Nagano Municipal Hospital

Lymphovenous anastomosis (LVA) is a microsurgical procedure that redirects stagnant lymph flow into the venous circulation, reducing fluid stasis in patients with secondary limb lymphedema. Although previous studies have reported that complex decongestive therapy redistributes fluid from the affected leg to other body segments, whether fluid reduction after LVA results from systemic elimination or intersegmental redistribution remains unclear. This study aimed to clarify the mechanism by analyzing the changes in segmental body water (SBW) volume using bioelectrical impedance analysis (BIA).We retrospectively analyzed the data of 40 Japanese women with unilateral stage II secondary leg lymphedema who underwent LVA from 2013 to 2021. Multifrequency segmental BIA was used to assess extracellular water, intracellular water, and SBW in the legs, trunk, and arms. Measurements were performed preoperatively and at least 12 months postoperatively. Changes in segmental and total body water (TBW) were statistically evaluated.Significant reductions were observed in SBW in the affected leg, and in the TBW (affected leg: 5.80-5.20 L, p < 0.001; TBW: 25.6-25.0 L, p = 0.002), with no significant changes in the unaffected leg, trunk, or arms. Extracellular and intracellular water in the affected leg decreased significantly (p = 0.001 and p < 0.001, respectively), whereas the percentage of extracellular water remained stable.LVA achieved sustained reductions in segmental and TBW volumes, localized to the affected leg, without compensatory increases in other body segments. These findings support the efficacy of leg LVA in achieving long-term fluid homeostasis through systemic elimination of excess lymphatic fluid rather than redistribution.

AimImproving sleep quality is a crucial clinical objective in schizophrenia care; however, the association between evidence‐based pharmacological treatment and sleep outcomes remains unclear. This study aimed to examine whether guideline adherence, assessed using the individual fitness score (IFS), correlated with actigraphy‐measured sleep in long‐term hospitalized patients.MethodsWe included 40 inpatients aged <65 years who were diagnosed with schizophrenia. Guideline adherence was assessed using the IFS and actigraphy was used to measure total sleep time (TST), sleep latency (SL), and sleep efficiency (SE). In 33 patients, these measures were re‐evaluated after 6 months.ResultsCross‐sectional analysis showed a positive correlation between IFS and TST (rho = 0.362, P = 0.022), which persisted after adjusting for Brief Psychiatric Rating Scale scores (β = 0.318, P = 0.024). IFS was not associated with SL or SE, and differences in hypnotic use did not significantly affect the sleep parameters. Additionally, longitudinal changes in IFS over 6 months were not significantly associated with changes in TST, SL, or SE (all P > 0.05).ConclusionIn this cohort of long‐term hospitalized patients with schizophrenia, guideline adherence (higher IFS) was associated with increased TST. However, no clear longitudinal effects of IFS on sleep were observed. These findings emphasize the importance of guideline adherence in optimizing sleep, although extended follow‐ups and larger sample sizes are required to confirm the long‐term impact of guideline‐based treatments on sleep in patients with schizophrenia.

The EMPA-REG OUTCOME trial confirmed empagliflozin reduced mortality and heart failure hospitalization risk. These findings raised the possibility that empagliflozin may modulate cardiac autonomic function in patients with type 2 diabetes (T2D). The EMPYREAN study was a prospective randomized open-label assessor-blinded multicenter investigation of patients with T2D without prior antidiabetic therapy with sodium-glucose cotransporter 2 or dipeptidyl peptidase 4 inhibitors. Electrocardiographic monitoring was performed at study onset and after 12 and 24 weeks of treatment. Heart rate variability was analyzed using the MemCalc method. The primary endpoint was the change in the low frequency (LF; 0.04-0.15 Hz)/high frequency (HF; 0.15-0.4 Hz) ratio from baseline to 24 weeks. In all, 113 patients were randomized. The median age in the empagliflozin and sitagliptin groups was 60 and 63 years, respectively. There were no significant differences in serial changes in the LF/HF ratio (0.52, 95% confidence interval [CI] -0.15 to 1.19, P=0.126) or HF (16.13, 95% CI -11.58 to 43.84, P=0.251) between the 2 groups. In time domain analysis, serial changes in root mean square successive difference (1.90, 95% CI -0.56 to 4.38, P=0.12) and percent of difference between adjacent normal RR intervals >50 ms (1.04, 95% CI -0.32 to 2.41, P=0.13) were not significantly different. The effects of empagliflozin and sitagliptin on autonomic nerve activity did not differ significantly in patients with T2D.

ABSTRACTIntroductionIn atrial fibrillation (AF) ablation procedures, the CARTO VIZIGO Bidirectional Guiding Sheath has previously shown promising results in reducing fluoroscopy times without compromising clinical effectiveness or safety compared with non‐steerable sheaths.MethodsThis non‐randomized, multicenter, retrospective cohort study (INSIGHT) aimed to determine the real‐world impact of the VIZIGO sheath on procedural efficiency, clinical effectiveness, and safety in paroxysmal AF (PAF) catheter ablation. Consecutive adults who underwent de novo radiofrequency (RF) ablation for PAF with a non‐VIZIGO sheath (January 2019–July 2021) or VIZIGO sheath (January 2020–July 2021) were included. Procedural characteristics, primary adverse events (PAEs), and 12‐month effectiveness (freedom from repeat ablation or recurrent atrial arrhythmia) were evaluated.ResultsOf 199 patients included (mean age, 69.7 years; 59.3% male), 97 had ablation with a VIZIGO sheath and 102 with a non‐VIZIGO sheath. Significantly shorter mean times were achieved in the VIZIGO vs. non‐VIZIGO group for time to left PVI (18.1 ± 7.5 vs. 19.9 ± 5.6 min, p = 0.046), right PVI (16.5 ± 6.1 vs. 23.1 ± 9.9 min, p < 0.001), total PVI (34.6 ± 9.7 vs. 42.9 ± 11.4 min, p = 0.002), and fluoroscopy time (7.3 ± 10.4 vs. 18.3 ± 13.3 min, p < 0.001). Mean fluoroscopy dose was significantly lower (45.9 ± 112.0 vs. 139.5 ± 251.5 mGy, p < 0.001) with VIZIGO vs. non‐VIZIGO sheaths. Catheter stability was comparable between groups. PAE rates were similar in the VIZIGO (3.1%) and non‐VIZIGO (4.9%) groups. Freedom from repeat ablation and recurrent atrial arrhythmia at 12 months were also similar in the two groups.ConclusionThese real‐world data demonstrate that use of the VIZIGO sheath in PAF ablation procedures allows for significantly lower fluoroscopy time and dose with significantly shorter PVI isolation time, without compromising acute and long‐term effectiveness or safety.

The HELT-E2S2 score has recently been proposed as a new risk stratification tool for ischemic stroke in Japanese patients with atrial fibrillation (AF). We aimed to evaluate the prognostic value of HELT-E2S2 score for cardiovascular events among patients undergoing percutaneous coronary intervention (PCI). Between August 2012 and July 2013, patients undergoing PCI enrolled in the SHINANO 5-year registry, a prospective, observational multicenter registry, were analyzed for the current study. Primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction, and ischemic stroke at 5 years. Key secondary endpoint was bleeding events at 5 years. A total of 1608 patients were divided into the low HELT-E2S2 score group (< 2, n = 915) and high HELT-E2S2 score group (≥ 2, n = 693). Major criteria of the HELT-E2S2 score were hypertension (74.7%), elderly age 75–84 years (31.3%), and AF (11.1%). Kaplan–Meier analysis revealed that the high HELT-E2S2 score group had a significantly higher incidence of MACE (33.4% vs. 14.8%, P < 0.001) and bleeding events (12.7% vs. 5.3%, P < 0.001) compared with the low HELT-E2S2 score group. Multivariable analysis demonstrated that the HELT-E2S2 score remained significantly associated with MACE (hazard ratio: 1.73, 95% confidence interval: 1.11–2.69; P = 0.015). The HELT-E2S2 score appears a useful tool for predicting future cardiovascular events in CAD patients undergoing PCI.Graphical abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS characterized by the production of disease-specific autoantibodies against aquaporin-4 (AQP4) water channels. Animal model studies suggest that anti-AQP4 antibodies cause a loss of AQP4-expressing astrocytes, primarily via complement-dependent cytotoxicity. Nonetheless, several aspects of the disease remain unclear, including: how anti-AQP4 antibodies cross the blood-brain barrier from the periphery to the CNS; how NMOSD expands into longitudinally extensive transverse myelitis or optic neuritis; how multiphasic courses occur; and how to prevent attacks without depleting circulating anti-AQP4 antibodies, especially when employing B-cell-depleting therapies. To address these knowledge gaps, we conducted a comprehensive 'stage-dependent' investigation of immune cell elements in situ in human NMOSD lesions, based on neuropathological techniques for autopsied/biopsied CNS materials. The present study provided three major findings. First, activated or netting neutrophils and melanoma cell adhesion molecule-positive (MCAM+) helper T (TH) 17/cytotoxic T (TC) 17 cells are prominent, and the numbers of these correlate with the size of NMOSD lesions in the initial or early-active stages. Second, forkhead box P3-positive (FOXP3+) regulatory T (Treg) cells are recruited to NMOSD lesions during the initial, early-active or late-active stages, suggesting rapid suppression of proinflammatory autoimmune events in the active stages of NMOSD. Third, compartmentalized resident memory immune cells, including CD103+ tissue-resident memory T (TRM) cells with long-lasting inflammatory potential, are detected under "standby" conditions in all stages. Furthermore, CD103+ TRM cells express high levels of granzyme B/perforin-1 in the initial or early-active stages of NMOSD in situ. We infer that stage-dependent compartmentalized immune traits orchestrate the pathology of anti-AQP4 antibody-guided NMOSD in situ. Our work further suggests that targeting activated/netting neutrophils, MCAM+ TH17/TC17 cells, and CD103+ TRM cells, as well as promoting the expansion of FOXP3+ Treg cells, may be effective in treating and preventing relapses of NMOSD.

Low-grade endometrial stromal sarcoma (LGESS) typically has a favorable prognosis. Hormone therapy is considered the first choice of treatment for recurrent LGESS. In this report, we describe a case of recurrent LGESS where hormonetherapy was ineffective, chemotherapy showed a partial response (PR), and pazopanib resulted in stable disease (SD). A 50-year-old patient with LGESS underwent a simple total hysterectomy and bilateral adnexectomy (pT1aN0M0, stage IA). Five years later, pelvic tumors and ascites were observed. Exploratory laparoscopy revealed bloody ascites, an 8 cm pelvic tumor, and extensive peritoneal dissemination. Nuclear atypia of the tumor cells was mild, pleomorphism and mitotic figures could not be confirmed, and necrosis was not observed. Immunostaining was positive for CD10 and estrogen receptor, negative for the BCL6 corepressor (BCOR), and showed a low Ki-67 index. Fluorescence in situ hybridization (FISH) examination of the tissue showed rearrangement of the JAZF zinc finger 1 (JAZF1) gene. Multigene panel testing revealed a homozygous deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A). Accordingly, the patient was diagnosed with recurrent LGESS and was treated with an aromatase inhibitor, followed by medroxyprogesterone acetate; both were ineffective. The patient had a PR to chemotherapy (doxorubicin/ifosfamide) and SD to pazopanib. The patient died 1.5 years after recurrence. In conclusion, we present a case of LGESS with a poor prognosis where hormone therapy was ineffective, and chemotherapy and pazopanib were both partially effective. The poor prognosis may have been associated with the CDKN2A homozygous deletion.