Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy.

BACKGROUND: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown. PATIENTS AND METHODS: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions. RESULTS: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. Programmed death-ligand 1 tumour expression in assessable patients (274, 90.7%) was ≥50% in 76 (25.2%), 1%-49% in 84 (27.9%) and <1% in 113 (37.5%). Multivariable analysis showed pATB-exposed patients to have similar OS {hazard ratio (HR) = 1.42 [95% confidence interval (CI): 0.91-2.22]; P = 0.1207} and PFS [HR = 1.12 (95% CI: 0.76-1.63); P = 0.5552], compared to unexposed patients, regardless of performance status. Similarly, no difference with respect to ORR was found across pATB exposure groups (42.6% versus 57.4%, P = 0.1794). No differential effect was found depending on pATB exposure duration (≥7 versus <7 days) and route of administration (intravenous versus oral). Similarly, cATB was not associated with OS [HR = 1.29 (95% CI: 0.91-1.84); P = 0.149] and PFS [HR = 1.20 (95% CI: 0.89-1.63); P = 0.222] when evaluated as time-varying covariate in multivariable analysis. CONCLUSIONS: In contrast to what has been reported in patients receiving single-agent ICIs, pATB does not impair clinical outcomes to first-line chemo-immunotherapy of patients with NSCLC. pATB status should integrate currently available clinico-pathologic factors for guiding first-line treatment decisions, whilst there should be no concern in offering cATB during chemo-immunotherapy when needed.

Fascitis nodular de localización mamaria / Nodular fasciitis of the breast

La fascitis nodular es una neoplasia fibrosa autolimitada, que a menudo se confunde con un sarcoma debido a su rápido crecimiento y a su alta celularidad e índice mitótico. Se caracteriza por lesiones solitarias generalmente localizadas en fascias superficiales o profundas de tejidos blandos, sobre todo en las extremidades superiores y tronco de adultos jóvenes. La fascitis nodular de localización mamaria es excepcional y tanto clínica como radiológicamente puede simular un carcinoma mamario. Describimos los hallazgos clínicos, radiológicos e histopatológicos de un caso de fascitis nodular de localización mamaria en una mujer de 69 años de edad, que se inició con una tumoración palpable en unión de cuadrantes superiores de mama derecha de aparición brusca y rápido crecimiento. La biopsia percutánea caracteriza la lesión. Se realizó biopsia escisional, confirmándose el diagnóstico

Nodular fasciitis is a self-limiting fibrous neoplasm that is often mistaken for a sarcoma due to its rapid growth, cellularity and mitotic activity. It commonly arises in the superficial or deep fascia of the soft tissue, mostly in the upper extremities and trunk of young to middle-aged adults. In the breast, although rare, it can clinically and radiologically mimic a malignant neoplasm. We describe the clinical, radiological and histopathological findings of a case of nodular fasciitis located in the breast in a 69-year-old woman who presented with a palpable mass in the junction of the upper quadrants of the right breast. The mass showed abrupt onset and rapid growth. The lesion was characterized by core biopsy and the diagnosis was confirmed by excisional biopsy

Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening.

We describe in this work a successful virtual screening and experimental testing aimed to the identification of novel inhibitors of superoxide dismutase of the worm Taenia solium (TsCu/Zn-SOD), a human parasite. Conformers from LeadQuest(®) database of drug-like compounds were selected and then docked on the surface of TsCu/Zn-SOD. Results were screened looking for ligand contacts with receptor side-chains not conserved in the human homologue, with a subsequent development of a score optimization by a set of energy minimization steps, aimed to identify lead compounds for in vitro experiments. Six out of fifty experimentally tested compounds showed µM inhibitory activity toward TsCu/Zn-SOD. Two of them showed species selectivity since did not inhibit the homologous human enzyme when assayed in vitro.

Expression profiles of Dax1, Dmrt1, and Sox9 during temperature sex determination in gonads of the sea turtle Lepidochelys olivacea.

Sex determination is controlled either by genetic or environmental factors. In mammals Sry initiates determination but no homologue of this gene exists in non-mammalian species. Other genes of the mammalian sex-determining pathway have been identified in gonads of different vertebrates. Sox9, Dax1, and Dmrt1 are expressed at the onset of gonadal development in birds and reptiles. In the sea turtle Lepidochelys olivacea, a species with temperature sex determination (TSD), Sox9 is expressed in undifferentiated gonads at male- (MPT) or female-promoting temperatures (FPT). At MPT, Sox9 remains expressed in male gonads, but at FPT it is downregulated coinciding with the onset of the ovarian morphologic differentiation and female sex determination. At MPT however, male sex is determined early than at FPT in still undifferentiated gonads suggesting that other genes maintain Sox9 expression in testis. Here we used RT-PCR to study the expression profiles of Dax1, Dmrt1, and Sox9 in gonads of embryos of L. olivacea incubated at MPT or at FPT. The profiles were correlated with sex determination during and after the temperature-sensitive period (TSP). Dax1 maintained similar levels at both temperatures during the TSP. The Dax1 expression level increased significantly in ovaries compared to testes at stage 27, once they were morphologically distinct. The expression levels of Dmrt1 were higher at MPT than at FPT at all stages, in contrast with Sox9 levels which were similar at both temperatures at stages 23-25. Together, current results suggest that, whereas Dax1 is not involved in TSD in L. olivacea, upregulation of Dmrt1 and downregulation of Sox9 may play a role in male and female sex determination, respectively.

Glutathione S-transferase in helminth parasites.

Glutathione S-transferases (GSTs; EC 2.5.1.18) are a large family of multifunctional dimeric enzymes that conjugate reduced glutathione to electrophilic centers in hydrophobic organic compounds. The GST enzymatic activity has been described in the adult and larval stages of helminths. Several forms and isoforms of the enzyme have been purified and GST genes have also been isolated and expressed as recombinant proteins. The helminth GSTs participate in detoxification of lipid hydroperoxides and carbonyl cytotoxics produced by oxygen-reactive intermediates (ORI). The ORIs can come from the endogenous parasite metabolism or from the host immune system. The helminth GSTs are able to conjugate glutathione to xenobiotic compounds or to bind to anthelminth drugs. GST is usually localized near to host-parasite interface. This enzyme has been identified as a potentially vulnerable target in immunotherapy and chemotherapy. The present review compiles current knowledge about the biochemical characteristics of the enzyme, its presence, localization, induction, structural heterogeneity, relationship with mammalian GSTs, detoxification capacity and ability to induce protection in several animal models.

El trauma craneal por accidente del tránsito en terapia de cirugía

Se estudió la morbilidad y mortalidad del trauma craneoencefálico por accidente del tránsito en 165 pacientes ingresados en la unidad de terapia de cirugía del Hospital Militar "Dr. Carlos J. Finlay" durante el año 1990. Se concluyó que la contusión cerebral y el hematoma subdural son las causas más frecuentes de la alta letalidad. Se plantea que la medición intracraneal es necesaria y que la tomografía axial computarizada de cráneo debe ser realizada de urgencia, si está disponible, para mejorar el diagnóstico y tratamiento del trauma craneoencefálico (AU)