Prevention and treatment of cisplatin-induced ototoxicity in adults: A systematic review.

OBJECTIVES: Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients. METHODS: Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales. RESULTS: Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions. CONCLUSIONS: Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.

Factores pronósticos de la supervivencia en pacientes con melanoma de piel metastásico, que reciben primera línea de tratamiento con inmunoterapia anti PD-1 o régimen con anti PD-1 y anti CTLA-4, en el Instituto Nacional de Cancerología de Colombia / Prognostic factors for survival in patients with metastatic skin melanoma, receiving first-line treatment with anti-PD-1 or anti-PD-1 and anti-CTLA-4 immunotherapy regimen at the Instituto Nacional de Cancerología (Bogotá, Colombia)

Introducción. En melanoma metastásico, uno de los estándares de tratamiento es la inmunoterapia anti-PD-1 y anti-CTLA-4. El objetivo de esta investigación fue determinar factores pronósticos asociados con la supervivencia de pacientes con melanoma metastásico, con primera línea con inmunoterapia anti-PD-1 o anti-PD-1 y anti-CTLA-4, en el Instituto Nacional de Cancerología de Colombia.Métodos. Se revisaron 63 historias clínicas del Instituto Nacional de Cancerología de enero de 2016 a abril de 2020. Se realizó un análisis de supervivencia con método de Kaplan-Meier, prueba log-rank y regresión de Cox.Resultados. La mayoría de los pacientes fueron mujeres (58,7%); 47,6% tenían subtipo lentiginoso acral, 17,4% BRAF mutado, 20,6% compromiso en SNC, 50,8% recibieron nivolumab, 41,3% pembrolizumab y 7,9% nivolumab + ipilimumab. La mediana de supervivencia libre de progresión fue de 7,3 meses, con una tasa a 1, 2 y 3 años de 38,0%, 22,0% y 12,0% respectivamente; la mediana de supervivencia global fue 12,2 meses con una tasa a 1, 2 y 3 años de 50,0%, 25,0% y 19,0%. Como factor pronóstico protector para SLP se encontró el recibir nivolumab en comparación con pembrolizumab (HR=0,427; IC95% 0,21-0,86) y para SG el estado funcional al diagnóstico (ECOG 2 HR=12,38; IC95% 2,20-69,45).Conclusión. La SLP y SG fueron menores a la de ensayos clínicos aleatorizados en población caucásica, pero similar a la encontrada en estudios que incluyen mayor proporción del subtipo histológico lentiginoso acral, como la nuestra. Se encontraron como factores pronósticos el tipo de inmunoterapia utilizada y el estado funcional al diagnóstico.

Introduction: In metastatic melanoma, one of the standard treatments is anti-PD-1 and anti-CTLA-4 immunotherapy. This research aimed to determine prognostic factors associated with the survival of patients with metastatic melanoma who started first-line treatment with anti-PD-1 or anti-PD-1 and anti-CTLA-4 immunotherapy at the Instituto Nacional de Cancerología (INC) (Bogotá, Colombia).Methods: A total of 63 medical records from the INC were reviewed from January 2016 to April 2020. A survival analysis was performed using the Kaplan-Meier method, log-rank test, and Cox regression.Results: Most patients were women (58.7%); 47.6% had acral lentiginous subtype, 17.4% BRAF-mutated melanoma, 20.6% CNS involvement, 50.8% received nivolumab, 41.3% pembrolizumab, and 7.9% nivolumab + ipilimumab. Median progression-free survival (PFS) was 7.3 months with a rate at 1, 2, and 3 years of 38%, 22%, and 12%, respectively, while median overall survival (OS) was 12.2 months with a rate of 50%, 25%, and 19% at 1, 2, and 3 years, respectively. A protective prognostic factor for PFS was to receive nivolumab compared to pembrolizumab (HR=0.427; CI95% 0.21-0.86), and for OS, functional status at diagnosis (ECOG 2 HR=12.38; CI95% 2.20-69.45).Conclusion: PFS and OS were lower than those of randomized clinical trials in the Caucasian population, but similar to those found in studies that include a higher proportion of the acral lentiginous histological subtype, such as ours. The type of immunotherapy used and functional status at diagnosis were found as prognostic factors

Seguimiento de la paciente con diagnóstico de cáncer de mama. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacionalde Cancerología - Colombia / Follow-up of the patient with breast cancer history. Review of the evidence and approach at the Instituto Nacional de Cancerología - Colombia

Los supervivientes de cáncer se definen como aquellos individuos que han completado su tratamiento inicial y no tienen evidencia de la enfermedad. Para el caso de las pacientes supervivientes de cáncer de mama, el seguimiento involucra no sólo la vigilancia de la recaída locorregional y a distancia, así como la tamización de segundos primarios mamarios, sino también la evaluación de los efectos relacionados con las terapias recibidas. Hoy en día, existe controversia sobre cuál debe ser el método, la frecuencia, la duración y tipo de personal de la salud que realice el seguimiento de estas pacientes. Las guías de las distintas sociedades científicas muestran una variabilidad importante en las recomendaciones a este respecto. Este documento pretende revisar la mejor evidencia disponible sobre los procedimientos para la detección de la recaída locorregional, de las metástasis a distancia, de un segundo cáncer de mama contralateral y de los eventos adversos relacionados con los tratamientos para el cáncer de mama. Adicionalmente, se examinan los porcentajes y sitios de recidiva tumoral con relación al estadio clínico y a la biología tumoral

Cancer survivors are defined as those individuals who have completed their initial treatment and have no evidence of disease. In the case of breast cancer survivors, follow-up involves not only surveillance of locoregional and distant relapse, as well as screening for second primary breast cancers, but also evaluation of the effects related to the therapies received. Nowadays, there is controversy about what should be the method, the frequency, the duration and the type of health personnel that carry out the follow-up of these patients. The guides of the different scientific societies show a significant variability in the recommendations in this regard. This document aims to review the best available evidence on procedures for the detection of locoregional relapse, distant metastases, contralateral second breast cancer, and adverse events related to breast cancer treatments. Additionally, the percentages and sites of tumor recurrence are examined in relation to clinical stage and tumor biology

Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes.

Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.

Engineering the Oxidative Potency of Non-Heme Iron(IV) Oxo Complexes in Water for C-H Oxidation by a cis Donor and Variation of the Second Coordination Sphere.

A series of iron(IV) oxo complexes, which differ in the donor (CH2py or CH2COO-) cis to the oxo group, three with hemilabile pendant donor/second coordination sphere base/acid arms (pyH/py or ROH), have been prepared in water at pH 2 and 7. The νFe═O values of 832 ± 2 cm-1 indicate similar FeIV═O bond strengths; however, different reactivities toward C-H substrates in water are observed. HAT occurs at rates that differ by 1 order of magnitude with nonclassical KIEs (kH/kD = 30-66) consistent with hydrogen atom tunneling. Higher KIEs correlate with faster reaction rates as well as a greater thermodynamic stability of the iron(III) resting states. A doubling in rate from pH 7 to pH 2 for substrate C-H oxidation by the most potent complex, that with a cis-carboxylate donor, [FeIVO(Htpena)]2+, is observed. Supramolecular assistance by the first and second coordination spheres in activating the substrate is proposed. The lifetime of this complex in the absence of a C-H substrate is the shortest (at pH 2, 3 h vs up to 1.3 days for the most stable complex), implying that slow water oxidation is a competing background reaction. The iron(IV)═O complex bearing an alcohol moiety in the second coordination sphere displays significantly shorter lifetimes due to a competing selective intramolecular oxidation of the ligand.

Salen­manganese complexes for controlling ROS damage: Neuroprotective effects, antioxidant activity and kinetic studies.

A new manganese(III) complex [MnL1(DCA)(H2O)](H2O),1 [H2L1 is the chelating ligand N,N'-bis(2-hydroxy-3-methoxybenzylidene)-1,2-diaminopropane, and DCA is dicyanamide], has been prepared and characterized by different analytical and spectroscopic techniques. The tetragonally elongated octahedral geometry for the manganese coordination sphere was revealed by X-ray diffraction studies for 1. The antioxidant behavior of this complex and other manganese(III)-salen type complexes was tested through superoxide dismutase and catalase probes, and through the study of their neuroprotective effects in SH-SY5Y neuroblastoma cells. In this human neuronal model, these model complexes were found to improve cell survival in an oxidative stress model. During studies aimed to getting a better understanding of the kinetics of the processes involved in this antioxidant behavior, an important effect on the solvent in the kinetics of reaction of the complexes with H2O2 was revealed that suggests a change in the mechanism of reaction of the complexes. The kinetic data in methanol and buffered aqueous solutions correlate well with the results of the test of catalase activity, thus showing that the rate determining step in the catalytic cycle corresponds to the initial reaction of the complexes with H2O2.

Pitfalls in the ABTS Peroxidase Activity Test: Interference of Photochemical Processes.

ABTS (2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid) oxidation to form its radical cation in the presence of H2O2 is frequently used as a test for determining the peroxidase activity of enzyme mimics. Detailed studies using salen-type Mn(III) complexes show that photochemical processes involving H2O2, ABTS, and the complex itself can lead to erroneous results. The capability of the complexes to act as •OH scavengers can be also relevant when the mechanism of their biological activity is considered.

Coordination Chemistry of Cu2+ Complexes of Small N-Alkylated Tetra-azacyclophanes with SOD Activity.

A new tetraaza-pyridinophane macrocycle (L1) N-alkylated with two isopropyl and one methyl groups symmetrically disposed has been prepared and its behavior compared with those of the unsubstituted pyridinophane (L3) and the related compound with three methyl groups (L2). The protonation studies show that, first, a proton binds to the central methylated amine group of L1, while, second protonation leads to a reorganization of the protons that are at this stage attached to the lateral isopropylated amines. The X-ray structure of [HL1]+ agrees with the UV-vis and NMR studies as well as with the results of DFT calculations. The stability of the Cu2+ complexes decreases on increasing the bulkiness of the alkyl substituents of the amine groups. The crystal structures of [CuL1Cl](ClO4) and [CuL1(H2O)](ClO4)2·H2O show square pyramidal coordination geometries with the ligands disposed in a bent L-shaped conformation. Kinetic studies indicate that the rates of both complexation and ligand dissociation decrease with the bulkiness of the substituents, so that the stability changes are surely the results of compensating effects, complex formation dominating over complex dissociation. The pH dependence of the rate constants for complex formation cannot be explained by consideration of rapid pre-equilibria involving the different protonated forms of the ligand, and it has been interpreted in terms of a mechanism involving an acid-base equilibrium for a reaction intermediate. NBT SOD studies show that the Cu2+ complex of the bulkiest L1 ligand is the one having the highest activity (IC50 = 0.26(5) µM, kcat = 13.7 × 106 M-1 s-1) which can be associated with the poorer σ-donor ability of the tertiary amino groups, and the rigidity of the system, caused by the bulky isopropyl groups.

Hemoperitoneo en el puerperio debido a ruptura de vasos venosos uterinos asociado a endometriosis. Presentación de un caso y revisión de la literatura / Post-partum hemoperitoneum following uterine vessel rupture associated with endometriosis. Case report and review of the literature

Objetivo: realizar una revisión de la literatura sobre la epidemiología, etiología, diagnóstico y manejo de la ruptura de vasos uterinos en el embarazo.Materiales y métodos: Se presenta el caso de una mujer de 32 años quien desarrolla un hemoperitoneo espontáneo en el puerperio inmediato, secundario a la ruptura de los vasos uterinos superficiales en el Hospital Universitario Fundación Santa Fe de Bogotá, instituto de cuarto nivel, que atiende pacientes del aseguramiento contributivo privado. Se realizó una laparotomía e histerectomía de urgencia en la que se encontró tejido endometrial en cara posterior del útero y en fondo de saco posterior con sangrado venoso activo. Se realizó una búsqueda bibliográfica en las bases de datos electrónicas Medline/Pubmed, Ebsco, Ovid y ProQuest a partir de los términos hemoperitoneum, pregnancy, uterine vessel rupture y endometriosis sin limitación de idioma y diseño epidemiológico, publicados desde 1966 hasta la fecha.Resultados: se encontraron 34 artículos de interés, de estos se seleccionaron un total de 13: una guía de práctica clínica, 2 artículos de revisión y 10 reportes de casos. Conclusión: el hemoperitoneo durante el embarazo, como resultado de ruptura de los vasos uterinos, es una complicación rara, de etiología no clara y cuadro clínico poco específico. Para el manejo es necesario realizar un enfoque multidisciplinario, intervención quirúrgica temprana y correcta reposición del volumen intravascular.

Objective: To undertake a review of the literature on the epidemiology, etiology, diagnosis and management of uterine vessel ruptures in pregnancy.Materials and methods: A case of a 32 year old woman with spontaneous hemoperitoneum in the immediate post-partum period secondary to a rupture of superficial uterine vessels at Hospital Universitario Fundación Santa Fe, a high complexity institution that provides care to patients with private contributive health insurance coverage. Emergency laparotomy and hysterectomy were performed with a finding of endometrial tissue in the posterior aspect of the uterus and the posterior cul-de-sac, and active venous bleeding. A search of the literature was done in Medline/Pubmed, Ebsco, Ovid and ProQuest, using the terms "hemoperitoneum", "pregnancy", "uterine vessel rupture" and "endometriosis" with no language limitation and epidemiologic design, published since 1966 to this date. Results: Out of 34 articles of interest, 13 were selected: 1 clinical practice guideline, 2 review articles and 10 case reports. Conclusion: Hemoperitoneum in pregnancy, secondary to uterine vessel rupture is a rare complication of unclear etiology and non-specific clinical presentation. Management requires a multidisciplinary approach with early surgical intervention and correct intravascular volume replacement.