Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing. Results: Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016). Conclusion High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.

A 77-year-old woman underwent endovascular abdominal aortic repair (EVAR) for an abdominal aortic aneurysm (AAA)．Five years after surgery, she visited the hospital with the chief complaint of a fever. Enhanced computed tomography (CT) showed enlargement of the AAA around the stent-graft and a mass, which was suspected to be an abscess, outside the aneurysm. A blood test revealed a high level of inflammatory response. The patient was diagnosed with infectious AAA. She received antibiotics; however, the inflammatory response did not completely improve. A second CT scan revealed that the suspected abscess had a spreading tendency. The patient was referred to our hospital for a highly suspected stent-graft infection. We performed Y-graft replacement using a rifampicin-immersed graft, and as much as possible of the wall around the aortic aneurysm was removed. The inflammatory response improved rapidly after the operation, and the patient was discharged 15 days later. According to the results of a pathological examination, a diagnosis of xanthogranulomatous inflammation and fibrosis was made. Here, we report a rare case of xanthogranulomatous inflammation of the aortic aneurysm wall after EVAR.

Purpose: This study aimed to investigate the current status and related factors of End of Life discussions between heart failure patients and medical professionals. Method: We conducted a survey of medical records of patients who died between April 2015 and March 2020 in the Department of Cardiology, Kyoto University Hospital. We examined the presence or absence of discussions about prognosis and end-of-life care and their associated factors. Result: Of the 109 patients, prognosis was explained to 40 (36.7%) and discussion of end-of-life care was provided to 25 (22.9%). Age (younger), number of hospitalizations, palliative care team intervention, and end-of-life care discussions were associated with the prognostic explanations. Gender (male), number of hospitalizations, history of heart failure hospitalization, palliative care team intervention, and prognosis explanation were associated with the end-of-life care discussions. Conclusion: The study suggested that End of Life discussions in heart failure patients are currently focused on patients with severe and end-stage heart failure.

Although the descriptions of shigyakukachotanto in “Waitaimiyaofang” and tsumyakushigyakukachotanjuto in “Songban Shanghanlun” are quite similar to each other, the specifications of the dosages of crude drugs and the water volume in the books were considerably different. Focused on the specified water volume to decoct these formulas, each reasonable decocting period was estimated, then the decoctions were prepared using hard water that was common in mainland China. The dosages of aconite root were 2­-fold different between these two formulas, but the contents of aconitine-­type diester alkaloids (ADA) in both decoctions were found in the range of 1.2—1.4­-fold. It was suggested that in order to control the efficacy and the safety of aconite, the decocting period was well regulated by the specification of water volume for decocting at this ancient era. Moreover, the dosages of aconite root and glycyrrhiza in bukuryoshigyakuto (BSGT) formula of “Songban Shanghanlun” are equal to those of shigyakuto (SGT) but the specified water volume to begin decocting is as about twice as that of SGT. When prepared using hard water, BSGT resulted to make the contents of ADA lower and those of non-­ester alkaloids higher compared with those of SGT decoction. It was suggested the spe­cific water volume for each formula prescribed in classical Chinese medicine had considerable significance to determine the dosages of chemical ingredients in the decoctions especially in the circumstances using hard water to prepare them.

The decoctions of unprocessed aconite root (uzu) were prepared with the tap water samples collected in Tianjin and Shanghai in China, and the contents of alkaloids in the decoctions were compared to those prepared with purified water or with tap water collected in Niigata, Japan. The contents of aconitine-type diester alkaloids (ADA) in the decoctions prepared with tap water collected in China were significantly lower than those with purified water or tap water in Niigata. It was speculated that this difference appeared by buffering effect of bicarbonic anion in tap water in China to decline pH of the decoction. When uzu was decocted with glycyrrhiza, ginger, or jujube, the contents of ADA in the decoctions exhibited the tendency to have higher levels than those prepared using unprocessed aconite root singly, and also this tendency was observed more remarkably when the decoctions were prepared with tap water collected in China. It was suggested that even the decocting period was fixed, unexpected change of the contents of ADAs might be induced by the differences in the properties of water used for decoction or the crude drugs decocted with aconite root. The physicians in the era when “Songban Shanghanlun” had established may have adjusted the contents of ADA in the decoction by carefully choosing the crude drugs combined to aconite root.

BACKGROUND/AIMS: Although daclatasvir with asunaprevir was approved in Japan for interferon ineligible or intolerant patients, patients aged ≥75 years were excluded in the phase III trial. The present study aimed to evaluate the safety and efficacy of this therapy for elderly patients aged ≥75 years and to clarify whether an extremely high sustained virological response (SVR) rate can be achieved, even in a real-world setting when patients with resistance-associated substitutions (RASs) to nonstructural protein 5A (NS5A) inhibitors or prior simeprevir failure are excluded. METHODS: Daclatasvir (60 mg) and asunaprevir (100 mg) were orally administered daily for 24 weeks. Patients without pre-existing NS5A RASs and simeprevir failure were enrolled in this study. RESULTS: Overall, 110 patients were treated. The median age was 73 years old. The SVR rates of total patients, those aged ≥75 years, and those aged < 75 years were 97% (107/110), 98% (46/47), and 97% (61/63), respectively. The treatment of two patients (2%) was discontinued because of adverse events. CONCLUSIONS: Daclatasvir with asunaprevir was a safe treatment, even in patients aged ≥75 years. When patients without pre-existing NS5A RASs and prior simeprevir failure were selected, an extremely high SVR rate could be achieved irrespective of age.
Aged ; Hepacivirus ; Humans ; Interferons ; Japan ; Simeprevir

BACKGROUND/AIMS: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). METHODS: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). RESULTS: The patients’ median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin-28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. CONCLUSIONS: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR.
Aged ; Genotype* ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Interferons* ; Multivariate Analysis ; Ribavirin* ; RNA ; Simeprevir ; Transferases

BACKGROUND/AIMS: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been used to diagnose gastrointestinal submucosal tumors (SMTs). Although rapid on-site evaluation (ROSE) has been reported to improve the diagnostic accuracy of EUS-FNA for pancreatic lesions, on-site cytopathologists are not routinely available. Given this background, the usefulness of ROSE by endosonographers themselves for pancreatic tumors has also been reported. However, ROSE by endosonographers for diagnosis of SMT has not been reported. The aim of this study was to evaluate the diagnostic accuracy of EUS-FNA with ROSE by endosonographers for SMT, focusing on diagnosis of gastrointestinal stromal tumor (GIST), compared with that of EUS-FNA alone. METHODS: Twenty-two consecutive patients who underwent EUS-FNA with ROSE by endosonographers for SMT followed by surgical resection were identified. Ten historical control subjects who underwent EUS-FNA without ROSE were used for comparison. RESULTS: The overall diagnostic accuracy for SMT was significantly higher in cases with than without ROSE (100% vs. 80%, p=0.03). The number of needle passes by FNA with ROSE by endosonographers tended to be fewer, although accuracy was increased (3.3±1.3 vs. 5.9±3.8, p=0.06). CONCLUSIONS: ROSE by endosonographers during EUS-FNA for SMT is useful for definitive diagnosis, particularly for GIST.
Biopsy, Fine-Needle* ; Diagnosis* ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Gastrointestinal Stromal Tumors* ; Humans ; Needles

BACKGROUND/AIMS: Transpapillary forceps biopsy is an effective diagnostic technique in patients with biliary stricture. This prospective study aimed to determine the usefulness of the wire-grasping method as a new technique for forceps biopsy. METHODS: Consecutive patients with biliary stricture or irregularities of the bile duct wall were randomly allocated to either the direct or wire-grasping method group. In the wire-grasping method, forceps in the duodenum grasps a guide-wire placed into the bile duct beforehand, and then, the forceps are pushed through the papilla without endoscopic sphincterotomy. In the direct method, forceps are directly pushed into the bile duct alongside a guide-wire. The primary endpoint was the success rate of obtaining specimens suitable for adequate pathological examination. RESULTS: In total, 32 patients were enrolled, and 28 (14 in each group) were eligible for analysis. The success rate was significantly higher using the wire-grasping method than the direct method (100% vs 50%, p=0.016). Sensitivity and accuracy for the diagnosis of cancer were comparable in patients with the successful procurement of biopsy specimens between the two methods (91% vs 83% and 93% vs 86%, respectively). CONCLUSIONS: The wire-grasping method is useful for diagnosing patients with biliary stricture or irregularities of the bile duct wall.
Bile Ducts ; Biliary Tract ; Biopsy* ; Constriction, Pathologic* ; Diagnosis ; Duodenum ; Hand Strength ; Humans ; Methods* ; Prospective Studies* ; Sphincterotomy, Endoscopic ; Surgical Instruments*

BACKGROUND/AIMS: This study aimed to predict sustained viral response (SVR) to low-dose pegylated interferon (PEG-IFN) plus ribavirin of elderly and/or cirrhotic patients with genotype 2 hepatitis C virus (HCV) using viral response within 2 weeks. METHODS: Low-dose PEG-IFN-α-2b plus ribavirin was administered to 50 elderly and/or cirrhotic patients with genotype 2 HCV for 24 weeks. The dynamics of HCV RNA and HCV core antigen levels within 2 weeks were measured. RESULTS: The patients' median age was 66 years. There were 21 male and 29 female patients. The median baseline HCV RNA level was 5.7 log IU/mL. Rapid viral response was achieved in 17 patients (34%), SVR in 28 (56%), and two (4%) discontinued treatment. Univariate analysis of factors contributing to SVR showed significant differences for sex, baseline virus level, and response within 4 weeks. When 40 fmol/L was set as the cutoff value for the core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 93%, 75%, 84%, 88%, and 85%, respectively. CONCLUSIONS: Low-dose PEG-IFN plus ribavirin was a safe and cost-effective treatment for elderly and/or cirrhotic patients with genotype 2 HCV, and the viral response within 2 weeks was a useful predictor of SVR.
Aged* ; Female ; Genotype* ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Interferons* ; Liver Cirrhosis ; Male ; Ribavirin* ; RNA ; Sensitivity and Specificity