Impact of pemafibrate in patients with metabolic dysfunction-associated steatotic liver disease complicated by dyslipidemia: A single-arm prospective study.

Background and Aim: This study aimed to clarify the efficacy and safety of 48-week pemafibrate treatment in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) complicated by dyslipidemia. Methods: A total of 110 patients diagnosed with MASLD complicated by dyslipidemia received pemafibrate at a dose of 0.1 mg twice daily for 48 weeks. Results: The participants were 54 males and 37 females, with a median age of 63 (52-71) years. Besides improvement in lipid profile, significant reductions from baseline to 48 weeks of treatment were found in liver-related enzymes, such as aspartate aminotransferase, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase, and alkaline phosphatase (P < 0.001 for all). A significant decrease in the homeostasis model assessment-insulin resistance (HOMA-IR) was observed in patients with insulin resistance (HOMA-IR ≥ 2.5) (4.34 at baseline to 3.89 at Week 48, P < 0.05). Moreover, changes in ALT were weakly correlated with those in HOMA-IR (r = 0.34; p < 0.05). Regarding noninvasive liver fibrosis tests, platelets, Wisteria floribunda agglutinin-positive Mac-2-binding protein, type IV collagen 7s, and the non-alcoholic fatty liver disease fibrosis score significantly decreased from baseline to Week 48. Most adverse events were Grades 1-2, and no drug-related Grade 3 or higher adverse events were observed. Conclusion: This study demonstrated that 48-week pemafibrate administration improved liver-related enzymes and surrogate marker of liver fibrosis in patients with MASLD. The improvement of insulin resistance by pemafibrate may contribute to the favorable effect on MASLD complicated by dyslipidemia.

Low vitamin D levels accelerates muscle mass loss in patients with chronic liver disease.

Sarcopenia frequently and progressively occurs in patients with chronic liver disease. This study aimed to clarify the relationship between vitamin D levels and muscle mass loss. A total of 166 patients with chronic liver disease were enrolled in this study. Skeletal muscle mass index (SMI) was measured by bioelectrical impedance analysis at baseline and after 1 year. The rate of change in SMI from baseline after 1 year was calculated: ΔSMI (%) = [(1-year SMI - baseline SMI) / baseline SMI] × 100. Muscle mass loss was defined as ΔSMI ≤ -2%. The median 25-hydroxyvitamin D was 15.2 (11.2-19.3) ng/mL. The median SMI were 6.8 (5.9-7.8) kg/m2 at baseline and 6.7 (5.9-7.6) kg/m2 after 1 year. The median ΔSMI was -1.23% (-2.21% to 1.61%). Multivariate analysis identified low 25-hydroxyvitamin D as an independent factor associated with muscle mass loss. The optimal cut-off value of 25-hydroxyvitamin D to predict muscle mass loss was 12.7 ng/mL. Muscle mass loss was found in 56.4% v.s. 18.0% of patients with 25-hydroxyvitamin D < 12.7 vs. ≥ 12.7 ng/mL, respectively (p = 9.01 × 10-7); with the highest incidence in patients with non-alcoholic fatty liver disease (NAFLD). Specifically, patients with NAFLD and 25-hydroxyvitamin D < 12.7 ng/mL had a significantly higher incidence of muscle mass loss than those with ≥ 12.7 ng/mL (p = 1.23 × 10-3). Low vitamin D levels are associated with muscle mass loss after 1 year in patients with chronic liver disease, especially NAFLD.

Desquamative Interstitial Pneumonia with Progressive Pulmonary Fibrosis.

A 70-year-old man who smoked was referred to our hospital because of progressive cough and dyspnea. Radiologic images showed ground-glass attenuation predominantly in the lower lung lobes. A surgical lung biopsy was performed, and a diagnosis of desquamative interstitial pneumonia (DIP) was made. The patient's symptoms improved with smoking cessation and steroid treatment, but the ground-glass attenuation did not completely resolve. At 10 years after the diagnosis, the fibrotic lesions deteriorated and treatment with nintedanib was subsequently initiated. Careful observation is needed in patients with DIP whose lung involvement does not completely improve with initial treatment.

A novel formula used for predicting hepatocellular carcinoma after the achievement of sustained virologic response by direct-acting antivirals in patients with chronic hepatitis C.

Although eliminating HCV can prevent hepatocellular carcinoma (HCC), some patients develop HCC even after obtaining sustained virologic response (SVR). Previously, we developed a new formula to predict advanced liver fibrosis. This study aimed to clarify the usefulness of this formula for predicting HCC after achieving SVR. Among 351 consecutive patients who had been treated with direct-acting antivirals, 299 were included in this study. New formula scores were used as a marker for predicting liver fibrosis and as a predictive model for HCC incidence. The participants were 172 men and 127 women with a median age of 68 years. The median new formula score was -1.291. The cumulative HCC incidence rates were 4.3%, 9.7%, and 12.5% at 1, 3, and 5 years, respectively. The cumulative incidence of HCC was significantly higher in patients with a history of HCC than in those without treatment history of HCC (P = 2.52×10-26). Multivariate analysis revealed that male (HR = 6.584, 95% CI = 1.291-33.573, P = 0.023) and new formula score (HR = 1.741, 95% CI = 1.041-2.911, P = 0.035) were independent factors associated with the development of HCC in patients without a treatment history of HCC. The optimal cutoff value for predicting the development of HCC was -0.214. The cumulative incidence rates of HCC in patients with new formula scores ≥-0.214 were 5.4%, 15.3%, and 15.3% at 1, 3, and 5 years, respectively, whereas the incidence rates of HCC in patients with new formula scores <-0.214 were 0.0%, 0.6%, and 4.8%, respectively (P = 2.12×10-4). In conclusion, this study demonstrated the usefulness of new formula scores as a predictor of HCC after achieving SVR, especially in patients without past treatment history of treatment for HCC.

Post-menopausal ovarian fibroma associated with steroid hormone synthesis: A case report.

OBJECTIVE: Ovarian fibromas are benign, sex cord-stromal tumors occurring in both peri- and post-menopausal women. Generally, these tumors are non-functional and do not produce hormones. However, this case report proves the first case of steroid hormone synthesis in an ovarian fibroma by immunohistochemistry. CASE REPORT: A 77-year-old post-menopausal woman presented with a left ovarian tumor, abnormal endometrial thickness, and high levels of estradiol (E2). The tumor was found to be a fibroma, which was positive for alpha-inhibin. We examined estrogen-producing enzymes using immunohistochemistry. The tumor was positive for estrogen receptor, progesterone receptor, 17ß-hydroxysteroid dehydrogenase (HSD)-1, adrenal 4 binding protein/steroidogenic factor 1, 17ß-HSD-5, steroid sulfatase, and P450c17. CONCLUSION: This case study shows that E2 can be locally produced from circulating inactive steroids, by estrogen-producing enzymes. This is the first report of steroid hormone synthesis in an ovarian fibroma.

[Analysis of Patients Discharged from a Palliative Care Unit].

For terminal-phase cancer patients, being discharged from a palliative care unit(PCU)is often challenging. To explore this reason, we compared patients who went home alive from the PCU with patients who died in the same unit. Among the survival cases, the average duration from their diagnosis to admission into the PCU was longer. Their slow progressions might allow them to leave the PCU. Patients with head and neck cancer were more often among those who died in the PCU, and the ratio of patient with endometrial cancer was higher in the survival cases. These ratios were relevant to the duration before their admission and variety of their symptoms.

Partial pressure of carbon dioxide levels reflect disease severity in idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: Hypercapnia can cause a disturbance of consciousness and adversely affect a patient's general condition. Patients with interstitial lung disease seldom experience hypercapnia. Hypercapnia is a typical phenomenon in patients with pleuroparenchymal fibroelastosis (PPFE), especially in advanced stages. However, the clinical significance of hypercapnia in patients with idiopathic PPFE (iPPFE) has not been studied in detail. METHODS: We retrospectively selected patients with iPPFE who had undergone blood gas analysis. The first blood gas data obtained after iPPFE diagnosis were examined. The partial pressure of carbon dioxide (PCO2) levels and their association with characteristic iPPFE parameters, including the flat chest index (the ratio of the anteroposterior diameter of the thoracic cage to the transverse diameter of the thoracic cage), were investigated. RESULTS: A total of 47 patients with iPPFE were included in this study. The PCO2 level was moderately and inversely correlated with the forced vital capacity. (r = -0.431, P = 0.014), flat chest index (r = -0.497, P < 0.001), and body mass index (r = -0.313, P = 0.038) and was positively correlated with residual volume/total lung capacity. (r = 0.514, P < 0.01). A higher PCO2 level was also significantly associated with poorer prognosis in patients with iPPFE. CONCLUSIONS: PCO2 levels could be used as an indicator of disease severity in patients with iPPFE.

Survey of psychiatric symptoms among inpatients with COVID-19 using the Diagnosis Procedure Combination data and medical records in Japan.

Physical symptoms such as fatigue and muscle weakness, and psychiatric symptoms like depression and anxiety are considered as complications and sequelae of COVID-19. This epidemiological study investigated the actual status of psychiatric symptoms and disorders caused by COVID-19, from four major university hospitals and five general hospitals in Fukuoka Prefecture, Japan, having a population of 5 million. We conducted a survey of psychiatric disorders associated with COVID-19 using Diagnosis Procedure Combination (DPC) data and the psychiatric records of the hospitals. In the study period from January 2019 to September 2021, 2743 COVID-19 admissions were determined from DPC data across the nine sites. These subjects had significantly more anxiety, depression, and insomnia, and were receiving higher rates of various psychotropic medications than controls influenza and respiratory infections. A review of psychiatric records revealed that the frequency of organic mental illness with insomnia and confusion was proportional to the severity of COVID-19 infection and that anxiety symptoms appeared independent of infection severity. These results indicate that COVID-19 is more likely to produce psychiatric symptoms such as anxiety and insomnia than conventional infections.

A case of welder's pneumoconiosis treated with corticosteroid followed by nintedanib.

A 32-year-old man who had worked as a welder for 13 years was hospitalized for a fever and hemosputum with dyspnea. He was diagnosed with welding fume-associated lung disease with alveolar hemorrhaging and acute respiratory failure. Despite surviving the acute phase with corticosteroid therapy, hypoxemia persisted after a month and a half, requiring home oxygen therapy. As a result of the introduction of nintedanib, his clinical findings gradually improved, and the patient was weaned from oxygen therapy after six months. Inhalation of a large amount of welding fumes in a short period can cause alveolar hemorrhaging and prolonged pulmonary dysfunction.

Antifibrotic effect and long-term outcome of SGLT2 inhibitors in patients with NAFLD complicated by diabetes mellitus.

The aim of this retrospective multicenter study was to clarify the antifibrotic effect and long-term outcome of sodium glucose cotransporter 2 inhibitors (SGLT2-Is) in patients with nonalcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Of the 1262 consecutive patients with T2DM who recently received SGLT2-Is, 202 patients with NAFLD had been receiving SGLT2-Is for more than 48 weeks and were subjected to this analysis. Furthermore, 109 patients who had been on SGLT2-I therapy for more than 3 years at the time of analysis were assessed for the long-term effects of SGLT2-Is. Significant decreases in body weight, liver transaminases, plasma glucose, hemoglobin A1c, and Fibrosis-4 (FIB-4) index were found at week 48. Overall, the median value of FIB-4 index decreased from 1.42 at baseline to 1.25 at week 48 (p < 0.001). In the low-risk group (FIB-4 index < 1.3), there was no significant change in the FIB-4 index. In the intermediate-risk (≥1.3 and <2.67) and high-risk (≥2.67) groups, the median levels significantly decreased from 1.77 and 3.33 at baseline to 1.58 and 2.75 at week 48, respectively (p < 0.001 for both). Improvements in body weight, glucose control, liver transaminases, and FIB-4 index were found at 3 years of SGLT2-I treatment. In the intermediate-risk and high-risk groups (≥1.3 FIB-4 index), the FIB-4 index maintained a significant reduction from baseline throughout the 3 years of treatment. Conclusion: This study showed that SGLT2-Is offered a favorable effect on improvement in FIB-4 index as a surrogate marker of liver fibrosis in patient with NAFLD complicated by T2DM, especially those with intermediate and high risks of advanced fibrosis, and this antifibrotic effect is sustained for the long term.

Efficacy and safety of oral semaglutide in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study.

Background and Aim: This study aimed to clarify the efficacy and safety of oral semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM). Methods: This was a single-arm, open-label pilot study. Sixteen patients with NAFLD who received oral semaglutide for T2DM were included in the analysis. Oral semaglutide was initiated at a dose of 3 mg once daily, and the dose was sequentially increased to 7 mg at 4 weeks and 14 mg at 8 weeks (maintenance dose) until the end of the 24-week trial. Results: Body weight and levels of liver-related biochemistry, plasma glucose, and hemoglobin A1c decreased significantly from baseline to 12 weeks. These significant decreases were maintained until the end of the trial. Additionally, levels of the homeostasis model assessment-insulin resistance and triglyceride significantly decreased at 24 weeks. Controlled attenuation parameter (CAP) values significantly decreased from baseline to 24 weeks. Changes in body weight were correlated with those in levels of alanine aminotransferase (r = 0.52) and CAP (r = 0.72). As for liver fibrosis markers, significant decreases from baseline to 24 weeks in levels of the fibrosis-4 index, ferritin, and type IV collagen 7 s were found; however, the liver stiffness measurement did not significantly decrease. Most adverse events were grade 1-2 transient gastrointestinal disorders. Conclusions: Oral semaglutide treatment in patients with NAFLD complicated by T2DM improved impaired liver function, hypertriglyceridemia, insulin resistance, and hepatic steatosis, as well as improving diabetic status and reducing body weight.

In Situ Grown Nanocrystalline Si Recombination Junction Layers for Efficient Perovskite-Si Monolithic Tandem Solar Cells: Toward a Simpler Multijunction Architecture.

The perovskite-Si tandem is an attractive avenue to attain greater power conversion efficiency (PCE) than their respective single-junction solar cells. However, such devices generally employ complex stacks with numerous deposition steps, which are rather unattractive from an industrial perspective. Here, we develop a simplified tandem architecture consisting of a perovskite n-i-p stack on a silicon heterojunction structure without applying the typically used indium-tin-oxide (ITO) recombination junction (RJ) layer between the top and bottom cells. It is demonstrated that an n-type hydrogenated nanocrystalline silicon (nc-Si:H) grown in situ on an amorphous silicon hole contact layer of the bottom cell acts as an efficient RJ layer, leading to a high open-circuit voltage (VOC) of >1.8 V and a PCE of 21.4% without optimizing the optical design. Compared to the tandem cell with an ITO RJ layer, the nc-Si:H RJ layer not only improves light management but also achieves a higher VOC due to superior contact properties with an overlying SnO2 electron transport layer of the perovskite top cell. Omitting the costly material and its deposition step offers the opportunity toward realizing industrially feasible high-efficiency tandem solar cells.

Limited efficacy of nintedanib for idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: The antifibrotic agent nintedanib has been reported to effectively prevent the decline in forced vital capacity (FVC) in a broad range of interstitial lung diseases. However, the efficacy of nintedanib against idiopathic pleuroparenchymal fibroelastosis (iPPFE) remains unclear. METHODS: We retrospectively examined patients with idiopathic PPFE or idiopathic pulmonary fibrosis (IPF) who received nintedanib for more than 6 months. We evaluated annual changes in %FVC, radiological PPFE lesions, and body weight before and during nintedanib treatment. To investigate radiological PPFE lesions, we examined the fibrosis score, which was defined as the mean percentage of the high attenuation area in the whole lung parenchyma using three axial computed tomography images. RESULTS: Overall, 15 patients with iPPFE and 27 patients with IPF were included in the present study. In patients with IPF, the annual rate of decline in %FVC was significantly lower during nintedanib treatment than that before treatment (-2.01%/year [-7.64 to 3.21] versus -7.64%/year [-10.8 to -4.44], p = 0.031). Meanwhile, in patients with iPPFE, the annual rate of decline in %FVC during nintedanib treatment was higher than that before treatment (-18.0%/year [-21.6 to -12.7] versus -9.40%/year [-12.3 to -8.23], p = 0.109). In addition, nintedanib treatment failed to inhibit the annual rate of increase in fibrosis score in patients with iPPFE (6.53/year [1.18-15.3] during treatment versus 2.70/year [0.27-12.2] before treatment, p = 0.175). CONCLUSIONS: Nintedanib efficacy may be limited in patients with iPPFE.

Platythorax progresses with lung involvement in pleuroparenchymal fibroelastosis.

BACKGROUND: Patients diagnosed with pleuroparenchymal fibroelastosis (PPFE) exhibit unique clinical features, including upper lobe-dominant lung involvement and platythorax (or flattened thoracic cage). Although platythorax have been shown to be a sign of disease progression, the temporal relationship between the progression of platythorax and the extent of lung involvement has not been closely investigated. METHODS: We retrospectively investigated patients diagnosed with PPFE, who did not exhibit fibrotic lesions other than PPFE in the lower lobes. We estimated the fibrosis score, which is a visual score indicating the percentage of lung parenchyma occupied by the disease on computed tomography images selected every 2 cm from the lung apex to the lung base, and the flat chest index (the ratio of the anteroposterior diameter of the thoracic cage to the transverse diameter of the thoracic cage). Additionally, we investigated serial changes in the flat chest index and fibrosis score. RESULTS: A total of 29 patients were included in this study. The fibrosis score was found to be weakly and inversely correlated with forced vital capacity %predicted at the diagnosis (r = -0.40, p = 0.038). Furthermore, the annual changes in the flat chest index and fibrosis score was found to be moderately and inversely correlated (r = -0.663, p = 0.0037). CONCLUSIONS: These results indicate that there is a causal relationship between the progression of fibroelastosis and that of platythorax in patients with PPFE.

Nodular Pulmonary Amyloidosis Associated with Sjögren's Syndrome.

Amyloidosis is a rare disease characterized by the deposition of abnormal proteins in extracellular tissues. We herein report a case with instructive radiologic features of nodular pulmonary amyloidosis associated with Sjögren's syndrome. A 67-year-old woman was referred to our department because of an abnormal chest radiograph. Chest computed tomography revealed multiple round cysts accompanied by calcified nodules. The patient was clinically diagnosed with primary Sjögren's syndrome and pathologically diagnosed with nodular pulmonary amyloidosis (light chain, kappa). Although multiple lung cysts have many etiologies, the presence of calcified nodules associated with multiple lung cysts is useful for narrowing down the differential diagnosis.

Study of factors related to recurrence within 30 days after pneumonia treatment for community-onset pneumonia.

INTRODUCTION: It is not uncommon for patients hospitalized with pneumonia to experience an early relapse. Here, we investigated the factors related to pneumonia recurrence in Japan. PURPOSE: We aimed to elucidate the factors related to early recurrence after completion of pneumonia treatment. METHODS: We examined 696 patients with community-acquired pneumonia (CAP) and nursing and healthcare-associated pneumonia (NHCAP) who were admitted to our hospital between October 2010 and February 2018, excluding those who died during hospitalization. Logistic regression analysis was used to assess the endpoint of recurrence within 30 days after the end of antibiotic treatment. RESULTS: NHCAP, chronic lung disease and duration of antibiotic treatment were significant risk factors for recurrence of pneumonia within 30 days after antibiotic discontinuation. Aspiration pneumonia was not be a significant factor in the early recurrence of pneumonia. CONCLUSIONS: Long-term use of antimicrobials may be a risk factor in early recurrence of pneumonia.

Oriented Thin Films of Insoluble Polythiophene Prepared by the Friction Transfer Technique.

A thin film of unsubstituted polythiophene (PT), an insoluble conjugated polymer, with molecular chains uniaxially oriented in plane was prepared by the friction transfer method. The structure of highly oriented thin films of PT was investigated using grazing-incidence X-ray diffraction (GIXD), ultraviolet-visible (UV-vis) spectroscopy, and infrared (IR) spectroscopy. The polarized UV-vis and IR spectra and GIXD measurements showed the PT molecular chains were well aligned in parallel to the friction direction. The GIXD studies clarified that the polymer backbones were aligned with very narrow distribution, such that the half-width was about 4 degrees. The degree of orientation of the PT friction-transferred film was higher compared with those of regioregular poly(3-alkylthiophene)s. Moreover, the GIXD results show a preferred orientation where the a-axis is perpendicular to the substrate plane.

Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.