A single-institution pre-post comparison of subcutaneous immunoglobulin replacement therapy in allogeneic haematopoietic cell transplantation recipients.

Immunoglobulin replacement therapy (IgRT) reduces the risk of infection in hypogammaglobulinaemia secondary to chronic lymphocytic leukaemia and multiple myeloma. However, the benefit of IgRT, especially subcutaneous IgRT (ScIgRT), has not been assessed in hypogammaglobulinaemia after allogeneic haematopoietic cell transplantation (allo-HCT). We performed a pre-post comparison of the clinical impact of ScIgRT after allo-HCT in a retrospective analysis of 209 patients who underwent allogeneic HCT at our institution from 2011 to 2019. Since ScIgRT became available at our institution in April 2017, we categorized patients treated from January 2011 to March 2017 as the Pre-ScIgRT group (n = 118) and those treated from April 2017 to December 2019 as the Post-ScIgRT group (n = 91). The 2-year overall survival rate was 65% in the Pre-ScIgRT group and 81% in the Post-ScIgRT group (p = 0.02). The cumulative incidence (CI) of non-relapse mortality at 2 years was 18% and 7% (p = 0.02). There were 78 infectious events in 44 patients in the Pre-ScIgRT group and 28 such events in 19 patients in the Post-ScIgRT group. The CI of the documented infection during the observation period was between 38% and 21% (p = 0.01). Our study suggests that ScIgRT may reduce infection rates and improve prognosis after allo-HCT.

Real-world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group.

AIM: The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection. METHODS: This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study. RESULTS: Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naïve patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P < 0.0001) was identified as an independent predictor of treatment failure. No serious adverse events were observed with EBR/GZR therapy. CONCLUSIONS: The SVR rate of EBR/GZR would have been 100% in patients without either a history of DAA therapy or double mutation. This combination of drugs could be safely given and is, thus, considered a highly useful first-line treatment for DAA-naïve patients with HCV.

Bilateral Subclavian Vein Occlusion in a SAPHO Syndrome Patient Who Needed an Implantable Cardioverter Defibrillator.

A 79-year-old Asian man was hospitalized because of progressive exertional dyspnea with decreasing left ventricular ejection fraction and frequent non-sustained ventricular tachycardia. Pre-procedure venography for implantable cardioverter defibrillator (ICD) implantation showed occlusion of the bilateral subclavian veins. In consideration of subcutaneous humps in the sterno-clavicular area and palmoplantar pustulosis, we diagnosed him as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and speculated that it induced peri-osteal chronic inflammation in the sterno-clavicular area, resulting in occlusion of the adjacent bilateral subclavian veins. An automatic external defibrillator (AED) was installed in the patient's house and total subcutaneous ICD was considered. Venous thrombosis in SAPHO syndrome is not frequent but has been reported. To the best of our knowledge, this is the first case of bilateral subclavian vein occlusion in a SAPHO syndrome patient who needs ICD implantation.

Generation of Induced Pluripotent Stem Cells From Patients With Duchenne Muscular Dystrophy and Their Induction to Cardiomyocytes.

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene which encodes dystrophin protein. Dystrophin defect affects cardiac muscle as well as skeletal muscle. Cardiac dysfunction is observed in all patients with DMD over 18 years of age, but there is no curative treatment for DMD cardiomyopathy. To establish novel experimental platforms which reproduce the cardiac phenotype of DMD patients, here we established iPS cell lines from T lymphocytes donated from two DMD patients, with a protocol using Sendai virus vectors. We successfully conducted the differentiation of the DMD patient-specific iPS cells into beating cardiomyocytes. DMD patient-specific iPS cells and iPS cell-derived cardiomyocytes would be a useful in vitro experimental system with which to investigate DMD cardiomyopathy.

Acute Myocardial Infarction That Resulted From Poor Adherence to Medical Treatment for Giant Coronary Aneurysm.

Coronary arterial complications associated with Kawasaki disease (KD), such as a giant coronary aneurysm, determine the relative risk of future cardiac events and require lifelong medical treatment. Here, we describe a 24-year-old man who developed myocardial infarction due to poor adherence to medical treatment for a giant coronary aneurysm in the chronic phase of KD. He was hospitalized two hours after the onset of chest pain. The presence of the giant coronary aneurysm made primary percutaneous coronary intervention (PCI) difficult. However, we were able to perform primary PCI successfully utilizing previous coronary computed tomography (CT) angiographic pictures as a reference. This case provides valuable insight for the management of coronary arterial complications associated with KD. Patients in the chronic phase of KD are usually asymptomatic, even in the presence of giant coronary aneurysms which have been reported to have a high risk of morbidity and mortality. Therefore, patient education is critical for preventing poor adherence to medical treatment for coronary arterial complications. In preparation for potential coronary intervention in the future, it is also useful to perform coronary CT angiography, coronary magnetic resonance (MR) angiography, and/or coronary angiography on a regular basis while patients remain free from serious cardiac events.

GVHD prophylaxis by tacrolimus and mini-MTX in single-unit CBT: a single institute experience.

Tacrolimus (TAC) combined with short-term methotrexate (MTX) is widely used to prevent graft-versus-host disease (GVHD) in cord blood transplantation (CBT). As short-term MTX aggravates mucositis and delays engraftment, we reduced the dose of MTX, as previously reported in the non-CBT setting. Here, we retrospectively analyze outcomes of 20 patients who received CBT from April 2017 to December 2018. All patients received TAC with mini-MTX as GVHD prophylaxis. Mini-MTX was administered at a dose of 5 mg/m2 of MTX on days 1, 3 and 6 after CBT. Median age was 54.5 years. Median follow-up time in surviving patients was 396 days. The primary disease was acute leukemia (n = 12) or malignant lymphoma (n = 8). Three patients and 17 patients received myeloablative and reduced-intensity conditioning, respectively. Rate and median time to engraftment of neutrophils were 90.0% and 20.5 days, respectively. Cumulative incidences of grade II-IV and grade III-IV acute GVHD were 35.0% and 5.0%, respectively. At one year after CBT, the overall survival rate was 80.5%, cumulative incidence of relapse/progression was 15.0%, and non-relapse mortality rate was 5.0%. In conclusion, TAC with mini-MTX may be a promising GVHD prophylaxis regimen in single-unit CBT.

Efficacy and safety of glecaprevir/pibrentasvir in patients with hepatitis C virus infection aged ≥75 years.

AIM: Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years. METHODS: We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged <75 years). We compared the clinical characteristics, virologic response and adverse events between the two groups. The predictive factors for adverse events were also assessed. RESULTS: The presence of cirrhosis (27.9%), a history of hepatocellular carcinoma (23.3%) and comorbidities (88.4%) were more frequently observed in the elderly group than in the younger group. Six (14.0%) patients in the elderly group and 19 (21.6%) in the younger group dropped out before the sustained virologic response 12 assessment. In the intention-to-treat population, 86.0% in the elderly group and 78.4% in the younger group achieved sustained virologic response 12 (P = 0.30). In the modified intention-to-treat population, all patients achieved sustained virologic response 12. A total of 27.5% of patients experienced adverse events. The most frequently observed adverse events was pruritus, and was significantly associated with female sex, the presence of hemodialysis and serum albumin at baseline <4.0 g/dL. CONCLUSION: Glecaprevir/pibrentasvir therapy was effective and well tolerated, even in elderly patients with hepatitis C virus infection aged ≥75 years. Geriatr Gerontol Int 2020; ••: ••-••.

Alpha-Blockers As Colorectal Cancer Chemopreventive: Findings from a Case-Control Study, Human Cell Cultures, and In Vivo Preclinical Testing.

A retrospective case-controlled analysis was performed to identify drug candidates in the current use that may prevent colorectal cancer, outside of aspirin. A total of 37,510 patients aged ≥20 years were assessed to identify subjects who had been diagnosed with colorectal cancer by colonoscopy without a previous diagnosis of colorectal cancer, inflammatory bowel disease (IBD), or gastrointestinal symptoms; 1,560 patients were identified who were diagnosed with colorectal cancer by colonoscopy. The patients with colorectal cancer were matched with 1,560 age, gender, family history of colorectal cancer and comorbidity-matched control patients who were not diagnosed with colorectal cancer at colonoscopy. The medication histories were compared between the two groups. Next, candidate drugs that were more frequently used by the control patients were selected and their effects on human colorectal cancer cell lines in vitro and an inflammation-induced mouse model of colorectal cancer were tested. Putative colorectal cancer preventative agents were identified, including aspirin, vitamin D, vitamin B, vitamin C, vitamin E, xanthine oxidase inhibitor, alpha-blockers, angiotensin receptor blocker, nateglinide, probiotics, thienopyridine, folic acid, nitrovasodilators, bisphosphonates, calcium channel blockers, steroids, and statins (P < 0.05). Alpha-blockers and xanthine oxidase inhibitors were selected for further study because these agents have not been analyzed previously as factors that may affect colorectal cancer outcomes. In vitro doxazosin (alpha-blocker), but not febuxostat (xanthine oxidase inhibitor), suppressed the proliferation of human colorectal cancer cells. Doxazosin also decreased tumorigenesis in an AOM/DSS mouse colorectal cancer model. Alpha-blockers may prevent colorectal cancer.

Endoscopic papillary balloon dilation for the management of bile duct stones in patients 85 years of age and older.

BACKGROUND: Endoscopic papillary balloon dilation (EPBD) is a possible alternative to endoscopic sphincterotomy for the treatment of bile duct stones. However, little information is available in the elderly. OBJECTIVE: Our purpose was to evaluate the safety and efficacy of EPBD for bile duct stones in patients of 85 years of age and older. DESIGN: Retrospective study from a single center. SETTING: Tertiary care facility with experience in bile duct stone removal with EPBD. PATIENTS: A total of 406 patients (74 patients >/=85 years old, group A; 332 patients <85 years old, group B) with bile duct stones underwent EPBD. MAIN OUTCOME MEASUREMENTS: Efficacy and safety of EPBD between the 2 groups. Baseline patient characteristics were also evaluated. RESULTS: The mean American Society of Anesthesiologists score in group A was significantly higher compared with that in group B (2.4 [0.5] vs 1.9 [0.7], P < .0001). Patients received anticoagulants more frequently and had larger and more numerous stones in group A than in group B with significant differences. Overall, bile duct clearance rates were similar in the 2 groups (91% vs 95%), but the mean number of sessions required for complete stone removal was significantly higher in group A (1.6 vs 1.4, P = .0081). The incidence of overall early complications after EPBD was lower in group A than in group B (2.7% vs 8.4%) but was not statistically different. None of the patients in group A had post-EPBD pancreatitis, whereas pancreatitis occurred in 5.7% in group B (P = .036). Bleeding was not observed after EPBD in 406 patients, including 7 patients in group A who received anticoagulation therapy at the time of EPBD. There was no significant difference in the cumulative stone nonrecurrence rate between group A and group B (log-rank test, P = .6225). CONCLUSIONS: EPBD is a safe and effective technique for the treatment of bile duct stones even in high-risk elderly patients without an increased risk of pancreatitis and bleeding. Because the evaluation of outcomes might be biased by our study design (an open study), further studies are needed.

Efficacy and safety of twice-daily rabeprazole maintenance therapy for patients with reflux esophagitis refractory to standard once-daily proton pump inhibitor: the Japan-based EXTEND study.

BACKGROUND: Rabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to be highly effective in the treatment of proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) that is refractory to the standard once-daily PPI regimen. We evaluated the efficacy and safety of rabeprazole maintenance therapy at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks. METHODS: Patients with RE refractory to standard PPI regimens for at least 8 weeks were enrolled. They were treated with rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive rabeprazole 10 mg q.d. (control) or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52. RESULTS: In total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%; p < 0.001, χ2 test) than in the q.d. group (44.8%). In particular, the b.i.d. regimen was more effective in all subgroups with Los Angeles Classification Grade B to D at treatment entry. CONCLUSIONS: In the maintenance treatment of PPI-resistant RE, rabeprazole at 10 mg b.i.d. exerted a stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No particular safety issues were noted during long-term administration. ClinicalTrials.gov number: NCT02135107.

Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group.

BACKGROUND AND AIM: This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. METHODS: This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. RESULTS: AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. CONCLUSIONS: There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Colonoscopy reduces colorectal cancer mortality: A multicenter, long-term, colonoscopy-based cohort study.

BACKGROUND: There are limited colonoscopy-based cohort data concerning the effectiveness of colonoscopy in reducing colorectal cancer deaths. The aim of this study was to clarify whether colonoscopy reduces colorectal cancer mortality. METHODS: A cohort of 18,816 patients who underwent colonoscopy without a diagnosis of colorectal cancer between 2001 and 2010 at high colonoscopy procedure volume centers was selected. Patient characteristics and colonoscopy findings were assessed. The main endpoint was colorectal cancer death (all, right-sided, and left-sided cancers), and data were censored at the time of the final visit or the final colonoscopy. The standardized all colorectal, colon, and rectal cancer mortality rates were estimated with reference to those of the general Japanese population. Additional outcome was all- cause death and the standardized all-cause mortality rate was also estimated. RESULTS: The total observed person-year mortality for colorectal cancer was 67,119. Of these, 4, 3, and 1 patients died from colorectal, colon, and rectal cancers, respectively; these values were significantly lower than the number of expected deaths in the general population, estimated to be 53.1, 34.0, and 19.1, respectively. The standardized mortalities for all colorectal, colon, and rectal cancers were 0.08 (95% confidence interval (CI), 0.02-0.17), 0.09 (95% CI, 0.02-0.22), and 0.05 (95% CI, 0.0002-0.21), respectively. There were 586 all-cause deaths (3.11%) during the observation period. The standardized all-cause mortality ratios were 0.22 (95% CI, 0.206-0.23). CONCLUSIONS: The colorectal cancer mortality of patients who received colonoscopy without colorectal cancer diagnosis decreased significantly compared with that of individuals in the general population. These results were compatible even in patients with right-sided colon cancer.

Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival.

BACKGROUND: Although cirrhosis is a major risk factor for development of hepatocellular carcinoma, no definitive prospective analyses have assessed the long-term efficacy of antiviral therapy in cirrhotic patients. OBJECTIVE: To elucidate the role of antiviral therapy in the suppression of liver tumors and survival over a long-term follow-up period. DESIGN: Prospective cohort study. SETTING: 25 clinical centers. PATIENTS: 345 patients with chronic hepatitis C and cirrhosis enrolled in previous trials. INTERVENTION: 271 patients received 6 to 9 million U of interferon 3 times weekly for 26 to 88 weeks; 74 received no treatment. MEASUREMENTS: Blood tests and abdominal ultrasonography were done regularly to detect hepatocellular carcinoma. RESULTS: Hepatocellular carcinoma was detected in 119 patients during a 6.8-year follow-up: 84 (31%) in the interferon-treated group and 35 (47%) in the untreated group. Cumulative incidence of hepatocellular carcinoma among interferon-treated patients was significantly lower than in untreated patients (Cox model: age-adjusted hazard ratio, 0.65 [95% CI, 0.43 to 0.97]; P = 0.03), especially sustained virologic responders. A total of 69 patients died during follow-up: 45 (17%) in the treated group and 24 (32%) in the untreated group. Interferon-treated patients had a better chance of survival than the untreated group (Cox model: age-adjusted hazard ratio, 0.54 [CI, 0.33 to 0.89]; P = 0.02). This was especially evident in sustained virologic responders. LIMITATION: This was not a randomized, controlled study. Patients enrolled in the control group had declined to receive interferon treatment even though they were eligible for treatment. CONCLUSION: Interferon therapy for cirrhotic patients with chronic hepatitis C, especially those in whom the infection had been cured, inhibited the development of hepatocellular carcinoma and improved survival.

Systematic cytological evaluation and immunocytochemistry of minichromosome maintenance protein 2 and p53 significantly improve cytological diagnosis of pancreaticobiliary adenocarcinoma.

Endoscopic retrograde cholangiopancreatography (ERCP) brushing cytology often cannot distinguish adenocarcinoma from reactive epithelial changes. We attempted to improve the diagnostic sensitivity of ERCP using the following methods: systematic cytological evaluation, immunocytochemical examination of minichromosome maintenance proteins (MCM) 2 and p53, and a combination of these methods. ERCP specimens from 53 patients (13 benign and 40 malignant cases) were studied. First, we reclassified the cases into three categories according to the systematic cytological evaluation: negative, suspicious, and positive. Secondly, immunocytochemistry was performed for MCM 2 and p53. The cut-off values were set at 25% labeling index (LI) for MCM 2 and 10% LI for p53, respectively. We evaluated the sensitivity, specificity, and diagnostic accuracy. The sensitivity of the systematic cytological evaluation alone did not improve significantly, compared with the original screening examination (77% vs. 68%). The sensitivity of immunocytochemistry for MCM 2 and p53 was 90% (P < 0.05) and 68%, respectively. Applying only the suspicious or positive categories, the sensitivity improved significantly to 93% for the combination of systematic cytological evaluation and immunocytochemistry for MCM 2 and p53 (P < 0.01). In conclusion, the combination of morphology and immunocytochemistry for MCM 2 and p53 may help to overcome the diagnostic cytological difficulties of pancreaticobiliary adenocarcinoma.

Successful Endosonography-Guided Drainage of an Intra-Abdominal Abscess in a 1-Year-Old Infant.

Endoscopic ultrasound (EUS)-guided intervention has been established as a safe, effective and minimally invasive procedure for various diseases in adults, but there have been limited reports in pediatric patients. Herein, we report our experience with successful EUS-guided drainage of an intraabdominal abscess in a 1-year-old infant concomitant with disseminated intravascular coagulation. The abscess was punctured via the stomach using a standard, convex-type echoendoscope, and the patient's condition improved after naso-cystic catheter placement. Although the clinical course was complicated by delayed hemorrhage from the puncture site, the bleeding was successfully managed by endoscopic hemostasis using a standard forward-viewing endoscope.

Impact of Preoperative Biliary Drainage on Surgical Outcomes in Periampullary and Hilar Malignancy: A Single-Center Experience.

The role of preoperative biliary drainage (PBD) for periampullary and hilar malignancy is still controversial. We retrospectively studied consecutive 144 patients (92 periampullary and 52 hilar malignancy) undergoing surgical resection to evaluate the effects of PBD on surgical outcomes. The rate of PBD was 59% and 56%, and postoperative complications developed in 27% and 19% in periampullary and hilar malignancy, respectively. Risk factors for postoperative complications were overweight [odds ratio (OR), 7.6] and depression (OR, 8.5) in distal malignancy and American society of anesthesiologists score of 3 (OR, 6.6), depression (OR, 13.8), and portal vein embolization (OR, 6.1) in hilar malignancy. PBD was not associated with postoperative complications but reinterventions for PBD were necessary in 43% and 27% in distal and hilar biliary obstruction. In conclusion, PBD in pancreatobiliary surgery was not associated with postoperative complications, but the improvement of PBD is necessary given the high rate of reinterventions.