Efficacy and safety of buccal midazolam for seizures outside the hospital: Real-world clinical experience.

INTRODUCTION: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice. METHODS: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023. RESULTS: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age. CONCLUSIONS: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone.

Feasibility and safety of EUS-guided biliary drainage in inexperienced centers: a multicenter study in southwest Japan.

BACKGROUND AND AIMS: EUS-guided biliary drainage (EUS-BD) has shown promising procedural outcomes in high-volume centers. Although inferior procedural outcomes were reported in inexperienced centers during the early days of EUS-BD, the current outcomes are unknown. This study aimed to clarify the feasibility and safety of EUS-BD in centers that recently introduced EUS-BD. METHODS: This multicenter retrospective study was conducted at 22 centers that introduced EUS-BD between 2017 and 2022. A maximum of 20 initial EUS-BD cases at each center were evaluated. The clinical outcomes and experience of 84 endoscopists who performed these procedures were examined. Primary outcomes were the rate of technical success and adverse events (AEs), whereas secondary outcomes were risk factors associated with technical failure and procedure-related AEs. RESULTS: Two hundred fifty-five patients were enrolled. The technical success rate was 91.4% (233/255). Among 22 technical failure cases, guidewire manipulation failure was the most common cause (n = 12) followed by tract dilation failure (n = 5). The AE rate was 10.2% (26/255). Multivariate analysis identified a puncture target diameter of <5 mm (odds ratio, 3.719; 95% CI, 1.415-9.776; P = .008) and moderate ascites extending to the liver surface (odds ratio, 3.25; 95% CI, 1.195-8.653; P = .021) as independent risk factors for technical failure and procedure-related AEs, respectively. Endoscopists' procedural experience was not a risk factor for technical failure or procedure-related AEs. CONCLUSIONS: The feasibility and safety of EUS-BD were maintained during the induction phase at inexperienced centers. These data will be helpful to better understand the current status of EUS-BD. (Clinical trial registration number: UMIN 000053615.).

Elevated cerebrospinal fluid neuronal injury biomarkers within 24 hours of onset in infection-triggered acute encephalopathy compared to complex febrile seizures.

OBJECTIVE: This study aimed to measure and compare cerebrospinal fluid neuronal injury biomarkers in the acute phase of complex febrile seizure (CFS) and infection-triggered acute encephalopathy (AE). Furthermore, we determined the pathogenesis of AE with biphasic seizures and late reduced diffusion (AESD). METHODS: Pediatric patients with febrile status epilepticus who visited Hyogo Prefectural Kobe Children's Hospital from November 1, 2016, to December 31, 2022, and whose cerebrospinal fluid samples were collected within 24 h of neurological symptom onset were included. Patients were classified as having CFS or infection-triggered AE according to their definitions. Patients with AE were further categorized into AESD or unclassified AE. Cerebrospinal fluid biomarkers (neuron-specific enolase, growth differentiation factor 15 [GDF-15], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein, and tau protein were measured and compared among the groups. RESULTS: Total of 63 patients (45 with CFS and 18 with AE) were included. Among the AE patients, nine were classified as having AESD and nine as having unclassified AE. S100B levels were significantly higher in patients with AESD than in patients with CFS (485 pg/ml vs. 175.3 pg/ml) and were even higher in patients with AESD and neurological sequelae (702.4 pg/ml). GDF-15 levels were significantly elevated in patients with AE compared to patients with CFS (85.8 pg/ml vs. 23.6 pg/ml). CONCLUSIONS: The elevation of S100B suggests that activated astrocytes may be closely associated with the early pathology of AESD. Elevated GDF-15 levels in infection-triggered AE suggest the activation of defense mechanisms caused by stronger neurological injury.

Inhibitory Effect of Pyra-Metho-Carnil on the Differentiation and Maturation of Macrophages in Normal and Cancer Microenvironments.

BACKGROUND/AIM: In a previous study, we have demonstrated heightened Pyra-Metho-Carnil (PMC) efficacy in nude mice with intact innate immunity that lack T and B cells. This has prompted hypothesizing that PMC may target macrophages that promote cancer growth. In this study, we conducted co-culture experiments with macrophages derived from THP-1 human monocyte cell lines and spheroids representing normal and cancer microenvironments. We then performed RNA sequencing and flow cytometry analysis to elucidate the mechanisms by which PMC affects macrophage differentiation and maturation. MATERIALS AND METHODS: THP-1 cells were differentiated by phorbol 12-myristate 13-acetate (PMA) and matured by PMA and lipopolysaccharide (LPS) either with or without PMC. Co-cultures were performed using stimulated THP-1 cells and HKe3-wild-type KRAS or HKe3-mutant (mt) KRAS spheroids. We then performed RNA-seq analysis of THP-1 cells stimulated by PMA (either with or without PMC) and flow cytometry analysis of mice peripheral blood obtained after PMC administration. RESULTS: THP-1 cells matured by PMA and LPS specifically increased the area of HKe3-mtKRAS cancer spheroids and the addition of PMC to THP-1 cells was found to inhibit cancer spheroid growth. RNA-seq data suggested that PMC treatment of THP-1 cells stimulated with PMA suppressed cell motility regulatory functions via down-regulation of the NF[Formula: see text]B pathway. Furthermore, flow cytometry results showed that PMC treatment suppressed monocyte maturation in B6 mice. CONCLUSION: The high level of in vivo tumor suppression caused by PMC may be due to inhibition of the differentiation and maturation of tumor-associated macrophages via the NF[Formula: see text]B signaling pathway.

Radial force and wire structure determine the onset of covered self-expandable metal stent migration in endoscopic ultrasound-guided hepaticogastrostomy: Measurement of sliding-resistance force using a porcine model.

BACKGROUND: Self-expandable metal stent (SEMS) migration after endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a severe complication. The migration risk could be related to the surface friction of SEMS, assumed to be affected by the wire structure and mechanical properties, including radial force (RF); however, their relevance remains unclear. This experimental study aimed to assess the mechanical properties of SEMS involved in the onset of stent migration by measuring the sliding-resistance force (SF) as the SEMS moves through the stomach wall. METHODS: The SF of seven types of 8-mm diameter SEMS (four braided and three laser-cut types) and porcine stomach wall was measured with a universal testing machine. The SF of each SEMS was measured three times, and the average maximum SF (SFmax) was used for analysis. The correlation between SFmax and RF of each SEMS was evaluated. RESULTS: SFmax and RF showed a very strong positive correlation (r = 0.92). Compared to the regression line predictions in the scatter plots of SFmax and RF, the SFmax of laser-cut and braided type SEMSs had positive and negative residuals, respectively. CONCLUSIONS: Selecting a laser-cut type SEMS with a higher RF may more effectively prevent the onset of stent migration against the stomach wall in EUS-HGS.

Remimazolam for simultaneous percutaneous mitral valve clip and percutaneous left atrial appendage closure in an elderly patient with impaired cardiac function: A case report.

Remimazolam is a short-acting benzodiazepine sedative with a short half-life and little circulatory depression. The safe use of remimazolam in the anesthetic management of an elderly patient with impaired cardiac function is reported. The patient's hemodynamics remained stable, and the patient was managed without serious complications. Remimazolam may be an option for sedation in elderly patients with reduced cardiac function.

Structural factors influencing the clinical performance of 0.025-inch guidewires for pancreatobiliary endoscopy: An experimental study.

Background and study aims To develop a pancreatobiliary endoscopic guidewire with good clinical performance, an understanding of its structure is necessary. This study aimed to investigate the structural factors influencing the clinical performance of pancreatobiliary endoscopic guidewires. Methods Eight types of 0.025-inch guidewires were evaluated. The following structural properties were measured: tip length, tip deflection height, tip weight (TW), ratio of tip core weight to TW, shaft coating type (flat or uneven), outer diameter, and core wire diameter (CWD). Four performance tests were conducted to evaluate shaft stiffness as bending force (BF), shaft lubricity as friction force (FF), torque response as torque response rate (TRR), and seeking ability as total insertion success (TIS) in a technical test using a 3D bile duct model. The correlation coefficients of each variable were analyzed. Results The BF and CWDs were strongly correlated, as well as the FF and CWDs and BF. Among the guidewires with similar CWDs, the guidewires with uneven coating had significantly lower FF than those with flat coating. The TRR was strongly correlated with the CWDs; furthermore, guidewires with lower FF had better TRR. TIS was strongly correlated with the TRR, TWs, and ratio of the tip core weight to TW. Conclusions CWD affects shaft stiffness; CWD and coating type affect shaft lubricity and torque response. Because TRR and TW are correlated with seeking ability, an appropriate combination of core wire thickness, TW, and coating design is required to develop a guidewire with good seeking ability.

A PEDIATRIC CASE OF PANNICULITIS INDUCED BY Pseudomonas aeruginosa WITH CLINICAL FEATURES SIMILAR TO ECTHYMA GANGRENOSUM.

The clinical features of panniculitis caused by Pseudomonas aeruginosa, in contrast to those caused by ecthyma gangrenosum, remain unknown. Here, we report a pediatric case of P. aeruginosa panniculitis. The patient had systemic involvement without bacteremia and also had a background of autoimmune neutropenia. These features are common in ecthyma gangrenosum but have not been reported in P. aeruginosa-induced panniculitis.

Anesthesia Management Using Remimazolam for Lower Limb Amputation in a Patient With Septic Shock Due to Necrotizing Fasciitis.

We report a case of a patient with necrotizing fasciitis and septic shock caused by streptococcal toxic shock syndrome, who was anesthetized and managed with remimazolam. The patient, a woman in her 40s, was admitted to the ICU with a diagnosis of necrotizing fasciitis of the right lower extremity and septic shock and was scheduled for above-the-knee amputation under general anesthesia. She was anesthetized with remimazolam for sedation and fentanyl and remifentanil for analgesia. Intraoperatively, we were able to maintain hemodynamic stability with similar or only slightly higher doses of circulatory agonists during admission. In the present case, remimazolam, an ultrashort-acting benzodiazepine, was safely used to provide anesthesia to a patient in septic shock due to necrotizing fasciitis, who was receiving high doses of vasopressor agents for cardiovascular support, as it was necessary to select an anesthetic drug that would cause minimal circulatory depression.

Safety of biliary drainage with 6-mm metallic stent for preoperative obstructive jaundice in pancreatic cancer: PURPLE SIX STUDY.

BACKGROUND AND AIM: The 10-mm self-expandable metal stent (SEMS) is the standard for endoscopic transpapillary biliary drainage before pancreatic cancer surgery. However, the efficacy of stents thinner than 10 mm has not been adequately validated. Therefore, we aimed to evaluate the safety of a 6-mm fully covered SEMS (FCSEMS) for distal malignant biliary obstruction (DMBO) during preoperative chemotherapy for pancreatic cancer. METHODS: This was a single-arm, multicenter, prospective phase II study of endoscopic transpapillary initial biliary drainage for DMBO before pancreatic cancer surgery. The primary endpoint was stent-related adverse events, and the key secondary endpoint was the non-recurrent biliary obstruction (non-RBO) rate during the observation period for both resectable (R) and borderline resectable (BR) pancreatic cancers. RESULTS: The study enrolled 33 patients, among whom 32 received the study treatment. There were 23 and 9 cases of R and BR pancreatic cancers, respectively. The technical and clinical success rates were 97.0% and 90.1%, respectively. The stent-related adverse event rate was 3.1% (n = 1, acute pancreatitis) (95% confidential interval, 0.00-16.2), which met the criteria to be considered safe. The overall non-RBO rate during the observation period (median 96 days) was 78.1% (82.6% and 66.7% for R and BR pancreatic cancer cases, respectively). CONCLUSIONS: The 6-mm FCSEMS is an extremely safe metallic stent with a low stent-related adverse event rate of 3.1% for preoperative biliary drainage in pancreatic cancer. It is considered the optimal stent for preoperative biliary drainage in terms of the non-RBO rate. UMIN Clinical Trial Registry (UMIN-CTR 000041704).

A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3 , were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.

A Case of Nerve Root Radiofrequency Thermocoagulation for Pain Due to Pleural Metastasis of Lung Cancer Leading to Improvement in the Patient's Quality of Life.

Advances in medicine have made long-term survival of cancer patients possible. Hence, it is now necessary to consider how to approach common symptoms, such as cancer-related pain, in these patients. In this study, we describe a lung cancer patient in whom relief of intractable thoracic pain caused by pleural metastasis was achieved through thoracic radiofrequency thermocoagulation (RF), improving his quality of life (QOL). The patient was a man in his 70s with right upper lobe lung cancer, left 9th -11th rib metastasis, and left thoracic pain associated with parietal pleural metastasis. The patient experienced insomnia and weight loss due to poor appetite caused by opioid analgesics and inadequate pain control. Therefore, RF was performed as interventional treatment, resulting in a decrease in the numerical rating scale score from 10/10 to 2/10, and an improvement in QOL. In cases wherein long-term survival is expected, a long-term treatment plan for chronic cancer-related pain, which has a tendency to become persistent, becomes necessary. RF for the nerve roots might be a viable option for pain caused by pleural metastasis in cancer survivors.

Severe acute cholecystitis successfully treated with endoscopic nasobiliary drainage tube insertion: A case report.

In this report, we present a case of a patient with bile peritonitis caused by gallbladder perforation associated with acute cholecystitis, which required intensive postoperative care. The patient was a woman in her 40s who presented with abdominal pain. Upon examination, she was diagnosed as having acute cholecystitis and bile peritonitis caused by gallbladder perforation. Subsequently, a partial cholecystectomy, omental pack, and drainage were performed. Initially, her bile duct enzyme levels improved; however, they subsequently increased again. An endoscopic nasobiliary drainage tube was inserted, and thereafter, a decrease in inflammatory response and bile duct enzyme levels was observed. During the course of treatment, respiratory failure and renal impairment occurred, necessitating mechanical ventilation management and continuous hemodiafiltration. In patients with severe acute cholecystitis, in addition to treating the underlying condition, it is crucial to perform procedures perioperatively, in anticipation of the development of additional organ dysfunctions postoperatively.

Prospective clinical trial of EUS-guided choledochoduodenostomy without fistula dilation for malignant distal biliary obstruction.

Background and Objectives: During EUS-guided choledochoduodenostomy (EUS-CDS), fistula dilation before stent insertion is associated with adverse events (AEs), such as bile leakage and peritonitis. We hypothesized that EUS-CDS without fistula dilation using a novel self-expandable metal stent (SEMS) with a thin delivery system could overcome this problem, and we conducted this study to evaluate its feasibility and safety. Methods: This was an open-label, single-arm, phase II study at a single institution. We planned EUS-CDS without fistula dilation using a fully covered SEMS with a 5.9-Fr delivery system for unresectable malignant distal biliary obstruction. The primary outcome was overall technical success. Secondary outcomes were technical success without fistula dilation, procedure time, functional success, time to recurrent biliary obstruction, and AEs. The planned sample size was 25 patients. Results: In total, 24 patients were included in this study. In 21 patients, EUS-CDS was performed as primary drainage. The overall technical success rate was 100% (24 of 24 patients). The technical success rate without fistula dilation was 96% (23 of 24). The median procedure time was 16 min (range, 10-66 min). The functional success rate was 96% (23 of 24). The median time to recurrent biliary obstruction was 148 days (95% confidence interval, 29-266 days). There were no procedure-related AEs. Furthermore, computed tomography immediately after the procedure showed no leakage of contrast medium into the abdominal cavity in any patient. Conclusions: EUS-guided choledochoduodenostomy without fistula dilation using a fully covered SEMS with a 5.9-Fr delivery system is feasible with a high probability and can be achieved quickly while effectively preventing bile leakage and peritonitis.

Anesthetic management of airway stent placement by rigid bronchoscopy with superior laryngeal nerve block while preserving spontaneous breathing: A case report.

Key Clinical Message: The combination of superior laryngeal nerve block can reduce the respiratory depression that occurs during management under total intravenous anesthesia. Abstract: Anesthetic management of endobronchial stent placement by rigid bronchoscopy requires the maintenance of spontaneous breathing while suppressing upper airway reflexes. The combination of superior laryngeal nerve block (SLNB) can reduce the respiratory depression that occurs during management under total intravenous anesthesia. The patient was diagnosed as having lung cancer with invasion into the right middle bronchus and stenosis of the right main bronchus on chest computed tomography, and emergency airway stent placement was performed. Sedation was initiated with propofol and dexmedetomidine, and ultrasound-guided SLNB was performed after local anesthetic spraying into the oral cavity and trachea. Bucking was minimally controlled during insertion of the rigid bronchoscope. The patient's intraoperative hemodynamics remained stable, and there were no hypoxic events. SLNB can provide the suppression of the upper airway reflex while minimizing effects on spontaneous breathing, and may be useful for achieving balanced anesthesia during rigid bronchoscopy.

Comparison of neurological manifestation in children with and without coronavirus 2019 experiencing seizures with fever.

Whether neurologic symptoms due to SARS-CoV-2 differ from those of non-SARS-CoV-2 viral infection is unclear. We aimed to describe these neurological manifestations and compare the clinical characteristics and treatments in children with seizures and fever with or without COVID-19. We retrospectively analyzed data from 105 hospitalized children (<18 years) with clinical seizures and fever between September 2021 and August 2022. We compared the clinical characteristics and treatments between the COVID-19 (n = 20) and non-COVID-19 (n = 85) groups. Patients with COVID-19 were older than those without (32.5 [20-86] months vs. 20 [16-32] months, p = 0.029). Seizure type and duration and impaired consciousness duration did not differ between groups. Six and 32 patients experienced status epilepticus lasting 30 min in the COVID-19 and non-COVID-19 groups, respectively. Most treatments did not differ between groups; however, electroencephalography was used less frequently for COVID-19. Neurological sequelae occurred in one and four patients in the COVID-19 and non-COVID-19 groups, respectively. In conclusion, seizures with fever due to SARS-CoV-2 were more common in older children. Seizure characteristics and neurologic sequelae did not differ in children with and those without COVID-19. In general, electroencephalography was used less during COVID-19 for infection control measures.

Presumed first episode of nonconvulsive status epilepticus as the cause of postoperative disorder of consciousness following the completion of general anesthesia: A case report.

Key Clinical Message: Disorder of consciousness can lead to irreversible sequelae without proper intervention. Consequently, early diagnosis and treatment are of paramount importance in patients with disorder of consciousness. Abstract: Disorder of consciousness (DOC) has various etiologies. Here, we report a case in which DOC following general anesthesia was suspected as being due to the first episode of nonconvulsive status epilepticus (NCSE). An elderly man in his 80s underwent uneventful tumor resection surgery under general anesthesia for extramammary Paget's disease. After the procedure, he regained consciousness following anesthesia discontinuation and was extubated. Soon after extubation, however, although his respiratory status remained stable, his level of consciousness deteriorated to a Glasgow Coma Scale (GCS) score of E1V1M1. Head computed tomography and magnetic resonance imaging scans indicated no abnormal findings. Subsequently, involuntary movements were noted in his left upper limb. Suspecting an epilepsy episode, diazepam was administered, leading to an improvement in the level of consciousness (GCS: E4V5M6). Based on the improvement in consciousness after diazepam administration, we strongly suspected NCSE.

Two Cases of Splanchnic Nerve Block With Epidural Anesthesia in Patients Unable to Maintain Prone Position Due to Pancreatic Pain.

Splanchnic nerve block is considered to be effective for abdominal visceral pain, and is performed for the purpose of controlling abdominal pain and back pain caused by upper abdominal cancer. The patients in this case report were candidates for splanchnic nerve block owing to cancer-associated pain. However, because they could not assume the prone position that is required for the block owing to their pain, combined epidural anesthesia was used, resulting in successful implementation of the splanchnic nerve block. Patients who are candidates for splanchnic nerve block often have advanced cancer, and it is hence often difficult to secure and maintain the position required for the procedure owing to their severe pain. The two patients presented here suggest the possibility that epidural anesthesia might be useful as an adjunct in such cases.