Laparoscopic Cytoreductive Surgery and HIPEC in Patients with Limited Pseudomyxoma Peritonei of Appendiceal Origin

Introduction. Increasing numbers of patients with pseudomyxoma peritonei (PMP) of appendiceal origin are being evaluated with a low tumor burden. We explored a minimally invasive approach for this group of patients. Materials and Methods. We designed a protocol in which patients with a PMP diagnosis would have a diagnostic laparoscopy. If limited carcinomatosis (PCI ≤ 10) is identified, the procedure will continue laparoscopically. If extensive carcinomatosis (PCI > 10) is found, then the procedure will be converted to an open approach. Results. From December 2008 to December 2011, 19 patients had a complete cytoreduction and HIPEC: 18 of them (95%) were done laparoscopically and 1 of them (5%) was converted to an open procedure. Mean PCI was 4.2. Grade 3 morbidity was 0, and one patient (5%) experienced a grade 4 complication, needing a reoperation for an internal hernia. There were no mortalities. Mean length of hospital stay was 5.3 days. At a mean follow-up of 17 months (1–37) all 19 patients are alive and free of disease. Conclusion. This study demonstrates that cytoreductive surgery and HIPEC via the laparoscopic route is feasible and safe and should be offered to patients with limited pseudomyxoma peritonei of appendiceal origin

Evaluación de sustentabilidad en dos niveles de análisis y dos escalas espaciales. El municipio de Ocoyoacac y la comunidad de San Juan Coapanoaya, Estado de México

En este trabajo se aplicó un marco metodológico para la evaluación de la sustentabilidad, que permite cuantificar y comparar en diferentes niveles de análisis, indicadores y atributos de sustentabilidad en dos escalas geográficas. La investigación se realizó en el municipio de Ocoyoacac y la Comunidad de San Juan Coapanoaya, en el Estado de México, México. El ciclo de evaluación fue dividido en dos fases: de análisis de la cual se derivaron los criterios e indicadores específicos para ambas escalas; y de síntesis del sistema, donde se llevó a cabo la cuantificación de indicadores y atributos. Se obtuvieron valores altos para los indicadores ambientales y sociales, y valores bajos para los indicadores económicos. La autogestión y la equidad fu eron los atributos relevantes.En este trabajo se aplicó un marco metodológico para la evaluación de la sustentabilidad, que permite cuantificar y comparar en diferentes niveles de análisis, indicadores y atributos de sustentabilidad en dos escalas geográficas. La investigación se realizó en el municipio de Ocoyoacac y la Comunidad de San Juan Coapanoaya, en el Estado de México, México. El ciclo de evaluación fue dividido en dos fases: de análisis de la cual se derivaron los criterios e indicadores específicos para ambas escalas; y de síntesis del sistema, donde se llevó a cabo la cuantificación de indicadores y atributos. Se obtuvieron valores altos para los indicadores ambientales y sociales, y valores bajos para los indicadores económicos. La autogestión y la equidad fu eron los atributos relevantes

a cross-sectional study

Objectives We sought to determine the prevalence of anti-Toxoplasma gondii antibodies in Yoremes and to identify associations of T. gondii exposure with sociodemographic, clinical and behavioural characteristics of Yoremes. Design A cross-sectional survey. Setting Yoremes were enrolled in the locality of Tierra Blanca in the municipality of Navojoa in Sonora State, Mexico. Participants We studied 200 Yoremes (Mayos); they are an indigenous ethnic group living in a coastal region in northwestern Mexico. Primary and secondary outcome measures We assessed the prevalence of anti-Toxoplasma IgG and IgM antibodies in participants using enzyme-linked immunoassays. We used a standardised questionnaire to obtain the characteristics of Yoremes. The association of T. gondii exposure and Yoremes’ characteristics was assessed by bivariate and multivariate analyses. Results Of the 200 Yoremes studied (mean age: 31.50±18.43 years), 26 (13.0%) were positive for anti-T. gondii IgG antibodies and 19 (73.1%) of them were also positive for anti-T. gondii IgM antibodies. Seroprevalence of T. gondii infection did not vary with sex, educational level, occupation or socioeconomic status. In contrast, multivariate analysis of sociodemographic and behavioural characteristics showed that T. gondii exposure was associated with increasing age (OR=1.02; 95% CI 1.00 to 1.04; p=0.03) and consumption of squirrel meat (OR=4.99; 95% CI 1.07 to 23.31; p=0.04). Furthermore, seroprevalence of T. gondii infection was significantly higher in Yoremes with a history of lymphadenopathy (p=0.03) and those suffering from frequent abdominal pain (p=0.03). In women, T. gondii exposure was associated with a history of caesarean sections (p=0.03) and miscarriages (p=0.02). Conclusions We demonstrate, for the first time, serological evidence of T. gondii exposure among Yoremes in Mexico. Results suggest that infection with T. gondii might be affecting the health of Yoremes. Results may be useful for an optimal design of preventive measures against T. gondii infection

Impact of a TAK-1 inhibitor as a single or as an add-on therapy to riociguat on the metabolic reprograming and pulmonary hypertension in the SUGEN5416/hypoxia rat model.

Background: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-β signaling is believed to be a critical factor in pulmonary vascular remodeling, we hypothesized that blocking TGFβ-activated kinase 1 (TAK-1), alone or in combination with a vasodilator therapy (i.e., riociguat) could achieve a greater therapeutic benefit. Methods: PAH was induced in male Wistar rats by a single injection of the VEGF receptor antagonist SU5416 (20 mg/kg) followed by exposure to hypoxia (10%O2) for 21 days. Two weeks after SU5416 administration, vehicle, riociguat (3 mg/kg/day), the TAK-1 inhibitor 5Z-7-oxozeaenol (OXO, 3 mg/kg/day), or both drugs combined were administered for 7 days. Metabolic profiling of right ventricle (RV), lung tissues and PA smooth muscle cells (PASMCs) extracts were performed by magnetic resonance spectroscopy, and the differences between groups analyzed by multivariate statistical methods. Results: In vitro, riociguat induced potent vasodilator effects in isolated pulmonary arteries (PA) with negligible antiproliferative effects and metabolic changes in PASMCs. In contrast, 5Z-7-oxozeaenol effectively inhibited the proliferation of PASMCs characterized by a broad metabolic reprogramming but had no acute vasodilator effects. In vivo, treatment with riociguat partially reduced the increase in pulmonary arterial pressure (PAP), RV hypertrophy (RVH), and pulmonary vascular remodeling, attenuated the dysregulation of inosine, glucose, creatine and phosphocholine (PC) in RV and fully abolished the increase in lung IL-1β expression. By contrast, 5Z-7-oxozeaenol significantly reduced pulmonary vascular remodeling and attenuated the metabolic shifts of glucose and PC in RV but had no effects on PAP or RVH. Importantly, combined therapy had an additive effect on pulmonary vascular remodeling and induced a significant metabolic effect over taurine, amino acids, glycolysis, and TCA cycle metabolism via glycine-serine-threonine metabolism. However, it did not improve the effects induced by riociguat alone on pulmonary pressure or RV remodeling. None of the treatments attenuated pulmonary endothelial dysfunction and hyperresponsiveness to serotonin in isolated PA. Conclusion: Our results suggest that inhibition of TAK-1 induces antiproliferative effects and its addition to short-term vasodilator therapy enhances the beneficial effects on pulmonary vascular remodeling and RV metabolic reprogramming in experimental PAH.This work was supported by the Instituto de Salud Carlos III-ISCIII (Grant numbers: PI15/01100 and PI19/01616 to LM), the Spanish Ministry of Science and Innovation MCIN (Grant numbers: PID 2019-107363RB-I00 to FP-V, PID 2020-117939RBI00 to AC and PID 2021-123238OB-I00, PDC 2021-121696-I00 to JRC and PID2019-106564RJ-I00 to JI-G), the Comunidad de Madrid-CAM (CM S2017/BMD-3727 to AC and LM and B2017/ BMD3875 to JI-G) and, as appropriate, by “ERDF A way of making Europe”, co-funded by the “European Union”. FP-V received funding from Fundación Contra la Hipertensión Pulmonar (Empathy grant) and JR-C from La Caixa Foundation (Health Research Call 2020: HR20-00075). This work was performed under the Maria de Maeztu Units of Excellence Programme–Grant MDM-2017-0720 funded by MCIN/AEI/10.13039/501100011033.S

a cross-sectional study

Objectives We determined the seroprevalence and correlates of Toxoplasma gondii infection in pregnant women in Aguascalientes City, Mexico. Design A cross-sectional survey. Setting Pregnant women were enrolled in the central Mexican city of Aguascalientes. Participants We studied 338 pregnant women who attended prenatal care in 3 public health centres. Primary and secondary outcome measures Women were examined for IgG/IgM antibodies to T. gondii by using commercially available enzyme immunoassays, and an avidity test. Multiple analyses were used to determine the association of T. gondii seropositivity with the characteristics of the pregnant women. Results Of the 338 pregnant women studied, 21 (6.2%) had IgG antibodies to T. gondii, and 1 (4.8%) of them was also positive for IgM antibodies to T. gondii. Avidity of IgG antibodies to T. gondii was high in the IgM-positive sample. Logistic regression analysis of sociodemographic, behavioural and housing variables showed that T. gondii seropositivity was associated with white ethnicity (OR=149.4; 95% CI 10.8 to 2054.1; p<0.01), not washing hands before eating (OR=6.41; 95% CI 1.73 to 23.6; p=0.005) and use of latrine (OR=37.6; 95% CI 4.63 to 306.31; p=0.001). Conclusions Results demonstrate that pregnant women in Aguascalientes City have a low seroprevalence of T. gondii infection. However, this low prevalence indicates that most pregnant women are at risk for a primary infection. Factors associated with T. gondii exposure found in this study, including food hygiene, may be useful to determine preventive measures against T. gondii infection and its sequelae

Evaluation of Best Supportive Care and Systemic Chemotherapy as Treatment Stratified according to the retrospective Peritoneal Surface Disease Severity Score (PSDSS) for Peritoneal Carcinomatosis of Colorectal Origin

Background: We evaluate the long-term survival of patients with peritoneal carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact of the of the retrospective peritoneal disease severity score (PSDSS) on outcomes. Methods: One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987-2006 were identified from a prospective institutional database. These patients either received no chemotherapy, 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy. Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinically relevant factors. Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test. Results: Median survival was 5 months (95% CI, 3-7 months) for patients who had no chemotherapy, 11 months (95% CI, 6-9 months) for patients treated with 5 FU/LV, and 12 months (95% CI, 4-20 months) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy. Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy (p = 0.026). PSDSS staging was identified as an independent predictor for survival on multivariate analysis [RR 2.8 (95%CI 1.5-5.4); p < 0.001]. Conclusion: A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy. The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin

Pensamiento Novohispano 17

La colección Pensamiento Novohispano, en este número 17, reúne las siguientes colaboraciones: siete trabajos de investigación pertenecientes al siglo XVI, cinco al siglo XVII y cuatro al siglo XVIII. Nuestro propósito es difundir estos temas vinculados con el Encuentro de Dos Mundos y su colonización. El proceso de Evangelización en el Período Colonial ha dado lugar a una diversidad de significaciones e interpretaciones; unas, acordes con la visión tradicional de la conquista (desde una perspectiva positiva, de aceptación); otras, en oposición al modo y consecuencias que sufrieron los pueblos conquistados (se asume una postura más crítica). En el primer caso, a decir de Boff, el camino de evangelización fue asumido por algunos misioneros que “supieron acercarse a los otros, distintos en cuanto a la raza, la lengua y la religión, mediante una convivencia pacífica, fraterna y amorosa. Trataron de proclamar el evangelio sin hacer uso del aparato del poder, sino únicamente con el amor, el diálogo, el encuentro, la inserción y el ejemplo de la vida.”1 Aquí se presentan manifestaciones y testimonios vivos de estos encuentros, aquellos en donde no es posible dar lugar a la inculturación o aculturación; sólo se puede evangelizar cuando se aprende a convivir con diferentes culturas en el respeto compartido por la diferencia y la preocupación por la calidad de vida común

Impact of a TAK-1 inhibitor as a single or as an add-on therapy to riociguat on the metabolic reprograming and pulmonary hypertension in the SUGEN5416/hypoxia rat model

Background: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-β signaling is believed to be a critical factor in pulmonary vascular remodeling, we hypothesized that blocking TGFβ-activated kinase 1 (TAK-1), alone or in combination with a vasodilator therapy (i.e., riociguat) could achieve a greater therapeutic benefit.Methods: PAH was induced in male Wistar rats by a single injection of the VEGF receptor antagonist SU5416 (20 mg/kg) followed by exposure to hypoxia (10%O2) for 21 days. Two weeks after SU5416 administration, vehicle, riociguat (3 mg/kg/day), the TAK-1 inhibitor 5Z-7-oxozeaenol (OXO, 3 mg/kg/day), or both drugs combined were administered for 7 days. Metabolic profiling of right ventricle (RV), lung tissues and PA smooth muscle cells (PASMCs) extracts were performed by magnetic resonance spectroscopy, and the differences between groups analyzed by multivariate statistical methods.Results:In vitro, riociguat induced potent vasodilator effects in isolated pulmonary arteries (PA) with negligible antiproliferative effects and metabolic changes in PASMCs. In contrast, 5Z-7-oxozeaenol effectively inhibited the proliferation of PASMCs characterized by a broad metabolic reprogramming but had no acute vasodilator effects. In vivo, treatment with riociguat partially reduced the increase in pulmonary arterial pressure (PAP), RV hypertrophy (RVH), and pulmonary vascular remodeling, attenuated the dysregulation of inosine, glucose, creatine and phosphocholine (PC) in RV and fully abolished the increase in lung IL-1β expression. By contrast, 5Z-7-oxozeaenol significantly reduced pulmonary vascular remodeling and attenuated the metabolic shifts of glucose and PC in RV but had no effects on PAP or RVH. Importantly, combined therapy had an additive effect on pulmonary vascular remodeling and induced a significant metabolic effect over taurine, amino acids, glycolysis, and TCA cycle metabolism via glycine-serine-threonine metabolism. However, it did not improve the effects induced by riociguat alone on pulmonary pressure or RV remodeling. None of the treatments attenuated pulmonary endothelial dysfunction and hyperresponsiveness to serotonin in isolated PA.Conclusion: Our results suggest that inhibition of TAK-1 induces antiproliferative effects and its addition to short-term vasodilator therapy enhances the beneficial effects on pulmonary vascular remodeling and RV metabolic reprogramming in experimental PAH

HIV transgene expression impairs K+ channel function in the pulmonary vasculature

Human immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH), however the pathogenesis of HIV-related PAH remains unclear. Since K+ channel dysfunction is a common marker in most forms of PAH, our aim was to analyse if the expression of HIV proteins is associated with impairment of K+ channel function in the pulmonary vascular bed. HIV transgenic mice (Tg26) expressing seven of the nine HIV viral proteins and wild type (Wt) mice were used. Hemodynamic assessment was performed by echocardiography and catheterization. Vascular reactivity was studied in endothelium-intact pulmonary arteries (PA). K+ currents were recorded in freshly isolated PA smooth muscle cells (PASMC) using the patch-clamp technique. Gene expression was assessed using RT-PCR. PASMC from Tg26 mice had reduced K+ currents and were more depolarized that those from Wt. While Kv1.5 currents were preserved, pH-sensitive non-inactivating background currents (IKN) were nearly abolished in PASMC from Tg26 mice. Tg26 mice had reduced lung expression of Kv7.1 and Kv7.4 channels and decreased responses to the Kv7.1 channel activator L634,373 assessed by vascular reactivity and patch-clamp experimental approaches. While we found pulmonary vascular remodelling and endothelial dysfunction in Tg26 mice, this was not accompanied by changes in hemodynamic parameters. In conclusion, the expression of HIV proteins in vivo impairs pH-sensitive IKN and Kv7 currents. This negative impact of HIV proteins in K+ channels, was not sufficient to induce PAH, at least in mice, but may play a permissive or accessory role in the pathophysiology of HIV-associated PAH

Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests

ests face increasing climate risk, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, Ψ50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk, little is known about how these vary across Earth’s largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters Ψ50 and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both Ψ50 and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM50 forests. We propose that this may be associated with a growth–mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon, with strong implications for the Amazon carbon sink