasal cannula (HFNC) therapy is an important non-invasive respiratory support in acute respiratory failure, including coronavirus disease (COVID-19) pneumonia. Although the respiratory rate and oxygenation (ROX) index is a simple and useful predictor for HFNC failure and mortality, there is limited evidence for its use in patients with COVID-19 pneumonia. We aimed to evaluate the ROX index as a predictor for HFNC failure in patients with COVID-19 pneumonia. We also evaluated the ROX index as a predictor for 28-day mortality. METHODS: In this single-center, retrospective, cohort study, 248 patients older than 18 years of age with COVID-19 pneumonia received HFNC therapy for acute respiratory failure. The ROX index was evaluated within 4 h from the start of HFNC therapy. Past medical history, laboratory data, and the ROX index were evaluated as predictors for HFNC failure and 28-day mortality. RESULTS: The ROX index < 4.88 showed a significantly high risk ratio for HFNC failure (2.13 [95% confidence interval [CI]: 1.47 - 3.08], p < 0.001). The ROX index < 4.88 was significantly associated with 28-day mortality (p = 0.049) in patients with COVID-19 pneumonia receiving HFNC therapy. Age, chronic hypertension, high lactate dehydrogenase level, and low ROX index showed significantly high risk ratio for HFNC failure. C-reactive protein level and low ROX index were predictors of 28-day morality. CONCLUSION: The ROX index is a useful predictor for HFNC success and 28-day mortality in patients with COVID-19 pneumonia receiving HFNC therapy. TRIAL REGISTRATION: An independent ethics committee approved the study (Research Ethics Review Committee of Kobe City Medical Center General Hospital [number: zn220303; date: February 21, 2022]), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Predictive factors and clinical impact of ICU-acquired weakness on functional disability in mechanically ventilated patients with COVID-19.

BACKGROUND: Patients with critical COVID-19 often require invasive mechanical ventilation (IMV) and admission to the intensive care unit (ICU), resulting in a higher incidence of ICU-acquired weakness (ICU-AW) and functional decline. OBJECTIVE: This study aimed to examine the causes of ICU-AW and functional outcomes in critically ill patients with COVID-19 who required IMV. METHODS: This prospective, single-center, observational study included COVID-19 patients who required IMV for ≥48 h in the ICU between July 2020 and July 2021. ICU-AW was defined as a Medical Research Council sum score <48 points. The primary outcome was functional independence during hospitalization, defined as an ICU mobility score ≥9 points. RESULTS: A total of 157 patients (age: 68 [59-73] years, men: 72.6%) were divided into two groups (ICU-AW group; n = 80 versus non-ICU-AW; n = 77). Older age (adjusted odds ratio [95% confidence interval]: 1.05 [1.01-1.11], p = 0.036), administration of neuromuscular blocking agents (7.79 [2.87-23.3], p < 0.001), pulse steroid therapy (3.78 [1.49-10.1], p = 0.006), and sepsis (7.79 [2.87-24.0], p < 0.001) were significantly associated with ICU-AW development. In addition, patients with ICU-AW had significantly longer time to functional independence than those without ICU-AW (41 [30-54] vs 19 [17-23] days, p < 0.001). The development of ICU-AW was associated with delayed time to functional independence (adjusted hazard ratio: 6.08; 95% CI: 3.05-12.1; p < 0.001). CONCLUSIONS: Approximately half of the patients with COVID-19 requiring IMV developed ICU-AW, which was associated with delayed functional independence during hospitalization.

Skeletal muscle atrophy and short-term mortality in patients with acute exacerbation of idiopathic pulmonary fibrosis: an observational cohort study.

BACKGROUND: Skeletal muscle atrophy, a common complication of idiopathic pulmonary fibrosis (IPF), and its presence upon diagnosis can indicate a poor prognosis. Patients with IPF frequently experience acute exacerbations (AE), which is associated with a high mortality rate. However, the association between skeletal muscle atrophy and short-term mortality remains unknown. METHODS: We performed a retrospective, multicenter cohort study of patients admitted for AE-IPF in Japan. The cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) were analyzed via single-slice computed tomography (CT). The primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. RESULTS: Of the 212 patients included, 94 (44%) died during the observation period. The low ESMCSA group (<25.6 cm2) had a significantly worse prognosis than that of the high ESMCSA group (≥25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00-2.33], P = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98-2.60]; model 2, 1.55 [0.95-2.56], and model 3, 1.67 [1.00-2.78], respectively). The adjusted HR of low PMCSA (<20.4 cm2) vs. high PMCSA (≥20.4 cm2) was 1.39 (95% CI: 0.88-2.20). CONCLUSIONS: Low ESMCSA on CT images is associated with a high 90-day mortality rate in patients with AE-IPF.

Longitudinal changes in mental health outcomes after COVID-19 hospitalization: A prospective study.

BACKGROUND: The long-term trends of COVID-19 mental sequelae remain unknown. Thus, this study aimed to survey the one-year temporal trends of PTSD and health-related quality of life of COVID-19 survivors. METHODS: Patients hospitalized with COVID-19 were followed up at three, six, and 12 months after discharge. Patients with COVID-19 who were able to communicate and complete the questionnaires were included in the study. All participants were asked to complete the Medical Outcomes Study 36-Item Short-Form Health (SF-36) survey and the Impact of Event Scale-Revised (IES-R). The cutoff point of 24/25 of IES-R was defined as preliminary PTSD. Patients exhibiting PTSD symptoms at six months or later were regarded as "delayed patients," while those exhibiting PTSD symptoms at all the time points were "persistent patients." RESULTS: Of the 98 patients screened between June and November 2020, 72 participated in the study. A total of 11 (15.3%) had preliminary PTSD at three months, 10 (13.9%) at six months, and 10 (13.9%) at 12 months; delayed and persistent patients were four patients (7.54%) each. Patients with preliminary PTSD had lower mental summary scores in SF-36; 47 (IQR 45, 53) for patients with preliminary PTSD and 60 (49, 64) without preliminary PTSD at three months, 50 (45, 51) and 58 (52, 64) at six months, and 46 (38, 52) and 59 (52, 64) at 12 months. CONCLUSION: Healthcare providers should care about the courses of PTSD in COVID-19 survivors and be aware that patients with PTSD symptoms may have a lower health-related quality of life.

Palliative care for interstitial lung disease: A nationwide survey of pulmonary specialists.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) is progressive with high symptom burdens and poor prognosis. Patients with ILD need optimal palliative care to maintain their quality of life, however, few nationwide surveys have addressed palliative care for ILD. METHODS: A nationwide, self-administered questionnaire was conducted. Questionnaires were sent by mail to pulmonary specialists certified by the Japanese Respiratory Society (n = 3423). The current practices of PC for ILD, end-of-life communication, referral to a PC team, barriers to PC for ILD, and comparison of PC between ILD and lung cancer (LC). RESULTS: 1332 (38.9%) participants completed the questionnaire, and the data of 1023 participants who had cared for ILD patients in the last year were analysed. Most participants reported that ILD patients often or always complained of dyspnoea and cough, but only 25% had referred them to a PC team. The timing of end-of-life communication tended to be later than the physician-perceived ideal timing. The participants experienced significantly greater difficulty in symptomatic relief and decision-making in PC for ILD compared to LC. Prescription of opioids for dyspnoea was less frequent for ILD than for LC. ILD-specific barriers in PC included an 'inability to predict prognosis', 'lack of established treatments for dyspnoea', 'shortage of psychological and social support', and 'difficulty for patients/families to accept the disease's poor prognosis'. CONCLUSION: Pulmonary specialists experienced more difficulty in providing PC for ILD compared to LC and reported considerable ILD-specific barriers in PC. Multifaceted clinical studies are needed to develop optimal PC for ILD.

Predictive performance of PD-L1 tumor proportion score for nivolumab response evaluated using archived specimens in patients with non-small cell lung cancer experiencing a postoperative recurrence.

OBJECTIVES: Postoperative recurrence in patients with non-small-cell lung carcinoma (NSCLC) is a major issue for life expectancy. Programmed cell death ligand 1 (PD-L1) expression on tumor cells is important in the prognosis of NSCLC. However, the predictive ability of PD-L1 evaluated with archived surgical specimens for nivolumab treatment have remained unknown. This study was aimed to analyze the predictive ability of the PD-L1 tumor proportion score (TPS) for nivolumab response in patients with NSCLC experiencing a postoperative recurrence using archived surgical specimens. MATERIALS AND METHODS: This retrospective cohort study involved patients with advanced NSCLC (N = 78) treated with nivolumab between April 2016 and September 2018. They were categorized into postoperative recurrence (N = 24) and non-postoperative recurrence (N = 54) groups. The predictive ability of PD-L1 TPS for response to nivolumab treatment in these two groups was determined using receiver operating characteristic (ROC) analysis. Additionally, we evaluated the predictive ability of PD-L1 TPS using rebiopsy specimens collected from the recurrent lesions in six patients of the postoperative recurrence group. RESULTS: PD-L1 TPS exhibited lower predictive performance in the postoperative recurrent group (area under the curve [AUC] = 0.58) compared with that in the non-post operative recurrent group (AUC = 0.81). Furthermore, PD-L1 TPS was significantly increased in rebiopsy specimens. The predictive performance of PD-L1 TPS in these specimens was higher (AUC = 0.90) than that in the archived surgical specimens. CONCLUSION: The study revealed that archived surgical specimens are inadequate for assessing the predictive ability of PD-L1 for nivolumab response, while rebiopsy specimens are adequate.

End-of-life care for idiopathic pulmonary fibrosis patients with acute exacerbation.

BACKGROUND: Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). AE-IPF patients require optimal palliative care; however, the real-world clinical situations are poorly understood. We aimed to survey the palliative care received by AE-IPF patients, especially with respect to opioid use for dyspnea and the end-of-life discussions (EOLd). METHODS: Self-administered questionnaires were dispatched to 3423 of the certified pulmonary physicians in Japan. They were asked to report a care report form of one patient each with AE-IPF who died very recently about opioid use for dyspnea and EOLd. We further explored the factors associated with the early use of opioids for dyspnea. RESULTS: Among the 3423 physicians, 1226 (35.8%) returned the questionnaire with the report forms of 539 AE-IPF patients. Of 539 AE-IPF patients, 361 (67.0%) received opioids for dyspnea. Of the 361 patients, 72 (20.0%) received opioids during the initial treatment with an intention of recovery (early use), while 289 (80.0%) did when the recovery was deemed impossible. EOLd was held before the onset of AE in 124 patients (23.0%); however, the majority of patients had EOLd after the admission for AE-IPF. EOLd before the onset of AE was significantly associated with the early use of opioids. CONCLUSION: In terminally ill AE-IPF patients, opioids are usually administered when the recovery is deemed impossible, and EOLd are rarely held before the onset of AE. Further studies are warranted on the efficacy of opioids for dyspnea and the appropriate timing of EOLd.

Early corticosteroid dose tapering in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF. METHODS: In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering. RESULTS: The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22-0.76] and 0.65 [0.36-1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14-0.99] and 0.27 [0.094-0.83] in the multi-center and administrative cohorts, respectively). CONCLUSION: Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

Morphine May Contribute to Improving Respiratory Failure in Severe COVID-19: A Case Report.

At present, the world is undergoing successive waves of the COVID-19 pandemic. When COVID-19 becomes severe, it causes respiratory failure and symptoms of dyspnoea. The patient's dyspnoea worsens to the IPOS of 3. One COVID-19 patient admitted to our medical institution developed severe illness characterised by hypoxaemia and dyspnoea. In addition to disease-modifying treatments such as remdesivir and dexamethasone, we administered morphine to relieve his dyspnoea. Surprisingly, we observed an improvement in both hypoxaemia and dyspnoea.

Impact of serum lactate dehydrogenase on the short-term prognosis of COVID-19 with pre-existing cardiovascular diseases.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) and underlying cardiovascular comorbidities have poor prognoses. Our aim was to identify the impact of serum lactate dehydrogenase (LDH), which is associated with mortality in acute respiratory distress syndrome, on the prognoses of patients with COVID-19 and underlying cardiovascular comorbidities. METHODS: Among 1518 patients hospitalized with COVID-19 enrolled in the CLAVIS-COVID (Clinical Outcomes of COVID-19 Infection in Hospitalized Patients with Cardiovascular Diseases and/or Risk Factors study), 515 patients with cardiovascular comorbidities were analyzed. Patients were divided into tertiles based on LDH levels at admission [tertile 1 (T1), <235 U/L; tertile 2 (T2), 235-355 U/L; and tertile 3 (T3); ≥356 U/L]. We investigated the impact of LDH levels on the in-hospital mortality. RESULTS: The mean age was 70.4 ± 30.0 years, and 65.3% were male. There were significantly more in-hospital deaths in T3 than in T1 and T2 [n = 50 (29.2%) vs. n = 15 (8.7%), and n = 24 (14.0%), respectively; p < 0.001]. Multivariable analysis adjusted for age, comorbidities, vital signs, and laboratory data including D-dimer and high-sensitivity troponin showed T3 was associated with an increased risk of in-hospital mortality (adjusted hazard ratio, 3.04; 95% confidence interval, 1.50-6.13; p = 0.002). CONCLUSIONS: High serum LDH levels at the time of admission are associated with an increased risk of in-hospital death in patients with COVID-19 and known cardiovascular disease and may aid in triage of these patients.

Effect of high-flow nasal cannula oxygen therapy on exercise tolerance in patients with idiopathic pulmonary fibrosis: A randomized crossover trial.

BACKGROUND AND OBJECTIVE: Exercise capacity in idiopathic pulmonary fibrosis (IPF) is limited by exercise-induced hypoxaemia. This study aimed to examine the effect of high-flow nasal cannula oxygen therapy (HFNC) on exercise tolerance in patients with IPF. METHODS: We conducted a single-centre, open-label, randomized crossover trial to compare HFNC and Venturi mask (VM) therapy in terms of exercise tolerance. Patients underwent constant-load symptom-limited exercise testing at 80% peak work rate with HFNC or a VM in a randomized order. The settings were 60 L/min and a 50% fraction of inspired oxygen (FiO2 ) for HFNC and 12 L/min and 50% FiO2 for VM. The primary outcome was endurance time, and the secondary outcomes were heart rate (HR), percutaneous oxygen saturation (SpO2 ), dyspnoea and leg fatigue, as determined by the modified Borg Scale at the isotime and endpoint, and the level of comfort while using the devices. RESULTS: Twenty-four participants (75.0% men; age, median [interquartile range]: 77.5 [68.8-83.0] years) were enrolled. Compared with VM, HFNC significantly improved the endurance time (647.5 s [454.0-1014.8] vs. 577.5 s [338.0-861.5]), minimum SpO2 (96.0% [95.0-98.0] vs. 94.0% [92.8-96.0]) and leg fatigue at the isotime (3.0 [1.6-4.0] vs. 5.0 [3.0-6.3]) and endpoint (4.0 [2.8-5.0] vs. 5.0 [3.8-6.3]). Differences in maximum HR, dyspnoea at the isotime and endpoint and comfort were non-significant between HFNC and VM therapy. CONCLUSION: HFNC increased exercise tolerance in patients with stable IPF experiencing exercise-induced hypoxaemia.

Sleep Apnea Syndrome (SAS) Clinical Practice Guidelines 2020.

The prevalence of sleep-disordered breathing (SDB) is reportedly very high. Among SDBs, the incidence of obstructive sleep apnea (OSA) is higher than previously believed, with patients having moderate-to-severe OSA accounting for approximately 20% of adult males and 10% of postmenopausal women not only in Western countries but also in Eastern countries, including Japan. Since 1998, when health insurance coverage became available, the number of patients using continuous positive airway pressure (CPAP) therapy for sleep apnea has increased sharply, with the number of patients about to exceed 500,000 in Japan. Although the "Guidelines for Diagnosis and Treatment of Sleep Apnea Syndrome (SAS) in Adults" was published in 2005, a new guideline was prepared to indicate the standard medical care based on the latest trends, as supervised by and in cooperation with the Japanese Respiratory Society and the "Survey and Research on Refractory Respiratory Diseases and Pulmonary Hypertension" Group, of Ministry of Health, Labor and Welfare and other related academic societies, including the Japanese Society of Sleep Research, in addition to referring to the previous guidelines. Since sleep apnea is an interdisciplinary field covering many areas, this guideline was prepared including 36 clinical questions (CQs). In the English version, therapies and managements for SAS, which were written from CQ16 to 36, were shown. The Japanese version was published in July 2020 and permitted as well as published as one of the Medical Information Network Distribution Service (Minds) clinical practice guidelines in Japan in July 2021.

The Accuracy of Japanese Administrative Data in Identifying Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

BACKGROUND: This study aimed to develop criteria for identifying patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) from Japanese administrative data and validate the pre-existing criteria. METHODS: This retrospective, multi-center validation study was conducted at eight institutes in Japan to verify the diagnostic accuracy of the disease name for AE-IPF. We used the Japanese Diagnosis Procedure Combination data to identify patients with a disease name that could meet the diagnostic criteria for AE-IPF, who were admitted to the eight institutes from January 2016 to February 2019. As a reference standard, two respiratory physicians performed a chart review to determine whether the patients had a disease that met the diagnostic criteria for AE-IPF. Furthermore, two radiologists interpreted the chest computed tomography findings of cases considered AE-IPF and confirmed the diagnosis. We calculated the positive predictive value (PPV) for each disease name and its combination. RESULTS: We included 830 patients; among them, 216 were diagnosed with AE-IPF through the chart review. We combined the groups of disease names and yielded two criteria: the criteria with a high PPV (0.72 [95% confidence interval 0.62 to 0.81]) and that with a slightly less PPV (0.61 [0.53 to 0.68]) but more true positives. Pre-existing criteria showed a PPV of 0.40 (0.31 to 0.49). CONCLUSION: The criteria derived in this study for identifying AE-IPF from Japanese administrative data show a fair PPV. Although these criteria should be carefully interpreted according to the target population, our findings could be utilized in future database studies on AE-IPF.

Impact of physical frailty on the clinical outcomes of older patients hospitalized for pneumonia.

AIM: This study aimed to assess the association between physical frailty and clinical outcomes among older patients hospitalized for pneumonia. METHODS: This study examined 852 consecutive patients hospitalized for pneumonia between October 2018 and September 2020. Patients who were <65 years old, scheduled for admission, did not receive inpatient rehabilitation, or died during admission were excluded. A short physical performance battery (SPPB) test was performed by physical therapists upon discharge. The primary outcome measure was a composite endpoint of readmission or mortality due to any cause within 6 months of discharge. RESULTS: In total, 521 patients (median age, 80 years; interquartile range, 74-86 years) were included in the analyses, and were divided into the following two groups: robust group with SPPB scores >9 (n = 150), and physical frailty group with SPPB scores ≤9 (n = 371). Of these, 346 (66.4%) patients were men; and the median SPPB score was 6 (interquartile range, 1-10). During the median follow-up period of 53 days (interquartile range, 4-180 days), 92 (17.6%) patients were readmitted and 25 (4.8%) patients died. Patients with physical frailty were at an increased risk for the primary endpoint (hazard ratio, 2.21; 95% confidence interval, 1.44-3.41; P < 0.001); the risk remained significant after adjusting for multiple variables (adjusted hazard ratio, 1.70; 95% confidence interval, 1.05-2.74; P = 0.028). CONCLUSIONS: Among older patients with pneumonia, physical frailty status at discharge was an independent risk factor for readmission and mortality within 6 months after initial discharge. Geriatr Gerontol Int 2021; 21: 926-931.

Apalutamide-induced severe interstitial lung disease: A report of two cases from Japan.

Apalutamide, a competitive inhibitor of the androgen receptor, is being increasingly used for the treatment of prostate cancer. There have been few reports of interstitial lung disease in clinical trials of apalutamide. However, two cases of apalutamide-induced interstitial lung disease with respiratory failure in Japanese males, who were successfully treated with high-dose corticosteroids, are presented here. These cases suggest that clinicians should be alert to the potentially life-threatening risk of pulmonary toxicity associated with apalutamide treatment.