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BackgroundObjective evaluations of cough frequency are considered important for assessing the clinical state of patients with respiratory diseases. While cough monitors with audio recordings are used in research settings, they are rarely used in clinical settings. Issues regarding privacy and background noise (especially the sounds of someone else’s cough) with audio recordings are barriers to the wide use of these monitors in clinical settings; to solve these problems, we developed a novel automatic cough frequency monitoring system combining a triaxial accelerator and a stretchable strain sensor.MethodsEleven healthy adult volunteers and 10 adult patients with cough were enrolled. The participants sat in a chair and wore two devices for 30 minutes for the cough measurements. An accelerator was attached to the epigastric region, and a stretchable strain sensor was worn around their neck. When the subjects coughed, these devices displayed specific waveforms. For the development of the algorithm, the participants’ measurement data from both devices were divided into consecutive small “units” lasting 5 seconds each. Whether each unit corresponded to a “cough unit” was determined by the observer who manually counted the cough records. Then, the data from all the participants were categorized into a training dataset and a test dataset. Using a variational autoencoder, a machine learning algorithm with deep learning, the components of the test dataset were automatically judged as being a “cough unit” or “non-cough unit”.ResultsThe sensitivity and specificity in detecting coughs among 21 participants were 92% and 96%, respectively. The triaxial accelerometer only yielded a sensitivity of 91% and specificity of 95%. Therefore, the diagnostic accuracy improved slightly when the accelerometer was combined with a stretchable strain sensor.Conclusions According to the results of the current study, a cough frequency monitor with good performance can be created by combining an accelerometer and another biometric sensor. Our cough monitor is suitable for ambulatory settings because the devices are small and light. Our cough monitoring system, which does not require audio recordings, has the potential to be widely used in clinical settings without any concerns regarding privacy or background noise.

Background Adequate tumor tissue is required to make the best treatment choice for non-small cell lung cancer (NSCLC). Transbronchial biopsy (TBB) by endobronchial ultrasonography with a guide sheath (EBUS-GS) is useful to diagnose peripheral lung lesions. The data of tumor cell numbers obtained by two different sizes of GSs is limited. We conducted this study to investigate the utility of a large GS kit to obtain many tumor cells in patients with NSCLC. Methods Patients with a peripheral lung lesion and suspected of NSCLC were prospectively enrolled. They underwent TBB with a 5.9-mm diameter bronchoscope with a large GS. When the lesion was invisible in EBUS, we changed to a thinner bronchoscope and TBB was performed with a small GS. We compared the tumor cell number prospectively obtained with a large GS (prospective large GS group) and those previously obtained with a small GS (small GS cohort). The primary endpoint was the tumor cell number per sample, and we assessed characteristics of lesions that could be obtained by TBB with large GS. Results Biopsy with large GS was performed in 55 of 87 patients (63.2%), and 37 were diagnosed with NSCLC based on histological samples. The number of tumor cells per sample was not different between two groups (658±553 vs. 532±526, estimated difference between two groups with 95% confidence interval (CI); 125 (-125–376), p = 0.32). The sample size of the large GS group was significantly larger than that of the small GS cohort (1.75 mm2 vs. 0.83 mm2, estimated difference with 95% CI; 0.92 (0.60–1.23) mm2, p = 0.00000019). The lesion involving a third or less bronchus generation was predictive factors using large GS. Conclusions The sample size obtained with large GS was significantly larger compared to that obtained with small GS, but there was no significant difference in tumor cell number. The 5.9-mm diameter bronchoscope with large GS can be used for lesions involving a third or less bronchus generation.

Parathyroid crisis, which might occur during the natural history of primary hyperparathyroidism, presents fatal hypercalcemia. Although hyperparathyroidism is known to cause metastatic pulmonary calcification, parathyroid crisis with respiratory failure is rarely reported. Here, we present a case of parathyroid crisis with respiratory failure due to parathyroid adenoma. For the first 2 weeks after admission to our hospital, the patient was treated with hydration, calcium-lowering agents, dialysis and extracorporeal membrane oxygenation, with gradual improvement in her respiratory condition as blood calcium levels decreased. However, she still needed oxygen even after that. Therefore, parathyroidectomy was performed on day 48, and she no longer needed oxygen after the surgery. Chest computed tomography scan also demonstrated improvement in pulmonary calcification, although it did not completely disappear even 4 months after parathyroidectomy. Parathyroid crisis is an endocrine emergency, and its possibility should be considered in patients with respiratory failure with hypercalcemia.

Introduction : When using portable oxygen, a demand oxygen delivery system (DODS), which senses the beginning of inhalation and delivers a bolus of oxygen, is often used. However, conventional DODS may not supply sufficient oxygen when reduced tidal flow fails to trigger the flow sensor. Recently, “auto-DODS,” which detects the negative pressure of inhalation and switches among 3 trigger sensitivity levels (standard, high, and extra high), has been developed to improve the efficacy of oxygenation. An auto-DODS can also supply pulsed-flow oxygen when it detects apnea, whereas a conventional DODS has only standard sensitivity. This randomized, open-label, crossover pilot study compared the performance of an auto-DODS with that of a conventional DODS. Methods : We recruited patients with chronic obstructive pulmonary disease (COPD) or interstitial pneumonia receiving long-term oxygen therapy. Interventions were performed on 2 different days for each participant. On each day, an auto-DODS or a conventional DODS were tested at rest for 30 minutes and during the 6-minute walk test. The primary outcome was mean oxygen saturation (SpO2). Secondary outcomes were the ratios of time for each sensitivity level and pulsed-flow oxygen when using the auto-DODS, total time desaturated below SpO2 90%, percentage of time desaturated below SpO2 90%, minimum SpO2, mean and maximum pulse rate, six-minute walk distance, recovery time after 6-minute walk test, modified Borg scale, comfort, and discomfort index. Results : When using the auto-DODS at rest, a high or extra high sensitivity level was observed in addition to standard sensitivity in 6 of 8 participants. During the 6-minute walk test, only standard sensitivity was observed in 6 participants. Mean SpO2 differences between the auto-DODS and conventional DODS at rest and during the 6-minute walk test were −0.6 [−4.5, 3.4] and 0.0 [−2.5, 2.5] ([95% confidence interval]), respectively, neither of which were significant (P = .73 and P = .99). There were no significant differences in secondary outcomes. There were no adverse events when using the auto-DODS. Conclusions : This study showed that the auto-DODS did not show superiority in oxygenation either at rest or during exercise compared to a conventional DODS. The auto-DODS was shown to supply oxygen safely and detect inhalations with various trigger sensitivities.

Background: It has not been determined that demand valve oxygen therapy is effective for nocturnal hypoxia. A portable oxygen concentrator with an auto-demand oxygen delivery system (auto-DODS; standard, high, and extra high) has recently been developed to improve oxygenation and comfort. This oxygen concentrator can supply a pulsed flow when it detects apnoea. The aim of this study is to demonstrate that this newly developed portable oxygen concentrator with an auto-demand function is non-inferior to a continuous-flow oxygen concentrator for nocturnal hypoxemia. Methods: Twenty patients with chronic obstructive pulmonary disease or interstitial pneumonia will be randomized to receive a portable oxygen concentrator with an auto-DODS or a continuous-flow oxygen concentrator during sleep. The primary endpoint is mean oxygen saturation (SpO2) during the total sleep time. The secondary endpoints are the ratios of time that the oxygen concentrator spends in each sensitivity mode (standard, high, and extra-high) and at a constant pulse rate to the total sleep time, the total time and ratio of time for which SpO2 is less than 90% during the total sleep time, the lowest value of SpO2 during the total sleep time, the mean and highest pulse rate during the total sleep time, the apnoea index during the total sleep time, the total sleep duration itself, and comfort and reliability as measured by numerical rating scale and questionnaires. Discussion: If the auto-DODS demonstrates non-inferiority to continuous flow in oxygenation during sleep, the auto-DODS can be used even at night, and the patient will need only 1 device. Trial Registration: The study was registered on Aug 23, 2019 (jRCTs052190042).

Introduction: Long-term oxygen therapy is reported to improve hypoxemia and survival in patients with respiratory failure. The demand oxygen delivery system (DODS) saves oxygen and extends the usable time of an oxygen cylinder 2- to 3-fold. A portable oxygen concentrator with an auto-DODS has been developed to switch its sensitivity among 3 levels (standard, high, and extra high) and to supply pulsed-flow oxygen when it detects apnea. The aim of this study is to evaluate the efficacy of this newly developed portable oxygen concentrator with auto-DODS compared to the efficacy of conventional DODS in oxygenation. Methods and analysis: Twenty-six patients with chronic obstructive pulmonary disease or interstitial pneumonia will be randomized to use auto-DODS or conventional DODS at rest and during a 6-minute walk test. Primary endpoints are mean oxygen saturation (SpO2) at rest and during the 6-minute walk test. Secondary endpoints are the ratios of the times during which the oxygen concentrator operates at each sensitivity mode (standard, high, and extra high) and at a constant pulse rate to the examination time, the ratio of the times during which SpO2 fall below 90% to the examination time, the lowest value of SpO2 during the examination time, the mean and highest pulse rates during the examination time, 6-minute walking distance, recovery time, Borg scale, comfort, and reliability, which are measured by a numerical rating scale and a questionnaire, respectively. Ethics and dissemination: The study was conducted in accordance with the Declaration of Helsinki and was registered on Aug 23, 2019 (https://jrct.niph.go.jp/en-latest-detail/jRCTs052190041). The results of the study will be presented at academic conferences and submitted to a peer-reviewed journal. Trial registration number: jRCTs052190041

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

Immune checkpoint inhibitors (ICIs) have drastically changed the clinical care of cancer. Although cancer immunotherapy has shown promise in various types of malignancies, thus far, the proportion of patients who can benefit from ICIs is relatively small. Immune-related adverse events and high cost are unavoidable problems. Therefore, biomarkers defining patients that are most likely to benefit from ICIs are urgently needed. The expression of programmed cell death-ligand 1 (PD-L1) is a logical biomarker for the prediction of response to anti-PD1/PD-L1 immunotherapies. However, its usefulness is currently debatable because of its varied definition, threshold, and spatial/temporal heterogeneity. Recently, it was reported that the tumor mutational burden, expression of neoantigens, mismatch repair status, and specific gene mutations may be markers for the success of treatment with ICIs. Moreover, it was suggested that the fecal microbiota prior to immunotherapy may play an important role in predicting the efficacy of ICIs. In this review, we focused on these potential biomarkers for cancer immunotherapy reported in recent clinical articles. Further studies are warranted to develop a predictive model using these biomarkers, with the aim of practicing precision medicine in cancer immunotherapy.

BACKGROUND: We evaluated the efficacy of high-flow nasal cannula (HFNC) therapy, a promising respiratory support method for acute hypoxemic respiratory failure (AHRF). METHODS: We conducted a retrospective single-center cohort study comparing the periods before (June 2010 to May 2012) and after (June 2012 to May 2014) HFNC introduction (pre- and post-HFNC periods). During these periods, we retrieved cases of AHRF treated with any respiratory support (invasive ventilation, noninvasive ventilation [NIV], and HFNC) and compared in-hospital mortality, ICU/intermediate care unit/hospital stay, and need for mechanical ventilation. RESULTS: Eighty-three subjects (65 treated with NIV, and 18 treated with invasive ventilation) and 89 subjects (33 treated with HFNC, 43 treated with NIV, and 13 treated with invasive ventilation) identified from 782 pre-HFNC and 930 post-HFNC records of acute respiratory failure who required emergent admissions to the respiratory care department were analyzed. Overall, the in-hospital mortality rate was similar, although there was a non-significant and slight decrease from 35 to 27% ( P = .26). There was no significant difference among ICU, intermediate care unit ( P = .80), and hospital ( P = .33) stay. In the post-HFNC period, significantly fewer subjects required mechanical ventilation (NIV or invasive ventilation) (100% vs 63%, P < .01). Additionally, there were significantly fewer ventilator days (median [interquartile range] of 5 [2–11] vs 2 [1–5] d, P < .05) and more ventilator-free days (median [interquartile range] of 18 [0–25] vs 26 [20–27] d, P < .01). CONCLUSIONS: HFNC might be an alternative for AHRF subjects with NIV intolerance.