Super-responder and clinical remission in patients with asthma on treatment with single biologic therapy or cycling therapy using dupilumab in a real-world setting.

BACKGROUND: Regarding the therapeutic target in asthma, super-responder status (SR) is a status without systemic corticosteroids. Recently, clinical remission (CR), being a status of prolonged absence of asthma symptoms without systemic corticosteroids and/or normal pulmonary function, has gained attention as a new therapeutic target in asthma. Here, we examined the percentage and features of asthma patients on treatment with dupilumab showing SR and CR. MATERIALS AND METHODS: 49 asthma patients used subcutaneous dupilumab for > 1 year between April 2019 and November 2022. The status of SR and CR for 1 year was evaluated. Patients without any maintenance oral corticosteroids and exacerbations requiring systemic corticosteroids were classified as SR. CR was defined using three definitions based on changes in asthma symptoms and pulmonary function in addition to achieving SR for 1 year: CR without pulmonary function criteria (CR w/o F), fulfilment of asthma symptom improvement (asthma control questionnaire score < 0.75 or asthma control test score ≥ 23); and CR-70 or CR-80, pulmonary function improvement (%forced expiratory volume in 1 second ≥ 70% or ≥ 80%) in addition to achieving CR w/o F, respectively. RESULTS: 38 (77.6%), 22 (44.9%), 13 (26.5%), 12 (24.5%) of patients had SR, CR w/o F, CR-70, and CR-80, respectively. Severe eosinophilic chronic rhinosinusitis was significantly more found in patients with SR and CR based on all three definitions than in those without. CONCLUSION: This study identified the percentage and features of patients on treatment with dupilumab showing SR and CR in a real-world setting. The outcome beyond CR on biologic treatment should be clarified.

Pharmacokinetics of GS-441524, the active metabolite of remdesivir, in patients receiving continuous renal replacement therapy: A case series.

Remdesivir plays a key role in the treatment of coronavirus disease in 2019 (COVID-19). Haemodialysis is sometimes required for hospitalised patients with COVID-19, and patients undergoing haemodialysis are at an increased risk of severe COVID-19. In the present study, we report the serum concentrations of GS-441524, the active metabolite of remdesivir, in four patients undergoing continuous renal replacement therapy (CRRT). Patient 1, a male aged 70s, received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg remdesivir from day 2, according to the package insert as in non-haemodialysis patients. The mean trough serum concentration of GS-441524 was 783.5 ng/mL, which was approximately 7-fold higher than the mean for patients with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min. Patients 2-4 received a loading dose of 200 mg remdesivir on day 1, followed by 100 mg once every 2 days from day 2. The mean trough serum concentrations of GS-441524 were 302.2 ng/mL, 585.8 ng/mL and 677.3 ng/mL, respectively. These were 3 to 6-fold higher than the mean for patients with eGFR ≥60 mL/min. The target doses for patients 1, 2, 3, and 4 receiving CRRT were 13.6 mL/kg/h, 6.0-12.5 mL/kg/h, 20.1 mL/kg/h, and 15.1 mL/kg/h, respectively, using a polysulphone membrane. The package insert dose of remdesivir is an overdose for CRRT patients with a target dose of 10-20 mL/kg/h. In low-intensity CRRT, as in Japan, it may be necessary to extend the interval between the doses of remdesivir.

Real-Time Particle Emission Monitoring for the Non-Invasive Prediction of Lung Deposition via a Dry Powder Inhaler.

Although inhalation therapy represents a promising drug delivery route for the treatment of respiratory diseases, the real-time evaluation of lung drug deposition remains an area yet to be fully explored. To evaluate the utility of the photo reflection method (PRM) as a real-time non-invasive monitoring of pulmonary drug delivery, the relationship between particle emission signals measured by the PRM and in vitro inhalation performance was evaluated in this study. Symbicort® Turbuhaler® was used as a model dry powder inhaler. In vitro aerodynamic particle deposition was evaluated using a twin-stage liquid impinger (TSLI). Four different inhalation patterns were defined based on the slope of increased flow rate (4.9-9.8 L/s2) and peak flow rate (30 L/min and 60 L/min). The inhalation flow rate and particle emission profile were measured using an inhalation flow meter and a PRM drug release detector, respectively. The inhalation performance was characterized by output efficiency (OE, %) and stage 2 deposition of TSLI (an index of the deagglomerating efficiency, St2, %). The OE × St2 is defined as the amount delivered to the lungs. The particle emissions generated by four different inhalation patterns were completed within 0.4 s after the start of inhalation, and were observed as a sharper and larger peak under conditions of a higher flow increase rate. These were significantly correlated between the OE or OE × St2 and the photo reflection signal (p < 0.001). The particle emission signal by PRM could be a useful non-invasive real-time monitoring tool for dry powder inhalers.

[Laparoscopic Surgery for Delayed Chylous Ascites in Unresectable Gastric Cancer Patient-A Case Report].

Chylous ascites is a rare post operative complication after gastrectomy, which commonly occurs in early postoperative period. Here, we successfully treated a patient with unresectable gastric cancer who occurred chylous ascites 9 months after first surgery and underwent laparoscopic surgery for chylous ascites. Since prolonged chylous ascites may cause malnutrition, surgical treatment should be considered for refractory chylous ascites.

Sleep disordered breathing and haemoglobin A1c levels within or over normal range and ageing or sex differences: the Nagahama study.

Recently an association between blood glucose dysregulation and sleep disruption was suggested. The association between sleep disordered breathing, most of which is due to obstructive sleep apnea (OSA) in the general population, and diabetic severity, as well as the impact of antidiabetic treatment, remains unclear. This study aimed to investigate these associations as well as age and sex differences. This cross-sectional study evaluated 7,680 community participants as the main cohort (population-based cohort). OSA was assessed by the 3% oxygen desaturation index from pulse oximetry, which was corrected for sleep duration obtained by wrist actigraphy. For arguing the limitations for using pulse oximetry, 597 hospitalised patients, who were assessed by the apnea-hypopnea index from attended polysomnography, were also evaluated as the validation cohort (hospital-based cohort). Moderate-to-severe OSA was more prevalent as haemoglobin A1c (HbA1c) levels increased (<5.6%/5.6%-<6.5%/6.5%-<7.5%/≥7.5%, respectively) in both cohorts (p < 0.001), but only in those without antidiabetic treatment. The HbA1c level was an independent factor for moderate-to-severe OSA (population-based cohort, odds ratio [OR] 1.26, 95% confidence interval [CI] 1.10-1.45; hospital-based cohort, OR 1.69, 95% CI 1.22-2.33, per 1% increase). These associations were more prominent in the middle-aged (aged <60 years) than in the elderly (aged ≥60 years) and in women than in men in both cohorts. The prevalence of moderate-to-severe OSA in patients with antidiabetic treatment in the hospital-based cohort was ≥75% regardless of HbA1c levels. In conclusion, an association between the prevalence of OSA and HbA1c level even within or over the normal range was found only in patients without antidiabetic treatment and was more prominent in the middle-aged and in women.

[A Case in Which a Distal Pancreatectomy Was Performed for Pancreatic Metastasis of Renal Cell Carcinoma after Nephrectomy, and a Total Pancreatectomy Was Performed for Residual Pancreatic Recurrence].

We reported a case in which a pancreatic resection was performed for pancreatic metastasis of renal cell carcinoma 24 years after nephrectomy, and a residual pancreatectomy was performed 4 years later for residual pancreatic recurrence. The patient was a 72-year-old. In 1991, he underwent right nephrectomy for right renal cell carcinoma. During follow-up, in 2015, mass lesions were noted in the pancreatic tail and distal pancreatectomy was performed on suspicion of pancreatic neuroendocrine tumor(NET). Pathological examination diagnosed metastasis of renal cell carcinoma. In 2019, mass lesions were noted in the residual pancreas and total pancreatectomy was performed. Pathological examination diagnosed metastasis of renal cell carcinoma. There was 5 cases in Japan, including an our case, in which pancreatectomy was performed again after pancreatectomy for pancreatic metastasis of renal cancer, and the average time until the first pancreatic metastasis was pointed out was 11.8 years, and the average time until pancreatic recurrence was 9.4 years. Pancreatic metastasis of renal cell carcinoma shows heterochronic and multiple metastasis occurs, requiring long-team follow-up. When determining the extent of resection, it was suggested that the minimum number of repetitions necessary may lead to a long-term prognosis, taking into account the patient's age, background.

A novel gene, Le-Dd10, is involved in fruiting body formation of Lentinula edodes.

The cDNA library prepared from Lentinula edodes, Hokken 600 (H600), primordia was screened using cDNA expressed specifically in Dictyostelium discoideum prestalk as a probe. Twenty-one clones, Le-Dd1 ~ 21, were isolated from the L. edodes primordia cDNA library. Functional analysis of each gene was carried out by transformation into protoplast cells from L. edodes Mori 252 (M252) mycelia with the overexpression vector pLG-RasF1 of each gene because M252 protoplast cells were transformed with an 11-fold higher efficiency than H600 cells. Transformants with the overexpression vector of Le-Dd10 formed a fruiting body at almost the same time as H600, a positive control, although M252, a negative control, did not form a fruiting body under culture conditions. This suggested that Le-Dd10 is involved in the formation of fruiting bodies. Single-strand conformation polymorphism analysis revealed that Le-Dd10 is located on No. 4 linkage group of L. edodes. The properties of Le-Dd10 products were investigated by Western blotting analysis using polyclonal antibodies against GST:Le-Dd10 fusion proteins. As a result, 56-kDa, 27-kDa, and 14-kDa protein bands appeared in primordial and fruiting body stages, although the expected molecular weight of the Le-Dd10 product was 50 kDa.

[Long-Term Elderly Survivor with Recurrent MSI-High Gastric Cancer Using Pembrolizumab as a Second-Line Chemotherapy].

KEYNOTE-158 and 061 trials revealed the efficacy and safety of pembrolizumab(KEYTRUDA®)treatment in patients with recurrent high microsatellite instability(MSI-high)gastric cancer following gastrectomy. Here, we successfully treated an elderly case with recurrences following radical gastrectomy for advanced gastric cancer using pembrolizumab as a second- line chemotherapy. Even in elderly patients, pembrolizumab might contribute to effective and safe treatment in late-line chemotherapy for recurrent MSI-high gastric cancer.

[A Case of Pembrolizumab Therapy Markedly Effective for Advanced Recurrent Colorectal Cancer].

We report a case of pembrolizumab therapy as the fourth-line therapy for colorectal cancer and multiple lymph node recurrence with high-frequency microsatellite instability(MSI-High). The patient was a 75-year-old woman diagnosed with ascending colon cancer(pT4aN2bM0, Stage Ⅲc)and underwent laparoscopic right hemicolectomy, D3 dissection, and functional end-to-end anastomosis after inserting a self-expandable metallic stent. Postoperative adjuvant chemotherapy was performed, and the patient was followed. Postoperative 1 year 8 months, lymph node recurrence was indicated, and FOLFOX plus panitumumab therapy was introduced. FOLFIRI plus ramucirumab therapy and FTD/TPI were introduced as the second-line and third-line treatments, respectively; however, recurrent lymph nodes were further exacerbated and showed treatment resistance. Lymph node biopsy confirmed MSI-High, and pembrolizumab therapy was initiated as the fourth-line treatment. After the therapy, the lymph nodes reduced markedly. The patient remains undergoing chemotherapy without any adverse events.

[Patient with Epstein-Barr Virus-Positive Esophagogastric Junctional Cancer with Splenic Metastasis and Underwent Metastasectomy following Immune Checkpoint Therapy].

Recurrent gastric cancer(GC)with splenic metastasis showed poor prognosis, and its treatment strategy remains unclear. Recently, studies identified the considerable prognostic effect of metastasectomy in GC following intensive chemotherapy. Here, we successfully treated a patient with Epstein-Barr virus-positive esophagogastric junctional cancer with splenic metastasis who underwent metastasectomy and obtained pathological complete response following immune checkpoint therapy and had long-term survival. We reviewed the literature to discuss the clinical significance of our treatment strategy.

The Small GTPase OsRac1 Forms Two Distinct Immune Receptor Complexes Containing the PRR OsCERK1 and the NLR Pit.

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we revealed that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane (PM). Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the PM and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1.

Prospective associations of sleep apnea, periodic limb movements, and plasma fibrinogen level.

PURPOSE: Our previous cross-sectional study showed that periodic limb movements during sleep (PLMS) were frequently found in patients with obstructive sleep apnea (OSA) and that both OSA and PLMS were associated with higher plasma fibrinogen levels. We explored the longitudinal relationships among these factors. METHODS: Plasma fibrinogen levels were measured in 333 consecutive patients who underwent polysomnography to diagnose OSA. Patients who initiated continuous positive airway pressure (CPAP) underwent follow-up polysomnography after 3 months of CPAP use. They were categorized into groups with good or poor adherence (% days with ≥ 4 h/night of CPAP use ≥ 70% or < 70%, respectively). Changes in sleep parameters and plasma fibrinogen levels during the treatment period were compared between these groups. RESULTS: The cross-sectional analysis of all reviewed 333 patients indicated that fibrinogen levels were associated with the severities of OSA and PLMS. The 60 patients (27 good and 33 poor adherence) who underwent follow-up polysomnography were included in the longitudinal analysis. The median (interquartile range) periodic limb movement index did not change significantly from CPAP titration to the 3-month follow-up (good adherence: 10.5 (0-23.8) to 10.8 (0-70.2) events/h, p = 0.21; poor adherence: 1.2 (0-14.3) to 0.8 (0-15.7) events/h, p = 0.67). However, the plasma fibrinogen level significantly decreased only in the good adherence group (good adherence: baseline 275 ± 46 to follow-up 255 ± 47 mg/dl, p < 0.01; poor adherence: 277 ± 52 to 284 ± 70 mg/dl, p = 0.48). CONCLUSIONS: These results did not support a longitudinal association between PLMS and OSA. However, good adherence to CPAP could reduce plasma fibrinogen levels, thus ameliorating elevations in plasma fibrinogen as a risk factor for future cardiovascular events.

Sleep disordered breathing and metabolic comorbidities across sex and menopausal status in East Asians: the Nagahama Study.

It is well known that the prevalence of sleep disordered breathing (SDB) is increased in patients with obesity or metabolic comorbidities. However, the way in which the prevalence of SDB increases in relation to comorbidities according to the severity of obesity remains unclear.This cross-sectional study evaluated 7713 community participants using nocturnal oximetry ≥2 nights. SDB was assessed by the 3% oxygen desaturation index corrected for sleep duration obtained by wrist actigraphy (acti-ODI3%). SDB severity was defined by acti-ODI3%. Obesity was defined as body mass index ≥25 kg·m-2The prevalence of SDB was 41.0% (95% CI 39.9-42.1%), 46.9% (45.8-48.0%), 10.1% (9.5-10.8%) and 2.0% (1.7-2.3%) in normal, mild, moderate and severe SDB, respectively, with notable sex differences evident (males>post-menopausal females>premenopausal females). Comorbidities such as hypertension, diabetes and metabolic syndrome were independently associated with the prevalence of moderate-to-severe SDB, and coincidence of any one of these with obesity was associated with a higher probability of moderate-to-severe SDB (hypertension OR 8.2, 95% CI 6.6-10.2; diabetes OR 7.8, 95% CI 5.6-10.9; metabolic syndrome OR 6.7, 95% CI 5.2-8.6). Dyslipidaemia in addition to obesity was not additively associated with the prevalence of moderate-to-severe SDB. The number of antihypertensive drugs was associated with SDB (p for trend <0.001). Proportion of a high cumulative percentage of sleep time with oxygen saturation measured by pulse oximetry <90% increased, even among moderate-to-severe SDB with increases in obesity.Metabolic comorbidities contribute to SDB regardless of the degree of obesity. We should recognise the extremely high prevalence of moderate-to-severe SDB in patients with obesity and metabolic comorbidities.

High-flow nasal cannula oxygen therapy: Alternative respiratory therapy for severe post-transplant hypoxemia in children with hepatopulmonary syndrome.

Severe post-transplant hypoxemia, which is defined as <50 mm Hg of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F) ratio, is a major post-operative complication with high mortality rates in patients with hepatopulmonary syndrome (HPS). Non-invasive positive pressure ventilation therapy and mechanical ventilation are options for respiratory support of patients with severe post-transplant hypoxemia. However, these therapies are associated with several problems, such as compliance, ventilator-associated pneumonia, and lung injury. We here firstly described two children with HPS who developed severe post-transplant hypoxemia (lowest post-operative P/F ratio, 49.7 and 34.0 mm Hg, respectively) that was successfully managed with high-flow nasal cannula (HFNC) oxygen therapy and vasodilation drugs without adverse complications or necessity of reintubation. We consider that HFNC oxygen therapy could become a safe alternative respiratory therapy or be added to the other such as inhaled nitric oxide (iNO), methylene blue (MB), inhaled epoprostenol, embolization of abnormal pulmonary vessels, and combination of iNO and MB for severe post-transplant hypoxemia in children with HPS.

Role of eosinophilic chronic rhinosinusitis in switching to benralizumab treatment in mepolizumab responders.

BACKGROUND: There are currently three anti-interleukin-5 (IL-5) pathway-directed therapies: mepolizumab, reslizumab, and benralizumab. Of these, benralizumab was most recently approved. Benralizumab is administered every 8 weeks after an initial 3 doses given every 4 weeks, whereas mepolizumab and reslizumab are administered every 4 weeks. This convenience in benralizumab administration indicates that it is potentially beneficial for patients. Therefore, we potentially have an opportunity to change to benralizumab in patients who responded to mepolizumab or reslizumab. However, other than eosinophil levels, factors that could predict patients responding to anti-IL-5 pathway-directed therapies have been unknown. In this study, we examine the clinical characteristics of mepolizumab responders who achieved successful switching to benralizumab. MATERIALS AND METHODS: A total of 18 consecutive severe asthmatic patients treated with sequential mepolizumab and benralizumab, each for at least 1 year, were enrolled in this study. This study was a single-center case series. Patients were defined as having achieved successful switching to benralizumab if they satisfied either of the following for 1 year before and after the benralizumab treatment: (1) they experienced no exacerbation; or (2) they experienced no exacerbation and discontinued oral corticosteroids. RESULTS: All 18 patients responded to mepolizumab treatment, and 11 of them achieved successful switching to benralizumab. The proportion of patients who achieved successful switching to benralizumab was higher in patients with eosinophilic chronic rhinosinusitis (ECRS) than in those without (76.9 vs. 20.0%; p = 0.025). CONCLUSION: Our findings imply that in responders to mepolizumab, there may be a higher response rate to benralizumab in patients with ECRS than in those without.

[Better Effect of Home Night Enteral Nutrition in an Elderly Patient Following Laparoscopic Total Gastrectomy for Advanced Gastric Cancer].

Postoperative low nutrition, body weight loss and poor QOL are pivotal clinical issues for elderly patients following total gastrectomy for advanced gastric cancer. Here, we report a successfully treated high-risk elderly case using home night enteral nutrition and adjuvant chemotherapy following laparoscopic total gastrectomy for advanced gastric cancer. Home night enteral nutrition might not impair oral intake and daily QOL, and could be a useful treatment strategy for elderly patients following total gastrectomy.

[Long-Term Survivor with Recurrent Gastric Cancer Using Trifluridine/Tipiracil as a Late-Line Chemotherapy].

TAGS trial revealed the efficacy and safety of trifluridine/tipiracil(Lonsurf®)treatment in patients with metastatic gastric cancer following gastrectomy. Here, we successfully treated 38 months survival case after recurrences following radical gastrectomy for advanced adenocarcinoma of esophago-gastric junction using historical recommended chemotherapy regimens and trifluridine/tipiracil as a fifth-line chemotherapy. Trifluridine/tipiracil therapy contributed to effective and safety treatment even in late-line chemotherapy for recurrent gastric cancer.

Effect of nasally exhaling budesonide/formoterol dry powder inhaled at "fast" inspiratory flow on eosinophilic chronic rhinosinusitis
.

BACKGROUND: Budesonide (BUD)/formoterol (FM) dry powder inhaler has a feature that the fine particle fraction output is dependent on users' inspiratory flow rate. The aim of this study was to assess the amount of nasally exhaled BUD/FM inhaled in the different inspiratory flow rate. We also examined the effect of nasal exhalation of BUD/FM dry powder inhaled on radiographic evidence of sinonasal inflammation in asthmatic patients with eosinophilic chronic rhinosinusitis (ECRS). MATERIALS AND METHODS: The quantitative amount of nasally exhaled BUD/FM was analyzed by high-performance liquid chromatography in 3 healthy subjects. We retrospectively evaluated the effect of nasal exhalation of BUD/FM dry powder inhaled at > 60 L/min on radiographic evidence of sinonasal inflammation, which was assessed according to the Lund-Mackay staging (LMS) system, in 7 consecutive patients with asthma and ECRS. RESULTS: The amount of nasally exhaled BUD in the setting of inhaling BUD/FM dry powder inhaler at 60 L/min (subject 1: 25.8 ng/mL; subject 2: 37.3 ng/mL; subject 3: 30.0 ng/mL) was high compared to at 30 L/min (subject 1: 9.3 ng/mL; subject 2: 4.1 ng/mL; subject 3: 9.2 ng/mL) in each healthy subject. Nasal exhalation of BUD/FM dry powder significantly reduced total (p = 0.018) and ethmoid LMS scores (p = 0.0077). CONCLUSION: Nasal exhalation technique of BUD/FM dry powder inhaled at "fast" inspiratory flow has a potential of simultaneously treating asthma and ECRS.
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Role of mitochondrial hydrogen peroxide induced by intermittent hypoxia in airway epithelial wound repair in vitro.

The airway epithelium acts as a frontline barrier against various environmental insults and its repair process after airway injury is critical for the lung homeostasis restoration. Recently, the role of intracellular reactive oxygen species (ROS) as transcription-independent damage signaling has been highlighted in the wound repair process. Both conditions of continuous hypoxia and intermittent hypoxia (IH) induce ROS. Although IH is important in clinical settings, the roles of IH-induced ROS in the airway repair process have not been investigated. In this study, we firstly showed that IH induced mitochondrial hydrogen peroxide (H2O2) production and significantly decreased bronchial epithelial cell migration, prevented by catalase treatment in a wound scratch assay. RhoA activity was higher during repair process in the IH condition compared to in the normoxic condition, resulting in the cellular morphological changes shown by immunofluorescence staining: round cells, reduced central stress fiber numbers, pronounced cortical actin filament distributions, and punctate focal adhesions. These phenotypes were replicated by exogenous H2O2 treatment under the normoxic condition. Our findings confirmed the transcription-independent role of IH-induced intracellular ROS in the bronchial epithelial cell repair process and might have significant implications for impaired bronchial epithelial cell regeneration.

Changes in Energy Metabolism after Continuous Positive Airway Pressure for Obstructive Sleep Apnea.

RATIONALE: Disrupted energy homeostasis in obstructive sleep apnea (OSA) may lead to weight gain. Paradoxically, treating OSA with continuous positive airway pressure (CPAP) may also promote weight gain, although the underlying mechanism remains unclear. OBJECTIVES: To explore the underlying mechanism by which patients with OSA gain weight after CPAP. METHODS: A comprehensive assessment of energy metabolism was performed in 63 newly diagnosed OSA study participants (51 men; 60.8 ± 10.1 yr; apnea-hypopnea index >20 h(-1)) at baseline, CPAP initiation, and at a 3-month follow-up. Measurements included polysomnography, body weight, body composition, basal metabolic rate (BMR), hormones (norepinephrine, cortisol, leptin, ghrelin, insulin-like growth factor-1), dietary intake, eating behavior, and physical activity. MEASUREMENTS AND MAIN RESULTS: BMR significantly decreased after CPAP (1,584 kcal/d at baseline, 1,561 kcal/d at CPAP initiation, and 1,508 kcal/d at follow-up; P < 0.001), whereas physical activity and total caloric intake did not significantly change. In multivariate regression, baseline apnea-hypopnea index, Δurine norepinephrine, and CPAP adherence were significant predictors of ΔBMR. The weight gainers had higher leptin levels, lower ghrelin levels, and higher eating behavior scores than the non-weight gainers, indicating a positive energy balance and disordered eating behavior among the weight gainers. Among the parameters related to energy metabolism, increased caloric intake was a particularly significant predictor of weight gain. CONCLUSIONS: Although a reduction in BMR after CPAP predisposes to a positive energy balance, dietary intake and eating behavior had greater impacts on weight change. These findings highlight the importance of lifestyle modifications combined with CPAP. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000012639).