Car T Cells in Solid Tumors: Overcoming Obstacles Rojas-Quintero, Joselyn; Díaz, María P; Palmar, Jim ...
International journal of molecular sciences,
04/2024, Letnik:
25, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has ...shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.
We developed and standardized an efficient and cost-effective in-house RT-PCR method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, and ...other statistical parameters by different RT-qPCR methods including triplex, duplex, and simplex assays adapted from the initial World Health Organization- (WHO) recommended protocol. This protocol included the identification of the E envelope gene (E gene; specific to the Sarvecovirus genus), RdRp gene of the RNA-dependent RNA polymerase (specific for SARS-CoV-2), and RNase P gene as endogenous control. The detection limit of the E and the RdRp genes were 3.8 copies and 33.8 copies per 1 µL of RNA, respectively, in both triplex and duplex reactions. The sensitivity for the RdRp gene in the triplex and duplex RT-qPCR tests were 98.3% and 83.1%, respectively. We showed a decrease in sensitivity for the RdRp gene by 60% when the E gene acquired Ct values > 31 in the diagnostic tests. This is associated with the specific detection limit of each gene and possible interferences in the protocol. Hence, developing efficient and cost-effective methodologies that can be adapted to various health emergency scenarios is important, especially in developing countries or settings where resources are limited.
Introduction
Frailty is a multicausal syndrome characterized by a decrease in strength, resistance and physiological function, which makes the individual vulnerable and dependent, and increases ...his/her mortality. This syndrome is more prevalent among older individuals, and chronic kidney disease patients, particularly those on dialysis. Dialysis dose is currently standardized for hemodialysis (HD) patients regardless of their age and functional status. However, it has been postulated that the dialysis dose required in older patients, especially frail ones, should be lower, since it could increase their degree of frailty. Then, the purpose of this study was to evaluate if there would be a correlation between the dose of Kt/V and the degree of frailty in a population of adult patients on HD.
Materials and methods
A cross-sectional study with 82 patients on HD in Barranquilla (Colombia) and Lobos (Argentina) was conducted. Socio-demographic and laboratory data, as well as dialysis doses (Kt/V) were recorded and scales of fragility, physical activity, gait and grip strength were applied. Then these data were correlated by a Spearman’s correlation and a logistic regression.
Results
CFS, social isolation, physical activity,
gait speed,
and
prehensile strength tests
were outside the reference ranges in the studied group. No significant correlation was found between dialysis dose and all the above mentioned functional tests. However, a significant and inverse correlation between physical activity and CFS was documented (score − 1.41 (CI − 2.1 to − 0.7).
Conclusion
No significant correlation was documented between Kt/V value and different parameters of the frailty status, but this status correlated significantly and inversely with physical activity in this group. Frailty status in hemodialysis patients was significantly higher in older individuals, although young individuals were not exempt from it.
Frailty status improvement after kidney transplantation Aroca-Martinez, Gustavo; Hernandez-Agudelo, Sandra; Castro-Hernández, Christian ...
Irish journal of medical science,
10/2023, Letnik:
192, Številka:
5
Journal Article
Recenzirano
Introduction
Frailty is a clinical syndrome characterized by a decrease in strength, resistance and body physiological condition, making the individual more vulnerable, and increasing his/her risk of ...dependence and death. Kidney transplant (KT) is currently the best end-stage renal disease therapeutic alternative for certain individuals. Frailty status occurs in approximately 20% of KT patients. Thus, it was evaluated if there would be any change in frailty status level in a population of adult patients on chronic HD after receiving KT.
Material and method
A cross-sectional study was conducted on a population of adult hemodialysis patients (n: 57), with the objective of evaluating if there was a significant change in their clinical frailty score (CFS) after 6 months of KT. For the statistical analysis, the Student’s
t
-test, and the test of statistical significance between two proportions were applied.
Results
Mean CFS before KT was 4 (vulnerable), and after KT was 3 (robust). CFS value was significantly lower after KT (
p
value < 0.01).
Conclusion
A significant improvement was found between pre- and post-transplant clinical frailty scores in hemodialysis adult patients.
This paper describes the main characteristics of coronavirus diseases 2019 (COVID-19) patients suffering from acute kidney injury (AKI) assisted at a high complexity clinic in Barranquilla, Colombia. ...The patients included in this study (n = 48) were those with a positive diagnosis of COVID-19 confirmed by polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2, who had developed AKI during their hospital stay. Serum and urine parameters, as well as patient's viral load and clinical frailty scale (CFS) were recorded. A statistical analysis of the recorded parameters, such as comparisons, and correlations between variables of interest, were explored. The prevalence of COVID-19 induced AKI was 41%, being the majority of them classified as AKI network classification 3, with a renal replacement therapy requirement of 29%, and an associated mortality of 73%. AKI patients' mortality showed a significant positive correlation (33%) with patients' CFS score but not with their viral load. COVID-19 induced AKI significantly correlated with patients' frailty status but not to their viral load.
Our study aimed to describe the glomerular diseases, both primary glomerular disease (PGD) and secondary glomerular disease (SGD) in the Colombian Caribbean based on the first regional Colombian ...Nephropathy Registry (NEFRORED®). A descriptive and retrospective study of adult patients with glomerular diseases from the Colombian Caribbean region was made. All diagnoses by renal biopsy with light microscopy and immunofluorescence obtained between January 2008 and June 2018 were recorded. Eight hundred and seventy-one renal biopsies were obtained. The main clinical indication for biopsy was nephritic syndrome (36%). SGD was more frequent than PGD (55% vs. 45%). Within SGD group, lupus nephritis (LN) was the most frequent etiology (83%). Within PGD group, membranous nephropathy (33%) and focal segmental glomerulosclerosis (FSGS) (19%) were the most common glomerular diseases. At a 24-month follow-up, the patients with FSGS and paraproteinemia-mediated glomerular disease had the worst renal survival prognosis. This is the first Colombian Nephropathy Registry in a Caribbean population, demonstrating a high predominance of SGD due to LN.
Triple-negative breast cancer (TNBC) occurs more frequently in young (<50 years) non-Hispanic black and Hispanic/Latina women. It is considered the most aggressive subtype of breast cancer, although, ...recently, immune infiltrate has been associated with long-term survival, lower risk of death and recurrence, and response to neoadjuvant chemotherapy. The aim of this review was to evaluate the clinical impact of the immune infiltrate in TNBC by discussing whether its prognostic value varies across different populations. A comprehensive systematic search in databases such as PubMed and Web of Science was conducted to include papers focused on tumor-infiltrating lymphocytes (TILs) in TNBC in different population groups and that were published before January 2021. TNBC patients with higher levels of TILs had longer overall survival and disease-free survival times compared with TNBC patients with low TIL levels. Similar results were observed for CD4+, CD8+ TIL populations. On the other hand, patients with high TIL levels showed a higher rate of pathological complete response regardless of the population group (Asian, European, and American). These results altogether suggest that TIL subpopulations might have a prognostic role in TNBC, but the underlying mechanism needs to be elucidated. Although the prognosis value of TILs was not found different between the population groups analyzed in the revised literature, further studies including underrepresented populations with different genetic ancestries are still necessary to conclude in this regard.
Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia and kidney injury from thrombotic microangiopathy. P-aHUS ...occurs in approximately 1 in 25,000 pregnancies and is strongly related to complement dysregulation and pregnancy-related disorders, such as preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, resulting in adverse perinatal and fetal outcomes. Complement dysregulation in P-aHUS is commonly attributed to genetic mutations or autoantibodies affecting complement factors, including
,
, and
We present a case of a 25-year-old primigravida who experienced severe preeclampsia and HELLP syndrome followed by the development of complicated P-aHUS during the early postpartum period. The patient exhibited severe clinical manifestations, including hypertensive emergency, central nervous system involvement, renal impairment, and microangiopathic hemolytic anemia. Timely initiation of eculizumab therapy resulted in successful disease remission. Further genetic analysis revealed a likely rare pathogenic
gene variant.
La tetralogía de Fallot es una cardiopatía congénita cianosante compleja, con prevalencia considerable a nivel mundial, la cual requiere intervención en el primer año de vida, cuyas características ...clínicas tendrán variación conforme al grado de obstrucción pulmonar y la edad de presentación. Objetivo: Presentar una revisión sistemática de cómo debe realizarse el abordaje integral de la tetralogía de Fallot de acuerdo con la literatura actual. Metodología: Se realizó una revisión sistemática utilizando términos del MeSH y DeCS como “Tetralogía de Fallot”, “defectos del tabique interventricular”, “hipertrofia ventricular derecha”, “hipertensión pulmonar”, “defectos cardíacos congénitos”, “enfermedades y anomalías congénitas, hereditarias y neonatales”. La fuente fueron Sciencedirect, PubMed, Scopus y WoS. Se escogieron artículos indexados originales y metaanálisis. Conclusión: El pronóstico y las secuelas a largo plazo dependerá del diagnóstico oportuno, manejo médico y quirúrgico óptimos y, por tanto, del conocimiento fisiopatológico de la misma.
Metodología: Se analizaron los valores de resistencia de bacterias Gram positivas, Enterobacterias y Gram negativos no fermentadores reportados en cinco institutos prestadores de salud (IPS) del ...departamento del Atlántico, en dos periodos (preintervención e intervención), de 12 meses cada uno, entre junio de 2015 y mayo de 2017. Palabras clave: resistencia a medicamentos antibacterianos, antibióticos, prescripciones, servicio farmacéutico.
PDF
