Similar Efficacy Research Articles

Surgical management for massive rotator cuff tears: a network meta-analysis of randomized controlled trials.

Multiple surgical strategies have been developed for treating massive rotator cuff tears (mRCTs). However, there is still no consensus on the best surgical option for mRCTs. Through a network meta-analysis, we aimed to comprehensively and systematically analyse the evidence in randomized controlled trials to help clinicians make evidence-based clinical decisions for patients with mRCTs. Our study was a network meta-analysis of the surgical management of mRCTs (PROSPERO Registration ID: CRD42023397971). We searched PubMed, EMBASE, Cochrane and Web of Science for randomized controlled trials that examined the efficacy of surgical management for mRCTs up to 3 November 2022. A three-step method was employed for the study process. Study selection, data extraction and risk of bias evaluation were conducted by two independent reviewers. R software (version 4.2.1) and Stata (version 15.1) were used for the data analysis. From 10,633 publications, we included 15 randomized controlled trials (996 participants) for the quantitative analysis. In terms of both long-term and short-term surgical effects, there were no statistically significant differences among surgical interventions such as patch-augmented rotator cuff repair (RCR), RCR with platelet-rich plasma, arthroscopic decompression, bridging reconstruction, arthroscopic RCR with platelet-leukocyte membrane, open RCR, mini-open RCR, arthroscopic debridement, superior capsular reconstruction, arthroscopic suture-spanning augmented repair, subacromial balloon spacer and latissimus dorsi tendon transfer. Based on algorithms, the probability ranking suggests that patch augmentation is the most highly ranked surgical intervention for achieving better short-term surgical outcomes. Furthermore, arthroscopic-associated mini-open RCR was ranked as the highest surgical intervention for achieving better long-term surgical effects. Based on the available data from the included studies, similar surgical efficacies were observed among the reported intervention measures for mRCTs. The patch augmentation technique was found to potentially achieve better short-term surgical outcomes, which is consistent with previous reports. However, the best surgical interventions for achieving long-term surgical effects remain unknown. More high-quality research is needed to evaluate the efficacy and safety of these interventions and to guide clinical practice.

Comparison of Metformin and Myoinositol on Clinical, Hormonal and Metabolic Profile of Patients with Polycystic Ovarian Syndrome: An Open-label Randomised Clinical Trial

Introduction: The prevalence of Polycystic Ovarian Syndrome (PCOS), one of the common endocrine disorders among women of reproductive age, varies from 2.2% to 26% globally. The treatment for PCOS aims to reduce Body Mass Index (BMI), improve underlying hormonal disturbances, prevent future reproductive and metabolic complications, and enhance the quality of life. Aim: To evaluate the efficacy of metformin and Myoinositol (MI) on the metabolic, hormonal, and clinical profiles in PCOS. Materials and Methods: An open-label randomised clinical trial was conducted at the Department of Obstetrics and Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur, Chengelpet, Tamil Nadu, India, from January 2019 to May 2020. The study included 80 women with PCOS who were randomly assigned to two groups. One group received metformin 1500 mg/day (in three divided doses), while the other group received MI 1 gram/day for three months. At the end of the 12-week therapy, the participants were evaluated for changes in clinical, metabolic, and hormonal profiles. The data were analysed using Statistical Package for Social Sciences (SPSS) version 20.0. Descriptive statistics such as frequency, proportion, mean, and standard deviation were used for quantitative data. Results: Both the metformin and MI-treated groups showed a significant reduction in BMI, fasting blood glucose, and fasting insulin. Both drugs were equally effective in changing the hormonal profile. There was a significant improvement in lipid parameters in both groups, with High-density Lipoprotein (HDL) levels being more significantly raised in the metformin group. The post-treatment HDL values in the metformin group were 75.69±19.16 mg/dL compared to 41.43±6.18 mg/dL in the MI group (p<0.0001). Both groups demonstrated similar efficacy in improving menstrual regularity, with 60% of the patients in the metformin group and 65% in the MI group having regular cycles at the end of treatment. Among infertility patients, the conception rate was 40% in the metformin group and 25% in the MI group (p=0.70). Conclusion: Both drugs were equally efficient in improving the clinical, metabolic, and hormonal profiles in PCOS. Metformin was found to be superior to MI in improving fertility and increasing HDL levels.

Treatment of BK Polyomavirus-Associated Nephropathy in Paediatric Kidney Transplant Recipients: Leflunomide Versus Cidofovir.

BK polyomavirus-associated nephropathy is a clinicopathological entity that negatively affects graft function in kidney transplant recipients. We compared the efficacy of leflunomide and cidofovir to treat BK polyomavirus-associated nephropathy in pediatric kidney transplant recipients. Medical records of pediatric recipients with BK viremia for the period 2004 through 2019 were reviewed retrospectively, and patients diagnosed with BK polyomavirusassociated nephro-pathy were included in the study. A serum BK virus level above 104 copies/mL was accepted as BK viremia. We defined BK polyomavirusassociated nephropathy as detection of BK virus SV40 antigen on immunochemistry staining of renal graft tissue accompanied by signs of tubulointerstitial nephritis or elevated serum creatinine in addition to BK viremia. Of 304 kidney transplant recipients, 53 had persistent BK viremia; 36 of these patients (61.1% male) were included in the study with the diagnosis of BK polyomavirus-associated nephropathy. Twelve patients (33.3%) received cidofovir, and 14 (38.8%) received leflunomide. Results were similar between the cidofovir and leflunomide groups for serum creatinine level at last follow-up (0.91 ± 0.29 vs 0.94 ± 0.37 mg/dL, respectively; P = .843) and graft failure rate (8.3% vs 14.2%, respectively; P = .632). Graft failure was observed in 8.3% of patients with BK polyomavirus-associated nephropathy. Leflunomide and cidofovir showed similar efficacy for treatment of BK polyomavirus-associated nephropathy.

A comparison between a gastroesophageal reflux disease questionnaire-based algorithm and multichannel intraluminal impedance-pH monitoring for the treatment of gastroesophageal reflux-induced chronic cough.

Empiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC. This study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC. For the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results. The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP. Overall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), -4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 (p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, -19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, -8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources. The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting. This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).

The Role of Digital Rectal Examination Prostate Volume Category in the Early Detection of Prostate Cancer: Its Correlation with the Magnetic Resonance Imaging Prostate Volume.

To relate the prostate volume category (PVC) assessed with digital rectal examination (DRE)-small, median, and large-and the prostate volumes (PVs) assessed with magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). To compare the clinically significant prostate cancer (csPCa) discrimination ability of two predictive models based on DRE-PVC and MRI-PV. A prospective trial of 2,090 men with prostate-specific antigen >3 ng/mL and/or PCa suspicious DRE were prospectively recruited in 10 centers from Catalonia (Spain), between 2021 and 2022, in whom DRE-PVC was assessed. Pre-biopsy MRI, and 12-core TRUS-random biopsy was always performed after 2- to 6-core TRUS-fusion targeted biopsy of prostate imaging-report and data system >3 lesions. In 370 men (17.7%) the DRE-PVC was unconclusive. Among the 1,720 men finally analyzed the csPCa (grade group >2) detection was 42.4%. The median (interquartile range) of TRUS and MRI-PVs of small prostates were 33 mL (19-37 mL) and 35 mL (23-30 mL), p=0.410; in median prostates they were 51 mL (38-58 mL) and 55 mL (48-63 mL) respectively, p<0.001; in large prostates 80 mL (60-100 mL) and 95 mL (75-118 mL) respectively, p<0.001. The predictive models sharing the MRI-PV and DRE-PVC showed areas under the curves of 0.832 (95% confidence interval [CI], 0.813-0.851) and 0.828 (95% CI, 0.809-0.848) respectively, p=0.632, as well as similar net benefit and clinical utility. PVC was unconclusive in 17% of DREs. MRI-PV overestimated the TRUS-PV in median and large prostates. The predictive models based on MRI-PV and DRE-PVC showed similar efficacy to predict csPCa. PVC assessed with DRE is helpful to predict the csPCa risk before MRI.

Intravenous versus intramuscular oxytocin injection for preventing uterine atonic primary postpartum haemorrhage in third stage of labour: A double-blind randomised controlled trial.

To compare the efficacy and safety of intravenous and intramuscular oxytocin in preventing atonic primary postpartum haemorrhage in the third stage of labour. A double-blind randomised clinical study on consenting women without risk factors for primary postpartum haemorrhage in labour at term. Two hundred and thirty-two women were randomly allotted into intravenous (n = 115) and intramuscular (n = 117) oxytocin groups in the active management of the third stage of labour. All participants received 10 IU of oxytocin, either IV or IM, and 1 ml of water for injection as a placebo via a route alternate to that of administration of oxytocin within 1 min of the baby's delivery. The primary outcome measures were mean postpartum blood loss and haematocrit change. Trial Registration No.: PACTR201902721929705. The baseline socio-demographic and clinical characteristics were similar between the two groups (p > 0.05). There was no statistically significant difference between the two groups with regards to the mean postpartum blood loss (254.17 ± 34.85 ml versus 249.4 ± 39.88 ml; p = 0.210), haematocrit change (2.4 (0.8%) versus 2.1 (0.6%); p = 0.412) or adverse effects (p > 0.05). However, the use of additional uterotonics was significantly higher in the intravenous group (25 (21.73%) versus 17 (14.53%); p = 0.032). Although oxytocin in both study groups showed similar efficacy in terms of preventing atonic primary postpartum haemorrhage, participants who received intravenous oxytocin were more likely to require additional uterotonics to reduce their likelihood of having an atonic primary postpartum haemorrhage. However, both routes have similar side effect profiles.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 μM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 μM, better than fluconazole (17.2% at 1 μM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Comparative Studies of Continuous Versus Pulsatile Delivery of a Novel Mammalian Cell-Derived Variant of GDNF (GDNFv) into the Rhesus Macaque Striatum

Glial cell line-derived neurotrophic factor (GDNF) remains a promising disease modifying therapeutic agent for the dopamine-containing neurons that are affected in Parkinson’s disease and recent clinical findings show renewed promise for its use in patients with Parkinson’s disease. However, translating this approach from research laboratories to the clinic has been met with obstacles, including insufficient brain biodistribution, immunogenicity, and poor stability of unglycosylated wildtype GDNF produced from bacteria. We have previously reported that continuous infusion of a novel glycosylated mammalian variant of GDNF (GDNFv) has increased biodistribution compared to wildtype GDNF along with increased dopamine turnover in the non-human primate brain. Here, we extend these findings by comparing continuous versus pulsatile intrastriatal infusion of GDNFv in intact rhesus macaques. Intermittent, pulsatile delivery paradigms were explored to possibly enhance drug distribution in the brain while decreasing the total amount of drug and infusion volume needed to achieve target activation. Vehicle or GDNFv was directly administered into the putamen via a pump and catheter system using a constant flow rate or using pulsatile profiles of two patterns: pulsatile infusion of 24-hour duration or 48-hour duration. Study endpoints involved comparisons of brain biodistribution, retrograde transport to nigral neurons and dopamine turnover. Each catheter was placed in or near the center of the putamen as confirmed by post-operative magnetic resonance imaging. Our results support that continuous and pulsatile administration of GDNFv was well tolerated in all animals. In addition, pulsatile delivery of GDNFv demonstrated favorable physiological activity of potential therapeutic value with biodistribution, retrograde transport to nigral cells and significant dopamine turnover modulation comparable or better than that achieved with continuous flow delivery. More importantly, the animals administered GDNFv via pulsatile protocols only received half the total drug amount and half the infused volume used in the continuously-infused animals, while still attaining a similar efficacy in increasing dopamine turnover. These data suggest that pulsatile delivery of trophic factors, such as GDNFv, may be a viable disease altering strategy for patients with Parkinson’s disease by offering a means to reduce the drug amount needed to improve dopamine function while limiting potential therapeutic barriers.

Combined pre-treatment and middle-treatment Epstein-Barr virus DNA load contributes to prognostication and treatment modification in nasopharyngeal carcinoma patients.

To investigate whether pre-treatment and middle-treatment plasma Epstein-Barr virus (EBV) DNA loads are useful predictors of prognosis and indicators of therapy modification in nasopharyngeal carcinoma (NPC) patients undergoing radical concurrent chemoradiotherapy (CCRT). Plasma EBV DNA load was measured by quantitative polymerase chain reaction before treatment (pre-DNA) and during the second cycle of DDP (mid-DNA). The primary endpoint was 5-year progression-free survival (PFS). A total of 775 NPC patients treated with CCRT were included. In total, 553 patients with pre-DNA <4000 copies/mL and 222 with ⩾4000 copies/mL. A total of 559 patients had mid-DNA undetectable and 216 had detectable. Multivariate analysis showed that pre- and mid-DNA were independent prognostic predictors of PFS [hazard ratio (HR), 2.035; 95% confidence interval (CI), 1.406-2.944; p < 0.001; HR, 1.597; 95% CI, 1.101-2.316; p = 0.014]. The area under the curve of the combination of pre-DNA and mid-DNA for 5-year PFS was higher than that of pre-DNA, mid-DNA, and tumor node metastasis (TNM) stage (0.679 versus 0.622, 0.608, 0.601). In the low-risk group (pre-DNA <4000 copies/mL and undetectable mid-DNA), patients receiving ⩽200 mg/m2 showed similar efficacy as those receiving >200 mg/m2 cumulative cisplatin dose (CCD) but were associated with fewer all-grade late toxicities. However, in the high-risk group (pre-DNA ⩾4000 copies/mL or detectable mid-DNA), patients receiving >200 mg/m2 CCD showed a higher 5-year PFS (73.1% versus 58.6%, p = 0.027) and locoregional relapse-free survival (88.5% versus 76.1%, p = 0.028) than those receiving ⩽200 mg/m2 CCD. The combination of pre-DNA and mid-DNA could be particularly useful for guiding risk stratification and early treatment modification for NPC treated with CCRT. A total of 200 mg/m2 cisplatin seemed to be the optimal dose for the low-risk patients, while >200 mg/m2 cisplatin may be adequate to achieve satisfactory survival outcomes in the high-risk group.

The Role of Diffusion Weighted MRI in Diagnosis of Sacroiliitis

Background: The main aim of this study is to investigate the effectiveness of Apparent Diffusion Coefficient (ADC) and Diffusion Weighted Imaging (DWI) in identifying and detecting active sacro-iliitis. The study seeks to evaluate the potential of these imaging techniques as diagnostic tools for this particular condition. Materials and Methods: A total of 79 people underwent MRI examination for low back pain. Thirty-four of these individuals did not show any pathology in the sacroiliac joints and were included in the control group. 45 people diagnosed with sacroiliitis formed the patient group. All participants underwent spin echo, planar echo, diffusion-weighted MR imaging at a b=1000 s/mm². ADC values were determined by assessing the subchondral regions adjacent to both sacroiliac joints. Relative ADC values were obtained for both the patient and control groups. Results: The study found a significant difference (p&amp;lt;0.05) in mean ADC values between the pa-tient group (1202.4±268.2 mm²/s) and the control group (423.9±71.9 mm²/s). These results indicate distinct diffusion patterns between the two groups. Additionally, the relative ADC values were significantly different (p&amp;lt;0.05) with 0.434 in the patient group and 0.153 in the control group, further supporting the observed disparities in diffusion characteristics. Conclusions: Diffusion-weighted imaging has similar diagnostic efficacy to other MRI methods in detecting active sacroiliitis. In addition, it is thought that the relative ADC values may contribute more to the diagnosis of sacroiliitis.

Conducting biological tests in the development of self-emulsifying drug delivery systems with simvastatin

The aim of the study was to compare the hypolipidemic activity of the developed self-emulsifying drug delivery systems with simvastatin with reference samples of the substance and the finished drug product of industrial production. Materials and methods. The substance of simvastatin (India, s. DK40-2005021, 99.09 %, introduced into the composition of self-emulsifying compositions based on castor oil (Ukraine), polyethylene glycol 40 hydrogenated castor oil (India), Tween 80 (Ukraine), glycerol monostearate (Gustav Heess GmbH, Germany) or polyethylene glycol 100 stearate (ERCA, Italy). Reference samples were Simvastatin-Sandoz (Salutas Pharma, Germany, series LX5161) and simvastatin in pure form. The experimental animals were Syrian hamsters aged 2 months. Hyperlipidemia was modeled by means of an alimentary load. To assess the state of lipid metabolism in animals, the content of triacylglycerols, total cholesterol, low-density lipoprotein and high-density lipoprotein in the blood serum was determined by colorimetric enzymatic methods using the appropriate standard reagent kits "Triacylglycerols F" HP022.02, "Cholesterol F" HP026.02, "Cholesterol-LDL F" HP026.05 and "Cholesterol-HDL F" HP026.04 (LLC SPE "Filicit-Diagnostics", Ukraine) on a semi-automatic biochemical analyzer MapLab Plus (BSI, Italy). Results. The reference samples had similar dose-dependent efficacy parameters. At the same time, the test samples, also having similar dose-dependent effects, in absolute terms at the maximum concentration reduced the amount of low-density lipoprotein and total cholesterol more effectively than the reference samples. When using the test samples in their average concentration, the level of triglycerols was significantly reduced, which is rather a concomitant effect of simvastatin. Conclusions. The improvement of the overall efficacy of simvastatin when it is introduced into self-emulsifying drug delivery systems has been proved, which is associated with the modification of pharmacokinetic parameters by improving the solubility of the substance in the aqueous environment of the gastrointestinal tract

Recombination map tailored to Native Hawaiians may improve robustness of genomic scans for positive selection

Recombination events establish the patterns of haplotypic structure in a population and estimates of recombination rates are used in several downstream population and statistical genetic analyses. Using suboptimal maps from distantly related populations may reduce the efficacy of genomic analyses, particularly for underrepresented populations such as the Native Hawaiians. To overcome this challenge, we constructed recombination maps using genome-wide array data from two study samples of Native Hawaiians: one reflecting the current admixed state of Native Hawaiians (NH map) and one based on individuals of enriched Polynesian ancestries (PNS map) with the potential to be used for less admixed Polynesian populations such as the Samoans. We found the recombination landscape to be less correlated with those from other continental populations (e.g. Spearman’s rho = 0.79 between PNS and CEU (Utah residents with Northern and Western European ancestry) compared to 0.92 between YRI (Yoruba in Ibadan, Nigeria) and CEU at 50 kb resolution), likely driven by the unique demographic history of the Native Hawaiians. PNS also shared the fewest recombination hotspots with other populations (e.g. 8% of hotspots shared between PNS and CEU compared to 27% of hotspots shared between YRI and CEU). We found that downstream analyses in the Native Hawaiian population, such as local ancestry inference, imputation, and IBD segment and relatedness detections, would achieve similar efficacy when using the NH map compared to an omnibus map. However, for genome scans of adaptive loci using integrated haplotype scores, we found several loci with apparent genome-wide significant signals (|Z-score|> 4) in Native Hawaiians that would not have been significant when analyzed using NH-specific maps. Population-specific recombination maps may therefore improve the robustness of haplotype-based statistics and help us better characterize the evolutionary history that may underlie Native Hawaiian-specific health conditions that persist today.

Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries

Recent studies suggest that acellular nerve allografts (ANA) have similar efficacy as nerve autografts in certain applications of nerve surgery. However, multiple studies also demonstrate the limitations of nerve allografts, resulting in poor patient outcomes. This submission discusses a recent case series of patients who failed allograft use with subsequent histologic analyses of these allografts. Recommendations on the treatment of nerve gaps are presented, drawing from our current understanding of allograft and autograft utility in reconstruction. Factors taken into account include recipient critical nerve function, existent nerve gap, and nerve diameter.

Comparative Evaluation of the Efficacy and Safety of Brimonidine Generics in Glaucoma Therapy

Glaucoma is a chronic neurodegenerative disease that eventually leads to irreversible blindness. The main risk factor for the development and progression of glaucoma is elevated IOP. In cases where the use of prostaglandin analogues is limited, brimonidine is the most rational choice as initial therapy. It is the only molecule that both reduces aqueous humor production and enhances uveoscleral outflow. The use of several hypotensive drugs for a long time can lead to pronounced changes in the tissues of the anterior segment of the eye. In this case, there are complaints characteristic of the dry eye syndrome. The aggravation of this condition can affect the adherence of patients to treatment and worsen the course of the disease. Therefore, it is important to prescribe hypotensive drugs that have a sufficient hypotensive effect with a good safety profile. Purpose. To evaluate the efficacy and safety of Brimonidine SZ in combination therapy for glaucoma after changing the hypotensive regimen. Patients and methods. The study was conducted in a group of 50 patients (50 eyes) with initial or advanced drug-compensated primary open-angle glaucoma (mean age 64.8 years), among them there were 27 (54 %) women and 23 (46 %) men. In patients included in the study, brimonidine 0.15 % or 0.2 % was replaced with Brimonidine SZ as part of combination hypotensive therapy. To analyze the results obtained, data on corneal-compensated IOP, the degree of corneal staining with fluorescein, assessments of conjunctival hyperemia, indicators of the OSDI questionnaire and the level of adherence to treatment at the initial visit, as well as 1 and 3 months after changing the hypotensive regimen, were compared. Results. There were no statistically significant differences in the level of IOP at different times after changing the hypotensive regimen. Objective indicators of the state of the tissues of the anterior surface of the eye did not change. According to the results of the evaluation of the main signs of dry eye syndrome (OSDI) and the degree of adherence of patients to treatment, no significant changes were found either. Conclusion. Brimonidine SZ has a similar hypotensive efficacy with brimonidine 0.15 % and 0.2 % as part of combination hypotensive therapy. The safety profile of Brimonidine SZ is comparable to analogues, which allows us to consider this drug as a possible alternative when choosing hypotensive therapy.

Morpho-Quantitative Traits and Interrelationships between Environmental Factors and Phytophthora infestans (Mont.) de Bary Attack in Tomato

The growing imperative for sustainable development generates research in the field and explores innovative approaches to manage vegetable crops to reduce the usage of synthetic inputs commonly associated with conventional practices as well as to promote the undertaking of organic solutions. Tomatoes are universally recognized as a highly significant and popular fruit vegetable due to their large use palette. Trials were carried out in the Gâlgău area, Transylvania, Romania. Bifactorial experiments were organized to quantify the influence of fertilization and treatments on the morpho-productive and quantitative traits of the Ruxandra tomato cultivar and on Phytophthora infestans levels of infection. The use of mixed fertilization resulted in the best performances of morphological traits (highest leaf area, highest number of leaves and fruits, highest chlorophyll content) and part of the productive traits (highest content of dry matter), and the lowest levels of infection in cv. Ruxandra, while the use of NPK soil fertilization led to the best performances in fruit weight and NUE, whatever the administered treatment. The treatment with herbal extracts showed a similar efficacy in increasing the averages of morpho-productive traits and diminishing the P. infestans level of infection compared with the conventional treatment. The treatment efficacy was mainly influenced by temperature and relative air humidity, regardless of the fertilization strategies applied.

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease.

Randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) included a low proportion of atrial fibrillation (AF) patients with chronic kidney disease (CKD), and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD. In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (vs warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD. But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD. The effectiveness and safety of DOACs in those patients are still subject to debate. To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population. A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation. Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. A total of 8899 included patients filled out a new oral anticoagulation therapy claim; 3335 for warfarin and 5564 for DOACs. Compared with warfarin, 15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk [Hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.65-0.88] and a similar safety risk (HR 0.94; 95%CI: 0.66-1.35). Apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95%CI: 0.79-1.26) and a lower safety risk (HR 0.65; 95%CI: 0.43-0.99. Although, apixaban 5.0 mg was associated with a better effectiveness (HR 0.76; 95%CI: 0.65-0.88), but a similar safety risk profile (HR 0.94; 95%CI: 0.66-1.35). The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality (HR 0.61; 95%CI: 0.43-0.88). In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines

AbstractLymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania. We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51.4% and 50.0% (P = .981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91.9% of patients receiving Flu/Cy vs 72.7% of patients receiving Benda (P = .048); any-grade neurotoxicity after Flu/Cy occurred in 45.9% of patients and after Benda in 18.2% of patients (P = .031). In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54.5%; P < .001), infections (78.4% vs 27.3%; P < .001), and neutropenic fever (78.4% vs 13.6%; P < .001). These results were confirmed both in patients with LBCL and those with FL. Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis. This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.

Adverse effects associated with ablative lasers when treating common dermatologic conditions: a systematic review of 946 patients

CO2 and Er:YAG are the two most common types of ablative lasers in use today. Ablative lasers are known for their superior efficacy in penetrating deeper through the skin layers when compared to non-ablative lasers. This review compares the outcomes and adverse events associated with CO2 and Er: YAG lasers, in conjunction with other therapeutic modalities, in the treatment of common skin conditions. A PRISMA-compliant systematic review of PubMed and Embase databases was conducted from January 2012 to December 2022. Study types that were eligible for this review included clinical trials, randomized controlled trials, case reports, case series, cohort studies, and meta-analyses. The study protocol was registered (PROSPERO 2022: CRD42022348569). The search strategy produced 27 studies comprising 946 patients who were treated for acne scars, postacne hyperpigmentation, solar lentigines, facial rejuvenation, refractory vitiligo, and epidermal verrucous nevi. Erythema, pain, and hyperpigmentation were the most commonly reported adverse effects. A higher rate of adverse events was observed in CO2 laser therapies (n=610, 64.5%) when compared to Er: YAG and other laser cohorts (n=40, 4.2%). Both CO2 and Er: YAG lasers demonstrate similar efficacy in the treatment of benign cutaneous conditions. Further research is needed for parallel comparison of CO2 and Er: YAG lasers.

Preparation of protein nanoparticles using diselenide functionalized gelatin for redox responsive release of doxorubicin

The present study demonstrates the fabrication of a nanocarrier system using diselenide conjugated gelatin (G-Se-Se-G) for the redox responsive delivery of a wide spectrum anticancer drug, doxorubicin (Dox). The method involves nanoprecipitation of the aqueous solution of G-Se-Se-G employing ethanol and F68 as the desolvating and stabilizing agents respectively. The drug, Dox is loaded within the nanocarrier by entrapment method during the nanoparticle synthesis. The physico-chemical characterizations confirm the formation of nanoparticles of regular spherical shape with hydrodynamic size, surface charge and loading efficiency of 181 ± 12.6 nm, -13.10 ± 0.83 mV and ∼9 % respectively. Notably, Dox loaded G-Se-Se-G carrier shows significantly higher drug release in response to acidic (pH = ∼5.5) and reducing (10 mM glutathione) sink conditions. Dox release kinetic data fitted to a universal Korsmeyer–Peppas model suggests that irrespective of the nature of stimuli, the release of Dox from G-Se-Se-G carrier follows non-Fickian mechanism which is attributed to the diffusion and erosion. The cytotoxicity studies employing human lung adenocarcinoma (A549) and human normal lung fibroblast (WI38) cells confirm the potency as well as selectively of Dox loaded G-Se-Se-G carrier towards cancer cells. The intracellular drug release studies through fluorescence imaging indeed corroborate the redox (reducing environment) mediated preferential release of Dox from G-Se-Se-G carrier in A549 cells as compared to WI38 cells. Finally, in vivo studies using A549 derived xenograft tumor model establishes that Dox loaded G-Se-Se-G nanocarrier is better tolerable than free Dox with almost similar efficacy.