Implementing medical abortion through telemedicine in Colombia: a qualitative study.

The non-governmental organisation Profamilia developed and implemented medical abortion through telemedicine in response to the Covid-19 pandemic. This service is now integrated as an alternative to in-person care and available to abortion-seekers across Colombia. Previous research has emphasised bottlenecks in abortion provision, but less is known about implementation processes and experiences. We assessed the feasibility and acceptability of telemedicine for medical abortion from the perspectives of key informants involved in the implementation in Colombia. We conducted 15 in-depth interviews with healthcare professionals, coordinators and support staff implementing telemedicine for medical abortion in the early phase of implementation, between March and October 2021. We analysed the data using the framework method and applied the normalisation process theory in our analysis and interpretation of findings. Our findings show that strong leadership, organisational efforts on pre-implementation training, monitoring and evaluation, and collaboration between diversely skilled and experienced providers are essential for successful implementation. Participants were generally positive towards the use of telemedicine for medical abortion; concerns related to effectiveness, safety and safeguarding existed mainly among providers with less clinical experience. We identified contextual barriers, such as social opposition, regulatory barriers, providers' unavailability, and poor phone and internet connections in rural areas, which impacted the feasibility of the intervention negatively. In conclusion, to ensure stakeholders' buy-in and for the service to reach all abortion seekers in need, future implementation endeavours must address concerns about safety and effectiveness, and tackle identified contexual barriers.Plain Language SummaryIn telemedicine for medical abortion, all or some components of abortion care, such as initial consultations, home delivery of abortion medication, and post-abortion follow up are provided with the use of telecommunications. Telemedicine for medical abortion has been shown to be a safe and effective form of service delivery.In this study, we interviewed 15 healthcare providers and staff involved in the implementation of a telemedicine service for medical abortion in Colombia to determine whether they deemed the service to be acceptable and feasible. We found that collaboration between providers of different backgrounds and levels of experience, appropriate training and strong leadership were key factors for successfully implementing the service. However, some healthcare providers, especially those with less clinical experience, were concerned that telemedicine for medical abortion may not be safe and may risk the health and well-being of abortion-seekers. Further, social opposition to abortion, unclear regulation and limited access to technology were identified as barriers that need to be addressed to ensure the service reaches all abortion-seekers in need.In conclusion, despite contextual barriers and some provider's concerns about medical safety, telemedicine for medical abortion was viewed as a positive and feasible form of service delivery in Colombia.

Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA2), UCM-14216, Ameliorates Spinal Cord Injury in Mice.

Spinal cord injuries (SCIs) irreversibly disrupt spinal connectivity, leading to permanent neurological disabilities. Current medical treatments for reducing the secondary damage that follows the initial injury are limited to surgical decompression and anti-inflammatory drugs, so there is a pressing need for new therapeutic strategies. Inhibition of the type 2 lysophosphatidic acid receptor (LPA2) has recently emerged as a new potential pharmacological approach to decrease SCI-associated damage. Toward validating this receptor as a target in SCI, we have developed a new series of LPA2 antagonists, among which compound 54 (UCM-14216) stands out as a potent and selective LPA2 receptor antagonist (Emax = 90%, IC50 = 1.9 µM, KD = 1.3 nM; inactive at LPA1,3-6 receptors). This compound shows efficacy in an in vivo mouse model of SCI in an LPA2-dependent manner, confirming the potential of LPA2 inhibition for providing a new alternative for treating SCI.

Ability of Boron to Act as a Nucleophile and an Electrophile in Boryl Shift Reactions Unveiled by Electron Density Distribution Analysis.

The behavior of the tetracoordinate boron of N-methyliminodiacetic acid (MIDA) boronates as a nucleophile and an electrophile during the 1,2-boryl migration promoted by a Lewis acid and the 1,4-boryl migration promoted by a neighboring atom, respectively, have been investigated using density functional theory and the quantum theory of atoms in molecules. We found that when boron acts as a nucleophile, the electron density of the B-N interaction of the BMIDA moiety maintains the charge concentration over the boron atom, facilitating its transport toward the electron-deficient center. In this process, the BMIDA remains as a tetracoordinate. On the other hand, the B-N weakening generates a charge depletion region over the boron, allowing it to interact with the electron-rich center of O1, developing the boron atom, a pentacoordinate form. Then, the B-N bond breaking triggers a series of changes in the electronic structure of the boron atom. Our results explain the role of the MIDA ligand upon the remarkable susceptibility of the boron atom for switching its structural and electronic characteristics in the migration processes. In addition, the dichotomous behavior was evaluated with a different scenario, considering tricoordinate pinacol boronate as a boryl migrating group.

Isoprenylcysteine Carboxylmethyltransferase-Based Therapy for Hutchinson-Gilford Progeria Syndrome.

Hutchinson-Gilford progeria syndrome (HGPS, progeria) is a rare genetic disease characterized by premature aging and death in childhood for which there were no approved drugs for its treatment until last November, when lonafarnib obtained long-sought FDA approval. However, the benefits of lonafarnib in patients are limited, highlighting the need for new therapeutic strategies. Here, we validate the enzyme isoprenylcysteine carboxylmethyltransferase (ICMT) as a new therapeutic target for progeria with the development of a new series of potent inhibitors of this enzyme that exhibit an excellent antiprogeroid profile. Among them, compound UCM-13207 significantly improved the main hallmarks of progeria. Specifically, treatment of fibroblasts from progeroid mice with UCM-13207 delocalized progerin from the nuclear membrane, diminished its total protein levels, resulting in decreased DNA damage, and increased cellular viability. Importantly, these effects were also observed in patient-derived cells. Using the Lmna G609G/G609G progeroid mouse model, UCM-13207 showed an excellent in vivo efficacy by increasing body weight, enhancing grip strength, extending lifespan by 20%, and decreasing tissue senescence in multiple organs. Furthermore, UCM-13207 treatment led to an improvement of key cardiovascular hallmarks such as reduced progerin levels in aortic and endocardial tissue and increased number of vascular smooth muscle cells (VSMCs). The beneficial effects go well beyond the effects induced by other therapeutic strategies previously reported in the field, thus supporting the use of UCM-13207 as a new treatment for progeria.

Malaria importada en niños: primer caso en Uruguay / Imported malaria in children: first case in Uruguay / Malária importada em crianças, o primeiro caso no Uruguai

Resumen: La malaria es un problema de salud a nivel mundial. Si bien en Uruguay existen ejemplares del género Anopheles, las especies descritas con mayor frecuencia no transmiten la enfermedad. Se comunica el primer caso de una niña con malaria importada, no complicada, por Plasmodium falciparum. El objetivo es sensibilizar al pediatra sobre una enfermedad reemergente y analizar su abordaje diagnóstico y terapéutico. Caso clínico: niña de 8 años, sana, procedente de Bolívar (Venezuela). Vive en Uruguay desde hace 15 días. Comienza cinco días previos al ingreso con fiebre de 41 °C, rinorrea y tos seca, vómitos ocasionales en las últimas 24 horas. Anorexia y marcado decaimiento. No lesiones de piel, cefalea, ni artromialgias. Examen físico: decaída, chucho febril, dolor abdominal difuso y hepatoesplenomegalia. Estudios complementarios: anemia, plaquetopenia, elevación de reactantes de fase aguda y de gamma glutamil transferasa. Ecografía abdominal: hepatoesplenomegalia moderada. Estudio parasitológico de sangre periférica: trofozoitos de Plasmodium falciparum, parasitemia menor a 10%. Se administra artemeter-lumefantrina durante tres días, seguido de primaquina por 14 días, con buena evolución. Conclusiones: la malaria debe ser considerada en un niño que proviene de zonas endémicas y se presenta con una enfermedad febril aguda, acompañada de chuchos, decaimiento y hepatoesplenomegalia. El estudio del frotis sanguíneo y gota gruesa realizado por el parasitólogo permitirá confirmar el diagnóstico y definir el abordaje terapéutico. Para disminuir la mortalidad es importante el diagnóstico oportuno y la identificación precoz de signos de malaria grave. El tratamiento será dirigido según la especie involucrada y riesgo de resistencia a los antimaláricos.

Summary: Malaria is a global health problem. Although there are specimens of the genus Anopheles, in Uruguay, the most frequently described species do not transmit the disease. We hereby report the first case of a girl with imported, uncomplicated Plasmodium falciparum malaria. The objective is to raise pediatricians' awareness regarding a re-emerging disease and analyze its diagnostic and therapeutic approach. Clinical case: 8-year-old, healthy girl from Bolívar (Venezuela) who had lived in Uruguay for 15 days. 5 days prior to admission started having 41°C fever, runny nose and dry cough and occasional vomit in the 24 hours prior to admittance. Anorexia and significant asthenia. No skin lesions, headaches or arthromyalgia. Physical exam: asthenia, feverish shivering, diffuse abdominal pain, and hepatosplenomegaly. Complementary studies: anemia, thrombocytopenia, high acute phase reactants and gamma glutamyl transferase. Abdominal ultrasound: moderate hepatosplenomegaly. Parasitological study of peripheral blood: Plasmodium falciparum trophozoites, parasitemia less than 10%. Artemether-lumefantrine was administered for 3 days, followed by primaquine for 14 days, with positive evolution. Conclusions: Malaria should be considered in cases of children from endemic areas who show acute febrile illness, accompanied by shivering, asthenia and hepatosplenomegaly. The study of the thick and peripheral blood smears carried out by the parasitologist will eventually confirm the diagnosis and define the therapeutic approach. In order to reduce mortality, it is essential to carry out a timely diagnosis and to identify symptoms of severe malaria early on. Treatment will depend on the species involved and risk of resistance to antimalarials.

Resumo: A malária é um problema de saúde global. Embora no Uruguai existam exemplares do gênero Anopheles, as espécies mais frequentemente descritas não transmitem a doença. Relatamos o primeiro caso de uma menina com malária importada não complicada por Plasmodium falciparum. O objetivo é sensibilizar o pediatra sobre uma doença reemergente e analisar sua abordagem diagnóstica e terapêutica. Caso clínico: menina saudável de 8 anos, procedente de Bolívar (Venezuela) que tinha morado no Uruguai por 15 dias. 5 dias antes da internação começa a ter febre de 41°C, rinorreia, tosse seca e vômitos ocasionais nas 24 horas anteriores à internação. Anorexia e astenia acentuada. Sem lesões cutâneas, dores de cabeça ou artromialgia. Exame físico: astenia, tremor febril, dor abdominal difusa e hepatoesplenomegalia. Estudos complementares: anemia, plaquetopenia, elevação dos reagentes de fase aguda e gama glutamil transferase. Ultrassonografia abdominal: hepatoesplenomegalia moderada. Estudo parasitológico do sangue periférico: trofozoítos por Plasmodium falciparum, parasitemia inferior a 10%. Administramos artemeter-lumefantrina por 3 dias, seguida de primaquina por 14 dias, com boa evolução. Conclusões: devemos considerar a malária em crianças procedentes de áreas endêmicas e com quadro febril agudo, acompanhado de tremores, astenia e hepatoesplenomegalia. O exame do esfregaço e de gota espessa quando feito pelo parasitologista vai confirmar o diagnóstico e definir a abordagem terapêutica. É importante realizar diagnóstico precoce e identificar os sinais de malária para diminuir o risco de mortalidade. O tratamento será administrado de acordo com a espécie envolvida e com o risco de resistência aos antimaláricos.

Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort.

INTRODUCTION: Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). CONCLUSION: In this real-life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAA treatment (NCT03775798; www. CLINICALTRIALS: gov).

Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma.

The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.

Hepatitis E infection is an infrequent cause of acute hepatitis in the metropolitan area of Buenos Aires.

Background Argentina is considered a region of low seroprevalence of hepatitis E virus (HEV), however; no studies have evaluated its burden among acute hepatitis cases. OBJECTIVES: We aimed to estimate the proportion of acute HEV and outcome in a cohort of patients with acute hepatitis from 6 liver units in the Metropolitan area of Buenos Aires (MABA). STUDY DESIGN: We performed a prospective cohort study including patients ≥18 years with acute hepatitis (increase in transaminases x 5 ULN) fromJuly 2016 to May 2018. Severe hepatitis was defined as acute hepatitis + INR> 1.5 and acute liver failure as severe hepatitis + encephalopathy. In patients in whom other etiologies were excluded, HEV tests were performed: anti-HEV IgM/G and HEV-RNA in serum and feces. RESULTS: Overall, 268 patients with acute hepatitis were included in the study. The most frequent etiologies of acute hepatitis were hepatitis B (67patients, 25 %), hepatotoxicity (65, 24 %) and autoimmune hepatitis (26, 10 %). Acute HEV infection was confirmed in 8 (2.98 %; 95 %CI 1.25-5.63) patients who tested positive for anti-HEV IgM. A total of 63 (23.5 %) patients were hospitalized and 9 (3.3 %) patients died. Overall, 48 (18 %) patients developed severe hepatitis, 6 (2.2 %) have acute liver failure, 6 (1.9 %) underwent liver transplantation and 9 (3.4 %) patients died. CONCLUSIONS: the proportion of acute HEV in MABA was low during the period studied. We believe our findings will aid physicians prioritize other etiologies of acute hepatitis over HEV in order to optimize diagnostic resources and offer better care to their patients.

Disease Progression in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antiviral Agents.

BACKGROUND & AIMS: Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS: We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS: During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS: Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.

A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration.

Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 µM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.

Intermediate-advanced hepatocellular carcinoma in Argentina: Treatment and survival analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of HCC. AIM: To describe real-life treatments performed in patients with intermediate-advanced HCC before the approval of new systemic options. METHODS: This longitudinal observational cohort study was conducted between 2009 and 2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer (BCLC) HCC stages (BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or death. Kaplan Meier survival curves and Cox regression analysis were performed, with hazard ratios (HR) calculations and 95% confidence intervals (95%CI). RESULTS: From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage D. Corresponding median survival were 15 mo (IQR 5-26 mo), 5 mo (IQR 2-13 mo) and 3 mo (IQR 1-13 mo) (P < 0.0001), respectively. Among BCLC-B patients (n = 135), 57% received TACE with a median number of 2 sessions (IQR 1-3 sessions). Survival was significantly better in BCLC-B patients treated with TACE HR = 0.29 (CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival [HR = 0.15 (CI: 0.04-0.56, P = 0.005)]. Eighty-two patients were treated with sorafenib, mostly BCLC-B and C (87.8%). However, 12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo (IQR 2.3-11.7 mo); which was lower among BCLC-D patients 3.2 mo (IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients, treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26 (CI: 0.09-0.71); P = 0.013]. CONCLUSION: In this real setting, our results were lower than expected. This highlights unmet needs in Argentina, prior to the introduction of new treatments for HCC.

Presumptive primary intrathoracic mast cell tumours in two dogs.

BACKGROUND: Mast cell tumours are the most common cutaneous neoplasms in dogs. Other primary sites include visceral organs, such as the gastrointestinal tract, liver, or spleen, and the oral cavity. Frequent metastatic sites include the local lymph nodes, skin, spleen, liver and bone marrow. The thorax is rarely affected by metastatic disease and no such cases have been reported in dogs. Mast cell tumours are usually not considered as a differential diagnosis for lung and intrathoracic chest wall masses in dogs. Chest wall tumours can be primary tumours of the ribs and sternum, an invasion of adjacent tumours into the chest wall, and metastasis from distant tumours. CASES PRESENTATION: A German Shepherd dog presented with a history of persistent cough and a large mass involving the thoracic wall and a small round pulmonary mass. The dog had a history of mammary tumours that were surgically excised. Thoracoscopy revealed a thoracic wall mass involving the internal intercostal muscle and a small mass in the left cranial lung lobe. Cytology and histopathology of the intrathoracic mass confirmed the large mass as a mast cell tumour and the small mass as a carcinoma. Cytology of the sternal lymph nodes showed no involvement. The dog received toceranib for 3 months, which failed to alleviate persistent cough. Radiology indicated that the large mass had a partial response to toceranib. The dog was euthanasied. A Maltese dog presented with a history of chronic regurgitation and cough, and a large mass involving the left caudal lung lobe. Cytology and histopathology of mass confirmed a mast cell tumour. The dog received toceranib for 2 months. Radiology indicated that the large mass had no response to toceranib. The dog was euthanasied. Confirmation of lungs mast cell tumour and the absence of any other Mast cell tumour was achieved by postmortem examination. CONCLUSIONS: The cases discussed are two unusual presentations of intrathoracic mast cell tumours, in the absence of cutaneous mast cell tumours, in dogs.

Treatment with direct-acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma.

BACKGROUND & AIMS: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. METHODS: This was a prospective multicentre cohort study from Latin America including 1400 F1-F4-treated patients with DAAs (F3-F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. RESULTS: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child-Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. CONCLUSIONS: Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.

Surveillance for Hepatocellular Carcinoma: Does the Place Where Ultrasound Is Performed Impact Its Effectiveness?

BACKGROUND: Biannual ultrasound (US) is recommended as the clinical screening tool for hepatocellular carcinoma (HCC). The effectiveness of surveillance according to the place where US is performed has not been previously reported. AIMS: To compare the effectiveness of US performed in the center responsible for follow-up as opposed to US proceeding from centers other than that of follow-up. METHODS: This is a multicenter cohort study from Argentina. The last US was categorized as done in the same center or done in a different center from the institution of the patient's follow-up. Surveillance failure was defined as HCC diagnosis not meeting Barcelona Clinic Liver Cancer (BCLC) stages 0-A or when no nodules were observed at HCC diagnosis. RESULTS: From 533 patients with HCC, 62.4% were under routine surveillance with a surveillance failure of 38.8%. After adjusting for a propensity score matching, BCLC stage and lead-time survival bias, surveillance was associated with a significant survival benefit [HR of 0.51 (CI 0.38; 0.69)]. Among patients under routine surveillance (n = 345), last US was performed in the same center in 51.6% and in a different center in 48.4%. Similar rates of surveillance failure were observed between US done in the same or in a different center (32% vs. 26.3%; P = 0.25). Survival was not significantly different between both surveillance modalities [HR 0.79 (CI 0.53; 1.20)]. CONCLUSIONS: Routine surveillance for HCC in the daily practice improved survival either when performed in the same center or in a different center from that of patient's follow-up.

Adherence to Barcelona Clinic Liver Cancer therapeutic algorithm for hepatocellular carcinoma in the daily practice: a multicenter cohort study from Argentina.

BACKGROUND AND AIM: Adherence to the Barcelona Clinic Liver Cancer (BCLC) staging algorithm for the treatment of hepatocellular carcinoma is challenging in the daily practice. We aimed to analyze adherence to BCLC along with its effect on patient survival. PATIENTS AND METHODS: A cohort study was conducted in 14 hospitals from Argentina including patients with newly diagnosed hepatocellular carcinoma (2009-2016). Adherence was considered when the first treatment was the one recommended by the BCLC. RESULTS: Overall, 708 patients were included. At diagnosis, BCLC stages were as follows: stage 0 4%, A 43%, B 22%, C 9% and D 22%. Overall, 53% of the patients were treated according to BCLC, 24% were undertreated, and 23% overtreated. Adherence to BCLC increased to 63% in subsequent treatments. Independent factors associated with adherence to BCLC were the presence of portal hypertension [odds ratio: 1.63; 95% confidence interval (CI): 1.11-2.39] and BCLC stage C (odds ratio: 0.32; 95% CI: 0.12-0.72). In a multivariable model adjusting for portal hypertension and BCLC stages, adherence to BCLC showed improved survival (hazard ratio: 0.67; 95% CI: 0.52-0.87). CONCLUSION: Adherence to BCLC represents a challenge in the daily practice, with almost half of the patients being treated accordingly, showing that the decision-making process should be tailored to each individual patient.

Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina.

AIM: To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years. METHODS: A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit. RESULTS: A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLD-HCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality. CONCLUSION: The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

Incidencia y etiología de la candidiasis invasiva en la Unidad de Cuidados Intensivos de Niños del Centro Hospitalario Pereira Rossell / Incidence and etiology of invasive candidiasis in the Pediatric Intensive Care Unit of of the Pereira Rossell Hospital Center

Introducción: en los últimos años ha aumentado la incidencia de candidiasis invasiva (CI) a nivel mundial. En nuestro país no se disponen de estudios epidemiológicos sobre CI. El objetivo fue determinar incidencia de CI en la Unidad de Cuidados Intensivos de Niños del Centro Hospitalario Pereira Rossell. Metodología: estudio descriptivo retrospectivo. Se incluyeron los niños con CI hospitalizados entre 1/1/2009-1/6/2014. A partir de los cultivos micológicos se identificaron las historias clínicas de los pacientes que desarrollaron CI. Se definió CI al aislamiento de Candida en algún sitio estéril. Se calcularon la densidad de incidencia y de prevalencia. Se registró motivo de ingreso y presencia de factores de riesgo para CI. Resultados: se identificaron 6 casos de CI, incidencia de 1,86 c/1000 ingresos. Los aislamientos se realizaron en hemocultivos (n=3) y líquido peritoneal (n=3). Las especies de Candida aisladas fueron C. albicans (n=3), C. parapsilosis (n=2) y C. tropicalis (n=1). Los factores de riesgo para CI presentes fueron dispositivos invasivos (n=6), antibióticos de amplio espectro (n=6), alimentación parenteral (n=5), cirugía abdominal(n=4). Todos los aislamientos fueron sensibles a los azoles. En 1 de las 6 CI se inició tratamiento empírico previo al aislamiento. Fallecieron 4 de los 6 pacientes. Discusión: la incidencia fue similar a otra experiencia realizada en cuidados intensivos pediátricos. Los pacientes que desarrollaron CI presentaron asociación de factores de riesgo. Los aislamientos fueron sensibles a fluconazol. Caracterizar a estos niños permitirá iniciar en forma oportuna el tratamiento antifúngico. Se destaca la importancia de desarrollar la vigilancia continua sobre las especies de Candida y su patrón de sensibilidad a los antifúngicos.

Introduction: invasive infections by Candida strains have increased around the world in the last years. There are no epidemiological studies on invasive candidiasis (IC) in Uruguay. The study aimed to find out the incidence of IC in the Pediatric Intensive Care Unit (PICU) at the Pereira Rossell Hospital Center (CHPR). Method: a retrospective and descriptive study was conducted. Children hospitalized in PICU of the CHPR between 1/1/2009 and 1/6/2014 were included in the study. The medical records of patients who developed IC were identified based on mycological cultures. Invasive candidiasis was defined as the isolation of the fungus in a sterile site. Incidence and prevalence density were calculated. Cause for hospitalization and risk factors for IC were recorded. Results: six cases of IC were identified and the incidence was of 1.86/1000 hospitalized children in PICU. Isolation of Candida was done in blood cultures (n=3) and peritoneal fluid (n=3). The species of Candida isolated were C. albicans (n=3), C.parapsilosis (n=2) and C. tropicalis (n=1). Risk factors for IC were identified in the 6 cases. Use of invasive prosthesis and a wide spectrum antibiotics were identified in the 6 cases, as well as parenteral nutrition (n=5) and abdominal surgery (n=4). All isolations of Candida were sensitive to fluconazole. Antifungal empiric treatment was started in one case prior to the isolation of Candida. Four out of six children died. Discussion: the incidence of IC found was similar to that in another study in a PICU. Children who developed IC presented several risk factors for IC. The 6 isolations of Candida were sensitive to fluconazole. Analyzing the clinical features of these children will allow the identification of patients with high risk of IC and to timely initiate antifungal treatment. It is necessary to maintain a continuous surveillance on Candida species and their sensitivity pattern to antifungal medication.

Esporotricosis linfocutánea. A propósito de un caso pediátrico / Lymphatic-cutaneous sporotrichosis. A pediatric case

La esporotricosis es la micosis subcutánea más frecuente en Uruguay. Es producida por hongos del complejo Sporothrix. Su reservorio son los restos vegetales y madera en descomposición. En su hábitat natural las condiciones climáticas, temperatura y humedad son variables, pero es inviable a 40°C. Afecta al hombre y animales. Es una enfermedad ocupacional y recreativa, poco frecuente en la edad pediátrica. En nuestro país el modo habitual de adquirirla es a través de arañazos de armadillos (mulitas). La forma clínica clásica y más frecuente de la esporotricosis se caracteriza por un chancro cutáneo de inoculación acompañado de una linfangitis de carácter nodular y troncular. Su evolución tiene un desarrollo subagudo y crónico. A pesar de su signología típica es muchas veces confundida con otras afecciones dermatológicas lo que retarda el diagnóstico. La presentación visceral u osteoarticular es excepcional. El diagnóstico definitivo requiere el aislamiento del hongo en cultivos a partir del sitio de infección. La resolución espontánea es poco común. El tratamiento recomendado es itraconazol administrado durante 3 a 6 meses. También puede utilizarse de manera alternativa yoduro de potasio y la terbinafina. La termoterapia local preconizada por la escuela micológica uruguaya significa muchas veces una valiosa alternativa terapéutica. El objetivo de esta comunicación es la presentación del caso clínico de un niño que cursó una esporotricosis cutáneo-linfática. La misma fue confirmada por estudio micológico y recibió tratamiento con itraconazol y termoterapia local, con buena respuesta.

Sporotrichosis is the most frequent subcutaneous mycosis in Uruguay. It is caused by fungi from the Sporothrix complex. This fungus lives in decaying plant matter, including wood. Climate, temperature and humidity vary in their natural habitat, although they cannot survive when it is hotter than 40°C. It affects both men and animals. Sporotrichosis is an occupational and recreational disease, rather unusual in children. In our country it is usually acquired through armadillo scratches. The classical and most frequent clinical presentation is characterized by a chancre following inoculation, accompanied by nodular and troncular lymphangitis. Evolution of the condition has a subacute and chronic development. In spite of its typical signs, it is often confused with other skin diseases, what delays diagnosis. Visceral or osteoarticular presentation is exceptional. Final diagnosis requires the fungus to be isolated in cultures from the site of the infection. Spontaneous resolution is rather unusual. Itraconazole during 3 to 6 months is the recommended treatment. Alternatively, potassium iodide and terbinafine may be used. Local thermotherapy, recommended by the Uruguayan mycological school often constitutes a valuable therapeutic alternative. This study aims to present the clinical case of a boy with a lymphatic-cutaneous sporotrichosis. The condition was confirmed by mycological studies and he was treated with itraconazole and local thermotherapy, the response being good.

Ascaris lumbricoides: complicaciones graves en niños hospitalizados en el Centro Hospitalario Pereira Rossell / Ascaris lumbricoides: serious complications in children hospitalized in the Centro Hospitalario Pereira Rossell

La infección por Ascaris lumbricoides (AL) es una geohelmintiasis que constituye un problema de salud pública, especialmente en niños con vulnerabilidad socio económica y ambiental. La carencia de saneamiento y agua potable, el hacinamiento, la precariedad de la vivienda y las malas condiciones de higiene constituyen los principales factores de riesgo. El impacto de esta enfermedad en Uruguay no está claramente definido. La existencia de casos graves de infección por AL sugiere la presencia de zonas de alta prevalencia. El objetivo de esta comunicación es alertar sobre la presencia de complicaciones y formas graves de esta enteroparasitosis. Se revisaron los aspectos patogénicos y modalidades de evaluación y tratamiento. Se incluyeron siete niños hospitalizados entre el 1 de enero de 2007 y el 31 de mayo de 2012, edad mínima 18 meses y máxima 59 meses. Todos habitaban viviendas precarias, de las cuales cinco carecían de saneamiento y cuatro de baño interno. Las complicaciones asociadas fueron: abscesos múltiples pulmonares y hepáticos, síndrome suboclusivo, oclusión intestinal, síndrome de Loffler, peritonitis biliar por perforación del conducto hepático común y colangitis. Los síntomas abdominales fueron los más frecuentes. La media de la estadía hospitalaria fue 11 días. Ingresaron a Unidad de cuidado intensivo cuatro niños, dos requirieron alimentación parenteral y dos apoyo ventilatorio. En todos los casos se realizaron estudios imagenológicos. Requirieron tratamiento quirúrgico tres niños. Todos sobrevivieron. Esta enfermedad es un “marcador de pobreza” y se relaciona directamente con las condiciones de vida de la población. Fortalecer las medidas de promoción y prevención contribuye al control de esta enfermedad. Erradicar el problema exige políticas dirigidas a superar las condiciones de exclusión social, identificando zonas de riesgo con intervenciones intersectoriales.