[Clostridium tertium bacteremia in patient with liver cirrhosis]. / Bacteriemia por Clostridium tertium en un paciente con cirrosis hepática.

Clostridium tertium is a bacterium of the Clostridiaceae family which can be found colonizing the gastrointestinal tract. Unlike other members of its family, it does not produce exotoxins. It was described for the first time in 1917 and in 1963 it was established as a pathogen in humans. Since then, cases have been reported mainly in immunosuppressed hosts, predominantly with primary focus at the abdominal level. The case of a 48-year-old man with a history of cirrhosis and hepatitis C virus infection is described. He presented an obstructed umbilical hernia that required intestinal resection and anastomosis, with positive blood and abdominal fluid cultures for Clostridium tertium. This case is of clinical importance due to the low prevalence of this germ, the possibility of resistance to usual antibiotic regimens and its sub diagnostic given the morphological and growth similarities with Bacillus or Lactobacillus.

Clostridium tertium es una bacteria de la familia Clostridiaceae que se puede encontrar colonizando el tracto gastrointestinal. A diferencia de otros miembros de su familia, no produce exotoxinas. Fue descripto por primera vez en 1917 y en el año 1963 se pudo establecer como patógeno en humanos. Desde entonces, se han reportado casos principalmente en huéspedes inmunosuprimidos, prevalentemente con foco primario abdominal. Se describe el caso de un hombre de 48 años de edad con antecedentes de cirrosis e infección por virus de la hepatitis C, presentó una hernia umbilical atascada que requirió resección y anastomosis intestinal, con cultivos de líquido abdominal y hemocultivos positivos para Clostridium tertium. Este caso es de importancia clínica por la baja prevalencia de este germen, la posibilidad de resistencia a los esquemas antibióticos usuales y de subdiagnóstico del microorganismo dada su similitud morfológica y de crecimiento con Bacillus o Lactobacillus.

Bacteriemia por Clostridium tertium en un paciente con cirrosis hepática / Clostridium tertium bacteremia in patient with liver cirrhosis

Resumen Clostridium tertium es una bacteria de la familia Clos tridiaceae que se puede encontrar colonizando el tracto gastrointestinal. A diferencia de otros miembros de su familia, no produce exotoxinas. Fue descripto por prime ra vez en 1917 y en el año 1963 se pudo establecer como patógeno en humanos. Desde entonces, se han reportado casos principalmente en huéspedes inmunosuprimi dos, prevalentemente con foco primario abdominal. Se describe el caso de un hombre de 48 años de edad con antecedentes de cirrosis e infección por virus de la hepatitis C, presentó una hernia umbilical atascada que requirió resección y anastomosis intestinal, con cultivos de líquido abdominal y hemocultivos positivos para Clostridium tertium. Este caso es de importancia clínica por la baja prevalencia de este germen, la posibilidad de resistencia a los esquemas antibióticos usuales y de subdiagnóstico del microorganismo dada su similitud morfológica y de crecimiento con Bacillus o Lactobacillus.

Abstract Clostridium tertium is a bacterium of the Clostridiaceae family which can be found colonizing the gastrointes tinal tract. Unlike other members of its family, it does not produce exotoxins. It was described for the first time in 1917 and in 1963 it was established as a pathogen in humans. Since then, cases have been reported mainly in immunosuppressed hosts, predominantly with primary focus at the abdominal level. The case of a 48-year-old man with a history of cirrhosis and hepatitis C virus infection is described. He presented an obstructed um bilical hernia that required intestinal resection and anastomosis, with positive blood and abdominal fluid cultures for Clostridium tertium. This case is of clinical importance due to the low prevalence of this germ, the possibility of resistance to usual antibiotic regimens and its sub diagnostic given the morphological and growth similarities with Bacillus or Lactobacillus.

Acute colonic pseudo-obstruction syndrome in patients with severe COVID-19 in Buenos Aires, Argentina.

BACKGROUND: Several gastrointestinal complications have been reported in patients with COVID-19, including motility disorders, such as acute colonic pseudo-obstruction (ACPO). This affection is characterized by colonic distention in the absence of mechanical obstruction. ACPO in the context of severe COVID-19 may be related to neurotropism and direct damage of SARS-CoV-2 in enterocytes. METHOD: We conducted a retrospective study of patients who were hospitalized for critical COVID-19 and developed ACPO between March 2020 and September 2021. The diagnostic criteria to define ACPO was the presence of 2 or more of the following: abdominal distension, abdominal pain, and changes in the bowel movements, associated with distension of the colon in computed tomography. Data of sex, age, past medical history, treatment, and outcomes were collected. RESULTS: Five patients were detected. All required admission to the Intensive Care Unit. The ACPO syndrome developed with a mean of 33.8 days from the onset of symptoms. The mean duration of the ACPO syndrome was 24.6 days. The treatment included colonic decompression with placement of rectal and nasogastric tubes, endoscopy decompression in two patients, bowel rest, fluid, and electrolytes replacement. One patient died. The remaining resolved the gastrointestinal symptoms without surgery. CONCLUSIONS: ACPO is an infrequent complication in patients with COVID-19. It occurs especially in patients with critical condition, who require prolonged stays in intensive care and multiple pharmacological treatments. It is important to recognize its presence early and thus establish an appropriate treatment, since the risk of complications is high.

Un caso de viruela símica en cuidados intensivos en Argentina / A case of monkeypox in intensive care in Argentina

Resumen La viruela símica es una enfermedad zoonótica poco frecuente. Fue descripta en humanos por primera vez en África en 1970. El 23 de julio del 2022, ante la cantidad ascendente de casos notificados en diversos países y territorios, la Organización Mundial de la Sa lud (OMS) concluyó que el brote mundial constituye una emergencia de salud pública de importancia internacional. En nuestro país el primer caso se noti ficó el 22 de mayo de 2022 hasta el 22 de noviembre se confirmaron 895 casos. Describimos el primer caso registrado en Argentina, según el boletín epidemiológico de la semana epidemiológica 46, del Ministerio de Salud de la Nación con requerimiento de cuidados intensivos. Se trata de un hombre de 44 años con síndrome de in munodeficiencia adquirida y viruela símica grave, que presentó insuficiencia ventilatoria obstructiva, por com promiso de vías aéreas y lesiones generalizadas extensas de tegumento, genitales y fauces. En conclusión, el caso presentado alerta sobre las potenciales complicaciones que pueden requerir cuidados críticos y poner en riesgo la vida del paciente.

Abstract Monkey pox is a rare zoonotic disease. It was first described in humans in Africa in 1970. On July 23, 2022, in view of the increasing number of cases reported in several countries and territories, the World Health Or ganization (WHO) concluded that the global outbreak constitutes a public health emergency of international concern. In our country, the first case was reported on May 22, 2022 and up to November 22 of this year, 895 patients were reported. We describe here the first case registered in Argentina requiring intensive care, accor ding to the Epidemiological Bulletin, 46th epidemio logical week, National Ministry of Health. The patient was a 44-year-old man with acquired immunodeficiency syndrome and severe Monkeypox, who presented obs tructive ventilatory failure due to airway compromise and extensive generalized lesions of the integument, genitalia and fauces. In conclusion, the case presented alerts about potential complications that may require critical care and risk the patient's life.

[A case of monkeypox in intensive care in Argentina]. / Un caso de viruela símica en cuidados intensivos en Argentina.

Monkey pox is a rare zoonotic disease. It was first described in humans in Africa in 1970. On July 23, 2022, in view of the increasing number of cases reported in several countries and territories, the World Health Organization (WHO) concluded that the global outbreak constitutes a public health emergency of international concern. In our country, the first case was reported on May 22, 2022 and up to November 22 of this year, 895 patients were reported. We describe here the first case registered in Argentina requiring intensive care, according to the Epidemiological Bulletin, 46th epidemiological week, National Ministry of Health. The patient was a 44-year-old man with acquired immunodeficiency syndrome and severe Monkeypox, who presented obstructive ventilatory failure due to airway compromise and extensive generalized lesions of the integument, genitalia and fauces. In conclusion, the case presented alerts about potential complications that may require critical care and risk the patient's life.

La viruela símica es una enfermedad zoonótica poco frecuente. Fue descripta en humanos por primera vez en África en 1970. El 23 de julio del 2022, ante la cantidad ascendente de casos notificados en diversos países y territorios, la Organización Mundial de la Salud (OMS) concluyó que el brote mundial constituye una emergencia de salud pública de importancia internacional. En nuestro país el primer caso se notificó el 22 de mayo de 2022 hasta el 22 de noviembre se confirmaron 895 casos. Describimos el primer caso registrado en Argentina, según el boletín epidemiológico de la semana epidemiológica 46, del Ministerio de Salud de la Nación con requerimiento de cuidados intensivos. Se trata de un hombre de 44 años con síndrome de inmunodeficiencia adquirida y viruela símica grave, que presentó insuficiencia ventilatoria obstructiva, por compromiso de vías aéreas y lesiones generalizadas extensas de tegumento, genitales y fauces. En conclusión, el caso presentado alerta sobre las potenciales complicaciones que pueden requerir cuidados críticos y poner en riesgo la vida del paciente.

Coinfección COVID-19 y tuberculosis: experiencia de una terapia intensiva durante el periodo enero 2020-junio 2022 / COVID-19 and tuberculosis co-infection: experience of an intensive care unit during the period of January-june 2022

Antecedentes: Se ha demostrado que la coinfección tu-berculosis y COVID-19 presenta peor evolución clínica. La inmunidad protectora se debilita frente a esta situación, generando fallo en el control de ambas infecciones, reac-tivación de formas latentes de tuberculosis y progresión exacerbada de los casos activos. Asimismo, la terapia con corticoides utilizada dentro del tratamiento de infecciones graves por COVID-19 puede generar inmunosupresión y precipitar la progresión de la tuberculosis.Objetivos: Describir las características clínicas, presenta-ción y evolución de los pacientes críticos con coinfección COVID-19 y tuberculosis. Evaluar la incidencia y letalidad de la asociación COVID-19 y tuberculosis en cuidados in-tensivos. Materiales y métodos: Se realizó un estudio retrospectivo, descriptivo. Se revisaron 12 historias clínicas de pacientes con coinfección COVID-19-tuberculosis sobre 1014 histo-rias clínicas de pacientes ingresados con diagnóstico de COVID-19, durante el periodo comprendido enero 2020 y junio 2022. Se utilizó estadística descriptiva. Resultados y discusión: Sobre un total de 1014 historias clínicas, se encontraron 12 pacientes con coinfección (in-cidencia de 0,011). La letalidad global en cuidados inten-sivos fue del 75%, a los 45 días fue del 83,3%, duplicando la letalidad general de los pacientes COVID-19 no coinfec-tados ingresados durante el mismo periodo (75% versus 37%). Los pacientes que requirieron ingreso a ventilación RESUMENARTÍCULO ORIGINALmecánica tuvieron una letalidad del 100% y aquellos que tenían infección por virus de inmunodeficiencia adquirida presentaron una letalidad de 100%. Resulta importante describir los hallazgos y alertar sobre la evolución desfavorable de aquellos pacientes que pre-sentan esta asociación a fin de optimizar el manejo y espe-cialmente recomendar la búsqueda de coinfección cuando el criterio clínico lo requiera

Background: Coinfection with tuberculosis and COVID-19 has been shown to have a worse clinical course. Protective immunity is weakened in this situation, leading to failure to control both infections, reactivation of latent forms of TB and exacerbated progression of active cases. Furthermore, corticosteroid therapy used in the treatment of severe COVID-19 infections can lead to immunosuppression and precipitate TB progression.Objectives: To describe the clinical characteristics, presentation and evolution of critically ill patients with COVID-19 and tuberculosis co-infection.To evaluate the incidence and lethality of COVID-19 and tuberculosis association in intensive care.Materials and methods: A retrospective, descriptive study was conducted. Twelve medical records of patients aged 18 years or older admitted to intensive care with a diagnosis of COVID-19 during the period January 2020 to July 2022 were reviewed. Descriptive statistics were used.Results and discussion: Out of a total of 1014 medical records, 12 patients were found with co-infection (incidence 0.011). The global intensive care case fatality was 75%, at 45 days it was 83.3%. This was twice the overall case fatality of non-co-infected COVID-19 patients admitted during the same period (75% versus 37%). Patients requiring admission to mechanical ventilation had a 100% case fatality and those with acquired immunodeficiency virus infection had a 100% case fatality.It is important to describe the findings and to alert to the worse evolution of those patients presenting with this association, in order to improve management and recommend searching for co-infection when clinical criteria require it

Aspergilosis invasiva: definiciones, diagnóstico y tratamiento / Invasive aspergillosis: definitions, diagnosis, and treatment

Resumen La aspergilosis invasiva (AI) es una enfermedad grave y con alta mortalidad. Existen factores de riesgo y se describen brotes intrahospitalarios relacionados con construcciones. También se des cribe una entidad relacionada con la infección por COVID-19, conocida como aspergilosis pulmonar asociada a COVID-19 (APAC). Es de vital importancia implementar un tratamiento adecuado y precoz, especialmente en pacientes inmunocomprometidos y críticamente enfermos. El diagnóstico se basa en reconocer los factores predisponentes, la clínica, la obtención de imágenes, exámenes directos, cultivos, histopatología y biomarca dores como el galactomanano. La droga de elección es el voriconazol, pero se deben conocer las alternativas terapéuticas dada la creciente presencia de aislamientos resistentes.

Abstract Invasive aspergillosis (IA) is a serious disease with high mortality. There are several risk factors and in-hospital outbreaks related with construction have been described. An entity related to COVID-19 infection, known as COVID-19 associated pulmonary aspergillosis (CAPA), has recently appeared. Early and appropriate treatment is of paramount importance, especially in immunocompromised and critically ill patients. Diagnosis is based on recognition of predisposing factors, clinical signs, imaging, direct examination, culture, histopathology, and biomarkers such as galactomannan. The drug of choice is voriconazole, but alternative therapies must be taken into account given the increasing presence of resistant isolates.

[Invasive aspergillosis: definitions, diagnosis, and treatment]. / Aspergilosis invasiva: definiciones, diagnóstico y tratamiento.

Invasive aspergillosis (IA) is a serious disease with high mortality. There are several risk factors and in-hospital outbreaks related with construction have been described. An entity related to COVID-19 infection, known as COVID-19 associated pulmonary aspergillosis (CAPA), has recently appeared. Early and appropriate treatment is of paramount importance, especially in immunocompromised and critically ill patients. Diagnosis is based on recognition of predisposing factors, clinical signs, imaging, direct examination, culture, histopathology, and biomarkers such as galactomannan. The drug of choice is voriconazole, but alternative therapies must be taken into account given the increasing presence of resistant isolates.

La aspergilosis invasiva (AI) es una enfermedad grave y con alta mortalidad. Existen factores de riesgo y se describen brotes intrahospitalarios relacionados con construcciones. También se describe una entidad relacionada con la infección por COVID-19, conocida como aspergilosis pulmonar asociada a COVID-19 (APAC). Es de vital importancia implementar un tratamiento adecuado y precoz, especialmente en pacientes inmunocomprometidos y críticamente enfermos. El diagnóstico se basa en reconocer los factores predisponentes, la clínica, la obtención de imágenes, exámenes directos, cultivos, histopatología y biomarcadores como el galactomanano. La droga de elección es el voriconazol, pero se deben conocer las alternativas terapéuticas dada la creciente presencia de aislamientos resistentes.

Microglial phagocytosis dysfunction in stroke is driven by energy depletion and induction of autophagy.

Microglial phagocytosis of apoptotic debris prevents buildup damage of neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse and preclinical monkey models of stroke (macaques and marmosets) by transient occlusion of the medial cerebral artery (tMCAo). By analyzing recently published bulk and single cell RNA sequencing databases, we show that the phagocytosis dysfunction was not explained by transcriptional changes. In contrast, we demonstrate that the impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrient deprivation (OND), which led to reduced process motility, lysosomal exhaustion, and the induction of a protective macroautophagy/autophagy response in microglia. Basal autophagy, in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using pharmacological and transgenic approaches. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro, where it even had a detrimental effect on microglia, suggesting that modulating microglial autophagy to optimal levels may be a hard to achieve goal. Nonetheless, our results show that pharmacological interventions, acting directly on microglia or indirectly on the brain environment, have the potential to recover phagocytosis efficiency in the diseased brain. We propose that phagocytosis is a therapeutic target yet to be explored in stroke and other brain disorders and provide evidence that it can be modulated in vivo using rapamycin.Abbreviations: AIF1/IBA1: allograft inflammatory factor 1; AMBRA1: autophagy/beclin 1 regulator 1; ATG4B: autophagy related 4B, cysteine peptidase; ATP: adenosine triphosphate; BECN1: beclin 1, autophagy related; CASP3: caspase 3; CBF: cerebral blood flow; CCA: common carotid artery; CCR2: chemokine (C-C motif) receptor 2; CIR: cranial irradiation; Csf1r/v-fms: colony stimulating factor 1 receptor; CX3CR1: chemokine (C-X3-C motif) receptor 1; DAPI: 4',6-diamidino-2-phenylindole; DG: dentate gyrus; GO: Gene Ontology; HBSS: Hanks' balanced salt solution; HI: hypoxia-ischemia; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MCA: medial cerebral artery; MTOR: mechanistic target of rapamycin kinase; OND: oxygen and nutrient deprivation; Ph/A coupling: phagocytosis-apoptosis coupling; Ph capacity: phagocytic capacity; Ph index: phagocytic index; SQSTM1: sequestosome 1; RNA-Seq: RNA sequencing; TEM: transmission electron microscopy; tMCAo: transient medial cerebral artery occlusion; ULK1: unc-51 like kinase 1.

Hyperbaric oxygen as an adjuvant treatment for patients with COVID-19 severe hypoxaemia: a randomised controlled trial.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO2 in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction. METHODS: This was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO2 ≤90% despite oxygen supplementation) were assigned to receive either HBO2 treatment or the standard treatment for respiratory symptoms for 7 days. HBO2 treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO2 ≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients. RESULTS: The trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO2 was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO2 sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0-4.5) versus median 9 days (IQR 5.5-12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO2 group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission. CONCLUSION: Our findings support the safety and efficacy of HBO2 in the treatment of COVID-19 and severe hypoxaemia. TRIAL REGISTRATION NUMBER: NCT04477954.

Exploring the role of climatic niche changes in the evolution of the southern South American genus Baripus (Coleoptera: Carabidae): optimization of non-hereditary climatic variables and phylogenetic signal measurement.

Baripus is a ground beetle genus endemic to southern South America, currently distributed across grassland and shrub habitats in mountain and lowland regions. The species of this genus are known to have been affected by the Andean orogeny and the climate changes that occurred during this process. In this study, we seek to understand how the orogeny of the Andes may have led to changes in the climatic niches of the species of Baripus over time. We integrated former ecological and historical biogeographic hypotheses, exploring the use of parsimony optimization of phylogenetically structured climate variables and ancestral character state reconstruction methods. We then performed regression analyses of the optimized climatic niche variables within the phylogenetic tree of Baripus. We were able to infer significant climatic niche constraints, and niche changes that provide new insights to the existing knowledge, supporting former ecological and biogeographic hypotheses for this genus. Such trends in climatic niche could be explained by the rain shadow effect caused by the Andean uplift as well as with other climate shifts associated with temperature and precipitation swings that occurred in this region from the Middle Miocene to the Pliocene.

Infecciones fúngicas en pacientes con COVID-19 / Fungal infections in patients with COVID-19

En diciembre de 2019 se identificó en Wuhan, China, un nuevo coronavirus denominado SARS-CoV-2, agente causal de la epidemia de neumonía atípica COVID-2019, que el 11 de marzo de 2020 fue declarada pandemia por la OMS.Hasta el 30 de septiembre de 2020, en Argentina fueron confirmados 751.001 casos y más de 16.937 muertes.La frecuencia y el impacto de las coinfecciones que afectan a los pacientes infectados por SARS-Cov-2 se ha estudiado junto con el avance de la pandemia. Entre las debidas a hongos se encuentran las fungemias por Candida sp, la aspergilosis invasora, las micosis sistémicas endémicas y la neumocistosis. Presentamos las distintas coinfecciones micosis-COVID-19 que fueron asistidas en nuestra institución entre abril y septiembre de 2020, y se realiza un análisis de las características de estas infecciones en pacientes con y sin sida. En este período se internaron 2837 pacientes, 2287 tuvieron diagnóstico confirmado de COVID-19. La coinfección de COVID-19 con micosis pulmonares o sistémicas fue menor al 1%.Dieciocho pacientes presentaron infecciones fúngicas pulmonares o sistémicas. Ocho padecieron candidemias, cinco criptococosis meningeas, dos histoplasmosis, dos aspergilosis invasoras agudas probables y una aspergilosis pulmonar crónica. La estadía prolongada en terapia intensiva facilitó las fungemias por Candida sp, los casos de histoplasmosis y criptococosis parecen relacionarse con la enfermedad avanzada por VIH y no con COVID-19. Los enfermos con un componente inflamatorio basal alto con neumonía grave por coronavirus se relacionan más con micosis invasoras que los enfermos VIH positivos con niveles bajos de LTCD4+

On December 2019 a new coronavirus (SARS-CoV2) result in atypical pneumonía epidemic, it was identified in Wuhan China and it was called COVID-19. Then on March 11 was declared pandemic by the WHO.Until September 30, 2020 in Argentina 751,001 cases and more than 16,937 deaths have been confirmed. The frequency and impact of co-infections affecting SARS-Cov2 infected patients has been studied with the advance of the pandemic. Among those due to fungi are Candida sp fungemias, invasive aspergillosis, endemic systemic mycoses, and pneumocystosis.We present the different mycosis-COVID-19 co-infections that were assisted in F. J. Muñiz Hospital between April and September of this year and review the characteristics of these infections in patients with and without AIDS is carried out.In this period, 2,837 patients were admitted in the Muñiz hospital, 2,287 had a confirmed diagnosis of COVID-19.Co-infection of COVID-19 with pulmonary or systemic mycoses was less than 1%.Eighteen patients had pulmonary or systemic fungal infections. Eight suffered from candidemia, five meningeal cryptococcosis, two histoplasmosis, two probable acute invasive aspergillosis, and one chronic pulmonary aspergillosis.Prolonged stay in intensive care facilitated fungemia due to Candida sp. Histoplasmosis and cryptococcosis cases seem to be related to advanced HIV disease and not to COVID-19.Patients with a high baseline inflammatory component with severe coronavirus pneumonia are more associated with invasive mycoses than HIV-positive patients with low levels of LTCD4 +

Is hepatitis C direct-acting antiviral therapy a risk factor for the development and recurrence of hepatocellular carcinoma? Narrative literature review and clinical practice recommendations.

The development of direct-acting antivirals (DAAs) has been a turning point in chronic hepatitis C treatment. With an efficacy rate on viral eradication close to 100% and an excellent safety profile, they have replaced interferon-based treatments as first-line therapy for hepatitis C virus (HCV). Following the encouraging results observed during the first years with these treatments, new publications suggested an unexpectedly high incidence of hepatocellular carcinoma (HCC) in patients previously treated with DAAs as well as a higher HCC recurrence rate in them. The possible interaction between DAAs and HCC and its impact on HCC incidence and recurrence still remains controversial. The aim of the present work is to review the current state of the matter by analyzing studies that evaluate the association between chronic hepatitis C treatment with DAAs and the development of HCC either de novo or as a recurrence. Following this, clinical practice recommendations are done.

Benznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive Patients.

Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1 µg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2 µg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations.

Lithium treatment reverses irradiation-induced changes in rodent neural progenitors and rescues cognition.

Cranial radiotherapy in children has detrimental effects on cognition, mood, and social competence in young cancer survivors. Treatments harnessing hippocampal neurogenesis are currently of great relevance in this context. Lithium, a well-known mood stabilizer, has both neuroprotective, pro-neurogenic as well as antitumor effects, and in the current study we introduced lithium treatment 4 weeks after irradiation. Female mice received a single 4 Gy whole-brain radiation dose on postnatal day (PND) 21 and were randomized to 0.24% Li2CO3 chow or normal chow from PND 49 to 77. Hippocampal neurogenesis was assessed on PND 77, 91, and 105. We found that lithium treatment had a pro-proliferative effect on neural progenitors, but neuronal integration occurred only after it was discontinued. Also, the treatment ameliorated deficits in spatial learning and memory retention observed in irradiated mice. Gene expression profiling and DNA methylation analysis identified two novel factors related to the observed effects, Tppp, associated with microtubule stabilization, and GAD2/65, associated with neuronal signaling. Our results show that lithium treatment reverses irradiation-induced loss of hippocampal neurogenesis and cognitive impairment even when introduced long after the injury. We propose that lithium treatment should be intermittent in order to first make neural progenitors proliferate and then, upon discontinuation, allow them to differentiate. Our findings suggest that pharmacological treatment of cognitive so-called late effects in childhood cancer survivors is possible.

The Secretome of Microglia Regulate Neural Stem Cell Function.

Brain injury is associated with neuroinflammation, and microglia are key players in this process. Microglia can acquire pro-inflammatory or anti-inflammatory properties, but how this affects neural stem cells (NSCs) remains controversial. Here, NSCs were grown in conditioned media collected from either non-stimulated microglia, or microglia stimulated with pro- or anti-inflammatory agents. NSC survival, proliferation, migration, and differentiation were investigated thereafter. We found that NSCs kept in conditioned medium from the anti-inflammatory microglial subtype had better survival, increased migration, and lower astrocytic differentiation compared to NSCs grown in conditioned medium collected from the pro-inflammatory subtype. Finally, we found that NSCs differentiated in microglial conditioned media generated cells expressing the pro-inflammatory chemokine CCL2, most pronounced when differentiated in medium from the pro-inflammatory microglia subtype. Our results show that microglial subtypes regulate NSCs differently and induce generation of cells with inflammatory properties.

[Intra-abdominal infections. Update and recommendations]. / Infecciones intraabdominales. Puesta al día y recomendaciones de la Sociedad Argentina de Infectología.

Intra-abdominal infections represent a group of intra and retroperitoneal processes, ranging from localized infections to complicated ones, sepsis and septic shock, associated with a significant mortality rate. They are the third most commonly identified cause of sepsis and the second cause of death in the intensive care unit. Although antimicrobial therapy must be started as soon as possible, especially in critically ill patients, the source control procedure is highly relevant. On account of the importance of this subject, members of the Argentine Society of Infectious Diseases (SADI) and intensive care specialists joined to develop recommendations on diagnosis, treatment, and prevention of intra-abdominal infections. The literature published within the last 10 years was reviewed and analyzed, in addition of expert opinions and local data. This statement provides a basic tool for diagnosis based on clinical and microbiological criteria, orientation on empirical antimicrobial therapy schemes according to source, acquisition place (community or healthcare associated infections), infection severity, treatment duration, importance of source control, and preventive measures aimed to reduce surgical site infection risk. Likewise, it provides a simple algorithm for diagnosis and treatment for use in clinical practice. The work reveals the concern about the management of intra-abdominal infections, establishing local guidelines to optimize diagnosis, treatment and prevention, with the aim of reducing morbidity, mortality, length of stay, costs and antimicrobial resistance.

Infecciones intraabdominales: Puesta al día y recomendaciones de la sociedad Argentina de infectología / Intra-abdominal infections. Update and recommendations

Las infecciones intraabdominales constituyen un grupo de procesos intra y retroperitoneales, desde cuadros localizados hasta infecciones complicadas, sepsis o shock séptico, con elevada mortalidad. Representan la tercera causa de sepsis y la segunda causa de muerte en unidades de terapia intensiva. El tratamiento antimicrobiano debe iniciarse lo antes posible, especialmente en pacientes en estado crítico, pero también es fundamental el procedimiento de control del foco. Dada la importancia del tema, representantes de la Sociedad Argentina de Infectología junto con especialistas en Terapia Intensiva elaboraron estas recomendaciones sobre su diagnóstico, tratamiento y prevención. A tal fin, revisaron y analizaron la bibliografía publicada sobre el tema en los últimos 10 años, además de la opinión de expertos y datos locales. El documento ofrece herramientas básicas de diagnóstico basadas en criterios clínicos y microbiológicos, orientación sobre esquemas antibióticos empíricos y dirigidos según foco de origen, lugar de adquisición (comunidad o asociadas al cuidado de la salud) y gravedad de la infección, duración del tratamiento, importancia del control del foco y medidas preventivas para reducir el riesgo de infección del sitio quirúrgico. Asimismo, se presenta un algoritmo sencillo de diagnóstico y tratamiento para uso en la actividad asistencial. El trabajo pone en evidencia la preocupación por el tratamiento de las infecciones intraabdominales, estableciendo pautas locales para mejorar su diagnóstico, tratamiento y prevención, con el objeto de disminuir morbimortalidad, días de internación, costos y resistencia antimicrobiana.

Intra-abdominal infections represent a group of intra and retroperitoneal processes, ranging from localized infections to complicated ones, sepsis and septic shock, associated with a significant mortality rate. They are the third most commonly identified cause of sepsis and the second cause of death in the intensive care unit. Although antimicrobial therapy must be started as soon as possible, especially in critically ill patients, the source control procedure is highly relevant. On account of the importance of this subject, members of the Argentine Society of Infectious Diseases (SADI) and intensive care specialists joined to develop recommendations on diagnosis, treatment, and prevention of intra-abdominal infections. The literature published within the last 10 years was reviewed and analyzed, in addition of expert opinions and local data. This statement provides a basic tool for diagnosis based on clinical and microbiological criteria, orientation on empirical antimicrobial therapy schemes according to source, acquisition place (community or healthcare associated infections), infection severity, treatment duration, importance of source control, and preventive measures aimed to reduce surgical site infection risk. Likewise, it provides a simple algorithm for diagnosis and treatment for use in clinical practice. The work reveals the concern about the management of intra-abdominal infections, establishing local guidelines to optimize diagnosis, treatment and prevention, with the aim of reducing morbidity, mortality, length of stay, costs and antimicrobial resistance.