Descriptive analysis of incidence and risk factors for short intramedullary nail breakage in femoral intertrochanteric fractures: a multicenter (TRON group) retrospective study.

BACKGROUND: The incidence of hip fractures is increasing. Femoral intertrochanteric fractures make up 50% of hip fractures and are treated by intramedullary nails. Implant breakage is a recognized complication that can have rare and serious implications. This study aimed to investigate implant breakage rates after surgical treatment for femoral intertrochanteric fractures. METHODS: This was a retrospective multicenter analysis. All 1854 patients who underwent surgical treatment for femoral intertrochanteric fractures were selected from 12 hospitals (TRON group) between 2016 and 2020. Exclusion criteria included implants other than those specified and follow-up periods less than three months. Demographic data, surgical details, and radiographic assessments were collected from medical records and X-ray evaluations. RESULTS: Among the 983 study patients, consisting of 245 males (24.9%) and 738 females (75.1%), the implant breakage rate was 0.31%, with three confirmed cases. The average age was 83.9 years. The mean follow-up period was 640.9 days. Two cases were linked to ASULOCK implants, and one to an OLSII implant. Statistical analysis showed a significantly higher incidence of ASULOCK implant breakage (p < 0.001). In the two cases of ASULOCK implant breakage and one case of OLSII implant breakage, breakage in all three implants occurred at the anti-rotation screws. CONCLUSIONS: There were no implant breakages of the main body of the implants; all breakages occurred in the additional anti-rotation screw. The necessity of the anti-rotation screw will require further discussion. These results can potentially inform clinical decisions and guide further research in preventing implant breakage.

Skill Proficiency, Efficacy, and Safety of the Transradial Approach in Transarterial Treatments for Hepatocellular Carcinoma.

Introduction Abdominal angiography procedures such as transarterial chemoembolization (TACE) are essential for hepatocellular carcinoma treatment. One method commonly used is transfemoral access (TFA). However, issues associated with this method, which include postoperative compression of the puncture site and long periods of bed rest, can affect patient satisfaction. Thus, transradial access (TRA), a minimally invasive treatment method that improves treatment quality, was developed for TACE. This retrospective, multicenter study aimed to investigate the efficacy and safety of abdominal angiography using the radial artery approach. Methods In total, 1,601 patients underwent abdominal angiography using TRA and received treatment (radial access for visceral intervention (RAVI)) at 14 institutions in Japan. The treatment time, procedure completion rate, patient satisfaction, and complications were investigated. Results The success rate of RAVI was 99.4%, and the complication rate was 1.2%. Approximately 98.2% of the patients requested the radial artery approach again. There were no significant differences in the success rate of RAVI and the incidence of complications based on the operator's years of experience or the patient's age. Some patients developed minor complications such as puncture site bleeding, hematoma, vascular pain, and vasospasm. Further, serious complications (cerebral infarction (n = 1), cerebellar infarction (n = 1), and aortic dissection (n = 1)) were observed. Conclusion Similar to the conventional TFA, RAVI helped in facilitating peritoneal angiography safely. In abdominal angiography, this method can reduce patient burden and can be widely used in the future from the perspective of clinical benefit.

Intestinal Microbiome Associated with Efficacy of Atezolizumab and Bevacizumab Therapy for Hepatocellular Carcinoma.

The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder (n = 28) and non-responder (n = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of Bacteroides stercoris and Parabacteroides merdae was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.

Histology of Bronchiolar Tumor Spread Through Air Spaces.

The clinical significance of lung tumor spread through air spaces (STAS) has been extensively studied, and is recognized as a unique pattern of invasion. Previous studies of STAS have focused primarily on STAS in alveolar spaces, whereas STAS in the bronchiolar spaces (bronchiolar STAS) has been described in only a few case reports only. Here, we examined 306 cases of primary lung adenocarcinoma and found that bronchiolar STAS was present in 18%. Bronchiolar STAS was associated with an inferior prognosis, more advanced stage, and higher histologic grade. No significant difference in clinicopathological factors or prognosis was observed between cases with bronchiolar STAS and those with alveolar STAS alone. Notably, bronchiolar STAS often occurred simultaneously with alveolar STAS and endobronchial spread of adenocarcinoma, particularly when bronchiolar STAS was present outside the main tumor. We also identified cases where bronchiolar STAS and endobronchial spread of adenocarcinoma occurred simultaneously in the same bronchi or bronchioles located outside the main tumor, as well as cases with bronchiolar STAS adjacent to intrapulmonary metastatic nodules. Our results highlight the significant role of bronchiolar STAS in the aerogenous spread of adenocarcinoma cells. Bronchiolar STAS can be regarded as a histologic variant of alveolar STAS. This study also supports the idea that STAS is not a tissue processing artifact, but a true biological process with clinical implications, offering histologic evidence of aerogenous spread in lung adenocarcinoma.

Single-centre observational study of the safety and efficacy of thoracoscopy under local anaesthesia for the management of thoracic infections.

OBJECTIVES: Thoracoscopy under local anaesthesia is widely performed to diagnose malignancies and infectious diseases. However, few reports have described the use of this procedure for diagnosing and treating intrathoracic infections. This study aimed to evaluate the safety and efficacy of thoracoscopy under local anaesthesia for the management of intrathoracic infections. RESULTS: Data from patients who underwent thoracoscopy procedures performed by chest physicians under local anaesthesia at our hospital between January 2018 and December 2023 were retrospectively reviewed. We analysed their demographic factors, reasons for the examinations, diseases targeted, examination lengths, anaesthetic methods used, diagnostic and treatment success rates, as well as any adverse events. Thirty patients were included. Of these, 12 (40%) had thoracoscopies to diagnose infections, and 18 (60%) had them to treat pyothorax. In terms of diagnosing pleurisy, the causative microorganism of origin was identified via thoracoscopy in only three of 12 (25.0%) patients. For diagnosing pyothorax, the causative microorganism was identified in 7 of 18 (38.9%) patients. Methicillin-resistant Staphylococcus aureus was the most common causative microorganism identified. The treatment success rates were very high, ranging between 94.4 and 100%, whereas the identification rate of the causative microorganisms behind infections was low, ranging between 25.0 and 38.9%. The most frequent adverse events included perioperative hypoxaemia and pain. There were two (6.7%) serious adverse events of grade ≥ 3, but none resulted in death. CONCLUSIONS: The efficacy of managing intrathoracic infections through thoracoscopy under local anaesthesia is commendable. Nonetheless, the diagnostic accuracy of the procedure, regarding the precise identification of the causative microorganisms responsible for intrathoracic infections, persists at a notably low level, presenting a substantial clinical hurdle.

Risk factors for decreased bone mineral density in patients with metabolic dysfunction-associated steatotic liver disease: A cross-sectional study at a health examination center.

BACKGROUND & AIMS: Steatotic liver disease (SLD) is often detected in health examinations. However, although individuals with metabolic dysfunction-associated SLD (MASLD) may have decreased bone mineral density (BMD), the specific risk factors remain unclarified. The objective of this study was to identify the factors associated with decreased BMD in patients with MASLD. METHODS: Individuals who underwent abdominal ultrasonography and BMD measurements at our healthcare center were included. The BMD of the calcaneus was assessed using an AOS-10SA bone densitometer. Decreased BMD was defined as a T-score below -1.0 SD or the administration of osteoporosis treatment. SLD was diagnosed based on specific ultrasonographic criteria. RESULTS: A total of 1410 patients were diagnosed with MASLD. The median age was 52 years. Multivariate analysis using a logistic regression model revealed that the independent predictors of decreased BMD were a low body mass index (BMI) or a small waist circumference (odds ratio (OR): 0.48, 95% confidence interval (CI): 0.34-0.67), hypertriglyceridemia (OR: 1.29, 95% CI: 1.00-1.65), and a weak grip strength (OR: 0.98, 95% CI: 0.97-1.00). Subgroup analyses of individuals aged 50 years or older, men, and individuals with a FIB-4 index of 1.3 or greater revealed that the absence of a high BMI or a large waist circumference was associated with decreased BMD. The subgroup analysis of men revealed that a weaker grip strength was associated with decreased BMD. CONCLUSION: The present study suggested several potential risk factors for decreased BMD in patients with MASLD. Individuals with the abovementioned risk factors should be encouraged to undergo BMD measurement from the perspective of preventive medicine.

Severe hepatic steatosis promotes increased liver stiffness in the early stages of metabolic dysfunction-associated steatotic liver disease.

BACKGROUND & AIMS: The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD. METHODS: We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors. RESULTS: A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa). CONCLUSIONS: Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa).

RECAM-J 2023-Validation and development of the Japanese version of RECAM for the diagnosis of drug-induced liver injury.

AIM: The diagnosis of drug-induced liver injury (DILI) is challenging. We modified the revised electronic version of the Roussel Uclaf Causality Assessment Method (RUCAM) for the diagnosis of DILI (RECAM), the scoring system developed in US and Spanish cohorts in 2022, and developed RECAM-J 2023 to align with the clinical practice in Japan. In the current study, we introduce RECAM-J 2023 and verify its performance in the context of Japanese patients with DILI. METHODS: After translation of RECAM into Japanese, modifications were made to develop RECAM-J 2023 without any alteration to the scores. To examine the validity and performance of RECAM-J 2023, clinical information on DILI and non-DILI cases in Japan were retrospectively collected. The diagnosis of DILI was made by expert's decision. Then we scored each case using RECAM-J 2023, and calculated area under curve (AUC) values for identification for DILI. RESULTS: We collected data from 538 DILI and 128 non-DILI cases. The sum of highly probable (HP) and probable (PR) cases categorized by RECAM-J 2023 were only 206 (38%) in DILI cases. As the primary cause of low scores was the deduction with missing hepatitis virus markers, which is unlikely to be an issue in prospective applications, we rescored without these deductions. At this time, the sum of HP and PR was raised to 421 (78%). The AUCs of RECAM-J 2023 without deductions were 0.70 and 0.88 for identifying at least HP, and at least PR, respectively. CONCLUSION: RECAM-J 2023, when prospectively used without any missing hepatitis virus markers, provides acceptable performance for identifying at least PR DILI cases in Japanese daily clinical practice.

Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team.

AIM: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity. METHODS: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023). RESULTS: The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period. CONCLUSION: A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. METHODS AND RESULTS: We evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52-69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan-Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326-2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017-5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391-2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997-6.105; p < 0.001]). CONCLUSIONS: The FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. CLINICAL TRIALS: The study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124-12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html.

Immunoglobulin-like transcript 2 as an impaired anti-tumor cytotoxicity marker of natural killer cells in patients with hepatocellular carcinoma.

Introduction: Natural killer (NK) cells play a pivotal role in immune surveillance in the liver. We aimed to identify potential targets for NK cell-mediated immune intervention by revealing the functional molecules on NK cells in HCC patients. Methods: To evaluate the impact of aging on NK cell phenotypes, we examined NK cells from healthy volunteers (HVs) of various ages. Because ILT2 expression on CD56dim NK cells increased with increasing age, we enrolled age-matched HCC patients and HVs. We determined the NK cell phenotypes in blood mononuclear cells (PBMCs) and intrahepatic lymphocytes (IHLs) from cancerous and non-cancerous tissues. We evaluated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) of NK cells in vitro. Results: ILT2-positive CD56dim NK cells in PBMCs were increased in HCC patients compared with HVs. In HCC patients, ILT2-positive CD56dim NK cells were increased in cancerous IHLs compared with non-cancerous IHLs and PBMCs. We examined the impact of macrophage migration inhibitory factor (MIF) on ILT2 expression in co-cultures of HCC cells and NK cells. The enhanced expression of ILT2 on CD56dim NK cells from HCC patients was inhibited by masking antibodies against MIF and CXCR4. ILT2-positive CD56dim NK cells exhibited lower capacities for cytotoxicity and ADCC than ILT2-negative cells, which were partially restored by ILT2 blockade. Conclusions: In HCC patients, ILT2 is a signature molecule for cancerous CD56dim NK cells with impaired cytolytic capacity. The MIF-CXCR4 interaction is associated with ILT2 induction on CD56dim NK cells and ILT2 serves as a target for functional NK cell restoration.

Identification of the Microbiome Associated with Prognosis in Patients with Chronic Liver Disease.

We investigated the prognostic role of the gut microbiome and clinical factors in chronic liver disease (hepatitis, cirrhosis, and hepatocellular carcinoma [HCC]). Utilizing data from 227 patients whose stool samples were collected over the prior 3 years and a Cox proportional hazards model, we integrated clinical attributes and microbiome composition based on 16S ribosomal RNA sequencing. HCC was the primary cause of mortality, with the Barcelona Clinic Liver Cancer staging system-derived B/C significantly increasing the mortality risk (hazard ratio [HR] = 8.060; 95% confidence interval [CI]: 3.6509-17.793; p < 0.001). Cholesterol levels < 140 mg/dL were associated with higher mortality rates (HR = 4.411; 95% CI: 2.0151-9.6555; p < 0.001). Incertae sedis from Ruminococcaceae showed a protective effect, reducing mortality risk (HR = 0.289; 95% CI: 0.1282 to 0.6538; p = 0.002), whereas increased Veillonella presence was associated with a higher risk (HR = 2.733; 95% CI: 1.1922-6.2664; p = 0.017). The potential of specific bacterial taxa as independent prognostic factors suggests that integrating microbiome data could improve the prognosis and treatment of chronic liver disease. These microbiome-derived markers have prognostic significance independently and in conjunction with clinical factors, suggesting their utility in improving a patient's prognosis.

Afatinib treatment of severe respiratory failure due to malignant lymphangitis in a dialysis patient with squamous cell carcinoma of the lung.

Patients on dialysis have limited treatment options for advanced lung cancer because some chemotherapeutic agents are unavailable due to renal dysfunction. A man in his 70s on peritoneal dialysis presented with persistent fever refractory to antibiotics for 2 weeks. Subsequent whole-body CT showed a 5 cm diameter mass in the right lower lobe of the lung with right-sided pleural effusion and osteolytic metastasis of the right iliac bone. The patient was diagnosed with squamous cell carcinoma (cT3N2M1b, stage IVB) harbouring the p.Gly719Ala point mutation on exon 18 of the epidermal growth factor receptor. The patient developed severe respiratory failure due to malignant lymphangitis after a bronchoscopy. He received 30 mg/day of afatinib, resulting in tumour shrinkage and recovery from respiratory failure. We advocate for aggressive screening of driver oncogenes in patients with lung cancer on dialysis, including those with squamous cell lung cancer.

Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

A Phase 2, Prospective, Multicenter, Single-Arm Trial of Transarterial Chemoembolization Therapy in Combination Strategy with Lenvatinib in Patients with Unresectable Intermediate-Stage Hepatocellular Carcinoma: TACTICS-L Trial.

Introduction: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods: Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14-21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0-2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0-1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results: A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1-31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months-NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion: The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. RESULTS: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). CONCLUSION: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Organizing pneumonia secondary to pulmonary cryptococcosis in immunocompromised patient.

Pulmonary cryptococcal infections are fungal infections that often occur in immunocompromised patients and present with a variety of radiographic patterns ranging from nodular to infiltrative shadows. In the present case, we experienced a rare case of organizing pneumonia due to cryptococcal infection in a 71-year-old woman with rheumatoid arthritis. Transbronchial lung biopsy showing fibrotic changes in the alveolar walls, small granulation lesions and cryptococcal organisms with positive Grocott staining. Serum cryptococcal antigen was also found to be positive. Based on these findings, we confirmed the diagnosis of secondary organizing pneumonia due to cryptococcal infection. Treatment with corticosteroids and antifungal drugs led to improvement of the cough and reduction of organizing pneumonia. In immunocompetent patients with organizing pneumonia, it is essential to perform bronchoscopic lung biopsies and serum antigen tests to search for the cause, whenever possible, as it may be due to an infection caused by Cryptococcus, as in the present case.

Safety of flexible bronchoscopy and clinical course for elderly patients with suspected primary lung cancer.

BACKGROUND: There have been several reports demonstrating the safety of flexible bronchoscopy (FB) in the elderly, but none have focused specifically on lung cancer, which is a frequent biopsy procedure. METHODS: In this study, we retrospectively evaluated the safety of FB and subsequent treatment in elderly patients with suspected primary lung cancer. Elderly patients were defined as 75 years of age or older. RESULTS: A total of 141 patients, 77 in the elderly group and 64 in the nonelderly group, were reviewed. The median age of the elderly group was 80 years. Transbronchial lung biopsy was performed in more than 80% of all patients. Primary lung cancer was diagnosed in 42 (54.4%) of the elderly group and 35 (54.7%) of the nonelderly group (p = 0.38). Approximately 70% of the elderly patients with a confirmed diagnosis were treated, while more than half of the undiagnosed elderly patients had best supportive care. Complications such as bleeding, pneumothorax, fever, and pneumonia were similar in the elderly and nonelderly groups. CONCLUSIONS: This study suggests that flexible bronchoscopy can be performed as safely in the elderly as in the nonelderly. Furthermore, even elderly patients may have a greater chance of receiving treatment when a definitive diagnosis is achieved.

A 70-year-old Woman with Asymptomatic Ferroportin Disease.

A 59-year-old Japanese woman presented with hyperferritinemia. We decided against iron removal treatment because there were no symptoms or signs of iron-induced organ damage. A follow-up study revealed a gradual increase in transferrin saturation. The patient underwent a second examination at 66 years old. A liver biopsy showed substantial iron deposits in hepatocytes and Kupffer cells but no inflammation or fibrosis. Serum hepcidin-25 levels were highly parallel with hyperferritinemia. A genetic analysis revealed a G80S mutation in SLC40A1. These features are compatible with those of ferroportin disease. The patient remained asymptomatic at 70 years old, suggesting that the iron-loading condition may have been benign.

Successful Treatment with Steroids in a Patient with Vanishing Bile Duct Syndrome and Acute Tubular Necrosis.

Vanishing bile duct syndrome (VBDS) is a rare but potentially serious cholestatic liver disease caused by various etiologies, including drugs. We herein report a complicated case of VBDS with acute tubular necrosis (ATN) that improved significantly with steroid treatment. An Asian man in his 30s was admitted with the acute onset of severe jaundice and a decline in the renal function. Although initial treatment with ursodeoxycholic acid did not reduce jaundice or renal dysfunction, steroid treatment remarkably improved the VBDS and ATN to within the respective normal ranges. Steroid treatment can be considered in cases of VBDS that appear to have an immune-mediated cause.