Prolonged use of pentoxifylline increases the life expectancy of patients with compensated cirrhosis: A 20­year retrospective study.

Liver cirrhosis is a pathology of varied etiology with a high prevalence and mortality, resulting in >1 million mortalities per year. Patients with liver cirrhosis typically have a survival time of 12 years following diagnosis. The treatment for this disease is directed at the complications of cirrhosis; however, to the best of our knowledge, the long-term management of patients with cirrhosis has been scarcely studied. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with rheological activity and antioxidant, anti-inflammatory and antifibrotic properties. PTX has been used in the treatment of peripheral arterial disease, inflammatory liver diseases and hepatocellular carcinoma with encouraging results. The aim of the present study was to evaluate the effect of PTX use on the survival of patients with compensated cirrhosis. For this purpose, a cross-sectional study was performed at the Gastroenterology and Hepatitis C Department of Dr. Valentín Gómez Farias Hospital (Institute for Security and Social Services for State Workers, Zapopan, Mexico) from June, 1996 to December, 2019. The follow-up time for these patients was 22.6 years (up to the end of the study period). In the present study, 326 patient files were analyzed and 118 patients with the disease were identified, 81 of whom (68.64%) died within 12 years after diagnosis. Of the included patients, 26 received PTX combined with PEG IFN-α-2a plus ribavirin, and 11 received PTX plus propranolol, with a median treatment duration of 20.6±0.8 years. Furthermore, 16 patients (43%) did not develop co-morbidities within this time, and the transition to decompensated cirrhosis was 16.6 years, with a survival time of 20 years. Therefore, the results of the present study suggest that PTX may improve the long-term survival of patients with compensated cirrhosis, rendering PTX a candidate for repurposing in the treatment of hepatic cirrhosis.

The Rochester Protocol for Living Donor Liver Transplantation of Unresectable Colorectal Liver Metastasis: A 5-Year Report on Selection, Approval, and Outcomes.

Living donor liver transplantation (LDLT) is a treatment option for select patients with unresectable colorectal liver metastasis (uCRLM). We describe our center's experience of patient selection, insurance approval, and outcomes after LDLT after first referral in March 2019. Of the 206 evaluated patients, twenty-three underwent LDLT. We found that patients who were referred earlier in their oncologic course were more likely to be eligible for transplantation. After completion of the Rochester Protocol for LDLT eligibility, recipients had a median delay of care of 10 days (IQR 0-36) related to insurance appeal, with six patients (30%) having a delay longer than 30 days. LDLT recipients had an overall survival proportion of 100% and 91% at 1, and 3 years; and a recurrence-free survival proportion of 100% and 40%, at 1 and 3 years, respectively. All donors underwent right hepatectomy, of which only one donor had a Clavien-Dindo IIIa complication and readmission. There was no donor mortality. We assert that multidisciplinary care and strict patient selection through the Rochester Protocol were paramount to our center's success. In the appropriately selected patient, LDLT for uCRLM may be justified, and patients should be referred to transplant oncology centers for evaluation.

Impact of climate change on the geographical distribution of ticks of public health significance in Colombia: Amblyomma ovale (Ixodida: Ixodidae), the Amblyomma maculatum (Ixodida: Ixodidae) complex and the Amblyomma cajennense (Ixodida: Ixodidae) complex.

Ticks of the Amblyomma maculatum (Ixodida Ixodidae) complex, the Amblyomma cajennense (Ixodida Ixodidae) complex and Amblyomma ovale (Ixodida Ixodidae) are known to transmit various Rickettsia species in Colombia, but their exact distribution is unknown. We built several models based on current climate and projected future climate changes using a maximum entropy approach. A total of 314 records of the A. cajennense complex (65.9%; n = 207), A. ovale (22.9%; n = 72), and the A. maculatum complex (11.1%; n = 35) were obtained. Amblyomma ovale has a current distribution in the Pacific, Caribbean and Andean regions and could be potentially found in the Amazon. Amblyomma maculatum has a current distribution in the Andean and could potentially be found in the Caribbean and Orinoco regions. Amblyomma mixtum can be found near the Caribbean Sea and in the Pacific region, and A. patinoi is likely to be found in the Andean region and the Caribbean. In 2070, it will be possible to find an expansion of A. ovale and A. maculatum and a decrease of A. mixtum and A. patinoi. The variables that best predict the distribution of these species are isothermality (small fluctuations in temperature) and annual precipitation. Amblyomma cajennense s.l and A. ovale, A. cajennese s.l and A. patinoi, as well as A. maculatum and A. patinoi, have an important environmental sympatry. Epidemiological and acarological surveillance is crucial to investigate rickettsiosis caused by R. parkeri in A. ovale regions, by R. rickettsii in A. patinoi and A. mixtum areas, and by R. parkeri s.s in A. maculatum regions.

Pan-lysyl oxidase inhibition disrupts fibroinflammatory tumor stroma, rendering cholangiocarcinoma susceptible to chemotherapy.

BACKGROUND: Cholangiocarcinoma (CCA) features highly desmoplastic stroma that promotes structural and functional resistance to therapy. Lysyl oxidases (LOX, LOXL1-4) catalyze collagen cross-linking, thereby increasing stromal rigidity and facilitating therapeutic resistance. Here, we evaluate the role of lysyl oxidases in stromal desmoplasia and the effects of pan-lysyl oxidase (pan-LOX) inhibition in CCA. METHODS: Resected CCA and normal liver specimens were analyzed from archival tissues. Spontaneous and orthotopic murine models of intrahepatic CCA (iCCA) were used to assess the impact of the pan-LOX inhibitor PXS-5505 in treatment and correlative studies. The functional role of pan-LOX inhibition was interrogated through in vivo and ex vivo assays. RESULTS: All 5 lysyl oxidases are upregulated in CCA and reduced lysyl oxidase expression is correlated with an improved prognosis in resected patients with CCA. Spontaneous and orthotopic murine models of intrahepatic cholangiocarcinoma upregulate all 5 lysyl oxidase isoforms. Pan-LOX inhibition reversed mechanical compression of tumor vasculature, resulting in improved chemotherapeutic penetrance and cytotoxic efficacy. The combination of chemotherapy with pan-LOX inhibition increased damage-associated molecular pattern release, which was associated with improved antitumor T-cell responses. Pan-LOX inhibition downregulated macrophage invasive signatures in vitro, rendering tumor-associated macrophages more susceptible to chemotherapy. Mice bearing orthotopic and spontaneously occurring intrahepatic cholangiocarcinoma tumors exhibited delayed tumor growth and improved survival following a combination of pan-LOX inhibition with chemotherapy. CONCLUSIONS: CCA upregulates all 5 lysyl oxidase isoforms, and pan-LOX inhibition reverses tumor-induced mechanical forces associated with chemotherapy resistance to improve chemotherapeutic efficacy and reprogram antitumor immune responses. Thus, combination therapy with pan-LOX inhibition represents an innovative therapeutic strategy in CCA.

Reappraisal of tacrolimus levels after liver transplant for HCC: A multicenter study toward personalized immunosuppression regimen.

Post-liver transplant (LT) immunosuppression is necessary to prevent rejection; however, a major consequence of this is tumor recurrence. Although recurrence is a concern after LT for patients with HCC, the oncologically optimal tacrolimus (FK) regimen is still unknown. This retrospective study included 1406 patients with HCC who underwent LT (2002-2019) at 4 US institutions using variable post-LT immunosuppression regimens. Receiver operating characteristic analyses were performed to investigate the influences of post-LT time-weighted average FK (TWA-FK) level on HCC recurrence. A competing risk analysis was employed to evaluate the prognostic influence of TWA-FK while adjusting for patient and tumor characteristics. The AUC for TWA-FK was greatest at 2 weeks (0.68), followed by 1 week (0.64) after LT. Importantly, this was consistently observed across the institutions despite immunosuppression regimen variability. In addition, the TWA-FK at 2 weeks was not associated with rejection within 6 months of LT. A competing risk regression analysis showed that TWA-FK at 2 weeks after LT is significantly associated with recurrence (HR: 1.31, 95% CI: 1.21-1.41, p < 0.001). The TWA-FK effect on recurrence varied depending on the exposure level and the individual's risk of recurrence, including vascular invasion and tumor morphology. Although previous studies have explored the influence of FK levels at 1-3 months after LT on HCC recurrence, this current study suggests that earlier time points and exposure levels must be evaluated. Each patient's oncological risk must also be considered in developing an individualized immunosuppression regimen.

First record of ectoparasites (Phthiraptera and Acari) from the Andean condor (Vultur gryphus) in Colombia.

Several species of ectoparasites, including chewing lice and mites are closely associated with their hosts. The Andean condor (Vultur gryphus) is globally listed as vulnerable by the IUCN and its population has been steadily declining in recent decades suggesting a potential extinction of associated entomofauna. The purpose of this study was to record the species of ectoparasites infesting three individuals of Andean condor found dead in the 'Páramo del Almorzadero' Santander Department, Northeastern Colombia. One juvenile (male) and two adults (male and female) Andean condors received for necropsy were carefully examined for ectoparasite infestation. Specimens were collected and preserved in ethanol (70%) for taxonomic studies. Morphologic identification and morphometric records were made under light microscopy. Some specimens were also prepared for scanning electron microscopy and others were subjected to DNA extraction to amplify and obtain sequences of the cytochrome-C oxidase subunit I (COI) gene for phylogenetic analyses. Lice were collected from the juvenile condor and the adult female and identified as Falcolipeurus assesor (Phthiraptera: Ischnocera) in the juvenile condor (8 females, 19 males and 8 nymphs) and the adult (1 female); Colpocephalum trichosum (Phthiraptera: Amblycera) in the juvenile (19 females, 24 males and 1 nymph) and the adult (2 females, 2 males and 3 nymphs); and Cuculiphilus zonatus (Phthiraptera: Amblycera) in the juvenile (40 females, 43 males and 15 nymphs) and the adult (1 male and 2 nymphs). Moreover, one mite collected from the juvenile condor was identified as Ancyralges cathartinus (Acari: Astigmata) (1 female). Morphometric data was obtained for the adult stages of F. assesor (6 females and 13 males), C. trichosum (9 females and 9 males) and C. zonatus (10 females and 10 males). We obtained the first DNA sequences of COI for F. assessor, and C. trichosum, where phylogenetic tree analysis showed that F. assessor is more closely related to Falcolipeurus marginalis, and C. trichosum to Colpocephalum kelloggi. This represents the first record of parasites in Andean condor from Colombia and contributes to the knowledge of chewing lice and mites associated with an endemic and endangered bird species. Further studies on Andean condor ectoparasites should be focused on documenting host-parasite interactions and potential health impacts in these wild birds.

Varias especies de ectoparásitos, incluidos piojos masticadores y ácaros están estrechamente asociados a sus hospedadores. El cóndor andino (Vultur gryphus) está catalogado por la UICN como una especie vulnerable y su población ha ido disminuyendo constantemente en las últimas décadas, lo que sugiere una posible extinción de la entomofauna asociada. El propósito de este estudio fue registrar las especies de ectoparásitos infestando a tres individuos de cóndor andino encontrados muertos en el Páramo del Almorzadero, Departamento de Santander, Noreste de Colombia. Un cóndor andino juvenil (macho) y dos adultos (macho y hembra) recibidos para necropsia fueron examinados cuidadosamente para detectar infestación por ectoparásitos. Los especímenes fueron recolectados y preservados en etanol (70%) para estudios taxonómicos. La identificación morfológica y los registros morfométricos se ejecutaron bajo microscopía óptica. Algunas muestras también se prepararon para microscopía electrónica de barrido y otras se sometieron a extracción de ADN para amplificar y obtener secuencias del gen de la subunidad I (COI) del citocromo­C oxidasa para análisis filogenéticos. Los piojos recolectados del cóndor juvenil y de la hembra adulta se identificaron como Falcolipeurus assesor (Phthiraptera: Ischnocera) en el cóndor juvenil (8 hembras, 19 machos y 8 ninfas) y en el adulto (1 hembra); Colpocephalum trichosum (Phthiraptera: Amblycera) en el juvenil (19 hembras, 24 machos y 1 ninfa) y en el adulto (2 hembras, 2 machos y 3 ninfas); y Cuculiphilus zonatus (Phthiraptera: Amblycera) en el juvenil (40 hembras, 43 machos y 15 ninfas) y en el adulto (1 macho y 2 ninfas). Además, un ácaro recolectado del cóndor juvenil fue identificado como Ancyralges cathartinus (Acari: Astigmata) (1 hembra). Se obtuvieron datos morfométricos para los estadios adultos de F. assesor (6 hembras y 13 machos), C. trichosum (9 hembras y 9 machos) y C. zonatus (10 hembras y 10 machos). Secuencias de ADN basadas en COI para las especies F. assesor y C. trichosum son reportadas por la primera vez, donde el análisis filogenetico mostró que F. assesor está más estrechamente relacionado con Falcolipeurus marginalis y C. trichosum con Colpocephalum kelloggi. Este representa el primer registro de parásitos en cóndor andino de Colombia y contribuye al conocimiento de los piojos masticadores y ácaros asociados a una especie de ave endémica de los Andes y en peligro de extinción. Otros estudios sobre los ectoparásitos del cóndor andino deberían centrarse en documentar las interacciones hospedador­parásito y los posibles impactos en la salud de estas aves silvestres.

In Silico Study of Interactions between the Methylene Blue Molecule and the (TiO2)20 Cluster by Means of DFT Calculations.

In this work, the (TiO2)20 cluster is proposed to adsorb the methylene blue (BM) dye; thus, the quantum parameters to explain the adsorption process are calculated by means of density functional theory calculations. Eight possible configurations are obtained and labeled from M1 to M8. According to the adsorption energy values, they reveal physisorption for at least two cases, and for the rest of the systems, they exhibit chemisorption. The preferential positions that lead to good adsorption for the BM dye are parallel to the semiconductor cluster; however, when one end of the BM dye formed by hydrogen atoms is interacting with the cluster, a weak chemical interaction is reached. The chemical interactions for M4 and M5 systems generate considerable increases of their electronic gap values (E g) with respect to the rest, and this effect is explained based on iso-surfaces of frontier orbitals and electronic charge transference. The chemical interactions between these chemical species are stable under vibrational and thermal criteria. This semiconductor cluster arises as a good candidate to adsorb some dyes like BM.

Survival benefit of living donor liver transplant for patients with hepatocellular carcinoma.

With the increasing incidence of hepatocellular carcinoma (HCC) in both the United States and globally, the role of liver transplantation in management continues to be an area of active conversation as it is often considered the gold standard in the treatment of HCC. The use of living donor liver transplantation (LDLT) and the indications in the setting of malignancy, both generally and in HCC specifically, are frequently debated. In terms of both overall survival and recurrence-free survival, LDLT is at least equivalent to DDLT, especially when performed for disease within Milan criteria. Emerging and compelling evidence suggests that LDLT is superior to DDLT in treating HCC as there is a significant decrease in waitlist mortality. As the oncologic indications for liver transplantation continue to expand and the gap between organ demand and organ availability continues to worsen, high volumes centers should consider using LDLT to shrink the ever-expanding waitlist.

Progression-Free Survival for Liver Transplant vs Alternative Therapy in Unresectable Colorectal Liver Metastasis.

This cohort study compares survival outcomes between patients with unresectable colorectal liver metastasis who received chemotherapy-based multimodal therapy and patients who underwent liver transplant.