-
Drug Design, Development and Therapy 2024The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy.
METHODS
Seventy-five patients aged ≥65 years and American Society of Anesthesiologists (ASA) class I-III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F, group F, and group F, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F, 0.2 mg/kg in group F, 0.15 mg/kg in group F. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate.
RESULTS
The ED50 of remimazolam tosilate in group F was lower than that in group F and F (0.095 [0.088-0.108] mg/kg vs 0.162 [0.153-0.171] mg/kg; 0.258 [0.249-0.266] mg/kg, < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264-0.295 mg/kg) in group F, 0.175 mg/kg (95% CI: 0.167-0.200 mg/kg) in group F and 0.109 mg/kg (95% CI: 0.101-0.135 mg/kg) in group F. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl ( < 0.001). The frequency of injection pain was higher in group F compared to groups F and F ( < 0.05). The patients in group F had a lower incidence of hypotension than in groups F and F ( < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups.
CONCLUSION
The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.
Topics: Humans; Aged; Benzodiazepines; Male; Female; Fentanyl; Gastroscopy; Dose-Response Relationship, Drug; Aged, 80 and over
PubMed: 38915865
DOI: 10.2147/DDDT.S462607 -
Frontiers in Cardiovascular Medicine 2024Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be...
BACKGROUND
Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed. This study aims to generate knowledge on pathogenesis and assess outcomes in cancer centers with intensified patient management.
METHODS
Patients with cardiac irAEs from the SERIO registry (www.serio-registry.org) were analyzed for demographics, ICI-related information (type of ICI, therapy line, combination with other drugs, onset of irAE, and tumor response), examination results, irAE treatment and outcome, as well as oncological endpoints. Cardiac biopsies of irMyocarditis cases ( = 12) were analyzed by Nanostring and compared to healthy heart muscle ( = 5) and longitudinal blood sampling was performed for immunophenotyping of irMyocarditis-patients ( = 4 baseline and = 8 during irAE) in comparison to patients without toxicity under ICI-therapy ( = 4 baseline and = 7 during ICI-therapy) using flow cytometry.
RESULTS
A total of 51 patients with 53 cardiac irAEs induced by 4 different ICIs (anti-PD1, anti-PD-L1, anti-CTLA4) were included from 12 centers in 3 countries. Altogether, 83.0% of cardiac irAEs were graded as severe or life-threatening, and 11.3% were fatal (6/53). Thus, in centers with established consequent troponin monitoring, work-up upon the rise in troponin and consequent treatment of irMyocarditis with corticosteroids and -if required-second-line therapy mortality rate is much lower than previously reported. The median time to irMyocarditis was 36 days (range 4-1,074 days) after ICI initiation, whereas other cardiotoxicities, e.g. asystolia or myocardiopathy, occurred much later. The cytokine-mediated signaling pathway was differentially regulated in myocardial biopsies as compared to healthy heart based on enrichment Gene Ontology analysis. Additionally, longitudinal peripheral blood mononuclear cell (PBMC) samples from irMyocarditis-patients indicated ICI-driven enhanced CD4+ Treg cells and reduced CD4+ T cells. Immunophenotypes, particularly effector memory T cells of irMyocarditis-patients differed from those of ICI-treated patients without side effects. LAG3 expression on T cells and PD-L1 expression on dendritic cells could serve as predictive indicators for the development of irMyocarditis.
CONCLUSION
Interestingly, our cohort shows a very low mortality rate of irMyocarditis-patients. Our data indicate so far unknown local and systemic immunological patterns in cardiotoxicity.
PubMed: 38915743
DOI: 10.3389/fcvm.2024.1408586 -
Aerospace Medicine and Human Performance Jul 2024The original Spacecraft Maximal Allowable Concentrations (SMACs) for toluene (set for 1 h, 24 h, 7 d, 30 d, and 180 d) were first established by NASA in 1996 based...
The original Spacecraft Maximal Allowable Concentrations (SMACs) for toluene (set for 1 h, 24 h, 7 d, 30 d, and 180 d) were first established by NASA in 1996 based on a human study in which no irritation or neurotoxicity was reported following 6-h exposure to 40 ppm toluene vapors. While the toluene SMACs were updated in 2008 to account for auditory, visual, and hormonal effects (for 7 d, 30 d, and 180 d) and to include a long-term SMAC (1000 d) in anticipation of longer spaceflight exploration missions, the short-term SMAC limits (1 h and 24 h) remained unchanged. Acute toluene exposure is reported to result in ocular and nasal irritation, although it is not a primary irritant, as well as central nervous system effects including headaches and dizziness. Long-term exposure to toluene can elicit hepatotoxicity, nephrotoxicity, neurotoxicity, and endocrine toxicity. Since publication of the original and revised toluene SMACs, the National Academy of Sciences developed interim Acute Exposure Guideline Limits reviewed by the National Research Council Committee. Based on these data, we have increased the limits for toluene in crewed spacecraft to 40 ppm for 1 h, 24 h, 7 d, and 30 d. SMACs for durations of 180 and 1000 d will remain unchanged.changed.
Topics: Humans; Toluene; Spacecraft; Occupational Exposure; Space Flight; Maximum Allowable Concentration; Aerospace Medicine; United States; Solvents
PubMed: 38915164
DOI: 10.3357/AMHP.6382.2024 -
Nature Medicine Jun 2024Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be...
Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. The primary endpoint was least square mean change in MADRS for each active treatment compared with placebo at 13 weeks, starting with the 180 mg dose, using a fixed sequence step-down closed test procedure. Between May 2019 and August 2021, 329 individuals were screened for eligibility, 231 entered the open-label enrichment phase (days 1-8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was -6.1 (95% confidence interval 1.0 to 11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. The most common adverse events were headache, dizziness and anxiety. During the randomized phase of the study, most patient dosing occurred at home. R-107 tablets were effective, safe and well tolerated in a patient population with TRD, enriched for initial response to R-107 tablets. ClinicalTrials.gov registration: ACTRN12618001042235 .
PubMed: 38914860
DOI: 10.1038/s41591-024-03063-x -
Laryngo- Rhino- Otologie Jun 2024
PubMed: 38914098
DOI: 10.1055/a-2318-6877 -
Updates in Surgery Jun 2024This study aims to explore the safety and efficacy of 3D laparoscopy in elderly patients undergoing transabdominal preperitoneal (TAPP) surgery for inguinal hernia....
This study aims to explore the safety and efficacy of 3D laparoscopy in elderly patients undergoing transabdominal preperitoneal (TAPP) surgery for inguinal hernia. Patients were divided into two groups based on the laparoscopic equipment used during surgery. Clinical data preoperatively, intraoperatively, and postoperatively were collected and subjected to statistical analysis. From January 2020 to August 2023, a total of 127 patients with primary unilateral inguinal hernia were evaluated in this study, 61 in the 3D TAPP group and 66 in the 2D TAPP group. There were no statistically significant differences in baseline data, including average age, gender distribution, BMI index, hernia type, hernia defect size and location, comorbidities, and usage of anticoagulant drugs between the two groups (P > 0.05). In terms of operative indicators, the 3D group showed shorter mean operation time (51.61 ± 7.16 min vs. 78.59 ± 13.51 min, P < 0.001), mean mesh placement time (6.07 ± 1.40 min vs. 9.77 ± 1.21 min, P < 0.001), and mean peritoneal suture time (7.34 ± 1.85 min vs. 9.73 ± 1.32 min, P < 0.001) compared to the 2D group. However, there were no statistically significant differences in mean blood loss, postoperative pain scores, postoperative hospital stay, and total hospital costs between the two groups (P > 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P > 0.05). No adverse reactions such as dizziness or nausea were reported by surgeons during the procedures in either group. Three-dimensional laparoscopy in TAPP surgery provides high-definition, three-dimensional surgical images, reducing the difficulty of operations and effectively shortening the operation time.
PubMed: 38913298
DOI: 10.1007/s13304-024-01923-2 -
Mayo Clinic Proceedings Jun 2024
PubMed: 38912989
DOI: 10.1016/j.mayocp.2023.10.020 -
Journal of Neurologic Physical Therapy... Jun 2024Functional recovery after stroke is often limited, despite various treatment methods such as robot-assisted therapy. Repetitive sensory stimulation (RSS) might be a...
BACKGROUND AND PURPOSE
Functional recovery after stroke is often limited, despite various treatment methods such as robot-assisted therapy. Repetitive sensory stimulation (RSS) might be a promising add-on therapy that is thought to directly drive plasticity processes. First positive effects on sensorimotor function have been shown. However, clinical studies are scarce, and the effect of RSS combined with robot-assisted training has not been evaluated yet. Therefore, our objective was to investigate the feasibility and sensorimotor effects of RSS (compared to a control group receiving sham stimulation) followed by robot-assisted arm therapy.
METHODS
Forty participants in the subacute phase (4.4-23.9 weeks) after stroke with a moderate to severe arm paresis were randomized to RSS or control group. Participants received 12 sessions of (sham-) stimulation within 3 weeks. Stimulation of the fingertips and the robot-assisted therapy were each applied in 45-min sessions. Motor and sensory outcome assessments (e.g. Fugl-Meyer-Assessment, grip strength) were measured at baseline, post intervention and at a 3-week follow-up.
RESULTS
Participants in both groups improved their sensorimotor function from baseline to post and follow-up measurements, as illustrated by most motor and sensory outcome assessments. However, no significant group effects were found for any measures at any time (P > 0.058). Stimulations were well accepted, no safety issues arose.
DISCUSSION AND CONCLUSIONS
Feasibility of robot-assisted therapy with preceding RSS in persons with moderate to severe paresis was demonstrated. However, RSS preceding robot-assisted training failed to show a preliminary effect compared to the control intervention. Participants might have been too severely affected to identify changes driven by the RSS, or these might have been diluted or more difficult to identify because of the additional robotic training and neurorehabilitation.
VIDEO ABSTRACT AVAILABLE
for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A478).
PubMed: 38912852
DOI: 10.1097/NPT.0000000000000486 -
The Indian Journal of Radiology &... Jul 2024Both computed tomography (CT) and magnetic resonance imaging (MRI) play significant roles in assessing patients with dizziness. However, understanding the... (Review)
Review
Comparative Diagnostic Accuracy of Computed Tomography Scan versus Magnetic Resonance Imaging in the Emergency Department for the Evaluation of Dizziness: A Systematic Review.
Both computed tomography (CT) and magnetic resonance imaging (MRI) play significant roles in assessing patients with dizziness. However, understanding the comparative capabilities of these imaging methods in detecting pathological causes is crucial for determining the most suitable modality. This review aims to evaluate the diagnostic accuracy and clinical utility of MRI and CT scans in managing patients with acute dizziness in the emergency department. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search in various databases (PubMed, Google Scholar, Cochrane library, British Medical Journals, and ScienceDirect) from 2010 to 2023. We used the QUADAS-2 tool to assess bias risk, considering MRI as the reference standard and CT scan as the index test. The final analysis included six studies, with 3,993 patients (48% male, 52% female; average age: 56.7 years). Three studies were of high quality, two of medium quality, and one of low quality. Central ischemia was the predominant diagnosis for dizziness. MRI demonstrated higher diagnostic efficacy for stroke compared with CT scans, while mixed results were observed for other multiple diseases when both MRI and CT scans were used. MRI outperforms CT scans in diagnosing dizziness-related strokes. However, for other causes of dizziness, there is no significant difference between these techniques. Nevertheless, it is crucial to acknowledge the limitations associated with MRI. Consequently, to address these concerns, the selection of an imaging technique should be tailored to the individual based on factors such as their clinical presentation, comorbidities, and socioeconomic circumstances.
PubMed: 38912244
DOI: 10.1055/s-0044-1778726 -
ENeurologicalSci Jun 2024Intractable hiccups, persisting beyond 48 h, pose a clinical challenge, particularly in demyelinating diseases like Neuromyelitis Optica (NMO) and Multiple Sclerosis...
BACKGROUND
Intractable hiccups, persisting beyond 48 h, pose a clinical challenge, particularly in demyelinating diseases like Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS). Understanding the complex neural pathways of the hiccup reflex and the impact of high-dose steroid therapy is crucial for managing this rare but distressing symptom. The hiccup reflex involves afferents from the vagus, phrenic, and sympathetic nerves, with the reflex center in the anterior horns at the C3 to 5 level and the medulla oblongata. The potential interplay between demyelination and corticosteroid therapy in triggering persistent hiccups requires exploration.
CASE REPORT
This case report details a 21-year-old male with undiagnosed demyelinating disorder, presenting persistent hiccups following high-dose steroid therapy for an acute disease flare. The patient's history included vertigo and progressive neurological symptoms, leading to an MS diagnosis with significant brain and spinal lesions. Persistent hiccups, initiated by steroid administration, were recurrent but responsive to metoclopramide after other measures failed.
DISCUSSION
The discussion centers on investigating the cause of hiccups in a patient with demyelination following steroid administration. Steroids' impact on neurological systems, including neurotransmitter function, and the potential disruption of neurological pathways due to demyelination may contribute to hiccups. Successful hiccup resolution with metoclopramide suggests a potential pharmacological approach for corticosteroid-induced hiccups in demyelinating diseases. This case emphasizes the need for further research into the intricate relationship between demyelination, steroid therapy, and hiccups to enhance management strategies for this uncommon yet impactful symptom.
PubMed: 38911508
DOI: 10.1016/j.ensci.2024.100509