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Introduction: Parenteral prostanoids are the most potent therapies for pulmonary arterial hypertension (PAH) but are associated with complications and lifestyle limitations. Carefully selected stable patients may be considered for a transition from parenteral prostanoids to a more convenient oral regimen. We present our experience transitioning patients on parenteral prostanoids to selexipag on an outpatient basis.

Methods: This was a retrospective cohort study of all group 1 PAH patients on parenteral prostanoids who transitioned to selexipag using a standardized outpatient-based protocol. Hospitalization and routine prognostic data were recorded.

Results: Fourteen patients were followed for a median of 1,240 (1,052-1,528) days; all were functional class (FC) II (n = 9) or III (n = 5). Thirteen patients completed the transition, including 11 who underwent catheterization 376 (321-735) days after discontinuing parenteral therapy. Three patients had unfavorable transitions requiring reinitiation of parenteral treatment. Overall, pulmonary vascular resistance increased (3.3-4.5 WU, p = 0.01), cardiac index fell (4.0-2.8 L/min/m², p = 0.01), N-terminal pro-hormone of brain natriuretic peptide worsened (111-205 pg/dL, p = 0.03), but PAH-related hospitalizations improved (27-8, p = 0.02). Cardiac imaging, FC, and 6-min walk distance (6MWD) were unchanged. Patients who failed were older (64 vs. 56 years old) with shorter 6MWD (274 vs. 392 m) and higher REVEAL 2.0 scores (11 vs. 3).

Conclusions: Transition from parenteral prostanoids to oral selexipag in carefully selected low-risk patients was well-tolerated in many patients, with up to 5 years of follow-up. Overall, the hemodynamic response to transition is unpredictable and close monitoring, particularly in the first year of follow-up, is recommended. Additional evaluation of potential predictors of success is necessary.

Basal cell adenocarcinoma (BCAC) is a rare malignant tumor of the salivary glands, representing 1-2% of salivary gland neoplasms. It is considered a low-grade tumor, often associated with a good prognosis. We report a case of a 60-year-old man with 3-month history of a growing, painless mass in the right ascending ramus of the mandible. Ultrasound and CT scan showed an asymmetry between parotid glands, depicting a nodular structure on the right side. A parotid fine needle aspiration cytology revealed neoplastic cells suggestive of adenoid cystic carcinoma. The patient underwent a total parotidectomy with lymph node dissection. Histopathology result was reported as BCAC. The patient concluded adjuvant radiotherapy and continued follow-up surveillance without evidence of relapse. The adjuvant approach in this case was decided by a multidisciplinary team given the absence of classically known risk factors. We highlight the importance of considering BCAC in the differential diagnosis in salivary gland tumors.

Although cardiovascular mortality in Japan is lower than in other industrialized countries, clinical outcomes in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM) remain poor despite multiple evidence-based drug therapies and interventions. We assumed that part of residual risk in these patients may be attributable to enhanced inflammation, which can be inhibited presumably by colchicine. However, dose-responsiveness of anti-inflammatory effect of colchicine has not been elucidated. Therefore, we designed a multicenter, randomized, double-blinded, parallel-group study to explore the dose-dependent effects of low-dose colchicine on serum high-sensitivity C-reactive protein (hs-CRP) concentration and safety in CAD patients with T2DM and enhanced inflammatory response as a phase 2 study. Enhanced inflammatory response was defined as peripheral white-blood cell count ≥7,000/μL. Patients (N = 63) will be randomly assigned to two doses of colchicine 0.25 mg/day, 0.5 mg/day, or placebo in a 1:1:1 ratio once daily for 12 weeks. Changes in serum hs-CRP levels will be evaluated as the primary endpoint, and changes in flow-mediated vasodilation and plasma myeloperoxidase levels will be evaluated as secondary endpoints. The results of this study will contribute to the development of a protocol for a planned future phase 3 trial to estimate the reduction in CAD. The present study describes the rationale, design, and methods of the trial.

Introduction: Multiple irrigation solutions are used in orthopedic surgeries although there are limited studies on their lasting effects on human tissues. The purpose of this work was to investigate the cytotoxic effects of the irrigation solutions Bacitracin, Clorpactin (sodium oxychlorosene), Irrisept (0.05% chlorhexidine gluconate), and Bactisure (ethanol 1%, acetic acid 0.6%, sodium acetate 0.2%, benzalkonium chloride 0.013%, and water) on 3D cultures of human fibroblasts.

Methods: Two independent experiments with 6 replicates were performed for the following conditions: Control (saline), bacitracin, Clorpactin, Irrisept, and Bactisure. Human fibroblast cell sheets were exposed to these solutions (1 or 2 min), followed by three washes with warm saline. Cell sheets were then cultured for additional 5- and 7-day posttreatment. Cell viability was measured using the alamarBlue (AB) assay. The more cytotoxic the irrigant, the lower the AB reduction.

Results: For 1-min exposure time, significant differences in AB reduction were noted in Clorpactin, Irrisept, and Bactisure groups compared to control at both 5 days (Clorpactin p = 0.0003, Irrisept p = 7.31 × 10^-15, Bactisure p = 6.86 × 10^-14) and 7 days posttreatment (all groups p < 0.0001). The results were similar in the 2-min exposure groups. Bacitracin-treated fibroblasts displayed no significant difference at all measurement times compared to control.

Discussion: Impacts of irrigation solution exposure on cell viability were varied. Irrisept and Bactisure showed the highest cell toxicity even after a brief exposure (1 min), while bacitracin and Clor-pactin exposure showed smaller impacts on cell viability as compared to saline controls. This in vitro study provided insight into the effects of the irrigants on human cells and provides the groundwork essential to move to in vivo studies. Our findings raised the concern that some irrigation solutions may have negative impacts on wound healing and healthy cellular response.

Introduction: Retinopathy of prematurity (ROP) is a multifactorial disease and a preventable cause of blindness in childhood. Hyperoxia and hypoxia can cause retinal neovascularization resulting in retinal detachment and blindness if left untreated. Besides oxygen treatment, other reasons for ROP development are well known. We prospectively adopt various strategies to keep oxygen saturation (SpO₂) within targets^, between 91 and 95% for those on supplemental oxygen. By adapting this, we postulated that the incidence of severe ROP might be reduced.

Methods: 2018-2019 provided pre-intervention and 2020 post-intervention data for the project. For all babies (≤32 weeks, ≤1,500 g with FiO₂ >0.21), target SpO₂ between 91 and 95% was measured as a percentage of time spent within and outside target SpO₂ during 1-4 weeks of life.

Results: 112 and 60 preterm neonates were screened for ROP during the pre- and post-intervention phase. Twenty neonates (18.3%) during pre-intervention and 16 (26.7%) in the post-intervention phase developed severe ROP requiring treatment. Despite a statistically significant increase of 10 percent points in time spent within target SpO₂ (91-95%) in the post-intervention phase (p < 0.05), the incidence of severe ROP did not decline. Using a multivariate model, odds of ROP development decreased with gestational age (25%) while increasing with PDA requiring treatment (4.33 times) and glucose ≥10 mg/dL (4.15 times), considering one variable at a time, keeping others constant.

Conclusion: Our QI project showed successful attainment of maximum time; the SpO₂ remained within targets during supplemental oxygen; however, the incidence of severe ROP had not declined. Factors other than SpO₂ might be responsible for a high incidence of ROP in our neonatal intensive care unit.

Purpose: The aim of this study was to investigate the effects of different anesthetic agents on electroretinograms (ERGs) in Spontaneously Diabetic Torii fatty rats (SDT fatty rats).

Methods: The ERG recordings were measured under general anesthesia using pentobarbital or a combination of medetomidine hydrochloride, midazolam, and butorphanol (MMB) tartrate anesthesia in 12 9-week-old normal Sprague-Dawley rats (Jcl:SD rats) and 16 SDT fatty rats. Each animal model was divided into 2 groups, the pentobarbital group and MMB group. The amplitudes and peak times of the a- and b-waves and oscillatory potentials (OPs) were measured from 0.0001 candela per square meter (cd.s/m²) to 10.0 cd.s/m².

Results: The amplitude of the a-wave was significantly higher in the MMB group of Jcl:SD rats, but there was no significant difference in amplitude between the two groups of SDT fatty rats. There was no significant difference in the OP1 amplitude between both groups of Jcl:SD rats, but the OP1 amplitude was significantly higher in the MMB group of SDT fatty rats. The OP2 amplitude was significantly higher in the pentobarbital group in both the Jcl:SD rats and SDT fatty rats. There was no significant difference in the OP3 amplitude between the Jcl:SD and SDT fatty rat groups. The amplitude of the OP4 waves was significantly higher in the MMB group for both Jcl:SD and SDT fatty rats. There was no significant difference in the sums of the OP1 to OP4 (ΣOPs) amplitudes between the Jcl:SD and SDT fatty rat groups. There was no significant difference in the b-wave amplitude between the Jcl:SD rat groups, but the b-wave amplitude was significantly higher in the SDT fatty rats that received pentobarbital. The peak times for a-wave, OP1, OP2, OP3, OP4, and ΣOPs were significantly longer in the pentobarbital group of SD rats. The peak time of the b-wave was significantly longer in the MMB group of Jcl:SD rats, but the same result was obtained in the SDT fatty rats except that there was no significant difference in the a-wave.

Conclusion: The overall ERG results vary depending on the anesthetic agent used. The OPs can be observed in detail when using MMB. Since the SDT fatty rat is a diabetic model animal, we recommend MMB as the anesthesia of choice when studying the OP waves in detail.

Introduction: This study aimed to describe the quantitative features of the microvasculature in the cystic lesions of branch retinal vein occlusion (BRVO).

Methods: A total of 43 eyes with BRVO, treated with anti-vascular endothelial growth factor therapy, were analyzed. Using wide-field swept-source optical coherence tomography angiography (OCTA), en face OCT images were obtained by depth-integrated reflectivity of the retina, and vascular density (VD), vascular length (VL), vascular lacunarity, and fractal dimension (FD) were evaluated in a 12 × 12-mm area of retinal nonperfusion.

Results: The mean area of affected lesions was 38.7 ± 19.8 mm², and cystic lesions were 8.5 ± 10.1 mm². VD, VL, and FD were significantly decreased in the cystic lesions compared to other affected lesions in the same eyes (p = 0.0010, p = 0.0001, and p = 0.0003, respectively) and in all eyes (p = 0.0281, p = 0.0050, and p < 0.0001, respectively). VD in cystic lesions within the vascular arcade (25 eyes) correlated with best-corrected visual acuity on OCTA (r = -0.433, and p = 0.0492).

Conclusions: Vascular structure in the cystic lesions was unpreserved compared to the other lesions in BRVO. These findings may help in understanding the pathophysiology of retinal edema in BRVO.

Background: Endophthalmitis is an infection of ocular tissues, often with devastating outcomes for vision. Immunomodulation is an emerging avenue for therapeutic intervention in endophthalmitis, with the expression of cytokines central to potential mechanisms. This literature review with a systematic approach characterizes the cytokine expression in both animal and human staphylococcal and streptococcal endophthalmitis.

Method and results: Four online databases were searched for studies profiling cytokine levels in animal models or human populations with staphylococcal and/or streptococcal endophthalmitis. Of the 1,060 articles identified, 14 studies were included in this review comprising eight animal models and six human populations. Mouse, rat, and rabbit models of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae endophthalmitis had elevated levels of IL-1β, IL-6, IFN-γ, TNF-α, and IL-8, with earlier peaks observed in S. epidermidis infection. Human endophthalmitis demonstrated significantly increased mediator levels compared to controls for a range of pro-inflammatory and anti-inflammatory cytokines, chemokines, and growth factors. Several associations were established between cytokine concentrations and both initial visual acuity and visual prognosis, with no consistent correlations across trials.

Conclusions: It may be that virulence factors and the combinations of toll-like receptors activated influence the pathogen-specific visual outcomes observed in endophthalmitis. Furthermore, disease severity and potential therapeutic targets may be dependent on synergistic and compensatory cytokine pathways and the expression of anti-inflammatory mediators. Future research should aim to better characterize the roles of inflammatory mediators and solidify associations between pathogens, inflammation, and endophthalmitis outcomes. This has exciting implications for the prevention and treatment of endophthalmitis in clinical settings.

Objectives: The study aimed to evaluate the impact of antenatal exposure of magnesium sulfate (MgSO₄) on short- and long-term outcomes in preterm neonates born less than 32 weeks gestation.

Methods: Single-center retrospective cohort study of 229 neonates born between 24 and 32 weeks gestation was conducted from January 2018 through December 2018 in a level III neonatal care unit in Kuwait. Antenatal MgSO₄ exposure was collected from the medical records, and the indication was for neuroprotection effect. Brain MRI was done on 212 neonates (median gestational age 36 weeks), and brain injury was assessed using the Miller's score. Neurodevelopmental outcome was assessed by Bayley-III scales of infant development at 36 months corrected age (N = 146). The association of exposure to MgSO4 with brain injury and neurodevelopmental outcomes was examined using multivariable regression analysis adjusting for gestational age at MRI and variables with p value <0.05 on univariate analysis.

Results: Among the 229 neonates, 47 received antenatal MgSO₄. There were no differences between the groups in gestational age and birth weight. MgSO₄ exposure was not associated with an increased risk of necrotizing enterocolitis, chronic lung disease, retinopathy of prematurity, and mortality. The incidence of cerebellar hemorrhage was significantly less in the MgSO₄ group (0% vs. 16%, p value = 0.002). Neonates who received MgSO₄ had lower risks of grade 3-4 intraventricular hemorrhage (IVH) adjusted OR 0.248 (95% CI: 0.092, 0.66), p = 0.006; moderate-severe white matter injury (WMI) adjusted odd ratio 0.208 (95% CI: 0.044, 0.96), p = 0.046; and grade 3-4 IVH and/or moderate-severe WMI adjusted OR 0.23 (95% CI: 0.06, 0.84), p = 0.027. Neurodevelopmental assessment at 36 months corrected age showed better motor (adjusted beta coefficient 1.08 [95% CI: 0.099, 2.06]; p = 0.031) and cognitive composite scores (adjusted beta coefficient 1.29 [95% CI: 0.36, 2.22]; p = 0.007) in the MgSO₄ group.

Conclusion: Antenatal exposure to MgSO₄ in preterm neonates less than 32 weeks was independently associated with lower risks of brain injury and better motor and cognitive outcomes.

Background: Comparative studies among the various cardiovascular medications used for the treatment of neonatal hypotension are lacking.

Methods: This systematic review and pairwise meta-analysis of the anti-hypotensive treatments in preterm and term infants was conducted to evaluate efficacy and impact on outcome. Electronic databases were searched up to February 2021 for relevant articles. As an extension of the current approach for study selection, a machine learning technique was used. Only randomized controlled trials (RCTs) of inotropes, pressors, volume therapy, and corticosteroids were included. Response to treatment was the primary outcome while secondary outcomes included mortality and common morbidities.

Results: Nineteen RCTs involving 758 preterm and term neonates were found, and 8 treatments were evaluated. Most studies involved subjects with early hypotension associated with prematurity. Pairwise meta-analysis among treatments showed that dopamine was more effective than dobutamine regarding the response to treatment (restoration of normotension or normalization of blood pressure) (7 trials, 286 neonates, odds ratio, 3.06 [95% CI = 1.06-8.87]; I² = 49%, very low quality of the evidence per GRADE). Comparisons of other treatments were not significant. No differences were found among regimens regarding survival and other secondary outcomes.

Conclusion: In this systematic review and pairwise meta-analysis, only the comparison of dopamine versus dobutamine provided evidence for efficacy of treatment and favored dopamine. No safe conclusions could be reached in regard to other treatments. Data regarding the management of arterial hypotension in conditions other than transition after birth in preterm newborns are sparse both in preterm and term infants.