Antimicrobial susceptibility analysis of isepamicin combination treatments in Mycobacterium abscessus species.

This study evaluated the antimicrobial potency of the combination of isepamicin (ISP) for Mycobacterium abscessus species (MABS). 34 clinical MABS strains were isolated from clinical samples. Of them, 11 (32.4 %) were M. abscessus subsp. abscessus (Mab), 22 (64.7 %) were M. abscessus subsp. massiliense (Mma), and one (2.9 %) was M. abscessus subsp. bolletii (Mbo). We compared susceptibility to sitafloxacin (STFX)-ISP and clarithromycin (CLR)-ISP combinations with those of the antimicrobial agents alone, and synergistic effects were observed in 41.2 % and 17.6 % when treated with STFX-ISP and CLR-ISP. By hierarchical cluster analysis, the isolates divided into treatment-sensitive and treatment-resistant groups. Non-Mma or rough colony isolates were significantly likely to belong to the treatment-sensitive group (p = 0.024, p < 0.001, respectively). These results suggest that the ISP-containing combination could be a new therapeutic strategy for MABS, especially in cases of non-Mma: treatment-refractory subspecies, and rough morphotypes: high-virulence morphotypes.

The epidemiology of pulmonary Mycobacterium abscessus species in Japanese population.

BACKGROUND: Mycobacterium abscessus species (MABS) is now a most virulent rapidly growing mycobacteria (RGM), and the rapid increase of MABS was recently observed worldwide, including in Japan. Thus, we gathered evidences of the presence of pulmonary MABS in Japanese population from Japanese articles. METHODS: we searched studies that addressed the isolation of pulmonary non-tuberculous Mycobacteria (NTM) or MABS from clinical respiratory specimens in Japan. RESULTS: the ratio of MABS to NTM was 3.04% (95% confidence interval [CI]: 2.51-3.68), found using the meta-analysis of single proportions. The estimated mean age of patients infected with MABS was 67.72 years (95% CI: 65.41-70.02), found using the meta-analysis of single means. The estimated proportion of females, never smoker, and the co-infection with Mycobacterium avium complex (MAC) was 66.75% (95% CI: 59.23-73.50), 67.57% (95% CI: 62.43-72.32), and 36.74% (95% CI: 25.30-49.90), respectively. The characteristics of MABS in Japan were considerably different from that in Europe and United States from the perspective of age, gender, and complications, wherein the patients in these countries tended to be younger, had lower number of females, and had more occurrences of hereditary diseases, including cystic fibrosis (CF). CONCLUSION: we hypothesized that the characteristics of MABS in the Japanese were involved in those of non-CF MABS, and the distribution of gender and age of MABS were similar to that of MAC in the Japanese.

The Utility of Urinary Titin to Diagnose and Predict the Prognosis of Acute Myocardial Infarction.

Early detection and management are crucial for better prognosis in acute myocardial infarction (AMI). Serum titin, a component of the sarcomere in cardiac and skeletal muscle, was associated with AMI. Thus, we hypothesized that urinary N-fragment titin may be a biomarker for its diagnosis and prognosis. Between January 2021 and November 2021, we prospectively enrolled 83 patients with suspected AMI. Their urinary N-fragment titin, serum high-sensitivity troponin I (hsTnI), creatine kinase (CK), and creatine kinase-MB (CK-MB) were measured on admission. Then, urinary titin was assessed as diagnostic and prognostic biomarker in AMI. Among 83 enrolled patients, 51 patients were diagnosed as AMI. In AMI patients who were admitted as early as 3 h or longer after symptom onset, their urinary titin levels were significantly higher than non-AMI patients who are also admitted 3 h or longer after symptom onset (12.76 [IQR 5.87-16.68] pmol/mgCr (creatinine) and 5.13 [IQR 3.93-11.25] pmol/mgCr, p = 0.045, respectively). Moreover, the urinary titin levels in patients who died during hospitalization were incredibly higher than in those who were discharged (15.90 [IQR 13.46-22.61] pmol/mgCr and 4.90 [IQR 3.55-11.95] pmol/mgCr, p = 0.023). Urinary N-fragment titin can be used as non-invasive early diagnostic biomarker in AMI. Furthermore, it associates with hospital discharge disposition, providing prognostic utility.

Efficient Drug Loading Method for Poorly Water-Soluble Drug into Bicelles through Passive Diffusion.

The bicelle, a type of solid lipid nanoparticle, comprises phospholipids with varying alkyl chain lengths and possesses the ability to solubilize poorly water-soluble drugs. Bicelle preparation is complicated and time-consuming because conventional drug-loading methods in bicelles require multiple rounds of thermal cycling or co-grinding with drugs and lipids. In this study, we proposed a simple drug-loading method for bicelles that utilizes passive diffusion. Drug-unloaded bicelles were placed inside a dialysis device and incubated in a saturated solution of ketoconazole (KTZ), which is a model drug. KTZ was successfully loaded into bare bicelles over time with morphological changes, and the final encapsulated concentration was dependent on the lipid concentration of the bicelles. When polyethylene glycol (PEG) chains of two different lengths (PEG2K and 5K) were incorporated into bicelles, PEG2k and PEG5k bicelles mitigated the morphological changes and improved the encapsulation rate. This mitigation of morphological changes enhanced the encapsulated drug concentration. Specifically, PEG5k bicelles, which exhibited the greatest prevention of morphological changes, had a lower encapsulated concentration after 24 h than that of PEG2k bicelles, indicating that PEGylation with a longer PEG chain length improved the loading capacity but decreased the encapsulation rate owing to the presence of a hydration layer of PEG. Thus, PEG with a certain length is more suitable for passive loading. Moreover, loading factors, such as temperature and vehicles used in the encapsulation process, affected the encapsulation rate of the drug. Taken together, the passive loading method offers high throughput with minimal resources, making it a potentially valuable approach during early drug development phases.

Ultrasound-based upper limb muscle thickness is useful for screening low muscularity during intensive care unit admission: A retrospective study.

BACKGROUND & AIMS: Malnutrition is associated with poor outcomes. Muscle mass is an important malnutrition indicator included in Global Leadership Initiative on Malnutrition (GLIM) criteria. Although bioelectrical impedance analysis and dual-energy X-ray absorptiometry are common muscle mass assessment methods, they are unreliable during intensive care unit (ICU) admission due to the influence of dynamic fluid changes. We hypothesized that ultrasound-based upper limb muscle assessment would be useful for assessing muscularity at ICU admission. METHODS: We retrospectively analyzed prospectively obtained ultrasound data from patients admitted to an ICU. We excluded patients without computed tomography (CT) imaging of the third lumbar vertebra within 2 days of ICU admission. Primary outcomes were the diagnostic utility of ultrasound-based upper limb muscle thickness for assessing low muscularity by CT. Low muscularity was defined as a skeletal muscle index of 36.0 cm2/m2 for males and 29.0 cm2/m2 for females at the cross-sectional area of the third lumbar vertebrae. Secondary outcomes of this study included the relationships between upper limb muscle thickness and biceps brachii muscle cross-sectional area, quadriceps femoris thickness, rectus femoris cross-sectional area. RESULTS: Among 64 patients assessed by ultrasound, 52 had CT examination records and were included in the analysis. The mean age was 70 ± 13 years, and the mean body mass index was 23.3 ± 4.2 kg/m2. Upper limb muscle thickness had the discriminative power to assess low muscularity at an area under the curve of 0.77 (95% CI [confidence interval], 0.63-0.91); the cutoff value (26.8 cm) had 84.6% sensitivity and 66.7% specificity. The upper limb muscle index had the discriminative power to assess low muscularity at an area under the curve of 0.80 (95% CI, 0.68-0.93); the cutoff value (9.9 mm/m2) had 76.9% sensitivity and 71.8% specificity. Upper limb muscle thickness was correlated with upper limb muscle cross-sectional area, quadriceps femoris muscle thickness, rectus femoris muscle cross-sectional area (r = 0.39-0.76, p < 0.01, n = 52). CONCLUSIONS: Ultrasound-based upper limb muscle thickness assessments can screen for low muscularity upon ICU admission.

Molecular-Level Structural Analysis of siRNA-Loaded Lipid Nanoparticles by 1H NMR Relaxometry: Impact of Lipid Composition on Their Structural Properties.

1H NMR relaxometry was applied for molecular-level structural analysis of siRNA-loaded lipid nanoparticles (LNPs) to clarify the impact of the neutral lipids, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol, on the physicochemical properties of LNP. Incorporating DSPC and cholesterol in ionizable lipid-based LNP decreased the molecular mobility of ionizable lipids. DSPC reduced the overall molecular mobility of ionizable lipids, while cholesterol specifically decreased the mobility of the hydrophobic tails of ionizable lipids, suggesting that cholesterol filled the gap between the hydrophobic tails of ionizable lipids. The decrease in molecular mobility and change in orientation of lipid mixtures contributed to the maintenance of the stacked bilayer structure of siRNA and ionizable lipids, thereby increasing the siRNA encapsulation efficiency. Furthermore, NMR relaxometry revealed that incorporating those neutral lipids enhanced PEG chain flexibility at the LNP interface. Notably, a small amount of DSPC effectively increased PEG chain flexibility, possibly contributing to the improved dispersion stability and narrower size distribution of LNPs. However, cryogenic transmission electron microscopy represented that adding excess amounts of DSPC and cholesterol into LNP resulted in the formation of deformed particles and demixing cholesterol within the LNP, respectively. The optimal lipid composition of ionizable lipid-based LNPs in terms of siRNA encapsulation efficiency and PEG chain flexibility was rationalized based on the molecular-level characterization of LNPs. Moreover, the NMR relaxation rate of tertiary amine protons of ionizable lipids, which are the interaction site with siRNA, can be a valuable indicator of the encapsulated amount of siRNA within LNPs. Thus, NMR-based analysis can be a powerful tool for efficiently designing LNP formulations and their quality control based on the molecular-level elucidation of the physicochemical properties of LNPs.

Nintedanib administration after the onset of acute exacerbation of interstitial lung disease in the real world.

Nintedanib reduces the decline in forced vital capacity and extends the time to the first acute exacerbation of interstitial lung disease (AE-ILD). However, the effect of additional nintedanib administration after AE-ILD onset is unknown. This study aimed to investigate the efficacy and safety of nintedanib administration after AE-ILD development. We retrospectively collected the data of 33 patients who developed AE-ILD between April 2014 and January 2022. Eleven patients who received nintedanib after AE-ILD development and the remaining who did not were classified into the N and No-N groups, respectively. The survival time in the N group tended to be longer than that in the No-N group. The generalized Wilcoxson test revealed that the cumulative mortality at 90 days from AE-ILD onset was significantly lower in the N group. The time to subsequent AE-ILD development was significantly longer in the N group than that in the No-N group. The incidence of adverse gastrointestinal effects and liver dysfunction in the N group was 9-18%. Treatment without nintedanib after AE-ILD development and the ratio of arterial oxygen partial pressure to fractional inspired oxygen were significant independent prognostic factors in the multivariate analysis. Thus, nintedanib administration may be a treatment option for AE-ILD.

The mechanism of thrombocytopenia caused by cholesterol-conjugated antisense oligonucleotides.

In this study, we investigated thrombocytopenia caused by cholesterol-conjugated antisense oligonucleotides (Chol-ASO). First, we evaluated platelet activation induced by Chol-ASO in mice by flow cytometry after administration of platelet-rich plasma (PRP). An increase in the number of large particle-size events with platelet activation was detected in the Chol-ASO-treated group. In a smear study, numerous platelets were observed to attach to nucleic acid-containing aggregates. A competition binding assay showed that the conjugation of cholesterol to ASOs increased their affinity for glycoprotein VI. Platelet-free plasma was then mixed with Chol-ASO to form aggregates. The assembly of Chol-ASO was confirmed by dynamic light scattering measurements in the concentration range in which the formation of aggregates with plasma components was observed. In conclusion, the mechanism by which Chol-ASOs causes thrombocytopenia is proposed to be as follows: (1) Chol-ASOs form polymers, (2) the nucleic acid portion of the polymers interacts with plasma proteins and platelets, which cross-links them to form aggregates, and (3) platelets bound to aggregates become activated, resulting in platelet aggregation, leading to a decrease in platelet count in vivo. The details of the mechanism revealed in this study could contribute to creating safer oligonucleotide therapies without the risk of thrombocytopenia.

The synergetic effect of sitafloxacin-arbekacin combination in the Mycobacterium abscessus species.

Mycobacterium abscessus species (MABS) is the most commonly isolated rapidly growing mycobacteria (RGM) and is one of the most antibiotic-resistant RGM with rapid progression, therefore, treatment of MABS is still challenging. We here presented a new combination treatment with sitafloxacin that targeted rough morphotypes of MABS, causing aggressive infections. Thirty-four clinical strains of MABS were isolated from various clinical samples at the Juntendo university hospital from 2011 to 2020. The susceptibility to a combination of sitafloxacin and antimicrobial agents was compared to that of the antimicrobial agents alone. Out of 34 MABS, 8 strains treated with sitafloxacin-amikacin combination, 9 of sitafloxacin-imipenem combination, 19 of sitafloxacin-arbekacin combination, and 9 of sitafloxacin-clarithromycin combination showed synergistic effects, respectively. Sitafloxacin-arbekacin combination also exhibited the synergistic effects against 10 of 22 Mycobacterium abscessus subspecies massiliense (Mma) strains and 8 of 11 Mycobacterium abscessus subspecies abscessus (Mab) strains, a highly resistant subspecies of MABS. The sitafloxacin-arbekacin combination revealed more synergistic effects in rough morphotypes of MABS (p = 0.008). We demonstrated the synergistic effect of the sitafloxacin-arbekacin combination against MABS. Further, this combination regimen might be more effective against Mab or rough morphotypes of MABS.

In vivo screening of subcutaneous tolerability for the development of novel excipients.

To develop safe subcutaneous formulations and minimize the risk of local irritation, it is essential to optimize the composition of active pharmaceutical ingredients and excipients. Depending on the physicochemical properties of the active pharmaceutical ingredient, additional excipients may be required to improve the stability and solubility of the active pharmaceutical ingredient. However, some of these excipients may not have been previously used in injectable drugs. Owing to the lack of safety data for such excipients, especially those used in subcutaneous dosing, it is important to evaluate their potential for local irritation during the early stages of formulation development. We evaluated the tolerability of 44 formulations with 24 candidate novel excipients, such as surfactants, polymers, and lipids, in a single subcutaneous dose in rats. Excipient formulations were administered as single bolus subcutaneous injections with an injection volume of 1 mL. The injection sites were observed for 2 days, and macroscopic and microscopic examinations were conducted. Local tolerability was evaluated on the basis of severity, incidence, and pathophysiology of each finding. Formulations that caused tissue degeneration or necrosis, which is indicative of tissue injury, were determined to be irritative and poorly tolerated. A single-dose subcutaneous screening study in rats was considered effective in ranking the safety of candidate excipients during the formulation optimization phase.

Independent lung ventilation for the management of acute allograft rejection after single-lung transplantation for end-stage emphysema.

Background : We herein report the use of independent lung ventilation (ILV) for managing acute allograft rejection after single-lung transplantation (SLT) for end-stage emphysema. Case presentation : A 54-year-old woman was transferred to our hospital with severe hypoxemia and respiratory distress due to unilateral lung disease with diffuse alveolar damage in the right donor lung associated with acute allograft rejection and with hyperinflation of the left native lung due to emphysema. She was unresponsive to immunosuppressive medications and conventional ventilation strategies, so different ventilator settings for each lung were required. A double-lumen endotracheal tube (DLT) was inserted, and ILV was initiated. The right lung was ventilated with high positive end-expiratory pressure (PEEP), intended for lung recruitment, and the left lung was ventilated with lung protective strategies using a low tidal volume and low levels of PEEP to avoid hyperinflation. Two days later, her lung function was dramatically improved, and the DLT was replaced with a single-lumen endotracheal tube. Gas exchange was maintained, and she was successfully weaned from mechanical ventilation on intensive-care unit day 15. Conclusions : ILV appears to be effective and safe for managing acute allograft rejection after SLT for emphysema. J. Med. Invest. 69 : 323-327, August, 2022.

A Case of Tuberculosis-related Cerebral Venous Sinus Thrombosis and Pulmonary Thromboembolism Successfully Treated with Edoxaban.

A 22-year-old woman was admitted to the hospital with complaints of headache and vomiting. Radiological examinations revealed cerebral sinus venous thromboses, pulmonary thromboembolism, and cavities in the left upper lung. Pulmonary tuberculosis was diagnosed based on sputum and gastric aspirate culture. Heparin followed by warfarin was administered. Anti-tuberculosis agents including rifampicin were also initiated. Since the effect of warfarin did not reach the therapeutic level because of interaction with rifampicin, edoxaban was administered and thromboses were ameliorated. This report illustrates rare thrombotic complications in a TB-induced hypercoagulable state and the potential benefits and safety of edoxaban in combination with rifampicin.

Increased physiological [18F]FDG uptake in the liver and blood pool among patients with impaired renal function.

BACKGROUND: In the daily clinical course, the liver uptake may seem to be increased in patients with renal failure. The purpose of this study was to investigate whether or not the FDG uptake of the liver, and the FDG uptake of blood pool which is generally used as a reference site as well as liver, is increased in patients with renal failure. MATERIAL AND METHODS: We retrospectively analyzed 233 patients who underwent FDG positron emission tomography/computed tomography (PET/CT). Renal failure is defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. We compared the FDG uptake in the liver and mediastinal blood pool of 67 patients with impaired renal function to that in 166 patients with a normal renal function (eGFR ≥ 60 mL/min/1.73 m2). Correlations between the liver or mediastinal blood pool FDG uptake and the eGFR were also analyzed by Spearman's correlation test. RESULTS: Maximum and mean standardized uptake values (SUVmax and SUVmean, respectively) of the liver and the SUVmean of the mediastinal blood pool were 3.48 ± 0.57, 2.56 ± 0.37, and 1.90 ± 0.28 in the impaired renal function group, respectively, and 3.13 ± 0.45, 2.29 ± 0.33, and 1.66 ± 0.23, in the normal group, respectively. The SUVmax and SUVmean of the liver and SUVmean of the mediastinal blood pool in the impaired renal function group were significantly higher than those in the normal group (p < 0.001, < 0.001, and < 0.001, respectively). The SUVmax and SUVmean of the liver and SUVmean of the mediastinal blood pool of patients showed a significant negative correlation with the eGFR (Spearman's p = -0.25, -0.30, and -0.40, respectively, each p < 0.001). CONCLUSIONS: FDG uptake in both the liver and mediastinal blood pool was higher in patients with impaired renal function.

Regiocontrolled Dimerization of Densely Functionalized 1,6-Dihydropyridines for the Biomimetic Synthesis of a Halicyclamine-type Scaffold by Preventing Disproportionation.

The biomimetic dimerization of 1,6-dihydropyridines (DHPs) remains a daunting challenge due to competitive disproportionation pathways. Herein we report the regioselective dimerization of densely functionalized 1,6-DHPs that allow direct access to the bis-nitrogen bicyclic scaffold of halicyclamines. Disproportionation triggered by the hydride shift of 1,6-DHP was suppressed by the use of geminal disubstituted substrates. Installation of an electron-withdrawing substituent at the C3 position was demonstrated to be crucial for facilitating biomimetic dimerization under metal-free conditions, with exquisite control of regioselectivity at ambient temperature. Our approach, featuring an appropriately functionalized and substantially stabilized substrate rather than merely adopting the highly reactive and labile hypothetical biosynthetic intermediate, allowed gram-scale and atom-economical synthesis of the bis-nitrogen bicyclic scaffold. Furthermore, conversion of a series of 1,6-DHPs provided mechanistic insights by circumventing the competitive disproportionation reaction. This revealed not only the innate reactivity of the conjugate diene system for [4 + 2] cycloaddition but also the reversibility of the dimerization reaction with multiple cationic intermediates in equilibrium.

A simple adaptive difference algorithm with CO2 measurements for evaluating plant growth under environmental fluctuations.

OBJECTIVE: The aim of this study is to demonstrate an adaptive method that is robust toward environmental fluctuations and provides a real-time measure of plant growth by measuring CO2 consumption. To verify the validity of the proposed method, the relation between the plant growth and variation in light conditions with a closed experimental system was investigated. RESULTS: The proposed method was used to measure the photosynthetic rate induced by photosynthetic photon flux density (PPFD) and to evaluate plant growth under continuous and pulsed light in arugula plants. The PPFD-dependent change in photosynthetic rate was measured. And in the condition range of 200-10,000 µs pulse period and 50% duty ratio of pulsed light, there was no change in the growth rate of plants assuming the same PPFD as continuous light. These experiments showed the validity of the adaptive method in removing environmental fluctuations without precise control of temperature and humidity.

Idiopathic dendriform pulmonary ossification diagnosed by bronchoscopic lung cryobiopsy: A case report.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by heterotopic bone production of unknown origin within the pulmonary tissue. Many cases are asymptomatic with slow progression and are often diagnosed incidentally during autopsy. Thus, only few cases are diagnosed while the patient is still alive since surgical lung biopsy is often needed for pathological diagnosis. This is the case of a 37-year-old man treated at our hospital due to abnormal findings on chest x-ray without any symptoms. His high-resolution computed tomography revealed diffuse reticular shadows and micronodules, consistent with calcification. He underwent transbronchial lung cryobiopsy (TBLC) and was diagnosed with idiopathic DPO based on pathological findings. To our knowledge, this is the first reported case of DPO diagnosed using TBLC. TBLC can be a useful yet minimally invasive diagnostic tool to diagnose DPO and other interstitial lung diseases.

Ultrasound assessment of muscle mass has potential to identify patients with low muscularity at intensive care unit admission: A retrospective study.

BACKGROUND & AIMS: Muscle mass is an important biomarker of survival from a critical illness; however, there is no widely accepted method for routine assessment of low muscularity at intensive care unit (ICU) admission. We hypothesize that ultrasound-based partial muscle mass assessments can reflect the trunk muscle mass. Therefore, we aimed to investigate whether ultrasound muscle mass measurements could reflect trunk muscle mass and identify patients with low muscularity. METHODS: We performed a retrospective analysis of prospectively obtained ultrasound data at ICU admission. We included patients who underwent computed tomography (CT) imaging at the third lumbar vertebra (L3) within 2 days before and 2 days after ICU admission. Primary outcomes included the correlation between the femoral muscle mass measurements using ultrasound and the cross-sectional area (CSA) at L3 obtained by CT. Low muscularity was defined as a skeletal muscle index of 36.0 cm2/m2 for males and 29.0 cm2/m2 for females. Secondary outcomes included the correlation with the ultrasound measurements of the biceps brachii muscle mass and diaphragm thickness. RESULTS: Among 133 patients, 89 underwent CT imaging, which included the L3. The patient mean age was 72 ± 13 years, and 60 patients (67%) were male. The correlation between the femoral muscle ultrasound and CT was ρ = 0.57 (p < 0.01, n = 89) and ρ = 0.48 (p < 0.01, n = 89) for quadriceps muscle layer thickness and rectus femoris muscle CSA, and these had the discriminative power to assess low muscularity, with the areas under the curve of 0.84 and 0.76, respectively. The ultrasound measurements of the biceps brachii muscle mass and diaphragm thickness were correlated with CT imaging [ρ = 0.57-0.60 (p < 0.01, n = 52) and ρ = 0.35 (p < 0.01, n = 79)]. CONCLUSIONS: Ultrasound measurements of muscle mass were correlated with CT measurements, and the measurements of femoral muscle mass were useful to assess low muscularity at ICU admission. TRIAL REGISTRATION: UMIN000044032 (retrospectively registered on April 25, 2021).

The effect of high-flow nasal cannula on diaphragm dysfunction including paradoxical diaphragmatic contraction in the intensive care unit.

Background : Diaphragm dysfunction is a serious problem. However, a few management techniques exist for diaphragm dysfunction. Methods : Adult patients treated with high-flow nasal cannula (HFNC) in the intensive care unit were included in this study. The diaphragm function was evaluated using ultrasound measurement of thickening fraction before and after HFNC liberation. Normal diaphragm contraction was defined as thickening fraction ≥ 15% without HFNC, whereas decreased or paradoxical diaphragm contractions were 0%-15% or < 0%, respectively. Results : Forty patients were enrolled, and 16 (40%) had normal diaphragm contraction, whereas 19 (48%) or 5 (13%) had decreased or paradoxical diaphragm contractions, respectively. Thickening fraction increased after HFNC liberation (27.0% ±â€…25.7% vs. 38.8% ±â€…34.5%, p = 0.03 in HFNC vs. no HFNC) in patients without diaphragm dysfunction. In patients with decreased diaphragm contraction, thickening fraction did not change with or without HFNC (8.9% ±â€…11.7% vs. 6.7% ±â€…5.2%, p = 0.35), whereas paradoxical contraction decreased with HFNC (1.0% ±â€…10.2% vs. -10.3% ±â€…2.7%, p = 0.04) in patients with paradoxical diaphragm contraction. Conclusions : The work of breathing decreased with HFNC in patients without diaphragm dysfunction, but did not decrease in patients with decreased diaphragm contraction. Paradoxical diaphragm contraction decreased with HFNC. J. Med. Invest. 68 : 159-164, February, 2021.