Direct-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to ...psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems.
A 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved.
Although DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based ...chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1 y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3-6 months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.
Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and ...low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients.
Intravenous recombinant tissue-type plasminogen activator (rt-PA) therapy is highly recommended to patients who are diagnosed with ischemic stroke within 4.5 hours after the onset while mechanical ...clot retrieval can be attempted in patients who are not indicated for or cannot effectively receive intravenous rt-PA therapy. In this article, we report early treatment outcomes and discuss the usefulness of mechanical clot retrieval using the Penumbra system (Penumbra Inc., Alameda, California, USA), especially in terms of technical cautions during the procedure and adaptability to elderly and high National Institutes of Health Stroke Scale (NIHSS) patients. We included 7 patients with thromboembolic occlusion. Pretreatment NIHSS score ranged from 11 to 36 (mean: 24.9). All patients achieved good recanalization thrombolysis in cerebral infarction (TICI) grade 2a or greater without complications. The NIHSS score at 30 days after the treatment ranged between 0 and 28 (mean: 12.4), and improved more than 10 points in 4 of the 7 patients (57.1%). To obtain good recanalization without complications, selection of suitable reperfusion catheter and careful manipulation of separator prefiguring the occluded distal vessels are essential. The improved NIHSS score at 30 days after the treatment may have led to favorable results, such as an increased participation in available rehabilitation programs and the alleviation of the burden of care. Our findings suggest that the Penumbra system might be effective for treatment in elderly patients or patients with high NIHSS score wherein rt-PA therapy is inadvisable or ineffective in ischemic stroke secondary to large vessel occlusion. Recanalization can improve their quality of life on condition that the procedure is performed successfully without serious complications.
We propose arrayed optical amplifiers that share a single pump laser with the aim of realizing full-add/drop colorless, directionless, contentionless ROADM nodes and demonstrate its feasibility in ...experiments. The experimental results show that the fabricated arrayed optical amplifiers can be made to correspond properly to wavelength path reconfigurations by adjusting a splitting ratio of the variable splitter between the pump laser and eight EDFAs, and cause no significant penalty for 128-Gbit/s PDM-QPSK signal transmission.
Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma ...(UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy.
Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded.
The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).
The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve.
This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Enfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV‐301 trial showed its superiority to non‐platinum‐based chemotherapy as later‐line treatment ...after platinum‐based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum‐based chemotherapy (i.e., “platinum rechallenge”) in that setting.
Methods
In total, 283 patients received pembrolizumab for advanced UC after platinum‐based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later‐line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression‐free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM).
Results
Analyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group.
Conclusions
EV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post‐platinum, post‐pembrolizumab advanced UC.
Gastrointestinal duplications are congenital malformations that are usually observed in pediatric patients. Diagnosis in adulthood is quite rare, and preoperative diagnosis of gastrointestinal ...duplication is difficult, particularly in the small intestine. We encountered an extremely rare adult case of duplication of the jejunum, which showed a stomach-like form diagnosed using double-balloon enteroscopy (DBE). The patient was an 18-year-old male who had been experiencing upper abdominal pain and vomiting repeatedly without any triggers for 3 years. Various examinations were performed, but no cause of symptoms was found. DBE revealed a narrow opening of the lumen at the upper jejunum, and the lumen was covered with mucosal folds similar to those of the stomach. Enteroclysis via DBE showed a tubular structure on the mesenteric side of the jejunum. We diagnosed a jejunal tubular duplication with ectopic gastric mucosa and underwent partial small bowel resection. The patient’s abdominal symptoms resolved. From this, DBE can be a useful tool for diagnosing intestinal duplication in adults. We believe that this case and literature review will facilitate the accurate and prompt diagnosis of small intestinal duplication.
OCCUPATIONAL EXPOSURE LIMITS FOR CHEMICAL SUBSTANCES Acetaldehyde CAS No. 75–07–0 is an irritating colorless liquid (boiling point 20.2℃, vapor pressure 101 kPa (20℃)) that is used as an intermediate ...raw material in the manufacture of chemical materials, preservatives, organic solvents, reducing agents, and glues as a substitute of formaldehyde. The NOAEL in male and female rats was considered 10 mg/kg body weight per day based on observed pathological changes: an increased incidence of pronounced cellular alterations of parotid and mandibular grands at or above 100 mg/kg body weight per day in 104 weeks. 4 Uncertainty factors for species and absorption rates were applied and weight, respiratory volume, and working hours were adjusted in the assessment. The NOAEL in male mice was considered 3.5 mg/m3 based on the absence of increases in inflammatory markers in the lung, e.g., neutrophils and cytokines other than macrophages in bronchoalveolar lavage fluid in a 13-week inhalation study. 5 Uncertainty factors for species and exposure duration were applied in the assessment. 2-Bromopropane CAS No. 75–26–3 is a nonflammable colorless liquid (melting point −90℃, boiling point 59.4℃, vapor pressure 315 hPa (25℃)). MEMBERS OF THE COMMITTEE FOR RECOMMENDATION OF OCCUPATIONAL EXPOSURE LIMITS, JAPAN SOCIETY FOR OCCUPATIONAL HEALTH Atsuko Araki1, Kenichi Azuma2, Ginji Endo3, Yoko Endo4, Tetsuhito Fukushima5, Kunio Hara6, Kouji Harada7, Hajime Hori6, Seichi Horie6, Hyogo Horiguchi8, Masayoshi Ichiba9, Gaku Ichihara10, Tatsuya Ishitake11, Akiyoshi Ito12, Yuki Ito13, Satoko Iwasawa14, Takeyasu Kakamu5, Michihiro Kamijima13, Kanae Karita15, Toshio Kawai16, Toshihiro Kawamoto3, Reiko Kishi1, Shinji Kumagai, Akiko Matsumoto9, Muneyuki Miyagawa17, Hiroyuki Miyauchi6, Yasuo Morimoto6, Kasuke Nagano18, Hisao Naito19, Tamie Nakajima20, Makiko Nakano21, Tetsuo Nomiyama22, Hirokazu Okuda23, Masayuki Okuda24, Kazuyuki Omae21, Kazuhiro Sato25, Tomotaka Sobue26, Yasushi Suwazono27, Toru Takebayashi21, Tatsuya Takeshita28, Akito Takeuchi3, Ayano Takeuchi21, Shigeru Tanaka29, Mayumi Tsuji6, Teruomi Tsukahara22, Susumu Ueno6, Jun Ueyama30, Yumi Umeda23, Kenya Yamamoto12, Yuko Yamano31, Takenori Yamauchi31 and Eiji Yano17. 1Hokkaido University, 2Kindai University, 3Japan Industrial Safety and Health Association, 4Endo Occupational Health Consultant Office, 5Fukushima Medical University, 6University of Occupational and Environmental Health, Japan, 7Kyoto University, 8Kitasato University, 9Saga University, 10Tokyo University of Science, 11Kurume University, 12National Institute of Occupational Safety and Health, Japan, 13Nagoya City University, 14National Defense Medical College, 15Kyorin University, 16Kansai Technical Center for Occupational Medicine, 17Teikyo University, 18Nagano Toxicologic-Pathology Consulting, 19Kinjo Gakuin University, 20Chubu University, 21Keio University, 22Shinshu University, 23Japan Bioassay Research Center, 24Yamaguchi University, 25University of Fukui, 26Osaka University, 27Chiba University, 28Wakayama Medical University, 29Jumonji University, 30Nagoya University, 31Showa University.
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