Hokushin General Hospital

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection with a growing incidence and mortality globally. Although the clinical features, treatment, and prognosis of Mycobacterium avium-intracellulare (MAI) pulmonary disease have been extensively reported, evidence regarding non-MAI NTM-PD remains limited. This retrospective cohort study included patients newly diagnosed with NTM-PD between 2010 and 2017at 18 hospitals in Kyushu, Japan. Data on baseline characteristics, causative organisms, radiological findings, treatment regimens, and clinical outcomes were collected and analysed. In total, 1317 patients were enrolled. M. intracellulare (50.4%), M. avium (40.5%), M. abscessus complex (MABC) (2.4%), and M. kansasii (2.4%) were identified as the major causative organisms. Compared with patients with MAI, those with MABC exhibited a lower body mass index and a higher AFB sputum smear positivity rate. Patients with M. kansasii infection were predominantly male, frequently had underlying chronic obstructive pulmonary disease, and presented with cavitary lesions. Treatment initiation rates for MABC and M. kansasii were 71.9% and 87.5%, respectively. The response rate to the treatment in sputum mycobacterial evaluation was comparable between the two groups. However, the re-treatment rate was higher in the MABC group (30.4% vs. 14.3%). The 10-year mortality rates were 25.0% and 15.6% for MABC and M. kansasii, respectively. Initial treatment responses for MABC and M. kansasii were favourable. However, long-term outcomes for MABC remained poor, potentially owing to the limited availability of effective continuation-phase therapies. Further large-scale prospective studies are warranted to understand the clinical management and prognosis of non-MAI NTM-PD.

Although aortic valvular disease has various etiologies, recently, calcific aortic valve stenosis has been increasing. We analyzed the trends in the pathological characteristics of aortic valvular disease in the past four decades in Japan. The pathology department data for aortic valvular disease operated in our hospital documented 4508 patients from 1978 to 2022. Subsequently, trend analyses were performed over four periods: Period 1, 1978-1989 (618 cases); Period 2, 1990-1999 (903 cases); Period 3, 2000-2010 (1179 cases); and Period 4, 2011-2022 (1808 cases). We reviewed the pathological characterization of the resected aortic valves and categorized them based on the representative etiology of aortic valvular disease as congenital bicuspid, chronic rheumatic change, infective endocarditis, degenerative calcific change, and myxoid change. Our pathologic analysis revealed a significant decrease in the proportion of chronic rheumatic disease from 47% to 14%, an increase in the congenital bicuspid valve from 8% to 24%, and a rise of the degenerative calcific change of the aortic valve from 4% to 27% (p < 0.001), especially significant increases in aortic stenosis. Calcification of the aortic valve may result from an active process similar to atherosclerosis, leading to aortic stenosis with increasing dyslipidemia in Japanese patients in 40 years.

Enteral nutrition (EN) has been reported to have some physiological importance for critically ill patients. However, the advantage of EN over parenteral nutrition remains controversial in recent paradigms. To maximize the benefits and efficiency of EN, implementing measures based on comprehensive evidence is essential. Here, we systematically reviewed EN-related studies and integrated them into the best and most up-to-date EN practices. We extracted studies from 13 systematic reviews during the development of Japanese Critical Care Nutrition Guidelines, summarizing findings on the assessment of enteral feeding intolerance (EFI), the timing of EN, formula composition and nutrients, and method of administration in critically ill adult patients. Multifaceted EFI assessment may be needed in patients for high-risk patients. Early EN may reduce infectious complications, and initiating EN even earlier may offer an additional advantage. High protein intake (≥1.2 g/kg/day) could maintain muscle mass and physical function without increasing gastrointestinal complications. Probiotics, prebiotics, and synbiotics may serve as beneficial options for preventing infection and gastrointestinal complications, although their efficacy depends on the strains, types, and combinations used. For patients with EFI, post-pyloric feeding could be an effective approach, while intermittent feeding may be a safer approach. Both methods should be utilized to achieve nutritional targets. Integrating these nutritional interventions into EN strategies may help maximize their effectiveness and minimize complications. However, careful consideration regarding timing, dosage, nutrient selection, administration methods, and patient selection is required.

The purpose of this study was to clarify the relationship between vertical ground reaction force (VGRF) and acceleration from wearable inertial measurement units (IMUs) during single-leg drop landing after anterior cruciate ligament reconstruction (ACLR). Twenty-six participants, 42.4 ± 5.3 weeks after ACLR, performed three single-leg drop landing trials bilaterally. The peak VGRF was assessed using a force plate. The resultant acceleration was calculated using IMUs attached to the shank, thigh, and lumbar region. Univariate regression analysis was performed to examine the linear relationship between the VGRF and resultant acceleration. The limb symmetry index (LSI) of the VGRF was linearly associated with the LSI of the resultant accelerations at the shank, thigh, and lumbar sensors (R2 = 0.166, p = 0.039; R2 = 0.525, p &lt; 0.001; and R2 = 0.250, p = 0.009, respectively). In the involved limb, only the resultant acceleration at the thigh was a significant predictor of VGRF (R2 = 0.490, p &lt; 0.001), whereas in the uninvolved limb, the resultant accelerations at the shank, thigh, and lumbar sensors were significant predictors of VGRF (R2 = 0.245, p = 0.010; R2 = 0.684, p &lt; 0.001; and R2 = 0.412, p &lt; 0.001, respectively). Caution may be required when using IMUs to predict VGRF asymmetry because the coefficient of determination for predicting VGRF is lower in the involved limb than in the uninvolved limb.

Background and objective: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection with increasing prevalence and mortality worldwide. Chronic pulmonary aspergillosis (CPA) is a significant complication of NTM-PD and is associated with a poor prognosis. In this multicenter, retrospective, cohort study, we examined the epidemiology, comorbidities, risk factors for CPA coinfection, and long-term prognoses of patients with NTM-PD infected with CPA in Japan. Methods: Patients aged ≥18 years with newly diagnosed NTM-PD who visited 18 acute-care hospitals in Kyushu, Japan, between 2010 and 2017 were included. Medical records were reviewed for patient characteristics, underlying diseases, mycobacterial species, laboratory data, radiological features, Aspergillus coinfection, and all-cause mortality. Risk factors for CPA coinfection were analyzed using multiple logistic regression, and survival analysis was performed before and after propensity score matching with risk factors. Results: Among 1,304 patients with NTM-PD, 45 (3.5%) were diagnosed with CPA during the observation period. Risk factors for CPA coinfection included male sex, chronic obstructive pulmonary disease, oral corticosteroid use, and cavity formation. All-cause mortality was significantly higher in patients with NTM-PD with CPA than in those without CPA (log-rank test, P &lt; .001; crude HR, 3.98). Survival analysis after propensity score matching confirmed that CPA was an independent poor prognostic factor (log-rank test, P = .036; adjusted HR, 1.59). Conclusion: CPA is an independent poor prognostic factor in patients with NTM-PD. Clinicians must consider CPA when treating patients with NTM-PD, particularly those with high-risk factors, to ensure their timely diagnosis and management.

Thyroid transcriptional factor-1 (TTF-1) is associated with the development of interstitial lung disease (ILD) and is a mutational target in lung adenocarcinoma with ILD. TTF-1 expression is also associated with the efficacy of pemetrexed-based chemotherapy for nonsquamous nonsmall cell lung cancer (NS-NSCLC). However, the relationship between TTF-1 expression and the efficacy of immunotherapy using programmed cell death 1 inhibitor (PD-1i), especially in lung cancer patients with ILD, remains unclear. Medical data of NS-NSCLC patients treated with PD-1i at multiple centres were analysed retrospectively. Patients were divided into those with or without concomitant ILD, with the two cohorts further stratified by TTF-1 expression. The study population included 62 NS-NSCLC patients, 34 with and 28 without ILD. Median progression-free survival (PFS) during PD-1i treatment was significantly shorter in TTF-1-negative than -positive patients (2.0 versus 12.1 months, p=0.004) in the ILD cohort but did not differ significantly in the non-ILD cohort (1.8 versus 2.6 months, p=0.63). Median overall survival (OS) was also significantly shorter in TTF-1-negative than -positive patients in the ILD cohort (14.5 versus 42.5 months, p=0.018) but not in the non-ILD cohort (33.7 versus 37.1 months, p=0.53). Cox regression analyses showed that absence of TTF-1 expression was an independent risk factor for PFS (hazard ratio (HR) 2.75, p=0.024) and OS (HR 2.81, p=0.012) in the ILD cohort. TTF-1 expression in NS-NSCLC patients with ILD may predict prognosis when treated with PD-1i.

PURPOSEHERALD/EPOC1806 was conducted as a multicenter phase II trial assessing trastuzumab deruxtecan (T-DXd) therapy for patients with human epidermal growth factor receptor 2 (HER2)–amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing.PATIENTS AND METHODSPatients exhibited advanced solid tumors with HER2 amplification that was identified via next-generation sequencing of cfDNA testing, without the requirement for immunohistochemical HER2 testing. The studied group was administered T-DXd at 5.4 mg/kg once every 3 weeks until onset of disease progression or intolerable toxicity.RESULTSOverall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated HER2 amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma HER2 copy number (CN) of 8.55 (range, 2.4-73.9). Confirmed overall response rate (ORR) by investigator assessment was 56.5% (95% CI, 43.3 to 69.0), thus showing a value beyond the 5% threshold. Responses were evaluated for 13 cancer types, including KRAS-mutant colorectal (1/3), PIK3CA-mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma HER2 CN above versus below the baseline median value did not differ for impact response; however, clearance of HER2 amplification in cfDNA on cycle 2 day 1 had higher response values compared with persistence. Median progression-free survival and response duration were 7.0 (95% CI, 4.9 to 9.7) and 8.8 (95% CI, 5.8 to 11.2) months, respectively, with the majority of complications being mild to moderate. Interstitial lung diseases were identified in 16 (26%) patients, including 14 patients with grade 1 disease, one patient with grade 2 disease, and one patient with grade 3 disease.CONCLUSIONT-DXd treatment demonstrated high ORR with durable response in patients with advanced HER2-amplified solid tumors determined with cfDNA testing.