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Frontiers in Immunology 2024Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC... (Comparative Study)
Comparative Study
INTRODUCTION
Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.
METHODS
We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m and cyclophosphamide 500 mg/m for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m and cyclophosphamide 500 mg/m for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.
RESULTS
From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).
DISCUSSION
As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.
Topics: Humans; Immunotherapy, Adoptive; Male; Middle Aged; Female; Antigens, CD19; Vidarabine; Retrospective Studies; Lymphoma, Non-Hodgkin; Aged; Cyclophosphamide; Adult; Lymphocyte Depletion; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Receptors, Antigen, T-Cell
PubMed: 38947326
DOI: 10.3389/fimmu.2024.1403145 -
World Journal of Gastroenterology Jun 2024The Baveno VII criteria redefine the management of decompensated liver cirrhosis, introducing the concept of hepatic recompensation marking a significant departure from... (Review)
Review
The Baveno VII criteria redefine the management of decompensated liver cirrhosis, introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline. Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies, including antivirals and lifestyle modifications. Studies on alcohol, hepatitis C virus, and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes. Transjugular intrahepatic portosystemic shunt (TIPS) emerges as a promising intervention, effectively resolving complications of portal hypertension and facilitating recompensation. However, optimal timing and patient selection for TIPS remain unresolved. Despite challenges, TIPS offers renewed hope for hepatic recompensation, marking a significant advancement in cirrhosis management. Further research is needed to refine its implementation and maximize its benefits. In conclusion, TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.
Topics: Humans; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Hypertension, Portal; Patient Selection; Treatment Outcome; Antiviral Agents; Liver
PubMed: 38946869
DOI: 10.3748/wjg.v30.i23.2954 -
Analytical Cellular Pathology... 2024Biliary atresia (BA) is a devastating congenital disease characterized by inflammation and progressive liver fibrosis. Activation of hepatic stellate cells (HSCs) plays...
BACKGROUND
Biliary atresia (BA) is a devastating congenital disease characterized by inflammation and progressive liver fibrosis. Activation of hepatic stellate cells (HSCs) plays a central role in the pathogenesis of hepatic fibrosis. Our study aimed to investigate the pharmacological effect and potential mechanism of pirfenidone (PFD) and andrographolide (AGP) separately and together on liver fibrosis of BA.
MATERIALS AND METHODS
The bile ducts of male C57BL/6J mice were ligated or had the sham operation. The effects of PFD and/or AGP on liver fibrosis of BA were evaluated. Human hepatic stellate cells (LX-2) were also treated with PFD and/or AGP .
RESULTS
PFD and/or AGP ameliorates liver fibrosis and inflammation in the mice model of BA, as evidenced by significant downregulated in the accumulation of collagen fibers, hepatic fibrosis markers (-SMA, collagen I, and collagen IV), and inflammatory markers (IL-1, IL-6, and TNF-). Moreover, compared with monotherapy, these changes are more obvious in the combined treatment of PFD and AGP. Consistent with animal experiments, hepatic fibrosis markers (-SMA, collagen I, and CTGF) and inflammatory markers (IL-1, IL-6, and TNF-) were significantly decreased in activated LX-2 cells after PFD and/or AGP treatment. In addition, PFD and/or AGP inhibited the activation of HSCs by blocking the TGF-/Smad signaling pathway, and the combined treatment of PFD and AGP synergistically inhibited the phosphorylation of Smad2 and Smad3.
CONCLUSION
The combined application of PFD and AGP exerted superior inhibitive effects on HSC activation and liver fibrosis by mediating the TGF-/Smad signaling pathway as compared to monotherapy. Therefore, the combination of PFD and AGP may be a promising treatment strategy for liver fibrosis in BA.
Topics: Hepatic Stellate Cells; Animals; Liver Cirrhosis; Signal Transduction; Diterpenes; Male; Transforming Growth Factor beta; Mice, Inbred C57BL; Smad Proteins; Humans; Pyridones; Cell Line; Mice; Biliary Atresia; Disease Models, Animal; Drug Therapy, Combination
PubMed: 38946862
DOI: 10.1155/2024/2751280 -
The Pan African Medical Journal 2024Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our...
Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4 month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.
Topics: Humans; Male; Young Adult; Antitubercular Agents; Magnetic Resonance Imaging; Epididymis; Tuberculosis, Male Genital; Immunocompetence; Orchiectomy; Seizures; Anticonvulsants; Tuberculoma, Intracranial
PubMed: 38946746
DOI: 10.11604/pamj.2024.48.2.42965 -
Journal of Indian Prosthodontic Society Jul 2024The aim of this study was to evaluate the effect of proanthocyanidin and C. sinensis-polyphenols on microtensile bonding properties of prepared teeth with resin-modified... (Comparative Study)
Comparative Study
Comparison of microtensile bond strength of prepared teeth treated with proanthocyanidin, Camellia sinensis - Polyphenols, and metal crowns luted with resin-modified glass ionomer cement: An in vitro study.
AIM
The aim of this study was to evaluate the effect of proanthocyanidin and C. sinensis-polyphenols on microtensile bonding properties of prepared teeth with resin-modified glass ionomer cement (GIC).
SETTING AND DESIGN
This was an in vitro study.
MATERIALS AND METHODS
Seventy-eight maxillary premolars were selected and mounted into auto-polymerizing acrylic resin blocks. The samples were prepared and metal crowns were fabricated. The samples were randomly divided into three groups. Samples under Group 1 were not treated with any of the extracts and followed conventional bonding protocol. Samples under Group 2 and Group 3 were treated with proanthocyanidin and C. sinensis-polyphenols, respectively. After dentin treatment, these samples were luted to metal crowns using resin-modified GIC. Universal testing machine was used to measure the load at which the crowns were debonded and microtensile bond strength in MPa was calculated.
STATISTICAL ANALYSIS
The results were statistically analyzed using one-way ANOVA and post hoc Tukey HSD.
RESULTS
Samples treated with C. sinensis polyphenols (Group 3) had maximum bond strength followed by Group 2, where the samples were treated with proanthocyanidin.
CONCLUSION
C. sinensis polyphenols due to their anti-proteolytic and antioxidant properties showed improved bond strength compared to proanthocyanidin, a cross-linking agent, followed by conventional bonding protocol.
Topics: Proanthocyanidins; Tensile Strength; Glass Ionomer Cements; Polyphenols; Humans; Crowns; Dental Bonding; Camellia sinensis; In Vitro Techniques; Resin Cements; Plant Extracts; Dental Stress Analysis
PubMed: 38946512
DOI: 10.4103/jips.jips_127_24 -
Journal of Indian Prosthodontic Society Jul 2024Occurrence of denture stomatitis and prosthesis breakage are common problems faced by elderly people wearing removable dentures. To overcome this, several attempts are...
AIM
Occurrence of denture stomatitis and prosthesis breakage are common problems faced by elderly people wearing removable dentures. To overcome this, several attempts are made to improve the denture material by addition of antimicrobials without compromising original properties. The aim of the study was to evaluate flexural strength and microhardness of self-cured polymethyl methacrylate (PMMA) denture base resin after addition of Vaccinium macrocarpon (commonly called as cranberry), extract as antimicrobial, at varying proportions.
STUDY SETTING AND DESIGN
Experimental in vitro study.
MATERIALS AND METHODS
Frozen cranberry fruits were subjected to extraction process in the presence of aqueous solvents. Lyophilized extract was added in proportions of 0, 0.5, 1.0, 1.5, and 2.0 dry wt/wt % into polymer of self-cure PMMA denture base resin. Based on cranberry inclusion, the study comprised one control (0%) and four test groups (0.5%-2%) with total of 100 samples. A three-point bending test for flexural strength was done for fifty study samples (n = 10). Surface of fractured samples was analyzed using a scanning electron microscope (SEM). Microhardness was determined using Vickers hardness test.
STATISTICAL ANALYSIS USED
One-way statistical ANOVA test was done to find the difference between groups, followed by Tukey's post hoc test for multiple pairwise comparison.
RESULTS
Flexural strength ranged from 66.80 to 69.28 MPa, and a statistically insignificant difference was observed between groups (P > 0.05). SEM evaluation showed uniformly dispersed strands of cranberry extract in PMMA matrix. With higher concentration, less voids were seen. Vickers microhardness value significantly decreased from 15.96 in the control group to 14.57 with 2% cranberry addition (P < 0.05).
CONCLUSION
Incorporation of cranberry extract into self-cure PMMA denture base resin, up to 2 dry wt %, did not decline the flexural strength. However, there was a significant decrease in Vickers microhardness values when compared against the control group (0% cranberry inclusion).
Topics: Polymethyl Methacrylate; Hardness; Flexural Strength; Vaccinium macrocarpon; Plant Extracts; Materials Testing; Humans; Denture Bases; Dental Materials; Anti-Infective Agents; In Vitro Techniques
PubMed: 38946510
DOI: 10.4103/jips.jips_25_24 -
European Review For Medical and... Jun 2024The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected...
OBJECTIVE
The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected patients by enabling tailored eradication treatments without the need for endoscopic procedures. This study aimed to assess the effectiveness of real-time PCR (RT-PCR) assays in identifying H. pylori infection and antibiotic resistance in stool and gastric biopsy specimens.
PATIENTS AND METHODS
Stool and gastric biopsy samples were collected from patients within three days of post-hospitalization. A total of 115 samples were analyzed for H. pylori infection, and an additional 115 samples were evaluated for resistance to clarithromycin and levofloxacin using an RT-PCR-based molecular test. Statistical analyses were performed using (SPSS 26.0 IBM Corp., Armonk, NY, USA).
RESULTS
Among 115 patients (53 males, average age 50.8±13.2 years), H. pylori was detected in 93.1% of stool samples and 93.9% of gastric biopsies. The RT-PCR assay demonstrated a sensitivity of 99.1% and a specificity of 100%, with an overall diagnostic accuracy of 99.1%. Clarithromycin resistance was found in 37.3% of stool and 46.9% of gastric biopsy specimens, with the assay showing 79.6% sensitivity and 98.4% specificity. Levofloxacin resistance was identified in 32.1% of stool samples and 31.3% of gastric biopsies, with 86.3% sensitivity and 91.1% specificity of the molecular test.
CONCLUSIONS
The RT-PCR-based detection of H. pylori and its resistance to clarithromycin and levofloxacin in stool samples represents a promising approach to enhance eradication therapy outcomes, potentially improving treatment efficacy. Chictr.org.cn: ChiCTR2300070267.
Topics: Humans; Levofloxacin; Clarithromycin; Helicobacter pylori; Feces; Male; Real-Time Polymerase Chain Reaction; Middle Aged; Female; Helicobacter Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Adult; Aged; Microbial Sensitivity Tests
PubMed: 38946381
DOI: 10.26355/eurrev_202406_36460 -
Acta Dermatovenerologica Croatica : ADC Mar 2024Cutaneous leishmaniasis (CL) is common in the pediatric population, but there are only a limited number of studies focused on the clinical and epidemiological...
Cutaneous leishmaniasis (CL) is common in the pediatric population, but there are only a limited number of studies focused on the clinical and epidemiological characteristics of patients in this age group. In this study, our objective was to investigate the epidemiological and clinical characteristics of pediatric subjects diagnosed with CL. A total of 8047 patients who had been diagnosed with CL between 2010 and 2021 in an endemic region were included in this retrospective study. The clinical and demographic characteristics such as age, gender, number, size, duration, location, and type of lesions and the administered CL treatments were recorded. In order to better understand the epidemiological and clinical characteristics of patients with pediatric CL (PCL), the study patients were divided into three groups according to their age (0-6, 7-12, and 13-18 years) and the clinical and epidemiological characteristics of these groups were compared. When patients with PCL were compared according to age groups, it was found that the highest number of patients were in the 13-18 age group. It was determined that the patients in the 6-12 age group had fewer lesions, that and the size of the lesions was smaller than the other groups. The disease duration was the longest in the 0-5 age group. The highest rate of nodular, ulcerated, and recurrent lesions was in the 13-18 age group, and the highest rate of papular lesions was in the 6-12 age group. Systemic pentavalent antimony therapy (IM or IV) was administered to 438 patients with PCL (5.44%), while intralesional pentavalent antimony therapy (IL) was administered to 7447 patients (92.54%). Patients receiving systemic therapy had larger lesions compared with patients receiving IL therapy and no treatment. The lesion duration was longer in patients who received systemic treatment, and the number of lesions was higher than those who received IL treatment. The highest rate of systemic treatment was in the 13-18 age group (43.8%). In conclusion, our study found that the intragroup comparison of the age group with the highest CL rate displayed similar clinico-epidemiological characteristics reported in previous studies conducted in the same region.
Topics: Humans; Leishmaniasis, Cutaneous; Child; Retrospective Studies; Turkey; Adolescent; Male; Female; Child, Preschool; Infant; Infant, Newborn; Antiprotozoal Agents
PubMed: 38946187
DOI: No ID Found -
Veterinary Medicine and Science Jul 2024Salmonellosis is one of the most common food-borne diseases in industrialised and developing countries. In recent year, an increase in antimicrobial resistance among...
BACKGROUND
Salmonellosis is one of the most common food-borne diseases in industrialised and developing countries. In recent year, an increase in antimicrobial resistance among different Salmonella serotypes has been observed.
OBJECTIVE
A cross-sectional study was conducted to assess the prevalence and antimicrobial susceptibility of Salmonella isolated from local chicken eggs in four selected towns in Ethiopia.
METHODS
A total of 115 eggs were examined to detect Salmonella by using standard microbiological methods. The susceptibilities of the isolates to nine antimicrobials were tested by the Kirby-Bauer disk diffusion method.
RESULT
The study revealed that of the 115 eggs examined, 22 (19.1%) were positive for Salmonella of which 14 (12.2%) and 8 (7%) of the isolates were from shells and contents, respectively. The occurrence of Salmonella in egg shells and content and between different altitudes did not differ significantly (p > 0.05). Most isolates were resistant to more than three antimicrobials with a high resistance to kanamycin, ampicillin, nalidixic acid, cotrimoxazole, oxytetracycline and chloramphenicol.
CONCLUSION
The results indicate the potential importance of local chicken eggs as source of multiple antimicrobial-resistant salmonellae and the need for proper cooking before consumption. Further studies are required to describe the epidemiology of Salmonella in various agroclimatic zones of Ethiopia.
Topics: Animals; Ethiopia; Chickens; Salmonella; Prevalence; Cross-Sectional Studies; Anti-Bacterial Agents; Poultry Diseases; Eggs; Drug Resistance, Bacterial; Salmonella Infections, Animal; Food Microbiology
PubMed: 38946179
DOI: 10.1002/vms3.1529 -
Medical Science Monitor : International... Jul 2024BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link...
BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.
Topics: Humans; Kidney Transplantation; COVID-19; Thrombosis; Male; Female; Middle Aged; Retrospective Studies; Incidence; Adult; Prognosis; Risk Factors; Transplant Recipients; SARS-CoV-2; Logistic Models; Aged; Cyclosporine; Kaplan-Meier Estimate
PubMed: 38946121
DOI: 10.12659/MSM.944285