Ome Municipal General Hospital

We report the case of a 40-year-old man with rheumatic heart disease (a condition where the cardiac valve is damaged due to prior streptococcal infection). He previously underwent mechanical mitral valve replacement with a bileaflet prosthesis and later developed recurrent episodes of acute obstructive prosthetic valve thrombosis. He presented first in 2023 and again in 2025 with rapidly progressive dyspnea, orthopnea, diminished mechanical valve sounds, and signs of hemodynamic compromise. Both events followed prolonged periods of inconsistent warfarin use and inadequate international normalized ratio (INR) monitoring related to financial limitations and restricted access to outpatient care. Transthoracic echocardiography during each admission demonstrated markedly elevated transmitral gradients and restricted leaflet motion, confirming obstructive thrombosis of the mechanical mitral valve. Because urgent surgical intervention was unavailable and transfer delays carried additional risk, each episode was managed with low-dose, slow-infusion streptokinase after multidisciplinary evaluation and informed consent. The patient showed prompt and sustained improvement during both thrombolytic courses, with resolution of respiratory distress, normalization of hemodynamics, and restoration of prosthetic leaflet mobility. Follow-up echocardiography confirmed thrombus resolution and a return to acceptable transvalvular gradients. No major bleeding, systemic embolization, or neurological complications occurred during either hospitalization. He was transitioned back to therapeutic warfarin levels and discharged in stable condition with reinforced counseling regarding anticoagulation adherence. This case demonstrates the successful use of repeated thrombolytic therapy for recurrent obstructive mechanical mitral valve thrombosis when surgical management is inaccessible. The consistent clinical and echocardiographic responses across two separate episodes emphasize the importance of early recognition, appropriate patient selection, and close monitoring during thrombolytic treatment. The case also highlights persistent challenges in maintaining reliable anticoagulation in resource-limited environments, where consistent INR monitoring and continuity of care may be difficult to achieve.

Dual-chamber open-window mapping (OWM) combined with high-density mapping revealed early atrioventricular conduction on the lateral tricuspid annulus, consistent with a Mahaim fiber. Catheter ablation targeting the ventricular insertion site led to successful elimination of the accessory pathway and noninducibility of tachycardia.

We aimed to investigate the impact of skin adverse events (AEs) of enfortumab vedotin (EV) on prognosis in patients with locally advanced or metastatic urothelial carcinoma in real-world practice. This study analyzed data from 115 patients with locally advanced or metastatic urothelial carcinoma. We evaluated the association between EV dose and skin AEs in these patients. The impact of skin AEs on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier curves and Cox regression analysis. The median PFS and OS were 8.1 and 14.5 months, respectively. EV dose reduction was observed in 68 (59.1%) patients. An estimated dose amount in the first, second, and seventh cycles was 95%, 85%, and 81%, respectively. We observed skin AEs in 69 (60%) cases, and they were observed within 1 month in 53 (76.8%) of cases. Patients with skin AEs had significantly longer PFS and OS compared to those without skin AEs. Multivariable Cox regression analysis showed a significant association of skin AEs with prolonged PFS and OS. Skin AEs were significantly associated with prolonged prognosis compared to those without skin AEs, although EV dose reduction was required in 59.1% of patients. Careful dose adjustment of EV may be crucial for long-term use and optimizing oncological outcomes.

447 Background: Ramucirumab (RAM) has shown efficacy in combination with paclitaxel (PTX) or irinotecan in the second-line treatment of advanced gastric cancer (AGC). However, the efficacy and safety regarding the combination therapy of RAM and docetaxel (DTX) have not been reported. We hypothesized that RAM plus DTX for patients with AGC could be as effective as RAM plus PTX and could reduce the incidence of neuropathy. Methods: HGCSG 1903 was a non-randomized, single arm, phase 2 trial carried out at 20 institutes in Japan. AGC patients with refractory or intolerance to primary chemotherapy were eligible. RAM (8 mg/kg on day1 and 15) plus DTX (60 mg/m 2 on day1) combination therapy administered in 28-day cycle were continued until disease progression or emergence of adverse events requiring discontinuation. The primary endpoint was response rate (RR) with threshold value of 10.7% and an expected value of 27.9%. A total of 35 cases are planned for registration. The secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. This trial was registered with Japan Registry of Clinical Trials, number jRCTs011200010. Results: Between Nov 2020 and Dec 2023, 36 patients were enrolled. Median age was 70 (range, 36–82); female/male were 7/29; ECOG PS 0/1, 16/20, respectively. One patient did not initiate study treatment at the onset of bowel obstruction after enrollment. In the efficacy and safety analysis set of 35 patients, RR was 25.7% (95%C.I., 12.5–43.3%) and disease control rate was 74.3% (95%C.I., 56.7–87.5%). Median OS and PFS were 11.9 months (95%C.I., 3.0–20.7) and 3.1 months (95%C.I., 2.1–4.2), respectively. Grade 3 or higher adverse events that occurred in more than 5% of patients were neutropenia (68.6%), leucopenia (57.1%), febrile neutropenia (17.1%), hypertension (14.3%), anorexia (11.4%), anemia (8.6%), and fatigue (5.7%). Grade 4 neutropenia occurred in 60.0% of patients. The protocol was amended to allow primary G-CSF prophylaxis during study period. The number of patients who received primary G-CSF prophylaxis after the amendment was 7/13 (53.8%). Neuropathy occurred in 65.7% of all grades, with no incidence of grade 3 or higher. No death and new safety signals with a causal relation to study treatment were observed. Conclusions: The primary endpoint of response rate was met in HGCSG 1903. Although neutropenia and febrile neutropenia may be more frequent, they were manageable. RAM plus DTX might be considered as an option for second-line treatment of patients with AGC. Clinical trial information: jRCTs011200010.

Rotavirus vaccines carry a small risk of intussusception mainly 1–7 days after vaccination in the United States of America, Europe, Australia, and Latin America where the background rate of intussusception is relatively low. Such risks are undetectable in Africa and India where the background rate is the lowest. Because few studies were carried out in high-background-rate countries such as Japan, we examined how intussusception occurred in infants living in Akita prefecture, Japan, while the vaccines were sold in the private market. Between 2011 and 2018, an estimated 21,677 infants (46%) were vaccinated and 54% were not. Through a retrospective survey of medical records in 18 hospitals in the prefecture, we identified 58 infants, 28 of whom were vaccinated and 30 of whom were unvaccinated, as having intussusception that met level 1 of the Brighton criteria. Thus, the intussusception rate was 123 per 100,000 infant-years (95% confidence interval [CI]: 94–160). Despite the high rate, none developed intussusception 1–7 days after the first dose of either the monovalent human rotavirus vaccine (GSK) or the pentavalent human–bovine reassortant vaccine (MSD). The incidence rate ratio of vaccinated to unvaccinated infants between 42 and 245 days of life was estimated at 0.96 (95%CI: 0.43–2.1; p = 0.92). Given that over 95% of infants received the first dose before 15 weeks of age, the risk of intussusception associated with the rotavirus vaccines in high-incidence-rate countries can be reduced to a minimum by adhering to the recommended schedule at 2, 3, and 4 months of age.

A 67-year-old man with cervical spondylotic myelopathy undergoing conservative treatment presented with subacute progression of fine motor and ambulatory disturbances, leading to admission at a previous hospital. Pre-cervical laminoplasty chest computed tomography (CT) revealed a tumor in the left upper lobe of the lung, prompting transfer to our institution.Transbronchial biopsy findings were consistent with adenocarcinoma, diagnosed as clinical stage T2bN0M0, Stage IIA. The neurological abnormalities could not be solely attributed to cervical spondylotic myelopathy, leading to a diagnosis of concurrent paraneoplastic neurological syndrome (PNS). During hospitalization, the patient's condition progressed to a state of constant bed rest within two weeks. On the 17th hospital day, a left upper lobectomy was performed, resulting in significant improvement, allowing the patient to ambulate with assistance after two weeks, and transfer to a convalescent rehabilitation hospital on the 58th hospital day. Subsequent cancer multigene panel testing revealed a positive MET exon 14 skipping mutation. Given the absence of reports on this mutation in lung adenocarcinoma associated with PNS, we consider it rare and thus report this case.