Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study.

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.

T-cell immune profile in blood of systemic mastocytosis: Association with disease features.

BACKGROUND: Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated mast cells (MC). KIT-mutated MC display activated features and release MC mediators that might act on the tumour microenvironment and other immune cells. Here, we investigated the distribution of lymphocyte subsets in blood of patients with distinct subtypes of SM and determined its association with other disease features. METHODS: We studied the distribution of TCD4+ and TCD4- cytotoxic cells and their subsets, as well as total NK- and B cells, in blood of 115 SM patients-38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)- and 83 age-matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage KITD816V , the alpha-tryptasemia genotype (HαT) and the clinical manifestations of the disease. RESULTS: SM patients showed decreased counts (vs. HD) of TCD4- cytotoxic cells, NK cells and several functional subsets of TCD4+ cells (total Th1, Th2-effector memory, Th22-terminal effector and Th1-like Tregs), together with increased T-follicular-helper and Th1/Th17-like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC-restricted KITD816V and in cases with a HαT+ versus HαT- genotype. Unique immune profiles were found among BMM and ISM patients with MC-restricted KITD816V who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms. CONCLUSION: Our results reveal altered T- and NK-cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by KITD816V , the HαT genotype and specific clinical manifestations of the disease.

Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals.

BACKGROUND: A close association between hereditary alpha-tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established. OBJECTIVE: To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease. METHODS: A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected. RESULTS: HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT- mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT- patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively). CONCLUSION: The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.

Germline Variants Incidentally Detected via Tumor-Only Genomic Profiling of Patients With Mesothelioma.

Importance: Patients with mesothelioma often have next-generation sequencing (NGS) of their tumor performed; tumor-only NGS may incidentally identify germline pathogenic or likely pathogenic (P/LP) variants despite not being designed for this purpose. It is unknown how frequently patients with mesothelioma have germline P/LP variants incidentally detected via tumor-only NGS. Objective: To determine the prevalence of incidental germline P/LP variants detected via tumor-only NGS of mesothelioma. Design, Setting, and Participants: A series of 161 unrelated patients with mesothelioma from a high-volume mesothelioma program had tumor-only and germline NGS performed during April 2016 to October 2021. Follow-up ranged from 18 months to 7 years. Tumor and germline assays were compared to determine which P/LP variants identified via tumor-only NGS were of germline origin. Data were analyzed from January to March 2023. Main Outcomes and Measures: The proportion of patients with mesothelioma who had P/LP germline variants incidentally detected via tumor-only NGS. Results: Of 161 patients with mesothelioma, 105 were male (65%), the mean (SD) age was 64.7 (11.2) years, and 156 patients (97%) self-identified as non-Hispanic White. Most (126 patients [78%]) had at least 1 potentially incidental P/LP germline variant. The positive predictive value of a potentially incidental germline P/LP variant on tumor-only NGS was 20%. Overall, 26 patients (16%) carried a P/LP germline variant. Germline P/LP variants were identified in ATM, ATR, BAP1, CHEK2, DDX41, FANCM, HAX1, MRE11A, MSH6, MUTYH, NF1, SAMD9L, and TMEM127. Conclusions and Relevance: In this case series of 161 patients with mesothelioma, 16% had confirmed germline P/LP variants. Given the implications of a hereditary cancer syndrome diagnosis for preventive care and familial counseling, clinical approaches for addressing incidental P/LP germline variants in tumor-only NGS are needed. Tumor-only sequencing should not replace dedicated germline testing. Universal germline testing is likely needed for patients with mesothelioma.

Characterization of the antioxidant activity, carotenoid profile by HPLC-MS of exotic colombian fruits (goldenberry and purple passion fruit) and optimization of antioxidant activity of this fruit blend.

The consumption of antioxidants can prevent chronic non-communicable diseases and the exotic Colombian fruits, goldenberry (Physalis peruviana L.) and purple passion fruit (Passiflora edulis f. Edulis Sims), are rich in bioactive compounds. The aim of this work was to characterize and optimize the antioxidant activity of these fruits blend. The fruits were classified according to their maturity stages, the freeze-dried extracts were physiochemically characterized, and polyphenols, carotenoids and antioxidant activity were quantified, and an experimental mixture design was applied to optimize the antioxidant activity of the bend. For the goldenberry the maturity stage 3 had higher iron-reducing capacity and higher content of polyphenols. Meanwhile, for the purple passion fruit, this maturity stage had higher antioxidant activity by all methodologies and a higher concentration of polyphenols; the ultrasound-assisted extraction showed statistical differences for polyphenols, ABTS and FRAP. Antioxidant activity showed significant differences (p < 0.05) between samples (TBARS (3.98 ± 0.14 and 7.03 ± 0.85 µM-MDA/g), ABTS (36.53 ± 2.66 and 29.4 ± 4.88 µMTrolox/g), DPPH (36.53 ± 2.66 and 23.90 ± 0.96µMTrolox/g), ORAC (23.02 ± 0.36 and 32.44 ± 0.94 µM Trolox/g) and total polyphenols (5, 29 ± 0.34 and 9.12 ± 0.37mgGA/g). Some of the carotenoids identified by HPLC-MS in both fruits were lutein, α and ß-carotene, phytoene and lycopene. The optimum bend was goldenberry 0.83 and purple passion fruit 0.17.

Clinical guideline variability in the diagnosis of hereditary hematopoietic malignancy syndromes.

A growing understanding of the complexities of hematopoietic malignancies necessitates the existence of clinical recommendations that are sufficiently comprehensive. Although hereditary hematopoietic malignancies (HHMs) are increasingly recognized for conferring risk of myeloid malignancy, frequently utilized clinical recommendations have never been appraised for the ability to reliably guide HHM evaluation. We assessed established society-level clinical guidelines for inclusion of critical HHM genes and graded the strength of testing recommendations. We uncovered a substantial lack of consistency of recommendations guiding HHM evaluation. Such heterogeneity in guidelines likely contributes to refusal by payers to support HHM testing, leading to underdiagnoses and lost opportunities for clinical surveillance.

The Lambda Variant in Argentina: Analyzing the Evolution and Spread of SARS-CoV-2 Lineage C.37.

The second wave of COVID-19 occurred in South America in early 2021 and was mainly driven by Gamma and Lambda variants. In this study, we aimed to describe the emergence and local genomic diversity of the SARS-CoV-2 Lambda variant in Argentina, from its initial entry into the country until its detection ceased. Molecular surveillance was conducted on 9356 samples from Argentina between October 2020 and April 2022, and sequencing, phylogenetic, and phylogeographic analyses were performed. Our findings revealed that the Lambda variant was first detected in Argentina in January 2021 and steadily increased in frequency until it peaked in April 2021, with continued detection throughout the year. Phylodynamic analyses showed that at least 18 introductions of the Lambda variant into the country occurred, with nine of them having evidence of onward local transmission. The spatial--temporal reconstruction showed that Argentine clades were associated with Lambda sequences from Latin America and suggested an initial diversification in the Metropolitan Area of Buenos Aires before spreading to other regions in Argentina. Genetic analyses of genome sequences allowed us to describe the mutational patterns of the Argentine Lambda sequences and detect the emergence of rare mutations in an immunocompromised patient. Our study highlights the importance of genomic surveillance in identifying the introduction and geographical distribution of the SARS-CoV-2 Lambda variant, as well as in monitoring the emergence of mutations that could be involved in the evolutionary leaps that characterize variants of concern.

Poly(vinyl alcohol)/Silk Fibroin/Ag-NPs Composite Nanofibers as a Substrate for MG-63 Cells' Growth.

Nanofiber scaffolds of polyvinyl alcohol, silk fibroin from Bombyx mori cocoons, and silver nanoparticles were developed as a substrate for MG-63 growth. The fiber morphology, mechanical properties, thermal degradation, chemical composition, and water contact angle were investigated. In vitro tests were performed by the cell viability MTS test of MG-63 cells on electrospun PVA scaffolds, mineralization was analyzed by alizarin red, and the alkaline phosphatase (ALP) assay was evaluated. At higher PVA concentrations, Young's modulus (E) increased. The addition of fibroin and silver nanoparticles improved the thermal stability of PVA scaffolds. FTIR spectra indicated characteristic absorption peaks related to the chemical structures of PVA, fibroin, and Ag-NPs, demonstrating good interactions between them. The contact angle of the PVA scaffolds decreased with the incorporation of fibroin and showed hydrophilic characteristics. In all concentrations, MG-63 cells on PVA/fibroin/Ag-NPs scaffolds had higher cell viability than PVA pristine. On day ten of culture, PVA18/SF/Ag-NPs showed the highest mineralization, observed by the alizarin red test. PVA10/SF/Ag-NPs presented the highest alkaline phosphatase activity after an incubation time of 37 h. The achievements indicate the potential of the nanofibers of PVA18/SF/Ag-NPs as a possible substitute for bone tissue engineering (BTE).

Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay.

INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

Optimizing the Effects of Nisin and NaCl to Thermal Inactivate Listeria monocytogenes in Ground Beef with Chipotle Sauce During Sous-vide Processing.

Mild cooking thermal treatments, like sous-vide, can compromise ground meat entrees such as meatballs with chipotle sauce, especially when salt levels are reduced during its preparation. Listeria monocytogenes is a thermoresistant pathogen that can be in ready-to-eat food. On the other hand, nisin, due to its thermal stability, can be a good alternative to aid on the thermal inactivation of L. monocytogenes and ensure meat safety. The objective was to optimize the amount of nisin and salt concentrations to thermally inactivate L. monocytogenes during the sous-vide cooking of ground beef marinated in chipotle sauce, and to generate a predictive model. A four-strain cocktail was prepared and inoculated in ground beef in combination (3:2) with chipotle sauce added with nisin (0-150 IU) and salt (0-2%). After that, meat samples were sous-vide cooked at different temperatures, nisin, and salt concentrations, established by a central composite design. Depending on the levels of these factors, D-values ranged from 49.71 to 0.27 min. A predictive model (p < 0.05) was obtained by response surface, which described that D-values variation was explained by the linear effects of the three factors, the interaction between nisin and temperature, and the quadratic effects of salt and temperature. It was also observed that nisin presented a bactericidal effect while salt presented a protective effect during the thermal inactivation of L. monocytogenes. Adding 120 IU of nisin and 0.4% of salt to the meat product at 63°C temperature can help to ensure food safety by making L. monocytogenes cells more sensitive to the lethal effect of heat. The model developed in this study can be used by food processors for planning and designing effective levels of salt and nisin to thermally inactivate L. monocytogenes in ground beef products marinated with chipotle sauce to ensure their safety.

Manejo de perforaciones, fugas y fístulas del tracto gastrointestinal con clip sobre el endoscopio. Experiencia de un centro oncológico Latinoamericano / Management of perforations, leaks and fistulas of the gastrointestinal tract with over the scope clip. Experience at a Latin American cancer center

Introducción. Las fístulas derivadas de enfermedades neoplásicas del tracto digestivo, así como las fugas posteriores a procedimientos quirúrgicos, no son infrecuentes y ocasionan una morbilidad importante cuando se manejan de forma quirúrgica. También durante los procedimientos endoscópicos se pueden presentar perforaciones y, si se logra un manejo no operatorio, se alcanza una adecuada recuperación. El objetivo de este estudio fue describir las características clínicas y los resultados de los pacientes con perforaciones, fístulas y fugas del tracto gastrointestinal, manejadas endoscópicamente con clip sobre el endoscopio. Métodos. Estudio descriptivo, retrospectivo, de pacientes con perforación, fuga o fístula postoperatoria, llevados a endoscopía digestiva con colocación de clip sobre el endoscopio, en el Instituto Nacional de Cancerología en Bogotá, D.C., Colombia, entre enero de 2016 y abril de 2020. Resultados. Se incluyeron 21 pacientes, 52,4 % de ellos mujeres. La mediana de edad fue de 66 años y del diámetro del defecto fue de 9 mm. En el 95 % se logró éxito técnico. Hubo éxito clínico temprano en el 85,7 % de los casos. El 76,1 % de los pacientes permanecieron sin síntomas a los 3 meses de seguimiento. Conclusiones. El manejo de perforaciones, fugas y fístulas con clip sobre el endoscopio parece ser factible y seguro. En la mayoría de estos pacientes se logró la liberación del clip y la identificación endoscópica del cierre inmediatamente después del procedimiento; sin embargo, en el caso de las fístulas, no se alcanzó el éxito clínico tardío en todos los casos

Introduction. Fistula of the digestive tract derived from neoplastic diseases as well as leaks following surgical procedures are not uncommon and usually cause significant morbidity when are managed surgically. Diagnostic and therapeutic endoscopic procedures may present perforations during their performance; if they are managed non-operatively, an adequate recovery is obtained. The purpose of this study was to describe the clinical characteristics and the short- and long-term outcomes of patients with perforations, fistulas and leaks of the gastrointestinal tract managed endoscopically with over the scope clip (OTSC). Methods. Descriptive, retrospective study of patients brought to digestive endoscopy with OTSC placement with diagnosis of postoperative perforation, leak or fistula at the National Cancer Institute in Bogota, Colombia, between January 2016 and April 2020. Results. Twenty-one patients were taken for OTSC application for the management of perforations, leaks and fistulas of the gastrointestinal tract, 52.4% of them were women. The median age was 66 years. The median diameter of the defect was 9 mm. Technical success was achieved in 95%. Early clinical success was described in 85.7% of the cases; 76.1% of patients remained symptom-free at 3-month follow-up. Conclusions. Management of perforations, leaks and fistulas with OTSC appears to be feasible and safe. In most of these patients, clip release and endoscopic identification of closure was achieved immediately after management; however, in the case of fistulas, late clinical success was not achieved in all cases

Situación actual de la laparoscopía de estadificación en pacientes con cáncer gástrico en Colombia: ¿Cómo lo estamos haciendo?

Introducción. La laparoscopía de estadificación permite identificar con gran precisión el compromiso locorregional avanzado y metastásico a peritoneo en los pacientes con cáncer gástrico. Las guías internacionales aún difieren en las indicaciones para incluir este procedimiento como parte del proceso de estadificación. Métodos. Se diseñó una encuesta dirigida a cirujanos residentes en Colombia, sobre el uso de la laparoscopía de estadificación en los pacientes con cáncer gástrico. Se analizaron los resultados y con base en la evidencia disponible se proponen algunas pautas en las indicaciones y técnica del procedimiento. Resultados. Respondieron la encuesta 74 cirujanos; el 43,8 % considera que el objetivo de la laparoscopía de estadificación es descartar la carcinomatosis peritoneal. El 54,1 % realiza el procedimiento en estadios tempranos, sin embargo, el 48,6 % considera realizarla solo en pacientes con sospecha de carcinomatosis por imágenes. Las áreas evaluadas con mayor frecuencia por los cirujanos (más del 85 %) son la superficie hepática, las cúpulas diafragmáticas, los recesos parietocólicos y la pelvis. Las zonas evaluadas en menor frecuencia son la válvula ileocecal (40,5 %) y el ligamento de Treitz (39 %). El 33 % de los cirujanos no toma rutinariamente citología peritoneal. Conclusión. Este trabajo muestra la tendencia de los cirujanos en el uso de la laparoscopía de estadificación en pacientes con cáncer gástrico. A pesar de encontrar resultados muy positivos en relación con las indicaciones y técnica del procedimiento, es necesario analizar la evidencia disponible para su uso según cada escenario y mejorar la sistematización del procedimiento.

Introduction. In patients with gastric cancer, staging laparoscopy allows advanced locoregional and metastatic involvement to the peritoneum to be identified with high accuracy. International guidelines still differ indications to include this procedure as part of the staging process. Methods. A survey was designed for surgeons practicing in Colombia on the use of staging laparoscopy in gastric cancer patients. The results were analyzed and based on the available evidence some guidelines on the indications and technique of the procedure were proposed. Results. 74 surgeons responded to the survey and 39.7% consider that staging laparoscopy is a reliable tool to define resectability. 43.8% of surgeons consider that the objective of staging laparoscopy is to rule out peritoneal carcinomatosis and 54.1% perform the procedure in early stages; however, 48.6% consider performing it only in patients with suspected carcinomatosis by imaging. The areas evaluated by most surgeons (>85%) were the hepatic surface, diaphragmatic domes, parietocolic recesses and pelvis. The least frequently evaluated areas were the ileocecal valve (40.5%) and the ligament of Treitz (39%). Peritoneal cytology is not routinely taken by 33% of surgeons. Conclusions. This study provides insight into surgeons' trends in the use of staging laparoscopy in gastric cancer patients. Despite finding very positive results in relation to the indications and technique of the procedure for many surgeons, it is necessary to analyze the available evidence for the use of staging laparoscopy according to each scenario of gastric cancer patients, and a better systematization of the procedure is necessary.

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis.

BACKGROUND: Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. OBJECTIVE: To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. METHODS: A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. RESULTS: Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1ß (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases. CONCLUSIONS: SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.

Mast Cell Activation Syndromes: Comparison Between Two Scoring Models to Predict for Mast Cell Clonality.

BACKGROUND: The Red Española de Mastocitosis (Spanish Network on Mastocytosis) score (REMAs) and the National Institutes of Health idiopathic clonal anaphylaxis score (NICAS) were developed for more efficient screening of mast cell (MC) clonality in MC activation syndromes. In a limited idiopathic anaphylaxis case series, the NICAS showed higher accuracy compared with the REMAs. OBJECTIVE: To compare the performance of the REMAs against the NICAS in the diagnosis of MC clonality. METHODS: We compared the diagnostic value of the REMAs against the NICAS in 182 patients (63% men, median age 56 years) who presented with anaphylaxis triggered by Hymenoptera venom allergy (45%), drugs (15%), food (11%), idiopathic anaphylaxis (20%), and mixed causes (10%). KIT mutation was assessed in parallel in whole blood and bone marrow (BM) and, when negative, in highly purified BM MC. TPSAB1 was genotyped in a subset of 71 patients. RESULTS: We found higher accuracy and rates of correctly classified patients for the REMAs (82% and 84%) compared with the NICAS (75% and 75%; P = .02 and P = .03, respectively), particularly among men (P = .05), patients with systemic mastocytosis (P = .05), those presenting anaphylaxis owing to any cause featuring urticaria (P = .04), cardiovascular symptoms (P = .02), and/or presyncope (P = .02) and those with a blood-negative/BM-positive KIT mutational profile (P = .002), but not hereditary α-tryptasemia-associated genotypes. Combined assessment of the REMAs and KITD816V in blood yielded an overall improved classification efficiency of 86% versus 84% for REMAs. CONCLUSIONS: The combined use of the REMAs and blood detection of KITD816V is recommended, but more sensitive blood-based molecular assays to detect KITD816V are needed.

KITD816V mutation in blood for the diagnostic screening of systemic mastocytosis and mast cell activation syndromes.

BACKGROUND: Current diagnostic algorithms for systemic mastocytosis (SM) rely on the detection of KITD816V in blood to trigger subsequent bone marrow (BM) investigations. METHODS: Here, we correlated the KITD816V mutational status of paired blood and BM samples from 368 adults diagnosed with mast cell activation syndrome (MCAS) and mastocytosis and determined the potential utility of investigating KITD816V in genomic DNA from blood-purified myeloid cell populations to increase diagnostic sensitivity. In a subset of 69 patients, we further evaluated the kinetics of the KITD816V cell burden during follow-up and its association with disease outcome. RESULTS: Our results showed a high correlation (P < .0001) between the KITD816V mutation burden in blood and BM (74% concordant samples), but with a lower mean of KITD816V-mutated cells in blood (P = .0004) and a high rate of discordant BM+ /blood- samples particularly among clonal MCAS (73%) and BM mastocytosis (51%), but also in cutaneous mastocytosis (9%), indolent SM (15%), and well-differentiated variants of indolent SM (7%). Purification of different compartments of blood-derived myeloid cells was done in 28 patients who were BM mast cell (MC)+ /blood- for KITD816V, revealing KITD816V-mutated eosinophils (56%), basophils (25%), neutrophils (29%), and/or monocytes (31%) in most (61%) patients. Prognostically, the presence of ≥3.5% KITD816V-mutated cells (P < .0001) and an unstable KITD816V mutation cell burden (P < .0001) in blood and/or BM were both associated with a significantly shortened progression-free survival (PFS). CONCLUSIONS: These results confirm the high specificity but limited sensitivity of KITD816V analysis in whole blood for the diagnostic screening of SM and other primary MCAS, which might be overcome by assessing the mutation in blood-purified myeloid cell populations.

Situación actual de la laparoscopía de estadificación en pacientes con cáncer gástrico en Colombia: Cómo lo estamos haciendo? / Current situation of staging laparoscopy in patients with gastric cancer in Colombia: How are we doing it?

Introducción. La laparoscopía de estadificación permite identificar con gran precisión el compromiso locorregional avanzado y metastásico a peritoneo en los pacientes con cáncer gástrico. Las guías internacionales aún difieren en las indicaciones para incluir este procedimiento como parte del proceso de estadificación. Métodos. Se diseñó una encuesta dirigida a cirujanos residentes en Colombia, sobre el uso de la laparoscopía de estadificación en los pacientes con cáncer gástrico. Se analizaron los resultados y con base en la evidencia disponible se proponen algunas pautas en las indicaciones y técnica del procedimiento. Resultados. Respondieron la encuesta 74 cirujanos; el 43,8 % considera que el objetivo de la laparoscopía de estadificación es descartar la carcinomatosis peritoneal. El 54,1 % realiza el procedimiento en estadios tempranos, sin embargo, el 48,6 % considera realizarla solo en pacientes con sospecha de carcinomatosis por imágenes. Las áreas evaluadas con mayor frecuencia por los cirujanos (más del 85 %) son la superficie hepática, las cúpulas diafragmáticas, los recesos parietocólicos y la pelvis. Las zonas evaluadas en menor frecuencia son la válvula ileocecal (40,5 %) y el ligamento de Treitz (39 %). El 33 % de los cirujanos no toma rutinariamente citología peritoneal. Conclusión. Este trabajo muestra la tendencia de los cirujanos en el uso de la laparoscopía de estadificación en pacientes con cáncer gástrico. A pesar de encontrar resultados muy positivos en relación con las indicaciones y técnica del procedimiento, es necesario analizar la evidencia disponible para su uso según cada escenario y mejorar la sistematización del procedimiento

Introduction. In patients with gastric cancer, staging laparoscopy allows advanced locoregional and metastatic involvement to the peritoneum to be identified with high accuracy. International guidelines still differ indications to include this procedure as part of the staging process. Methods. A survey was designed for surgeons practicing in Colombia on the use of staging laparoscopy in gastric cancer patients. The results were analyzed and based on the available evidence some guidelines on the indications and technique of the procedure were proposed. Results. 74 surgeons responded to the survey and 39.7% consider that staging laparoscopy is a reliable tool to define resectability. 43.8% of surgeons consider that the objective of staging laparoscopy is to rule out peritoneal carcinomatosis and 54.1% perform the procedure in early stages; however, 48.6% consider performing it only in patients with suspected carcinomatosis by imaging. The areas evaluated by most surgeons (>85%) were the hepatic surface, diaphragmatic domes, parietocolic recesses and pelvis. The least frequently evaluated areas were the ileocecal valve (40.5%) and the ligament of Treitz (39%). Peritoneal cytology is not routinely taken by 33% of surgeons. Conclusions. This study provides insight into surgeons' trends in the use of staging laparoscopy in gastric cancer patients. Despite finding very positive results in relation to the indications and technique of the procedure for many surgeons, it is necessary to analyze the available evidence for the use of staging laparoscopy according to each scenario of gastric cancer patients, and a better systematization of the procedure is necessary

Moderate ethanol exposure during early ontogeny of the rat alters respiratory plasticity, ultrasonic distress vocalizations, increases brain catalase activity, and acetaldehyde-mediated ethanol intake.

Early ontogeny of the rat (late gestation and postnatal first week) is a sensitive period to ethanol's positive reinforcing effects and its detrimental effects on respiratory plasticity. Recent studies show that acetaldehyde, the first ethanol metabolite, plays a key role in the modulation of ethanol motivational effects. Ethanol brain metabolization into acetaldehyde via the catalase system appears critical in modulating ethanol positive reinforcing consequences. Catalase system activity peak levels occur early in the ontogeny. Yet, the role of ethanol-derived acetaldehyde during the late gestational period on respiration response, ultrasonic vocalizations (USVs), and ethanol intake during the first week of the rat remains poorly explored. In the present study, pregnant rats were given a subcutaneous injection of an acetaldehyde-sequestering agent (D-penicillamine, 50 mg/kg) or saline (0.9% NaCl), 30 min prior to an intragastric administration of ethanol (2.0 g/kg) or water (vehicle) on gestational days 17-20. Respiration rates (breaths/min) and apneic episodes in a whole-body plethysmograph were registered on postnatal days (PDs) 2 and 4, while simultaneously pups received milk or ethanol infusions for 40-min in an artificial lactation test. Each intake test was followed by a 5-min long USVs emission record. On PD 8, immediately after pups completed a 15-min ethanol intake test, brain samples were collected and kept frozen for catalase activity determination. Results indicated that a moderate experience with ethanol during the late gestational period disrupted breathing plasticity, increased ethanol intake, as well brain catalase activity. Animals postnatally exposed to ethanol increased their ethanol intake and exerted differential affective reactions on USVs and apneic episodes depending on whether the experience with ethanol occur prenatal or postnatally. Under the present experimental conditions, we failed to observe, a clear role of acetaldehyde mediating ethanol's effects on respiratory plasticity or affective states, nevertheless gestational acetaldehyde was of crucial importance in determining subsequent ethanol intake affinity. As a whole, results emphasize the importance of considering the participation of acetaldehyde in fetal programming processes derived from a brief moderate ethanol experience early in development, which in turn, argues against "safe or harmless" ethanol levels of exposure.

Asociación entre tiempo de uso de teléfono celular, nivel de actividad física y rendimiento académico en universitarios / Association between time spent on a cell phone, physical activity level, and academic performance in college students

Introducción: El aumento del uso de teléfono celular y la baja actividad física en universitarios se han asociado a un bajo rendimiento académico. Objetivo: Analizar la relación entre tiempo de uso del teléfono celular, el nivel de actividad física y rendimiento académico en estudiantes universitarios. Materiales y métodos: Estudio de alcance correlacional y temporalidad longitudinal. Participaron 36 estudiantes universitarios, a quienes se evaluó durante un semestre, el tiempo que destinaron al uso de teléfono celular, a través de la aplicación "Moment" y la actividad física mediante la aplicación "Pacer". Se registró el rendimiento académico con el promedio de notas. Resultados: Durante el semestre, los hombres realizaron mayor actividad física y utilizaron por mayor tiempo el teléfono. En periodos de evaluación, las mujeres tuvieron mayor actividad física y menor uso del teléfono celular (p=0,019 y p=0,033, respectivamente). Además, los hombres que tuvieron mejores notas promedio hacían un menor número de pickups diarios (p=0,032). Conclusiones: Los hombres universitarios son físicamente más activos y usan más el celular durante el semestre, aunque en periodo de evaluaciones las mujeres tienden a ser más activas y usar menos tiempo su celular. Los universitarios que usan menos el teléfono celular tienen mejor rendimiento académico.

Introduction: Low academic performance of college students has been associated with an increase in time spent on cell phones and a low physical activity. Objective: To analyze the relationship between time spent on cell phones, physical activity level, and academic performance in college students. Materials and methods: A study with a correlational and longitudinal temporality approach. During a semester, 36 college students were assessed on the time they spent using cell phones and their physical activity levels through the Moment and Pacer applications, respectively. Academic performance was monitored through report cards. Results: Men engaged in more physical activity and used cell phones more frequently during the analyzed period, while women showed higher physical activity levels and lower cell phone usage during evaluation periods (p=0.019 y p=0.033, respectively). Also, men who had better grade averages showed lower number of daily pickups (p=0.032). Conclusions: College men show higher physical activity levels and longer cell phone usage during the semester, while women tend to be more active and use their cell phones less frequently during evaluation periods. College students who use cell phones less regularly also have a better academic performance.