Periodontal disease has been reported to increase the risk of threatened preterm labor (TPL). However, studies analyzing the oral, vaginal, and rectal lumen commensal flora in women with TPL are limited. In this study, a total of 60 women were enrolled, including 30 with TPL and 30 without TPL. We assessed periodontal clinical parameters, salivary hormone levels, and the microbiome using next-generation sequencing. Probing pocket depth (PPD) and bleeding on probing were greater in the TPL than in the non-TPL group. The TPL group was associated with lower progesterone levels and an increase in PPD ≥ 4 mm. Significant differences in alpha diversity in only vaginal Faith’s phylogenetic diversity, and significant differences in beta diversity at all sites were observed. ANCOM showed decreased Lactobacillales in the saliva and Bifidobacterium in the rectal lumen, and increased Staphylococcus in the oral cavity and vagina in the TPL group. The peptidoglycan synthesis pathway was significantly upregulated in the oral and vaginal tissues in the TPL group. Overall, the TPL group had lower progesterone levels and more severe periodontal disease; furthermore, the low progesterone levels in the TPL group were associated with oral and vaginal dysbiosis of the microbiota.
Small bowel atresia (SBA) presents with variable clinical features depending on anatomical location. We investigated the relationship between atresia location and preterm delivery. We retrospectively reviewed 58 patients who underwent surgery for SBA at two institutions between April 2000 and March 2024. Patients were divided into preterm (<37 weeks, n=28) and term (≥37 weeks, n=30) groups. Clinical characteristics, prenatal findings, anatomical location, and surgical outcomes were compared. A logistic regression analysis identified independent predictors of preterm delivery. Preterm infants showed lower birth weight (1988±731 g vs. 3062±395 g, p<0.001) and higher rates of prenatal diagnosis (85.7
BACKGROUND:The efficacy and safety of early direct oral anticoagulant (DOAC) (re)initiation in patients with non-valvular atrial fibrillation (NVAF) after acute onset of intracranial hemorrhage (ICH) are unknown. This study evaluated ischemic and hemorrhagic risks following early DOAC (re)initiation after ICH in patients with NVAF. METHODS AND RESULTS:SAFE-ICH is a multicenter prospective observational single-arm registry study at 32 Japanese hospitals. Eligible patients had NVAF, were aged ≥20 years, and (re)initiated DOAC ≤14 days following symptomatic ICH. Among 240 patients who (re)initiated DOAC (61.3% male; mean [±SD] age 79.4±9.3 years), intraparenchymal hemorrhage predominated (84.6%), followed by subdural (12.9%), intraventricular (1.7%), and epidural (0.8%) hemorrhage. The median (interquartile range) baseline National Institutes of Health Stroke Scale score was 10 (3-16) and time to DOAC (re)initiation was 7 days (5-10 days). Edoxaban, apixaban, and rivaroxaban were used in 55.0%, 35.8%, and 9.2% of patients, respectively. The primary endpoint (composite of symptomatic ICH, any stroke, or death ≤30 days following DOAC [re]initiation) occurred in 12 (5.0%) patients. There were 4 recurrent ICH events (1.7%; all recurrent subdural hemorrhages). Five (2.1%) patients died of non-vascular causes. CONCLUSIONS:In Japanese patients with NVAF, early DOAC (re)initiation ≤14 days after ICH appears to have an acceptable risk for ischemic and hemorrhagic events, particularly in patients with intraparenchymal hemorrhage. In patients with subdural hematoma, early DOAC (re)initiation requires vigilant monitoring.
BACKGROUND:Recombinant factor VIIa has been shown to slow bleeding in patients with intracerebral haemorrhage (ICH), but no haemostatic agent has been shown to improve clinical outcomes. We aimed to evaluate the safety, clinical efficacy, and effect on growth of ICH and intraventricular haemorrhage (IVH) of recombinant factor VIIa in patients with acute spontaneous ICH who were most likely to benefit from treatment with this agent. METHODS:We conducted a multicentre, prospective, double-blind, randomised, placebo-controlled, adaptive, phase 3 trial (FASTEST) at 93 sites across the USA, Japan, Canada, Spain, Germany, and the UK. Adults aged 18-80 years with a spontaneous ICH of 2-60 mL, IVH in less than two-thirds of one lateral ventricle or in less than a third of both lateral ventricles, a Glasgow Coma Scale score of at least 8, no evidence of recent ischaemic stroke or myocardial infarction, no recent use of anticoagulation medication or other structural cause of ICH, and who had been treated with study medication within 2 h of stroke onset or last known well were eligible for inclusion. Patients were randomly assigned (1:1) by a simple randomisation scheme to either 80 μg/kg recombinant factor VIIa (intervention group) or an identical placebo (placebo group), administered intravenously over 2 min. All investigators and participants were masked to allocated group assignment. The primary outcome was functional outcome at 180 days, measured by modified Rankin Scale (mRS; score 0-2, 3, and 4-6) and analysed by intention to treat in all randomly assigned patients. The primary safety outcome was life-threatening thromboembolic events during the first 4 days, assessed in all randomly assigned participants. The secondary aim was change in ICH volume and ICH plus IVH volume between baseline and 24 h of treatment administration. We performed an ordinal logistic regression, adjusted for age, baseline ICH volume, baseline IVH volume, and pre-stroke mRS. Preplanned interim analyses, including adaptive sample size re-estimation and enrichment to a younger subgroup (aged ≤70 years), were also conducted. This trial is registered with ClinicalTrials.gov (NCT03496883) and is closed to new participants. FINDINGS:Between Dec 3, 2021, and Oct 1, 2025, we screened 3288 patients, of whom 626 participants were randomly assigned and included in the intention-to-treat analyses: 298 (48%) in the placebo group and 328 (52%) in the intervention group. 216 (35%) participants were female and 410 (65%) were male, with a mean age of 61 years (SD 12). Mean time from stroke onset to administration of study drug was 100 min (SD 22). The trial met the prespecified stopping criteria for futility at the second interim analysis. There was no differential effect in the primary clinical outcome measure of mRS at 180 days between the intervention group and placebo group (adjusted common odds ratio 1·09 [95% CI 0·79-1·51]; p=0·61). Life-threatening thromboembolic complications within 4 days occurred in 15 (<5%) participants in the intervention group and in four (1%) in the placebo group (relative risk 3·41 [95% CI 1·14-10·15]; p=0·020). Compared with placebo, recombinant factor VIIa was associated with decreased growth of ICH (-3·7 mL [95% CI -5·4 to -1·9]) and of ICH plus IVH growth (-5·2 mL [-7·6 to -2·8]) between baseline and CT scan at 24 h. INTERPRETATION:Recombinant factor VIIa administered within 2 h of ICH onset slowed haematoma growth, but did not improve functional outcomes and showed a small increased risk of life-threatening thromboembolic complications. Further testing of recombinant factor VIIa in patients with the greatest risk of continued bleeding is ongoing. FUNDING:National Institute of Neurological Diseases and Stroke, Japan Agency for Medical Research and Development, and Novo Nordisk.
Chronic limb-threatening ischemia (CLTI) is a severe form of lower extremity artery disease. CLTI is an umbrella term for conditions in which the lower limb is threatened by ischemia, tissue defects, neural disorders, or infection. In Japan, CLTI primarily affects patients with diabetes and those on hemodialysis. The severity of CLTI is assessed using the Wound, Ischemia, and foot Infection (WIfI) classification. CLTI needs multidisciplinary therapy. Rheocarna is a novel direct hemoperfusion device and can adsorb low-density lipoprotein (LDL) cholesterol and fibrinogen, thereby improving hemorheology. However, reports describing its use after distal bypass surgery are limited. In this report, we present three initial cases of successful combined treatment for WIfI clinical stage 4 CLTI in patients undergoing hemodialysis, including distal bypass, minor amputation, debridement, and Rheocarna therapy. Case 1 is a 67-year-old man with CLTI in the left foot. Endovascular therapy (EVT) failed to revascularize the anterior tibial artery (ATA). Necrosis of the left fifth toe progressed, and the ulcerative purulent wound tested positive for Pseudomonas aeruginosa (W3I3fI1; stage 4). A left below-knee popliteal-to-dorsal artery in situ bypass was performed, and the necrotic fifth toe was amputated, followed by maintenance debridement. Rheocarna therapy was initiated on postoperative day (POD) 13 (a nonhemodialysis day following the fifth postoperative dialysis) and administered twice weekly for a total of 12 sessions. Three months after surgery, the wound healed. Case 2 is a 71-year-old man with CLTI and necrosis of the left fourth and fifth toes. EVT failed to revascularize the chronic total occlusion (CTO) at the distal ATA. The ulcerative purulent wound tested positive for Escherichia coli (W3I2fI3; stage 4). A left below-knee popliteal-to-posterior tibial artery (PTA) in situ bypass was performed, and the necrotic third and fifth toes were amputated. Maintenance debridement with negative pressure wound therapy was performed. Rheocarna therapy was initiated on POD 7 (a nonhemodialysis day following the third postoperative dialysis) and administered twice weekly for a total of eight sessions. Three months after surgery, the wound healed. Case 3 is a 79-year-old man with CLTI and necrosis of the right first and fifth toes. EVT failed to revascularize the CTO at the distal ATA and PTA. Necrosis worsened, complicated by cellulitis, and the purulent wound tested positive for Staphylococcus aureus (W2I3fI3; stage 4). A right below-knee popliteal-to-dorsal artery in situ bypass was performed, and the necrotic first and fifth toes were amputated, followed by maintenance debridement. Rheocarna therapy was initiated on POD 9 (a nonhemodialysis day following the fourth postoperative dialysis) and administered twice weekly for a total of nine sessions. Three months after surgery, the wound healed. Rheocarna therapy may reduce postoperative fibrinogen, LDL cholesterol and lipoprotein(a), improving microcirculation and avoiding bypass graft failure, surgical site infection and delayed wound healing. Given the limited reports on the use of Rheocarna after distal bypass, it is important to accumulate more cases and long-term outcome data. Further multicenter studies or registry data are needed to validate the optimal timing and frequency of Rheocarna therapy.
