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Multifunctional Phase-Transition Nanoparticles for Effective Targeted Sonodynamic-Gene Therapy Against Thyroid Papillary Carcinoma

Int J Nanomedicine. 2023 May 2;18:2275-2293. doi: 10.2147/IJN.S394504. eCollection 2023.

ABSTRACT

INTRODUCTION: In order to diagnose and treat papillary thyroid carcinoma (PTC) accurately, phase-transition nanoparticles, P@IP-miRNA (PFP@IR780/PLGA-bPEI-miRNA338-3p), was engineered. The nanoparticles (NPs) can target the tumor cells, realize the multimodal imaging, and provide sonodynamic-gene therapy for PTC.

METHODS: P@IP-miRNA NPs were synthesized through double emulsification method, and miRNA338-3p was attached to the surface of the NPs by electrostatic adsorption. The characterization of NPs was detected to screen out qualified nanoparticles. In vitro, laser confocal microscopy and flow cytometry were used to detect the targeting and subcellular localization of NPs. Western blot, qRT-PCR, and immunofluorescence were used to detect the ability to transfect miRNA. CCK8 kit, laser confocal microscopy and flow cytometry were used to detect the inhibition on TPC-1 cells. In vivo experiments were performed based on tumor-bearing nude mice. The efficacy of combined treatment by NPs was comprehensively evaluated, and the multimodal imaging ability of NPs in vivo and in vitro was detected.

RESULTS: P@IP-miRNA NPs were successfully synthesized which have spherical shape, uniform size, good dispersion and positive potential. The encapsulation rate of IR780 was (82.58±3.92) %, the drug loading rate was (6.60±0.32) %, and the adsorption capacity of miRNA338-3p was 41.78 μg/mg. NPs have excellent tumor targeting ability, miRNA transfection ability, ROS production ability and multimodal imaging ability in vivo and in vitro. The antitumor effect of combined treatment group was the best, and the efficacy was better than that of single factor treatment group, and the difference was statistically significant.

CONCLUSION: P@IP-miRNA NPs can realize multimodal imaging and sonodynamic-gene therapy, providing a new idea for accurate diagnosis and treatment of PTC.

PMID:37159806 | PMC:PMC10163883 | DOI:10.2147/IJN.S394504

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MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis

Pharmgenomics Pers Med. 2023 May 2;16:407-423. doi: 10.2147/PGPM.S404949. eCollection 2023.

ABSTRACT

PURPOSE: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms.

PATIENTS AND METHODS: In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy.

RESULTS: The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups.

CONCLUSION: Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.

PMID:37159804 | PMC:PMC10163902 | DOI:10.2147/PGPM.S404949

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Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry

Pulm Circ. 2023 Apr 1;13(2):e12233. doi: 10.1002/pul2.12233. eCollection 2023 Apr.

ABSTRACT

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR’s inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publicly-sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness.

PMID:37159803 | PMC:PMC10163321 | DOI:10.1002/pul2.12233

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Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019

Clin Epidemiol. 2023 May 2;15:535-546. doi: 10.2147/CLEP.S406361. eCollection 2023.

ABSTRACT

PURPOSE: This study aimed to investigate Graves’ disease (GD) associated cancer and mortality risk using a Korean population-based study.

PATIENTS AND METHODS: We included 6435 patients with GD using the Korean National Health Insurance Service-National Sample Cohort database from 2010 to 2019. Data concerning such patients were compared in a 1:5 ratio with age- and sex-matched non-GD group (n=32,175). Eighteen subdivided types of cancer and cancers-in-total were analyzed. In addition to the mortality analysis, subgroup analyses were performed according to age and sex.

RESULTS: After adjustment, the hazard ratio (HR) of the GD group for cancer-in-total was 1.07 (95% confidence interval [CI], 0.91-1.27), showing no difference when compared to the non-GD group. However, among different types of cancer, the thyroid cancer risk of the GD group was higher than that of the non-GD group (HR=1.70; 95% CI, 1.20-2.39). When subdivided by age and sex, the thyroid cancer risk of the GD group in males aged 20-39 years was higher than that of the non-GD group (HR=7.00; 95% CI, 1.48-33.12). The mortality risk of the GD group was not different from that of the non-GD group (HR=0.86; 95% CI, 0.70-1.05).

CONCLUSION: In South Korea, patients with GD had a higher risk of thyroid cancer than the non-GD group. In particular, males aged 20-39 years with GD were more likely to have thyroid cancer than the non-GD group.

PMID:37159800 | PMC:PMC10163882 | DOI:10.2147/CLEP.S406361

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Clinical Application of Proximal Arch Cannulation in the Surgical Treatment of Acute Type I Aortic Dissection

Cureus. 2023 Apr 6;15(4):e37214. doi: 10.7759/cureus.37214. eCollection 2023 Apr.

ABSTRACT

Objective The goal is to determine the best location for inserting a catheter into the aortic arch of patients with a certain type of aortic dissection (DeBakey type I) by analyzing images of the patient’s aortic arch before surgery. This analysis will take into account the shape and structure of the patient’s aortic arch to find the most optimal location for cannulation. Methods A retrospective analysis was conducted on 100 patients with acute DeBakey type I aortic dissection diagnosed between January 2021 and February 2023, utilizing the Carestream medical imaging software Image Suite V4 (New York, USA). The study included 67 cases that underwent surgery and 33 cases that did not. The study aimed to evaluate the optimal intubation position on the patient’s aortic arch by analyzing the true and false lumen classification, true and false lumen area, and hematoma thickness on the patient’s aortic arch, as observed in the aortic computed tomography angiography (CTA) conducted upon admission. Results The vascular axis analysis showed a significant difference in the true lumen area among the three regions that were examined (P < 0.001). Zone 1 had a larger true lumen area of 6.40 ± 2.71 cm2 compared to zone 2 with 5.75 ± 2.13 cm2 and zone 3 with 4.85 ± 1.70 cm2, as determined by statistical analysis. In addition, the statistical analysis of hematoma thickness in the three regions where cannulation can be performed revealed a significant difference among the three groups (P = 0.027). Further analysis showed that there was no significant difference between zone 1 and zone 2 (P = 1.000), a significant difference between zone 1 and zone 3 (P < 0.046), and no significant difference between zone 2 and zone 3 (P = 0.080). The difference between zone 1 false lumen thickness of 1.55 ± 0.51 cm and zone 3 false lumen thickness of 1.33 ± 0.55 cm was found to be small. Conclusion Cannulation of the aortic arch is a common strategy used in cardiac surgery. Accurate cannulation is critical to the success of the procedure. The use of CTA provides valuable guidance for the cannulation procedure. A thorough examination of CTA and precise measurement of relevant parameters can help guide the surgeon to determine the optimal cannulation site. The study found that zone 1 of the aortic arch has the largest area and is the most suitable for cannulation, in accordance with the physiological characteristics and surgical practices of a surgeon. Furthermore, cannulation of the aortic arch has been found to be a safe and effective strategy for cannulation. Overall, careful examination of CTA and accurate measurement of relevant parameters can have a significant guiding effect on the cannulation of the aortic arch, which can lead to improved outcomes in cardiac surgery.

PMID:37159794 | PMC:PMC10163934 | DOI:10.7759/cureus.37214

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Effects of Flapless Laser Corticotomy in Upper and Lower Canine Retraction: A Split-mouth, Randomized Controlled Trial

Cureus. 2023 Apr 6;15(4):e37191. doi: 10.7759/cureus.37191. eCollection 2023 Apr.

ABSTRACT

Aim One of the major difficulties in orthodontic treatment is the lengthy course of therapy, particularly in situations involving extractions. Hence, various methods for accelerating tooth movement rate had been devised. Flapless corticotomy is one of those methods. This study aimed to evaluate the effects of flapless laser corticotomy (FLC) compared to the conventional retraction (CR) method on the rate of canine retraction. Methods A split-mouth, randomized controlled trial included 56 canines from 14 patients (12 females and two males) with a mean age of 20.4 ± 2.5 years, who were complaining of bimaxillary protrusion requiring extraction of four premolars. All canines were randomly assigned to four groups (maxillary FLC, maxillary control CR, mandibular FLC, and mandibular control CR). Randomization was performed by creating two equal, random computer-generated lists with a 1:1 allocation ratio-one list for the right side and one for the left. The allocation concealment was achieved using opaque sealed envelopes until the time of intervention. FLC was applied on the experimental sides before canine retraction by drilling six holes penetrating 3 mm into the bone on the mesial and distal sides of the canines. Subsequently, all canines were retracted employing closed coil springs to deliver a force of 150 g using indirect anchorage from temporary anchorage devices (TADs). All canines were assessed at T0 (before retraction), T1 (one month after retraction), T2 (two months), and T3 (three months) using three-dimensional (3D) digital models. Additionally, canine rotation, molar anchorage loss assessed using 3D digital models, root resorption assessed using cone beam computed tomography (CBCT), probing depth, plaque, gingival indices, and pulp vitality were all evaluated as secondary outcomes. It was possible to blind only the outcome analysis expert (single-blinded). Results The measurements of canine retraction during the follow-up period from T0 to T3 were 2.46 ± 0.80 mm and 2.55 ± 0.79 mm in maxillary FLC and control groups, respectively, and 2.44 ± 0.96 mm and 2.31 ± 0.95 mm in mandibular FLC and control groups, respectively. The results demonstrated a statistically non-significant difference in the distance of canine retraction between the FLC and control groups at all time points. Moreover, no differences were observed between groups in canine rotation, molar anchorage loss, root resorption, probing depth, plaque, gingival indices, and pulp vitality (p > 0.05). Conclusion In the FLC procedure performed in this study, the rate of upper and lower canine retraction could not be accelerated and no significant differences were observed between FLC and control groups in canine rotation, molar anchorage loss, root resorption, periodontal condition, and pulp vitality.

PMID:37159786 | PMC:PMC10163364 | DOI:10.7759/cureus.37191

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Risk of Neonatal Sepsis With Rescue Steroids in Preterm Premature Rupture of Membranes

Cureus. 2023 Apr 6;15(4):e37207. doi: 10.7759/cureus.37207. eCollection 2023 Apr.

ABSTRACT

Objective To evaluate whether a rescue course of corticosteroids, when given at least 14 days after the initial course, is associated with an increased risk of neonatal sepsis after preterm premature rupture of membranes (PPROM). Methods We performed a retrospective, descriptive cohort study of women with singleton gestations from 23+0 to 34+0 weeks of gestation who received a rescue course of corticosteroids within the Indiana University Health Network from January 2009 through October 2016. Patients were separated into three groups based on amniotic membrane status at the time of each corticosteroid administration: Group 1 (intact membranes at initial/intact membranes at rescue), Group 2 (intact membranes at initial/PPROM at rescue), and Group 3 (PPROM at initial/PPROM at rescue). The primary outcome (neonatal sepsis) was compared between the groups. Patient characteristics and neonatal outcomes were analyzed with Fisher’s exact test for categorical variables and ANOVA for continuous variables. Relative risk (RR) was calculated by comparing those with ruptured membranes to those with intact membranes at the time of rescue course administration. Results A total of 143 patients were eligible. Neonatal sepsis occurred in 6.8% of patients in Group 1, 21.1% of patients in Group 2, and 23.8% of patients in Group 3. Groups 2 and 3 had a statistically significant higher rate of neonatal sepsis than Group 1 (p = 0.021). The RR of neonatal sepsis after a rescue course in patients with PPROM (Groups 2 and 3) was 3.31 (95% CI = 1.32, 8.29) compared to those with intact membranes at the time of rescue course administration (Group 1). Conclusion A rescue course of corticosteroids in women with PPROM at the time of rescue administration was associated with an increased risk of neonatal sepsis. This increased risk was seen in women with intact membranes as well as ruptured membranes during their initial course of steroids. Larger studies are needed to further investigate this association.

PMID:37159785 | PMC:PMC10163895 | DOI:10.7759/cureus.37207

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Serum LDH Levels in Normotensive and Preeclamptic-Eclamptic Pregnant Women and Its Correlation With Fetomaternal Outcome

Cureus. 2023 Apr 6;15(4):e37220. doi: 10.7759/cureus.37220. eCollection 2023 Apr.

ABSTRACT

Background One of the most prevalent medical issues observed during pregnancy is hypertension. Hypertensive disorders of pregnancy (HDP) and their consequences affect around 5-10% of all pregnancies globally. Preeclampsia is caused by endothelial dysfunction, which causes widespread endothelial leakage and contributes to potentially fatal consequences, such as eclampsia, placental abruption, disseminated intravascular coagulation (DIC), severe renal failure, pulmonary edema, and hepatocellular necrosis. As a result, looking for predictive markers for at-risk pregnancies that can suggest poor maternal or fetal outcomes is critical. Elevated levels of lactate dehydrogenase (LDH), as a sign of cellular damage and dysfunction, can be utilized as a biochemical marker in pregnancy-induced hypertension (PIH) as it represents the severity of the disease, and the occurrence of problems, and has also been demonstrated to co-relate with fetomaternal outcomes. Methodology A total of 230 singleton pregnant women of 28-40 weeks of gestational age were enrolled in this study. All women were divided into two groups – normotensive and preeclamptic-eclamptic groups; the second group was further divided into mild preeclampsia, severe preeclampsia, and eclampsia, based on blood pressure and the presence of proteinuria. Serum lactate dehydrogenase levels were measured in both groups and correlated with their fetomaternal outcome. Results Mean serum lactate dehydrogenase (LDH) level in eclamptic women was 1515.86 ± 754, in severely preeclamptic women was 932.2 ± 448, mild preeclamptic women were 580.5±213, while in normotensive women mean LDH level was 378.6 ± 124. The difference between normotensive and preeclamptic-eclamptic women was statistically significant (p < 0.001). The complications in the preeclamptic-eclamptic group were increased significantly in women with LDH > 800 IU/L, 600-800 IU/L compared to those who had < 600 IU/L LDH levels. Conclusions Serum LDH levels were significantly higher in women of preeclamptic-eclamptic group compared to the normotensive pregnant women. Higher LDH levels were positively correlated with disease severity and maternal complications like placental abruption, hemolysis elevated liver enzymes low platelet count (HELLP), disseminated intravascular coagulation (DIC), acute renal failure, intracranial hemorrhage, pulmonary edema, and maternal death and for fetal complications like preterm, intrauterine growth restriction (IUGR), APGAR at 1 minute < 7, APGAR at 5 minutes < 7, low birth weight (LBW), neonatal intensive care unit (NICU) admission and intrauterine fetal death (IUFD).

PMID:37159784 | PMC:PMC10163943 | DOI:10.7759/cureus.37220

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Comparison of the Rate of Posterior Capsule Opacification Following Combined Treatment With Topical Dexamethasone 0.1% Plus Ketorolac 0.5% Eye Drops Versus Dexamethasone 0.1% Alone: A Two-Year, Randomized Clinical Investigation

Cureus. 2023 Apr 6;15(4):e37223. doi: 10.7759/cureus.37223. eCollection 2023 Apr.

ABSTRACT

Background and aim The use of non-steroidal anti-inflammatory drugs in animals decreases the incidence of posterior capsular opacification (PCO) following cataract surgery. We evaluated the rate of PCO in patients with cataract surgery and foldable “in the bag” posterior chamber intraocular lens (PC-IOL) implantation treated with combined dexamethasone 0.1% plus ketorolac tromethamine 0.5% versus dexamethasone 0.1% alone. Materials and methods A total of 114 eyes of 101 patients underwent uneventful corneal small-incision phacoemulsification with primary implantation of a foldable acrylic PC-IOL (AcrySof®, Alcon, Fort Worth, USA). Postoperatively for four weeks, group 1 eyes were treated with dexamethasone 0.1% plus ketorolac tromethamine 0.5% ophthalmic solutions four times daily for each whereas group 2 eyes were treated with dexamethasone 0.1% alone. Other regiments were the same for each group. Patients were evaluated between one- and four-year following surgery. The frequency and timing of severe PCO following surgery that needed Nd:YAG laser posterior capsulotomy were recorded and evaluated. Results The mean (SEM) age of group 1 (n = 54) and group 2 (n = 60) at operation was similar (62.8 ± 2.2 vs. 60.6 ± 1.7 years, respectively). Eighty-eight patients had unilateral cataract and 13 cases had bilateral disease. Overall, the mean follow-up duration was 24.7 months postoperatively (range, 15-48). Clinically significant PCO that finally needed Nd:YAG laser application developed in two eyes (3.7%) in group 1 and in four eyes (6.6%) in group 2, and the difference was not statistically significant (p>0.05). The mean month at capsulotomy was 26.5 in group 1 and 24.3 months in group 2 eyes (p>0.05). Conclusions Topical instillation of ketorolac ophthalmic solution in the immediate period after phacoemulsification and PC-IOL implantation did not seem to influence the incidence of PCO formation two years after cataract surgery.

PMID:37159777 | PMC:PMC10163951 | DOI:10.7759/cureus.37223

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The Effect of Timing of Debridement and Surgical Intervention in Open Fractures on the Rate of Infection and Surgical Outcomes: A Prospective Study in a Tertiary Care Setup

Cureus. 2023 Apr 6;15(4):e37204. doi: 10.7759/cureus.37204. eCollection 2023 Apr.

ABSTRACT

Introduction Open fractures remain one of the true orthopedic emergencies. Despite recent advances in orthopedic surgery, the management of compound fractures is still a challenge to an orthopedic surgeon. Open fractures are a result of high-speed injuries and are associated with several complications such as infections, non-unions, or sometimes an eventual amputation. Infection is the major problem associated with open fractures due to soft tissue damage, contamination, and neurovascular compromise. Presently, management of open fractures requires early aggressive debridement followed by limb salvage by definitive reconstruction or amputation, depending upon the extent and location of the injury. Early aggressive debridement of open fractures has always been the rule. However, it has been observed that open fractures managed even after six hours of injury fare well, and there are no definite guidelines available to decide the safe period of debridement following open fractures so as to prevent infection. The “six-hour rule” is a hotly debated topic with fervent perseverance of this dogma despite a gross lack of support from the literature. Objective The objective of this study was to analyze the relationship between the timing of operation/debridement on infection rates in open fractures, particularly if surgery is performed after six hours. Methods This is a prospective study of 124 patients (R=5-75 years) presenting with open fractures to the outpatient department (OPD) and emergency section of a tertiary care hospital from January 2019 to November 2020. Patients were divided into four groups based on the time to operation/debridement: groups A, B, C, and D, with patients operated within six hours, six to 12 hours, 12-24 hours, and 24-72 hours after injury, respectively. Infection rates were obtained based on the above data. ANOVA was applied using SPSS 20 software (IBM Inc., Armonk, New York). Results This study concludes that the infection rate for fractures treated in less than six hours was 18.75%; in the six to 12 hours group, it was 18.50%, and in the 12-24 hours group, it was 14.28%. The infection rate increased to 38.8% if surgery was performed after 24 hours of injury. On statistical analysis, the time to debridement was not found to be a significant factor. The infection rate in Gustilo-Anderson classification compound grade I was 2.7%, grade II 9.8%, grade IIIA 45%, and grade IIIB 61%. Also, in this study, the union rate in grade I was 97.22%, grade II 96.07%, grade IIIA 85%, and grade IIIB 66.66%. Thus, the degree of wound contamination and compounding gives a prognostic indication regarding the final outcome of the compound fracture. Conclusion Time to debridement is not a significant factor in the management of compound fractures, and these fractures can be safely debrided up to 24 hours after injury. Gustilo and Anderson’s classification provides a prognostic indicator of the outcome of a compound fracture. Infection rates and non-union rates increase with increasing grades of compound fractures.

PMID:37159766 | PMC:PMC10163843 | DOI:10.7759/cureus.37204