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1.
Article in English | MEDLINE | ID: mdl-38715896

ABSTRACT

Immunoglobulin G4 (IgG4)-related diseaseis a systemic inflammatory condition of unknown etiology characterized by increases in serum IgG4 and in the number of IgG4-positive cells in affected tissues. One of the commonly involved locations is the pancreas; this condition is known as type 1 autoimmune pancreatitis (AIP). Type 1 AIP, which shows a biliary stricture in the intrapancreatic bile duct, can be misdiagnosed as a malignancy due to similar cholangiography findings and clinical presentation. In rare cases complicated by post-bulbar duodenal ulcers, differentiating between type 1 AIP and malignancies is even more difficult. An 81-year-old male was referred to our hospital for the treatment of a pancreatic head mass and obstructive jaundice. Serological and radiological findings were consistent with both type 1 AIP and a malignancy. Gastroduodenoscopy revealed a post-bulbar duodenal ulcer with endoscopic features that evoked malignant duodenal invasion. Although biopsies were negative for malignant cells, subsequent bleeding from the lesion suggested the progression of malignancy, which led to surgical resection. Pancreatoduodenectomy and pathological examination indicated that type 1 AIP was present. Simultaneously, the involvement of IgG4-related disease in the ulcerative lesion was suggested. To our knowledge, this is the first reported case of type 1 AIP complicated by post-bulbar duodenal ulcers, which was misdiagnosed as malignancy and considered an IgG4-related gastrointestinal disease associated with type 1 AIP.

3.
Polymers (Basel) ; 16(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39000688

ABSTRACT

Microplastics' spreading in the ocean is currently causing significant damage to organisms and ecosystems around the world. To address this oceanic issue, there is a current focus on marine degradable plastics. Polycaprolactone (PCL) is a marine degradable plastic that is attracting attention. To further improve the biodegradability of PCL, we selected a completely new protein that has not been used before as a functional filler to incorporate it into PCL, aiming to develop an environmentally friendly biocomposite material. This novel protein is derived from the mucus bubbles of the violet sea snail (VSS, Janthina globosa), which is a strong bio-derived material that is 100% degradable in the sea environment by microorganisms. Two types of PCL/bubble composites, PCL/b1 and PCL/b5, were prepared with mass ratios of PCL to bubble powder of 99:1 and 95:5, respectively. We investigated the thermal properties, mechanical properties, biodegradability, surface structure, and crystal structure of the developed PCL/bubble composites. The maximum biochemical oxygen demand (BOD) degradation for PCL/b5 reached 96%, 1.74 times that of pure PCL (≈55%), clearly indicating that the addition of protein fillers significantly enhanced the biodegradability of PCL. The surface morphology observation results through scanning electron microscopy (SEM) definitely confirmed the occurrence of degradation, and it was found that PCL/b5 underwent more significant degradation compared to pure PCL. The water contact angle measurement results exhibited that all sheets were hydrophobic (water contact angle > 90°) before the BOD test and showed the changes in surface structure after the BOD test due to the newly generated indentations on the surface, which led to an increase in surface toughness and, consequently, an increase in surface hydrophobility. A crystal structure analysis by wide-angle X-ray scattering (WAXS) discovered that the amorphous regions were decomposed first during the BOD test, and more amorphous regions were decomposed in PCL/b5 than in PCL, owing to the addition of the bubble protein fillers from the VSS. The differential scanning calorimeter (DSC) and thermal gravimetric analysis (TGA) results suggested that the addition of mucus bubble protein fillers had only a slight impact on the thermal properties of PCL. In terms of mechanical properties, compared to pure PCL, the mucus-bubble-filler-added composites PCL/b1 and PCL/b5 exhibited slightly decreased values. Although the biodegradability of PCL was significantly improved by adding the protein fillers from mucus bubbles of the VSS, enhancing the mechanical properties at the same time poses the next challenging issue.

4.
JACC Adv ; 3(4): 100887, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38939653

ABSTRACT

Background: A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established. Objectives: The purpose of this study was to identify patients in whom a treat and repair strategy was considered and to examine pretreatment variables associated with successful defect repair. Methods: Patients with atrial or ventricular septal defect and PAH (pulmonary vascular resistance [PVR] ≥ 5 Wood units) eligible for the treat and repair strategy were included. Hemodynamics among pretreatment, pre-repair, and post-defect repair were compared. Clinical outcomes in patients with or without defect repair were also compared. Clinical outcomes included all-cause death, hospitalization for worsening pulmonary hypertension, and lung transplantation. Results: Among 25 eligible for the treat and repair strategy, 20 underwent successful repair (repaired group) and 5 did not have a repair (unrepaired group). In the repaired group, PVR significantly decreased from 9.6 ± 2.6 WU at pretreatment to 5.0 ± 3.4 pre-repair (ß coefficient -4.6 [95% CI: -5.9 to -3.3]). The pulmonary to systemic blood flow ratio (Qp/Qs) increased from 1.5 ± 0.6 at pretreatment to 2.4 ± 1.3 pre-repair (ß coefficient 0.9 [95% CI: 0.4-1.38]). In the unrepaired group, pretreatment PVR decreased with treatment; however, PVR remained elevated. Qp/Qs did not change between pretreatment and post-treatment. The repaired group had a better prognosis than the unrepaired group (HR 0.092 [95% CI: 0.009-0.905]). Pretreatment mean pulmonary artery pressure, PVR, Qp/Qs, and arterial oxygen saturations were associated with undergoing defect repair. Conclusions: In this small cohort, a treat and repair strategy was successfully used in a significant proportion of the patients with congenital heart defects with moderate to severe PAH.

5.
Cureus ; 16(5): e61002, 2024 May.
Article in English | MEDLINE | ID: mdl-38910668

ABSTRACT

Calcific tendinitis of the rectus femoris is rare. This clinical report presents five cases of management of calcific tendinitis of the rectus femoris. Between July 2018 and March 2023, five patients visited our institution, where they were treated for calcific tendinitis of the rectus femoris. All patients presented with severe acute hip pain. Radiographs, computed tomography, magnetic resonance imaging, and an ultrasound examination of the hip showed calcification outside the joint, suggesting calcific tendinitis of the rectus femoris. All patients were orally administered 200 mg cimetidine and nonsteroidal anti-inflammatory drugs twice daily. A pain-free status was achieved in 2 weeks on average. Calcium deposits disappeared in three patients and decreased in two. Symptoms did not recur. Furthermore, no recurrence or enlargements in calcium deposits were observed. It appears to be an effective treatment for calcific tendinitis of the rectus femoris; however, the underlying mechanisms of action of cimetidine on calcific tendinitis have not yet been elucidated in detail.

6.
PCN Rep ; 3(1): e177, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38868484

ABSTRACT

Aim: This study aimed to clarify the abnormalities in dopamine transporter (DAT) availability in drug-naive adult patients with attention-deficit/hyperactivity disorder (ADHD) and the relationship between ADHD symptoms and abnormalities in DAT availability. Methods: Single-photon emission tomography (SPECT) was performed using iodine-123-ß-carbomethoxy-3ß-(4-iodophenyltropane) (I-123 ß CIT) as a tracer to measure in vivo DAT availability in 20 drug-naive patients with ADHD [mean age ± standard deviation (SD)]: 25 ± 3.44 years; male:female = 11:9] and 20 age- and sex-matched healthy controls (HCs) (mean age ± SD: 23.9 ± 2.27 years). Comparisons of DAT availability between HCs and adult patients with ADHD and the association between symptom severity and DAT availability within the ADHD group were analyzed using Statistical Parametric Mapping 12. Results: Drug-naive adults with ADHD showed significantly reduced DAT availability in the bilateral nucleus accumbens compared with HCs. Correlation analyses revealed a negative correlation between the severity of inattentive symptoms in adult patients with ADHD and DAT availability in the bilateral heads of the caudate nucleus, indicating the association between severe inattentive symptoms and lower DAT availability in the caudate nucleus. Conclusion: In drug-naive adult patients with ADHD, DAT availability was reduced in the nucleus accumbens, an important part of the reward system. This finding indicates the importance of the DAT in the reward system in the pathogenesis of ADHD. Inattentiveness was associated with DAT availability in the caudate nucleus, suggesting involvement of the cortico-striato-thalamo-cortical circuit.

7.
J Acute Med ; 14(2): 90-93, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38855047

ABSTRACT

Fenitrothion is one of the most globally used organophosphorus pesticides, which can cause neurological symptoms, including involuntary movements. However, due to the limited number of case report, information on its treatment is also scarce. Here we presented a 74-year-old Japanese woman who was admitted to our hospital due to a persistent nausea and vomiting after ingesting 200 mL of 50% fenitrothion for a suicidal attempt. She received continuous intravenous infusion of atropine and 2-pyridine aldoxime methiodide under mechanical ventilation and continuous hemodiafiltration. However, she developed fasciculations of the face and right arm on day 11, which raised suspicions of delayed neuropathy associated with organophosphorus poisoning. To reduce the risk of respiratory depression, she received intravenous levetiracetam at a dosage of 1,000 mg/day. However, as her fasciculations persisted, the levetiracetam dosage was adjusted to 2,000 mg/day on day 14. On the following day, her fasciculations subsided. Neurologic symptoms of lipid-soluble organophosphorus poisoning, including fenitrothion, can sometimes delay following ingestion. Temporary administration of levetiracetam may prove effective in alleviating fasciculations.

8.
Ann Nucl Med ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902587

ABSTRACT

OBJECTIVE: Centiloid (CL) scales play an important role in semiquantitative analyses of amyloid-ß (Aß) PET. CLs are derived from the standardized uptake value ratio (SUVR), which needs Aß positron emission tomography (PET) normalization processing. There are two methods to collect the T1-weighted imaging (T1WI) for normalization: (i) anatomical standardization using simultaneously acquired T1WI (PET/MRI), usually adapted to PET images from PET/MRI scanners, and (ii) T1WI from a separate examination (PET + MRI), usually adapted to PET images from PET/CT scanners. This study aimed to elucidate the correlations and differences in CLs between when using the above two T1WI collection methods. METHODS: Among patients who underwent Aß PET/MRI (using 11C-Pittuberg compound B (11C-PiB) or 18F-flutemetamol (18F-FMM)) at our institution from 2015 to 2023, we selected 49 patients who also underwent other additional MRI examinations, including T1WI for anatomic standardization within 3 years. Thirty-one of them underwent 11C-PiB PET/MRI, and 18 participants underwent 18F-FMM PET/MRI. Twenty-five of them, additional MRI acquisition parameters were identical to simultaneous MRI during PET, and 24 participants were different. After normalization using PET/MRI or PET + MRI method each, SUVR was measured using the Global Alzheimer's Association Initiative Network cerebral cortical and striatum Volume of Interest templates (VOI) and whole cerebellum VOI. Subsequently, CLs were calculated using the previously established equations for each Aß PET tracer. RESULTS: Between PET/MRI and PET + MRI methods, CLs correlated linearly in 11C-PiB PET (y = 1.00x - 0.11, R2 = 0.999), 18F-FMM PET (y = 0.97x - 0.12, 0.997), identical additional MRI acquisition (y = 1.00x + 0.33, 0.999), different acquisition (y = 0.98x - 0.43, 0.997), and entire study group (y = 1.00x - 0.24, 0.999). Wilcoxon signed-rank test revealed no significant differences: 11C-PiB (p = 0.49), 18F-FMM (0.08), and whole PET (0.46). However, significant differences were identified in identical acquisition (p = 0.04) and different acquisition (p = 0.02). Bland-Altman analysis documented only a small bias between PET/MRI and PET + MRI in 11C-PiB PET, 18F-FMM PET, identical additional MRI acquisition, different acquisition, and whole PET (- 0.05, 0.67, - 0.30, 0.78, and 0.21, respectively). CONCLUSIONS: Anatomical standardizations using PET/MRI and using PET + MRI can lead to almost equivalent CL. The CL values obtained using PET/MRI or PET + MRI normalization methods are consistent and comparable in clinical studies.

9.
ACS Appl Mater Interfaces ; 16(24): 31788-31797, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38850559

ABSTRACT

This study explores the adhesive properties of copolymers comprising glycidyl methacrylate (GMA) and 3-(trimethoxysilyl)propyl methacrylate (MPTMS), focusing on their suitability for adhesive applications. Peel resistance measurements revealed a substantial impact of the GMA/MPTMS ratio on adhesion capabilities, identifying an optimal ratio of 30/70 for copolymerization with tert-butyl acrylate (tBA) to improve foaming performance. tBA, a foaming monomer activated by a photoacid generator and heat, enhances the copolymerized adhesive's adhesion strength and foamability for postuse delamination. Chemical structure analysis through Nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR) confirmed successful polymerization, while rheological properties indicated decreased complex viscosity and adhesive strength with an increasing tBA content. The deprotection of the t-butyl group facilitated foam formation, supported by morphology analysis. These findings provide insights into foamable adhesive development with potential applications in delamination processes and implications for further exploration in polymer adhesion.

10.
BMC Musculoskelet Disord ; 25(1): 430, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831297

ABSTRACT

BACKGROUND: Following spinal cord injury (SCI), gait function reaches a post-recovery plateau that depends on the paralysis severity. However, the plateau dynamics during the recovery period are not known. This study aimed to examine the gait function temporal dynamics after traumatic cervical SCI (CSCI) based on paralysis severity. METHODS: This retrospective cohort study included 122 patients with traumatic CSCI admitted to a single specialized facility within 2 weeks after injury. The Walking Index for Spinal Cord Injury II (WISCI II) was estimated at 2 weeks and 2, 4, 6, and 8 months postinjury for each American Spinal Injury Association Impairment Scale (AIS) grade, as determined 2 weeks postinjury. Statistical analysis was performed at 2 weeks to 2 months, 2-4 months, 4-6 months, and 6-8 months, and the time at which no significant difference was observed was considered the time at which the gait function reached a plateau. RESULTS: In the AIS grade A and B groups, no significant differences were observed at any time point, while in the AIS grade C group, the mean WISCI II values continued to significantly increase up to 6 months. In the AIS grade D group, the improvement in gait function was significant during the entire observation period. CONCLUSIONS: The plateau in gait function recovery was reached at 2 weeks postinjury in the AIS grade A and B groups and at 6 months in the AIS grade C group.


Subject(s)
Gait , Recovery of Function , Spinal Cord Injuries , Humans , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/complications , Male , Female , Retrospective Studies , Middle Aged , Adult , Gait/physiology , Time Factors , Cervical Vertebrae/physiopathology , Cervical Vertebrae/injuries , Aged , Cervical Cord/injuries , Cervical Cord/physiopathology , Young Adult
11.
Eur J Neurosci ; 59(12): 3151-3161, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38752321

ABSTRACT

Regarding the stage of arousal level required for working memory to function properly, limited studies have been conducted on changes in working memory performance when the arousal level of consciousness decreases. This study aimed to experimentally clarify the stages of consciousness necessary for optimal working memory function. In this experiment, the sedation levels were changed step-by-step using anaesthesia, and the performance accuracy during the execution of working memory was assessed using a dual-task paradigm. Participants were required to categorize and remember words in a specific target category. Categorization performance was measured across four different sedative phases: before anaesthesia (baseline), and deep, moderate and light stages of sedation. Short-delay recognition tasks were performed under these four sedative stages, followed by long-delay recognition tasks after participants recovered from sedation. The results of the short-delay recognition task showed that the performance was lowest at the deep stage. The performance of the moderate stage was lower than the baseline. In the long-delay recognition task, the performance under moderate sedation was lower than that under baseline and light sedation. In addition, the performance under light sedation was lower than that under baseline. These results suggest that task performance becomes difficult under half sedation and that transferring information to long-term memory is difficult even under one-quarter sedation.


Subject(s)
Arousal , Consciousness , Memory, Short-Term , Humans , Memory, Short-Term/physiology , Memory, Short-Term/drug effects , Male , Female , Consciousness/physiology , Consciousness/drug effects , Arousal/physiology , Young Adult , Adult , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/administration & dosage , Recognition, Psychology/physiology
12.
J Am Coll Cardiol ; 84(1): 27-40, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38819334

ABSTRACT

BACKGROUND: The glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. OBJECTIVES: This study sought to determine if semaglutide 2.4 mg reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with obesity-related HFpEF and compare treatment responses by baseline NT-proBNP. METHODS: This was a prespecified secondary analysis of pooled data from 2 double-blind, placebo-controlled, randomized trials (STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes]) testing effects of semaglutide in patients with obesity-related HFpEF. The main outcomes were change in NT-proBNP at 52 weeks and change in the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and body weight by baseline NT-proBNP. RESULTS: In total, 1,145 patients were randomized. Semaglutide compared with placebo reduced NT-proBNP at 52 weeks (estimated treatment ratio: 0.82; 95% CI: 0.74-0.91; P = 0.0002). Improvements in health status were more pronounced in those with higher vs lower baseline NT-proBNP (estimated difference: tertile 1: 4.5 points, 95% CI: 0.8-8.2; tertile 2: 6.2 points, 95% CI: 2.4-10.0; tertile 3: 11.9 points, 95% CI: 8.1-15.7; P interaction = 0.02; baseline NT-proBNP as a continuous variable: P interaction = 0.004). Reductions in body weight were consistent across baseline NT-proBNP levels (P interaction = 0.21). CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide reduced NT-proBNP. Participants with higher baseline NT-proBNP had a similar degree of weight loss but experienced larger reductions in HF-related symptoms and physical limitations with semaglutide than those with lower NT-proBNP.


Subject(s)
Glucagon-Like Peptides , Heart Failure , Natriuretic Peptide, Brain , Obesity , Peptide Fragments , Stroke Volume , Humans , Natriuretic Peptide, Brain/blood , Heart Failure/drug therapy , Heart Failure/blood , Heart Failure/physiopathology , Peptide Fragments/blood , Glucagon-Like Peptides/therapeutic use , Male , Female , Double-Blind Method , Aged , Obesity/blood , Obesity/complications , Obesity/drug therapy , Stroke Volume/drug effects , Stroke Volume/physiology , Middle Aged , Treatment Outcome
13.
Article in English | MEDLINE | ID: mdl-38693083

ABSTRACT

OBJECTIVE: The aim of the study is to reveal the respiratory displacement of the right adrenal vein (RAV) to predict the exact location of the RAV during adrenal venous sampling (AVS). METHODS: Computed tomography (CT) scans obtained 45 seconds (breath-hold at inhalation) and 70 seconds (breath-hold at exhalation) after contrast material injection were compared to venograms of the RAV of patients with primary aldosteronism who underwent AVS between January 2016 and December 2020. The craniocaudal distance between the center of the Th11/12 disc and the RAV orifice was measured; the craniocaudal location of the RAV orifice was also specified relative to vertebral bodies and intervertebral discs on inspiratory phase CT (In-CT), expiratory phase CT (Ex-CT), and catheter venography. The transverse and vertical angles of the RAV and the position of the RAV orifice on the inferior vena cava (IVC) circumference were measured on In-CT and Ex-CT. RESULTS: In total, 51 patients (30 males, 21 females; mean age, 54.9 ± 11.1 years) were included. Craniocaudal distances between the center of the Th11/12 disc and RAV orifice were significantly different among the following 3 acquisitions: catheter venography versus In-CT (15.2 ± 8.4 mm); venography versus Ex-CT (5.6 ± 4.1 mm); and In-CT versus Ex-CT (19.6 ± 8.0 mm) (all, P < 0.001). The craniocaudal location of the RAV orifice on venography was significantly closer to that on Ex-CT than on In-CT (P < 0.001); measurements using venograms compared with In-CT and Ex-CT scans were within 1 level difference in 18 (35.3%) and 47 (92.2%) patients, respectively (P < 0.001). The vertical angle of the RAV was significantly more likely to be smaller on In-CT than on Ex-CT (P < 0.001). CONCLUSIONS: RAV locations and angles change with respiratory motion. It is crucial to consider the respiratory phase of CT because it can enable a more accurate prediction of the location of the RAV during AVS.

14.
Jpn J Radiol ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38705937

ABSTRACT

OBJECTIVE: This study aimed to compare the occupational radiation exposure of medical workers between general hospitals and university hospitals. METHODS: Radiation exposure data from three hospitals in Hiroshima city, including one university hospital and two general hospitals, were collected using personal dosimeters. Monthly radiation doses were analyzed, and the annual sum of radiation exposure dose was calculated for 538 subjects in general hospitals and 1224 subjects in the university hospital. To assess the impact of locality, additional data from Nagasaki University Hospital and Fukushima Medical University Hospital were included for comparative analysis. Professional affiliations, such as doctors, nurses, and radiological technologists, were considered in the evaluation. RESULTS: The study revealed slight but significant differences in radiation doses between general and university hospitals. In general hospitals, except for radiological technologists, a slightly higher radiation dose was observed compared to university hospitals. Despite the annual increase in the use of medical radiation, the majority of hospital workers in both settings adhered to safety guidelines, with occupational radiation exposure remaining below the limit of detection (LOD). Workers who involved in fluoroscopic procedure, whether at university or general hospitals, had higher radiation doses than those who did not. CONCLUSION: The study's primary conclusion is that workers in general hospitals experience a slight but significantly higher radiation dose and a lower percentage below the LOD compared to university hospitals. The observed difference is attributed to the greater workload at general hospitals than at university hospitals, and also may be due to the different nature of university hospital and general hospital. University hospitals, characterized by greater academic orientation, tend to benefit from comprehensive support systems, specialized expertise, and advanced technology, leading to more structured and regulated radiation control. These findings provide a basis for targeted interventions, improved safety protocols.

16.
J Chromatogr A ; 1727: 465009, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38776605

ABSTRACT

Previous in vitro toxicological assessments have demonstrated that almost no mutagenic and genotoxic activities in electronic cigarette (e-cigarette) and heated tobacco product (HTP) aerosols were detected even at the maximum recommended concentration. To accurately compare the toxicity levels between cigarette smoke and e-cigarette or HTP aerosols, higher exposure concentrations increasing the possibility to detect toxicity in in vitro tests are necessary, while avoiding solvent-induced toxicity. This study aimed to develop a solvent-free extraction method to obtain concentrated aerosol extracts for improved toxicological evaluation. Our novel approach involved squeezing several Cambridge filter pads, which collected aerosol constituents, in closed containers to achieve solvent-free extraction with comparable efficiency to the conventional method using organic solvents. The optimized squeezing method yielded extracts with concentrations approximately 10 times higher than those obtained in conventional extraction methods. Yield comparison of various constituents, such as flavoring compounds, in e-cigarette aerosol extracts revealed similar extraction efficiencies between the squeezing and conventional methods. However, the extraction efficiency for constituents with high log Pow values, predominantly found in HTP aerosol extracts, was unacceptably low using the squeezing method. In addition, solvent-free centrifuging, another type of extraction method, exhibited unsatisfactory results for even e-cigarette aerosols compared with the conventional method. Our findings suggest that the solvent-free squeezing method is suitable for extracting aerosol collected mass from e-cigarette aerosol but not from HTP aerosol. We anticipate that the solvent-free squeezing method will contribute to a deeper understanding of toxicological differences between e-cigarettes and conventional combustible cigarettes.


Subject(s)
Aerosols , Electronic Nicotine Delivery Systems , Tobacco Products , Aerosols/analysis , Aerosols/chemistry , Tobacco Products/analysis , Hot Temperature , Solvents/chemistry , Chemical Fractionation/methods , Flavoring Agents/isolation & purification , Flavoring Agents/analysis , Gas Chromatography-Mass Spectrometry/methods
17.
PLoS One ; 19(5): e0303623, 2024.
Article in English | MEDLINE | ID: mdl-38805424

ABSTRACT

BACKGROUND: Pheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy, such as the combination of cyclophosphamide, vincristine, and dacarbazine or therapeutic radiopharmaceuticals such as [131I] meta-iodobenzylguanidine (MIBG), may be administered in cases of locally advanced tumors or distant metastases. However, the current therapies are limited in terms of efficacy and implementation. [211At] meta-astatobenzylguanidine (MABG) is an alpha-emitting radionuclide-labeled ligand that has demonstrated remarkable tumor-reducing effects in preclinical studies, and is expected to have a high therapeutic effect on pheochromocytoma cells. METHODS: We are currently conducting an investigator-initiated first-in-human clinical trial to evaluate the pharmacokinetics, safety, and efficacy of [211At] MABG. Patients with locally unresectable or metastatic PPGL refractory to standard therapy and scintigraphically positive [123I] MIBG aggregation are being recruited, and a 3 + 3 dose escalation design was adopted. The initial dose of [211At] MABG is 0.65 MBq/kg, with a dose escalation in a 1:2:4 ratio in each cohort. Dose-limiting toxicity is observed for 6 weeks after a single bolus dose of [211At] MABG, and the patients are observed for 3 months to explore safety and efficacy profiles. The primary endpoint is dose-limiting toxicity to determine both maximum tolerated and recommended doses. The secondary endpoints include radiopharmacokinetics, urinary radioactive excretion rate, urinary catecholamine response rate, objective response rate, progression free survival, [123I] MIBG scintigraphy on reducing tumor accumulation, and quality of life. TRIALS REGISTRATION: jRCT2021220012 registered on 17 June 2022.


Subject(s)
Adrenal Gland Neoplasms , Paraganglioma , Pheochromocytoma , Radiopharmaceuticals , Adult , Aged , Female , Humans , Male , Middle Aged , Adrenal Gland Neoplasms/drug therapy , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/pathology , Adrenal Gland Neoplasms/metabolism , Guanidines/pharmacokinetics , Guanidines/therapeutic use , Paraganglioma/drug therapy , Paraganglioma/pathology , Paraganglioma/diagnostic imaging , Paraganglioma/metabolism , Pheochromocytoma/drug therapy , Pheochromocytoma/diagnostic imaging , Pheochromocytoma/pathology , Pheochromocytoma/metabolism , Radiopharmaceuticals/pharmacokinetics , Treatment Outcome , Clinical Trials, Phase I as Topic
18.
Lancet ; 403(10437): 1635-1648, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38599221

ABSTRACT

BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.


Subject(s)
Glucagon-Like Peptides , Heart Failure , Obesity , Stroke Volume , Humans , Heart Failure/drug therapy , Glucagon-Like Peptides/therapeutic use , Glucagon-Like Peptides/administration & dosage , Male , Stroke Volume/drug effects , Female , Aged , Middle Aged , Double-Blind Method , Obesity/complications , Obesity/drug therapy , Treatment Outcome , Randomized Controlled Trials as Topic
19.
Nucl Med Commun ; 45(7): 573-580, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38618748

ABSTRACT

OBJECTIVE: We aimed to elucidate the factors underlying the difference between estimated glomerular filtration rate (eGFR) calculated from serum creatinine and Gate's GFR (gGFR) measured using technetium-99m diethylene triamine pentaacetic acid ( 99m Tc-DTPA) scintigraphy. METHODS: This study was based on consecutive patients who underwent 99m Tc-DTPA scintigraphy at our hospital between January 2021 and December 2022 and whose blood serum creatinine data were obtained on the same day as the 99m Tc-DTPA scintigraphy. Relationships between the ratio of gGFR and eGFR (gGFR/eGFR) and age, sex, BMI, visceral fat, psoas muscle index (PMI), serum blood urea nitrogen, and creatinine level were investigated based on 75 patients. Additionally, for 44 patients who had two or more follow-up DTPA studies, we compared gGFR values for studies that used iodine contrast media (ICM) for computed tomography before same-day 99m Tc-DTPA studies and those that did not in the same patients. RESULTS: Weak correlations were observed between gGFR/eGFR and PMI ( r  = 0.30), BMI ( r  = 0.24), and the visceral fat area ( r  = 0.33). Multi-regression analyses showed that gGFR/eGFR was correlated with PMI ( ß â€…= 0.34, P  < 0.01) and approached significance with the visceral fat area ( ß â€…= 0.24, P  = 0.05). A significant difference was observed in gGFR between patients who received ICM before the 99m Tc-DTPA renogram and those who did not ( P  < 0.001, eGFR 80.5 ±â€…19.0 vs. 91.7 ±â€…27.8 ml/min). CONCLUSION: ICM administration temporarily decreased gGFR, and increased muscle mass increased the difference between eGFR and gGFR values.


Subject(s)
Contrast Media , Creatinine , Gamma Cameras , Glomerular Filtration Rate , Iodine , Technetium Tc 99m Pentetate , Humans , Female , Male , Middle Aged , Creatinine/blood , Aged , Adult , Radionuclide Imaging , Aged, 80 and over , Retrospective Studies
20.
Radiol Case Rep ; 19(6): 2282-2285, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38559651

ABSTRACT

Coil migration can occur when coil embolization is used for treating pseudoaneurysms associated with large arteries. The double microcatheter technique is useful for preventing coil migration; the balloon catheter can reduce blood flow and active bleeding upon balloon inflation, and can also compress the bleeding point and arrest bleeding temporarily. We report a case describing the management of a pseudoaneurysm with coil embolization using double microcatheters and a balloon catheter to control blood flow and prevent coil migration. A 73-year-old male patient presented with a pseudoaneurysm of the celiac artery arising from the splenic artery stump following surgery. Coil embolization of the pseudoaneurysm using a double microcatheter embolization technique with a balloon catheter was considered. A balloon catheter was inserted into the celiac artery and active bleeding was temporarily arrested with the inflated balloon. First, a microcatheter was inserted into the balloon catheter, and another microcatheter was placed in the celiac artery. An electrical detachable coil was inserted into the proximal common hepatic artery just distal to the pseudoaneurysm. The second electrically detachable coil was inserted while the first coil remained attached. After detachment of the second coil, additional electrically detachable coils were inserted for similar embolization. The balloon was gradually deflated. Finally, the first coil was detached and we confirmed absence of the bleeding. Our case report demonstrated that a balloon catheter can control the flow vessels, and the double microcatheter embolization technique with a balloon catheter is useful for coil embolization in high-flow or large vessels.

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