Cutaneous immune-related adverse events: incidence rates, risk factors and association with extracutaneous toxicity - a prospective study of 189 patients treated with checkpoint inhibitors at a Spanish tertiary care hospital.

BACKGROUND: Clinicians are increasingly prescribing immune checkpoint inhibitors (ICIs) to treat cancer, but the real-world incidence, characteristics and risk factors of cutaneous immune-related adverse events (cirAEs) are unclear. OBJECTIVES: To determine the incidence, features and risk factors of cirAEs and to measure their possible association with extracutaneous toxicity. METHODS: We conducted a prospective observational study in a Spanish tertiary care hospital, including people who started an ICI between March 2020 and May 2022. We used a survival analysis and a log-rank test to obtain and compare incidence rates, and a multivariate Cox model to detect risk factors for cirAEs. RESULTS: We included 189 patients, 82 (43.4%) of whom presented cutaneous toxicity. The incidence of cirAEs was 75.0 per 100 person-years, with a 50.0% probability of the appearance of a cirAE at 10 months of follow-up. The most frequent cirAE category was inflammatory dermatoses, and the most frequent types were pruritus, eczema and maculopapular eruptions. ICI combination therapy, a family history of psoriasis and rheumatological and pulmonary immune-related adverse events increased the risk of cirAEs. CONCLUSIONS: We found a high incidence of cirAEs, and they occurred early in the follow-up period. Dermatologists should be involved in the management of cirAEs, especially in people with risk factors.

Atypical pediatric presentation of lymphocytic thrombophilic arteritis: Diagnostic difficulties and recent nosological clarification.

A 4-year-old girl presented with a 2-month history of round, hypopigmented, slightly scaly patches measuring 1-6 cm and encircled by an erythematous halo, first appearing on the lower limbs then spreading to the whole body. Three biopsies were taken as the condition progressed, each showing a lymphocytic infiltrate affecting a medium-sized artery at the dermal-subcutaneous junction, with a concentric fibrin ring. These findings are characteristic of lymphocytic thrombophilic arteritis (LTA). The young age of our patient and the type of skin lesions she developed make this an atypical presentation of LTA, which usually manifests as hyperpigmented macules on the lower extremities, predominantly in dark-skinned women.

High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes.

An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.

Frontal and Insular Input to the Dorsolateral Temporal Pole in Primates: Implications for Auditory Memory.

The temporal pole (TP) has been involved in multiple functions from emotional and social behavior, semantic processing, memory, language in humans and epilepsy surgery, to the fronto-temporal neurodegenerative disorder (semantic) dementia. However, the role of the TP subdivisions is still unclear, in part due to the lack of quantitative data about TP connectivity. This study focuses in the dorsolateral subdivision of the TP: area 38DL. Area 38DL main input originates in the auditory processing areas of the rostral superior temporal gyrus. Among other connections, area 38DL conveys this auditory highly processed information to the entorhinal, rostral perirhinal, and posterior parahippocampal cortices, presumably for storage in long-term memory (Muñoz-López et al., 2015). However, the connections of the TP with cortical areas beyond the temporal cortex suggest that this area is part of a wider network. With the aim to quantitatively determine the topographical, laminar pattern and weighting of the lateral TP afferents from the frontal and insular cortices, we placed a total of 11 tracer injections of the fluorescent retrograde neuronal tracers Fast Blue and Diamidino Yellow at different levels of the lateral TP in rhesus monkeys. The results showed that circa 50% of the total cortical input to area 38DL originates in medial frontal areas 14, 25, 32, and 24 (25%); orbitofrontal areas Pro and PAll (15%); and the agranular, parainsular and disgranular insula (10%). This study sets the anatomical bases to better understand the function of the dorsolateral division of the TP. More specifically, these results suggest that area 38DL forms part of the wider limbic circuit that might contribute, among other functions, with an auditory component to multimodal memory processing.

Umbilical Cord Blood Cytomegalovirus Serostatus Does Not Have an Impact on Outcomes of Umbilical Cord Blood Transplantation for Acute Leukemia.

Several studies have reported an impact of adult hematopoietic stem cell donor cytomegalovirus (CMV) serostatus on allogeneic hematopoietic cell transplantation outcomes. Limited data, however, are available on the impact of cord blood unit (CBU) CMV serostatus on allogeneic umbilical cord blood transplantation (UCBT) outcomes. We analyzed, retrospectively, the impact of CBU CMV serostatus on relapse incidence (RI) and 2-year nonrelapse mortality (NRM) of single-unit CBU transplantation for acute leukemia. Data from 1177 de novo acute leukemia pediatric and adult patients transplanted within European Group for Blood and Marrow Transplantation centers between 2000 and 2012 were analyzed. CBUs were provided by the European Cord Blood Banks. The median follow-up time for live patients was 59.9 months. The recipients of CMV-seropositive and -seronegative CBUs showed a comparable RI (33% versus 35%, respectively, P = .6) and 2-year cumulative incidence of NRM (31% versus 32%, respectively, P = .5). We conclude that CBU CMV serostatus did not influence RI and NRM in de novo acute leukemia patients after allo-UCBT and should not be included as a criteria for cord blood choice.

[Emphysematous cystitis: Report of 2 cases with different outcomes]. / CYSTITIS ENFISEMATOSA: 2 CASOS CON DIFERENTE EVOLUCIÓN.

OBJECTIVE: To report two cases of emphysematous cystitis, a rare, potentially serious disease. METHODS: Analysis of two different cases treated in our center and review of the existing literature. RESULTS: One patient underwent emergency surgery (radical cystectomy) due to the advanced stage of the disease. The second patient, whose was in an initial stage, benefited from a new treatment, consisting of hyperbaric oxygen and wide spectrum antibiotics. CONCLUSIONS: Early diagnosis is the cornerstone of the conservative management of the disease. Hyperbaric oxygen therapy may be beneficial due to the improvement in oxygenation of the tissues affected by the disease.

An engineered plant that accumulates higher levels of heavy metals than Thlaspi caerulescens, with yields of 100 times more biomass in mine soils.

Nicotiana glauca transformed with TaPCS1 was tested for its application in phytoremediation. When plantlets were grown in mine soils containing Cu, Zn, and Pb (42, 2600, and 1500 mg kg(-1)) the plant showed high levels of accumulation especially of Zn and Pb. Adult plants growing in mine soils containing different heavy metal concentrations showed a greater accumulation as well as an extension to a wider range of elements, including Cd, Ni and B. The overexpressed gene confers up to 9 and 36 times more Cd and Pb accumulation in the shoots under hydroponic conditions, and a 3- and 6-fold increase in mining soils. When the hyperaccumulator Thlaspi caerulescens was compared, the results were higher values of heavy metal and Boron accumulation, with a yield of 100 times more biomass. Thlaspi was unable to survive in mining soils containing either a level higher than 11000 mg kg(-1) of Pb and 4500 mg kg(-1) of Zn, while engineered plants yielded an average of 0.5 kg per plant.

Terapia floral para estudiantes de violín / Floral therapy for violin students

La doble carga docente que afrontan los estudiantes de música, particularmente los de violín y viola, provoca en esos alumnos diferentes manifestaciones sintomáticas, que de no ser estudiadas y tratadas a tiempo pueden ocasionar enfermedades diversas, lo cual justifica entre otros métodos, el empleo de sencias florales, como tratamiento causal, medicamentoso, holístico, reccional y clínico. Los compuestos obtenidos a partir de las esencias de las flores actuan sobre el desequilibrio eneérgético del individuo, y curan, entre otras alteraciones, los trastornos causados por los estados emocionales. Los remedios florales legados por el Dr. Edward Bach ayudan a aliviar los dolores, brindan armonía y como no poseen principios químicos activos, no son tóxicos y pueden ser ingeridos sin ningún riesgo