Canine neutrophils cooperate with macrophages in the early stages of Leishmania infantum in vitro infection.

Leishmania infantum is the aetiological agent of human visceral leishmaniasis and canine leishmaniasis, both systemic and potentially fatal diseases. Polymorphonuclear neutrophils (PMN) are the first cells to phagocyte this parasite at the inoculation site, but macrophages (MØ) are the definitive host cells, ensuring parasite replication. The interaction between dog MØ, PMN and L infantum promastigotes was in vitro investigated. It was observed that promastigotes establish contact with blood monocyte-derived MØ mainly by the tip of the flagellum. These cells, that efficiently bind and internalize parasites, underwent major morphological changes, produced nitric oxide (NO) and released histone H1 in order to inactivate the parasite. Transfer of intracellular parasites from PMN to MØ was confirmed by flow cytometry, using L infantum expressing a green fluorescent protein. The interaction of MØ with L infantum-infected PMN lead to NO production and release of extracellular traps, which may contribute to parasite containment and inactivation. This study highlights for the first time the diversity of cellular and molecular events triggered by the interaction between canine PMN and MØ, which can promote a reduction of parasite burden in the early phase of L infantum infection.

Ponatinib-Induced Pneumonitis with Severe Acute Respiratory Distress Syndrome.

Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) that can effectively treat patients with acute lymphoblastic leukaemia (ALL), particularly those with Philadelphia chromosome-positive (Ph+ALL) subtype, who are resistant or have previously received other TKIs. We report a case of a 42-year-old female with Ph+ALL who was admitted to the intensive care unit with respiratory failure and severe acute respiratory distress syndrome (ARDS), while on treatment with ponatinib. Despite being treated with multiple antibiotics and antivirals, the patient's condition continued to worsen, and pulmonary complications secondary to TKI were suspected. After starting a steroid regimen, the patient's condition improved drastically with resolution of the pulmonary complications. While many adverse events (AEs) happen in the beginning stages of TKI treatment, certain toxicities may not arise until months after therapy initiation. Cardiovascular complications are the most common AE of ponatinib, including heart failure and arterial hypertension. Pulmonary complications may occur, and management includes drug cessation and individualised steroid therapy. In case of respiratory failure without signs of infection and no improvement with antimicrobial treatment, clinicians should consider the possibility of pulmonary toxicity associated with ponatinib. LEARNING POINTS: Although rarely reported, ponatinib may have pulmonary toxicity presenting as new onset of respiratory insufficiency.Management of pulmonary complications includes adjusting or discontinuation of ponatinib and simultaneous treatment with steroids.

Multiple Victims of Carbon Monoxide Poisoning in the Aftermath of a Wildfire: A Case Series.

INTRODUCTION: Carbon monoxide poisoning may occur in several contexts. MATERIAL AND METHODS: Retrospective of 37 carbon monoxide poisoning cases that underwent hyperbaric oxygen during wildfires in Funchal in August 2016. RESULTS: The studied sample included 37 patients, mean age of 38 years, 78% males. Ten were firefighters, four children and two pregnant victims. Neurological symptoms were the most reported. Median carboxyhemoglobin level was 3.7% (IQR 2.7). All received high-flow oxygen from admission to delivery of hyperbaric oxygen. Persistence of symptoms was the main indication for hyperbaric oxygen. Median time to hyperbaric oxygen was 4.8 hours (IQR 9.5), at 2.5 ATA for 90 minutes, without major complications. Discharge in less than 24 hours occurred in 92% of the cases. Thirty days follow-up: five patients presented clinical symptoms of late neurological syndrome; twelve patients were lost to follow-up. Carboxyhemoglobin levels on admission and mean time to hyperbaric oxygen were no different between those who did and did not develop the syndrome at 30 days (p = 0.44 and p = 0.58, respectively). DISCUSSION: Late neurological syndrome at 30 days occurred in 20% and no new cases were reported at 12 months. CONCLUSION: Use of hyperbaric oxygen appears to have reduced the incidence of the syndrome. This seems to be the first Portuguese series reporting use of hyperbaric oxygen in carbon monoxide poisoning due to wildfires. The authors intend to alert to the importance of referral of these patients because the indications and benefits of this treatment are well documented. This is especially important given the ever-growing issue of wildfires in Portugal.

Introdução: A intoxicação por monóxido de carbono pode ocorrer em diversos contextos. Material e Métodos: Retrospectiva de 37 casos de intoxicação por monóxido de carbono submetidos a oxigenoterapia hiperbárica nos fogos do Funchal de agosto de 2016. Resultados: Foram analisados 37 doentes, com média de 38 anos e 78% do sexo masculino; o universo de casos analisados incluiu 10 bombeiros, quatro crianças e duas grávidas; 80% reportaram sintomas neurológicos. O nível mediano de carboxihemoglobina foi de 3,7%. Todos receberam oxigénio alto débito até iniciarem oxigenoterapia hiperbárica. A persistência de sintomas foi a principal indicação para oxigenoterapia hiperbárica. O tempo mediano para oxigenoterapia hiperbárica foi 4,8 horas, a 2,5 ATA durante 90 minutos, sem intercorrências relevantes. O tempo até alta foi inferior a 24 horas em 92% dos casos. Follow-up 30 dias: cinco doentes apresentavam sinais clínicos de síndrome neurológico tardio; doze foram perdidos no follow-up. Os níveis de carboxihemoglobina durante a admissão e tempo médio até oxigenoterapia hiperbárica não diferiram entre os doentes que desenvolveram a síndrome a 30 dias e os restantes (p = 0,44 e p = 0,58, respetivamente). Discussão: A ocorrência de síndrome neurológico tardio a 30 dias ocorreu em 20% dos doentes, não se tendo verificado novos casos ao fim de 12 meses. Conclusão: A oxigenoterapia hiperbárica parece ter permitido reduzir a incidência de síndrome neurológico tardio. Esta é a primeira série de casos portuguesa que reporta exclusivamente a utilização de oxigenoterapia hiperbárica na intoxicação por monóxido de carbono por fogos florestais. Os autores pretendem alertar para importância destes doentes, cuja indicação terapêutica e benefício clínico deste tratamento está bem documentada, sobretudo atendendo à crescente problemática dos incêndios florestais em Portugal.