Predictive factors for decompensating events in patients with cirrhosis with primary biliary cholangitis under different lines of therapy.

BACKGROUND AND AIMS: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients. APPROACH AND RESULTS: Multicenter study enrolling 388 patients with PBC-cirrhosis from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and PBC OCA international study of efficacy criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the propensity score-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, clinically significant portal hypertension, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin (OR 0.21 [95% CI: 0.06-0.73]) and AST (OR 0.97 [95% CI: 0.95-0.99]), while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95% CI: 0.95-0.98]). In patients treated with OCA, drug response (sHR 0.23 [95% CI: 0.08-0.64]), diabetes (sHR 5.62 [95% CI: 2.02-15.68]), albumin (sHR 0.34 [95% CI: 0.13-0.89]), and platelets (sHR 0.99 [95% CI: 0.98-1.00]) were related to decompensation. In patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (sHR 3.70 (95% CI: 1.17-11.70]) were associated with decompensated cirrhosis. CONCLUSIONS: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.

Deubiquitinase USP9X loss sensitizes renal cancer cells to mTOR inhibition.

Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase gene USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients' primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients' sensitivity to mTOR inhibitors. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.

Efficacy and Safety of Celiac Plexus Neurolysis in the Treatment of Chronic Pain Secondary to Oncological Pathology of the Upper Hemiabdomen: A Systematic Review and Meta-Analysis.

Objectives: The management of chronic pain among patients with abdominal cancer is complex; against that, the neurolysis of the celiac plexus (CPN) is the best technique at the moment to determine the efficacy and safety in the treatment of chronic pain secondary to oncological pathology of the upper abdomen. Material and Methods: This was a systematic review of controlled clinical trials between 2000 and 2021, in the sources MEDLINE/PubMed, Cochrane, Scopus, Web of Science, and Google Scholar. Three independent evaluators analysed the results of the bibliographical research. The quality of the studies was assessed with the Jadad scale and the mean difference (95% confidence interval) and heterogeneity of the studies (I2) were calculated with Review Manager 5.3. Results: Seven hundred and forty-four publications were identified, including 13 studies in the qualitative synthesis and three studies in the quantitative synthesis. No difference was found in the decrease in pain intensity between 1 and 12 weeks after the intervention, comparing the experimental group with the control (P > 0.05). The adverse effects related to neurolysis were not serious and transitory, mentioning the most frequent adverse effects and reporting a percentage between 21% and 67% (with 17% for echoendoscopic neurolysis and 49% for percutaneous neurolysis). Conclusion: Celiac plexus neurolysis for the treatment of severe chronic pain secondary to oncological pathology in the upper hemiabdomen produces similar pain relief as conventional pharmacological analgesic treatment. It is a safe analgesic technique since the complications are mild and transitory.

The North American Forest Database: going beyond national-level forest resource assessment statistics.

Forests cannot be managed sustainably without reliable data to inform decisions. National Forest Inventories (NFI) tend to report national statistics, with sub-national stratification based on domestic ecological classification systems. It is becoming increasingly important to be able to report statistics on ecosystems that span international borders, as global change and globalization expand stakeholders' spheres of concern. The state of a transnational ecosystem can only be properly assessed by examining the entire ecosystem. In global forest resource assessments, it may be useful to break national statistics down by ecosystem, especially for large countries. The Inventory and Monitoring Working Group (IMWG) of the North American Forest Commission (NAFC) has begun developing a harmonized North American Forest Database (NAFD) for managing forest inventory data, enabling consistent, continental-scale forest assessment supporting ecosystem-level reporting and relational queries. The first iteration of the database contains data describing 1.9 billion ha, including 677.5 million ha of forest. Data harmonization is made challenging by the existence of definitions and methodologies tailored to suit national circumstances, emerging from each country's professional forestry development. This paper reports the methods used to synchronize three national forest inventories, starting with a small suite of variables and attributes.

PBRM1 and KDM5C cooperate to define high-angiogenesis tumors and increased antiangiogenic response in renal cancer.

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are key antiangiogenic drugs for renal cancer treatment. While Von Hippel-Lindau dysfunction constitutes the base for VEGFR-TKIs sensitivity, the role for individual and concurrent mutations in the genes encoding for the chromatin remodelers Polybromo-1 (PBRM1) and Lysine Demethylase 5C (KDM5C) is poorly understood. Here, we analyzed the tumor mutational and expression profiles of 155 unselected clear cell RCC (ccRCC) cases treated with first-line VEGFR-TKIs and the ccRCC cases of IMmotion151 trial were used for validation. We found that concurrent PBRM1 and KDM5C (PBRM1&KDM5C) mutations occurred in 4-9% of cases and were enriched in Memorial Sloan Kettering Cancer Center favorable-risk patients. In our cohort, tumors only mutated in PBRM1 or concurrently mutated in PBRM1 and KDM5C had increased angiogenesis (P=0.0068 and 0.039; respectively), and tumors only mutated in KDM5C showed a similar trend. Best response to VEGFR-TKIs corresponded to PBRM1&KDM5C mutated cases, followed by those mutated only in KDM5C or only in PBRM1 (P=0.050, 0.040 and 0.027 versus non-mutated cases, respectively), with a trend for longer progression free survival (PFS) in the group with only PBRM1 mutated (HR=0.64; P=0.059). Validation in the IMmotion151 trial revealed a similar correlation with increased angiogenesis and the PFS of patients in the VEGFR-TKI-arm was the longest in PBRM1&KDM5C mutated cases, intermediate for only PBRM1 or only KDM5C mutated patients and the shortest in non-mutated cases (P=0.009 and 0.025, for PBRM1&KDM5C and PBRM1 versus non-mutated cases). In conclusion, somatic PBRM1 and KDM5C mutations are common in patients with metastatic ccRCC and likely cooperate increasing tumor angiogenesis and VEGFR-TKI-based antiangiogenic therapy benefit.

An updated list of the Mexican herpetofauna: with a summary of historical and contemporary studies.

The growth in our knowledge of the diversity of the herpetofauna of Mexico has occurred over the period of approximately 445 years from the work of Francisco Hernández to that of a broad multinational array of present-day herpetologists. The work of this huge group of people has established Mexico as one of the most significant centers of herpetofaunal biodiversity in the world. This status is the result of a complex orography, in addition to diverse habitats and environments and the biogeographic history of Mexico. The current herpetofauna consists of 1,421 native and introduced species, allocated to 220 genera, and 61 families. This figure is comprised of 1,405 native species and 16 non-native species (as of April 2023). The non-native species include two anurans, 13 squamates, and one turtle. The level of endemism is very high, presently lying at 63%, with this level expected to increase with time. Species richness varies among the 32 federal entities in the country, from a low of 50 in Tlaxcala to a high of 492 in Oaxaca. Amphibian species richness by state-level can be envisioned as comprising three levels of low, medium, and high, with the lowest levels occurring in the Peninsula of Baja California, a group of seven states in north-central and central Mexico, and a group of three states in the Yucatan Peninsula, with the highest levels occupying the southern states of Guerrero, Puebla, Veracruz, Oaxaca, and Chiapas, and the medium level in the remaining states of the country. Reptile species richness also can be allocated to three categories, with the lowest level occupying Baja California Sur, a group of central states, and the states of the Yucatan Peninsula, and the highest level found in a cluster of the states of Veracruz, Guerrero, Oaxaca, and Chiapas. Knowledge of the Mexican herpetofauna will continue to grow with additional studies on systematics, conservation, and the construction of checklists at various levels.

Hospital Epidemics Tracker (HEpiTracker): Description and pilot study of a mobile app to track COVID-19 in hospital workers.

BACKGROUND: Hospital workers have been the most frequently and severely affected professional group during the COVID-19 pandemic, and have a big impact on transmission. In this context, innovative tools are required to measure the symptoms compatible with COVID-19, the spread of infection, and testing capabilities within hospitals in real time. OBJECTIVE: We aimed to develop and test an effective and user-friendly tool to identify and track symptoms compatible with COVID-19 in hospital workers. METHODS: We developed and pilot tested Hospital Epidemics Tracker (HEpiTracker), a newly designed app to track the spread of COVID-19 among hospital workers. Hospital staff in 9 hospital centers across 5 Spanish regions (Andalusia, Balearics, Catalonia, Galicia, and Madrid) were invited to download the app on their phones and to register their daily body temperature, COVID-19-compatible symptoms, and general health score, as well as any polymerase chain reaction and serological test results. RESULTS: A total of 477 hospital staff participated in the study between April 8 and June 2, 2020. Of note, both health-related (n=329) and non-health-related (n=148) professionals participated in the study; over two-thirds of participants (68.8%) were health workers (43.4% physicians and 25.4% nurses), while the proportion of non-health-related workers by center ranged from 40% to 85%. Most participants were female (n=323, 67.5%), with a mean age of 45.4 years (SD 10.6). Regarding smoking habits, 13.0% and 34.2% of participants were current or former smokers, respectively. The daily reporting of symptoms was highly variable across participating hospitals; although we observed a decline in adherence after an initial participation peak in some hospitals, other sites were characterized by low participation rates throughout the study period. CONCLUSIONS: HEpiTracker is an already available tool to monitor COVID-19 and other infectious diseases in hospital workers. This tool has already been tested in real conditions. HEpiTracker is available in Spanish, Portuguese, and English. It has the potential to become a customized asset to be used in future COVID-19 pandemic waves and other environments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04326400; https://clinicaltrials.gov/ct2/show/NCT04326400.

La escarificación mecánica aumenta la germinación de semillas de Neltuma alba (Fabaceae), un árbol amenazado del desierto de Atacama / Mechanical scarification increases seed germination of Neltuma alba (Fabaceae), a threatened tree from the Atacama Desert

Resumen Neltuma alba es un árbol cuyas semillas probablemente fueron dispersadas por animales ya extintos. Actualmente, los frutos son consumidos por zorros, guanacos, burros y cabras, quienes al comerlos escarificarían las semillas, aumentando su germinación. Sin embargo, al masticar los frutos, los animales podrían dañar los cotiledones, reduciendo la sobrevivencia y crecimiento de las plantas, aunque infrecuentemente. Hipotetizamos que la escarificación mecánica de las semillas aumenta su germinación, pero no la sobrevivencia y crecimiento de las plantas. Nuestro objetivo fue evaluar los efectos de la escarificación mecánica sobre la germinación de semillas y posterior sobrevivencia de plantas. Escarificamos las semillas lijándolas para luego sembrarlas en vivero con riego diario por 6 meses. Posteriormente, las plantas fueron trasladadas al campo, recibiendo riego diario por 6 meses, después recibieron riego quincenal por los siguientes 12 meses, para finalmente no recibir riego los próximos 2 años. La escarificación de las semillas aumentó significativamente en 1.5 veces la germinación: 58 y 39% de germinación en semillas escarificadas y no escarificadas, respectivamente. La escarificación no afectó significativamente la sobrevivencia de las plantas. El 93, 67, 67 y 26% de las plantas sobrevivieron al término del primer, segundo, tercer y cuarto año, respectivamente. Similarmente, la escarificación no afectó significativamente la estatura de las plantas, las que alcanzaron tallas de 28, 59, 74 y 118 cm el primer, segundo, tercer y cuarto año. Comprender los factores limitantes para la reproducción de las plantas amenazadas del desierto de Atacama es fundamental para proponer acciones de conservación efectivas.

Abstract Neltuma alba is a tree whose seeds were probably dispersed by now-extinct animals. Currently, its fruits are consumed by foxes, guanacos, donkeys, and goats, which may scarify the seeds during ingestion, thereby enhancing germination. However, these animals might damage the cotyledons when chewing the fruits, potentially reducing the survival and growth of the plants, although this occurs infrequently. We hypothesize that mechanical scarification of seeds increases their germination but does not affect the survival and growth of the plants. Our objective was to evaluate the effects of mechanical scarification on seed germination and subsequent plant survival. We scarified the seeds by sanding them before sowing them in a nursery with daily watering for six months. Subsequently, the plants were transplanted to the field, where they received daily watering for six months, biweekly watering for the next twelve months, and no watering for the following two years. Seed scarification significantly increased germination by 1.5 times: 58 and 39% germination in scarified and non-scarified seeds, respectively. Scarification did not significantly affect plant survival. Survival rates were 93, 67, 67, and 26% at the end of the first, second, third, and fourth years, respectively. Similarly, scarification did not significantly affect plant height, with plants reaching heights of 28, 59, 74, and 118 cm in the first, second, third, and fourth years, respectively. Understanding the limiting factors for the reproduction of endangered plants in the Atacama Desert is crucial for proposing effective conservation actions.

Amphibian life history in a temperate environment of the Mexican Plateau: dimorphism, phenology and trophic ecology of a hylid frog, Hyla eximia (=Dryophytes eximius).

The study of demographic and life history aspects of an organism provides valuable information for its conservation. Here, we analyze the phenology of the Mountain Treefrog Hyla eximia (= Dryophytes eximius) in a temperate environment of the Mexican Plateau. Females were larger in snout-vent length and body mass than males. The peak period of activity occurred in the rainy season (May-September), with amplexus and egg deposition occurring between June and July, and larval development from July to August. A logistic model best explained observed male growth patterns, while the Von Bertalanffy model better described female growth. Notably, males grew faster than females, although females reached a larger overall body size. The diet of this species is made up of 10 prey categories. The index of diet importance indicated that males feed mainly on Coleoptera and Diptera, while females feed on Coleoptera, Diptera, Hemiptera, and Aranea. Both females and males showed a significant abundance of plant material in their stomachs, suggesting that H. eximia might exhibit highly specialized feeding behavior. Reproduction was seasonal, and both female and male reproductive cycles are synchronized with the rainy season. These natural history characteristics provide information to better understand their responses to environmental conditions.

Trombicula autumnalis (isangos) en un jardín de niños de la selva Peruana / Trombicula autumnalis (isangos) in children of kindergarten in Peruvian jungle

Los isangos (Trombicula autumnalis) son conocidos popularmente en la selva peruana pero no se ha documentado su frecuencia. Se realizó un estudio transversal en un caserío de Lamas, región San Martín, se evaluó a 18 menores de cinco años los cuales todos tenían lesiones producidas por isangos, estos ejemplares fueron remitidos al Instituto Nacional de Salud los cuales fueron identificados como T. autumnalis. Se evaluó también a escolares y población adulta de esa localidad encontrando que 56/70 niños y 85/130 adultos tenían lesiones compatibles por infestación con T. autumnalis. Las zonas más afectadas fueron las piernas, ingle y nalgas.

Isangos (Trombicula autumnalis) are popularly known in the Peruvian jungle has not been documented their frequency. We performed a cross-sectional study in a village of Lamas, San Martín region, 18 children under five years were evaluated who all had injuries due isangos, these specimens were sent to the National Institute of Health (Lima, Peru) which were identified as T. autumnalis. It also assessed school students and adult population of this village found that 56/70 children and 85/130 adults had lesions compatible with infestation by T. autumnalis. The zones most affected were the legs, groin and buttocks.

Apendicectomías laparoscópicas en el Hospital Nacional Daniel A. Carrión-Callao / Laparoscopic Appendectomy at the Hospital Nacional Daniel A. Carrión-Callao

Se describe la experiencia temprana del Hospital Nacional Daniel Alcides Carrión, Callao, en el tratamiento de la apendicitis aguda por abordaje videolaparoscópico, entre enero y diciembre de 1997. De 35 pacientes operados, veinte (57,1 por ciento) fueron varones. El promedio global de edad fue 23,8 años (rango 10-47), en 10 de ellos (28,5 por ciento) el cuadro apendicular estaba complicado. En el 14,2 por ceinto (5 pacientes) hubieron complicaciones intraoperatorias menores, todas sin alteración de los resultados finales. Tres pacientes presentaron infección en el sitio del trócar. No hubieron reoperaciones. El promedio de hospitalización fue 2 días en los no complicados y 7 en los complicados. Un paciente falleció por problemas posquirúrgicos. Se describe la técnica utilizada y se hace una revisión acerca de ella.

Cancer de páncreas en el Hospital Regional Honorio Delgado de Arequipa, 1960-1995

En el presente trabajo se realizó un estudio retrospectivo, sobre 64 casos con diagnóstico histiopatológico de cáncer de páncreas registrados en el Hospital Regional Honorio Delgado de Arequipa, en el lapso de 35 años comprendidos entre enero de 1960 a diciembre de 1995. Se hace notar que no se consideraron como casos en nuestro estudio, aquellos que no tuvieron comprobación histopatológica, como se explica en el capítulo III con la finalidad de uniformizar criterios, se realizó una revisión teórica de la etiopatogenia, cuadro clínico patología tratamiento evolución y el pronóstico en el cáncer de pancreas. El cáncer de páncreas es una neoplasia poco frecuente, se presenta con mayor frecuencia en la quinta década de la vida y afecta a más del sexo femenino, en nuestro estudio. El tiempo de nefermedad referido por los pacientes en su mayoría fue de 0 a 3 meses. Los síntomas predominales fueron el dolor abdominal y la pérdida de peso, y los signos de mayor presentación fueron la icteria y la coluria. Los examenes auxiliares sirvieron de ayuada para valorar el estado de los pacientes pero no establecieron el diagnóstico. En el cáncer de páncreas la localización más frecuente de la lesión estuvo a nivel de la cabeza del páncreas, respecto al tipo histológico, el más frecuente fue el adenocarcinoma ductal. El tratamiento quirúrgico que se realizó en 36 pacientes de los cuales 64 en el estudio 35 de ellos recibieron tratamiento paliativo, por lo avanzado del proceso neoplásico, 1 realizó tratamiento curativo, la operación paliativa utilizada con mayor frecuencia fue el drenaje externo. Las complicaciones post-operatorias se presentaron en 21 pacientes de los 52 que fueron intervenidos quirúrgicamente siendo las bronconeumonías la de mayor presentación. La mortalidad operatoria reportada en el presente trabajo es de 15,38. Respecto a la mortalidad en el cáncer de páncreas, la muerte ocurrio en 33 de ellos entre 0 a 6 meses después del diagnóstico clínico de la neoplasia. hubo un pacienete que sobrevivió 15 meses. Finalmente, se comparó los resultados obtenidos en este estudio con los de otros autores nacionales como extranjeros.