Severe hepatopulmonary syndrome with hypoxemia refractory to liver transplant: Recovery after 67 days of ECMO support.

Hepatopulmonary syndrome (HPS) is a complication of end stage liver disease (ESLD) and is manifested by severe hypoxemia, which usually responds to liver transplantation (LT). As compared to patients undergoing LT for other etiologies, patients with HPS present an increased risk of postoperative morbidity and mortality. There is no effective treatment for patients whose hypoxemia does not respond to LT. This subset of patients is at a highly increased risk of death. There are very few reports on the use of extracorporeal membrane oxygenation (ECMO) in this setting with rapid response. However, there is no prior report of ECMO utilization for longer than 4 weeks. We present the case of a 17 year-old male patient who underwent LT for ESLD secondary to chronic portal vein thrombosis and HPS. He received a liver from a deceased donor and presented with severe HPS after LT, requiring ECMO support for 67 days. The patient was discharged home and is breathing in ambient air. He is currently asymptomatic and has a normal liver function.

Emprego do modelo matemático SEIHDR para auxiliar gestores na estimativa de ocupação de leitos de UTI em uma pandemia: simulação para pacientes com COVID-19 no município de Porto Alegre / Use of the SEIHDR mathematical model to assist health managers in estimating ICU bed occupancy in a pandemic: simulation for patients with COVID-19 in the city of Porto Alegre, Brazil

Introdução: A pandemia de COVID-19, no Brasil, constituiu uma ameaça ao sistema de saúde pelo risco de esgotamento dos leitos de Unidade de Terapia Intensiva (UTI). O objetivo do estudo foi projetar a ocupação de leitos de UTI com casos de COVID-19 no pico em Porto Alegre. Para isso, resolvemos utilizar uma ferramenta matemática com parâmetros da pandemia desta cidade.Métodos:Utilizamos o modelo matemático SEIHDR. Analisamos os casos de hospitalização por COVID-19 em Porto Alegre e RS até 3 de agosto de 2020 a fim de extrair os parâmetros locais para construir uma curva epidemiológica do total de casos prevalentes hospitalizados em UTI. Também analisamos as taxas de reprodução básica (R0) e reprodução efetiva (Re).Resultados: O modelo matemático projetou um pico de 344 casos prevalentes, em UTI, para o dia 22 de agosto de 2020. Calculamos 1,56 para o R0 e 1,08 no dia 3 de agosto para o Re.Conclusão: O modelo matemático simulou uma primeira onda de casos ocupando leitos de UTI muito próxima dos dados reais. Também indicou corretamente uma queda no número de casos nos dois meses subsequentes. Apesar das limitações, as estimativas do modelo matemático forneceram informações sobre as dimensões temporal e numérica de uma pandemia que poderiam ser usadas como auxílio aos gestores de saúde na tomada de decisões para a alocação de recursos frente a calamidades de saúde como o surto de COVID-19 no Brasil.

Introduction: The COVID-19 pandemic in Brazil has been a threat to health services due to the risk of bed shortage in the intensive care unit (ICU). This study aimed to estimate the bed occupancy at the ICU with patients with COVID-19 during the peak of the pandemic in Porto Alegre, capital of Rio Grande do Sul (RS), the southernmost state of Brazil. To this end, we used a mathematical model with pandemic parameters from the city.Methods: We used the SEIHDR mathematical model. We analyzed hospitalizations for COVID-19 in Porto Alegre and RS until August 3, 2020, to extract local parameters to create an epidemiological curve of the total number of prevalent cases in the ICU. We also analyzed the basic reproduction rate (R0) and effective reproduction rate (Re). Results: The mathematical model estimated a peak of 344 prevalent cases in the ICU on August 22, 2020. The model calculated an R0 of 1.56 and Re of 1.08 on August 3, 2020.Conclusion: The mathematical model accurately estimated the first peak of cases in the ICU. Also, it correctly indicated a drop in the number of cases in the following two months. Despite the limitations, the mathematical model estimates provided information on the temporal and numerical dimensions of a pandemic that could be used to assist health managers in making decisions on the allocation of resources in a state of public calamity such as the COVID-19 outbreak in Brazil.

Estimation of patients hospitalized for COVID-19 in an intensive care unit at the peak of the pandemic in Porto Alegre: Study with epidemiological model SEIHDR / Estimativa de pacientes hospitalizados por COVID-19 em unidade de terapia intensiva no pico da pandemia em Porto Alegre: Estudo com modelo epidemiológico SEIHDR

Objective: Estimate the maximum number of prevalent cases of COVID-19, admitted to intensive care units, and the time of this peak, in Porto Alegre. Methods: A mathematical model of differential equations called SEIHDR (Susceptible, Exposed, Infected, Hospitalized, Dead, Recovered) have been used to analyze the cases of hospitalization for COVID-19 in Porto Alegre and RS, from March 9 to July 25, 2020 in order to extract the parameters to make up an epidemiological curve of the prevalent cases hospitalized in general ward and in intensive care units, as well as how to estimate the prevalence of patients on invasive mechanical ventilation. Finally, we adjusted some parameters of this curve based on the current prevalent cases hospitalized. Results: The mathematical model corrected for the pandemic data until July 25 projected a peak of 1,354 prevalent hospitalized cases: 562 patients admitted to the intensive care unit with 378 under mechanical ventilation on September 12, 2020 (37th epidemiological week). In addition, there would be a peak of 62,514 prevalent cases of infected with COVID-19 at the beginning of the same month (36th epidemiological week. We calculated for the pandemic a basic reproduction number of 1.53 and effective reproduction number of 1.29 to July 25, 2020. Conclusion: As the current number of beds in the intensive care unit would be insufficient to meet this demand, we suggest an increase in the number of critical beds in order to avoid the collapse of the health system in Porto Alegre.

Objetivo: Estimar o número máximo de casos prevalentes de COVID-19, internados em unidades de terapia intensiva, e o momento deste pico, em Porto Alegre. Métodos: Empregamos um modelo matemático de equações diferenciais denominado SEIHDR (Suscetível, Exposto, Infectado, Hospitalizado, Morto, Recuperados). Analisamos os casos de hospitalização por COVID-19 em Porto Alegre e RS, desde 9 de março até 25 de julho de 2020 a fim de extrair os parâmetros para construir uma curva epidemiológica do total de casos prevalentes hospitalizados e em unidade de terapia intensiva, assim como estimar a prevalência de pacientes em ventilação mecânica invasiva. Finalmente, ajustamos alguns parâmetros desta curva a partir dos casos reais prevalentes de internados em enfermaria e em unidades de terapia intensiva. Resultados: O modelo matemático corrigido para os dados da pandemia até 25 de julho projetou um pico de 1.354 casos prevalentes hospitalizados: 562 pacientes internados na unidade de terapia intensiva com 378 sob ventilação mecânica no dia 12 de setembro de 2020 (37º semana epidemiológica). Ainda, haveria o pico de 62.514 casos prevalentes de infectados com COVID-19 no início do mesmo mês (36º semana epidemiológica. Calculamos para a pandemia um número de reprodução básico de 1,53 e de reprodução efetiva de 1,29 para 25 de julho de 2020. Conclusão: Como o número atual de leitos de unidade de terapia intensiva seria insuficiente para atender a esta demanda, sugerimos um aumento no número de leitos críticos a fim de evitar o colapso do sistema de saúde em Porto Alegre.

Repeated systemic administration of adipose tissue-derived mesenchymal stem cells prevents tracheal obliteration in a murine model of bronchiolitis obliterans.

OBJECTIVE: To investigate the effect of adipose tissue-derived mesenchymal stem cell (ASC) administered either systemically or locally in a murine model of bronchiolitis obliterans. RESULTS: When compared to controls, systemic treatment with 106 ASCs on D0 and a second dose on D7 significantly prevented tracheal obliteration 28 days after heterotopic tracheal transplantation (median of 94 vs. 16%; P < 0.01). A single dose tended towards less stenosis than controls, but did not reach statistical significance (28 vs. 94%; P = 0.054). On the contrary, repeated local injection was incapable of preventing tracheal obliteration when compared to a single injection or controls (37 vs. 71 vs. 87%). Two intravenous doses also tended to be better than two local injections (16 vs. 37%; P = 0.058), and were better than a single local dose (16 vs. 71%; P < 0.01). CONCLUSION: A second dose of ASC, given systemically after 7 days, reduces luminal obliteration in a heterotopic tracheal transplantation model in mice, suggesting that ASC can be used to prevent obliterative bronchiolitis after lung transplantation.

Anatomic pulmonary resection by video-assisted thoracoscopy: the Brazilian experience (VATS Brazil study).

OBJECTIVE: The objective of this study was to describe the results of anatomic pulmonary resections performed by video-assisted thoracoscopy in Brazil. METHODS: Thoracic surgeons (members of the Brazilian Society of Thoracic Surgery) were invited, via e-mail, to participate in the study. Eighteen surgeons participated in the project by providing us with retrospective databases containing information related to anatomic pulmonary resections performed by video-assisted thoracoscopy. Demographic, surgical, and postoperative data were collected with a standardized instrument, after which they were compiled and analyzed. RESULTS: The surgeons provided data related to a collective total of 786 patients (mean number of resections per surgeon, 43.6). However, 137 patients were excluded because some data were missing. Therefore, the study sample comprised 649 patients. The mean age of the patients was 61.7 years. Of the 649 patients, 295 (45.5%) were male. The majority-521 (89.8%)-had undergone surgery for neoplasia, which was most often classified as stage IA. The median duration of pleural drainage was 3 days, and the median hospital stay was 4 days. Of the 649 procedures evaluated, 598 (91.2%) were lobectomies. Conversion to thoracotomy was necessary in 30 cases (4.6%). Postoperative complications occurred in 124 patients (19.1%), the most common complications being pneumonia, prolonged air leaks, and atelectasis. The 30-day mortality rate was 2.0%, advanced age and diabetes being found to be predictors of mortality. CONCLUSIONS: Our analysis of this representative sample of patients undergoing pulmonary resection by video-assisted thoracoscopy in Brazil showed that the procedure is practicable and safe, as well as being comparable to those performed in other countries. OBJETIVO: O objetivo deste estudo foi descrever os resultados de ressecções pulmonares anatômicas por videotoracoscopia no Brasil. MÉTODOS: Cirurgiões torácicos (membros da Sociedade Brasileira de Cirurgia Torácica) foram convidados, por correio eletrônico, a participar do estudo. Dezoito cirurgiões participaram do projeto enviando seus bancos de dados retrospectivos referentes a ressecções anatômicas de pulmão por videotoracoscopia. Dados demográficos, cirúrgicos e pós-operatórios foram coletados em um instrumento padronizado e posteriormente compilados e analisados. RESULTADOS: Dados referentes a 786 pacientes foram encaminhados (média de 43,6 ressecções por cirurgião), sendo 137 excluídos por informações incompletas. Logo, 649 pacientes constituíram nossa população estudada. A média de idade dos pacientes foi de 61,7 anos, 295 eram homens (45,5%), e a maioria - 521 (89,8%) - foi submetida à cirurgia por neoplasia, mais frequentemente classificada como estádio IA. A mediana do tempo de drenagem pleural foi de 3 dias, e a do tempo de internação, 4 dias. Dos 649 procedimentos realizados, 598 (91,2%) foram lobectomias. A taxa de conversão para toracotomia foi de 4,6% (30 casos). Complicações pós-operatórias ocorreram em 124 pacientes (19,1%), sendo pneumonia, escape aéreo prolongado e atelectasia as mais frequentes. A mortalidade em 30 dias foi de 2,0%, tendo como preditores idade avançada e diabetes. CONCLUSÕES: A casuística brasileira mostra que as ressecções pulmonares por cirurgia torácica videoassistida são factíveis e seguras, além de comparáveis àquelas de registros internacionais.

Anatomic pulmonary resection by video-assisted thoracoscopy: the Brazilian experience (VATS Brazil study) / Ressecção pulmonar anatômica por videotoracoscopia: experiência brasileira (VATS Brasil)

ABSTRACT Objective: The objective of this study was to describe the results of anatomic pulmonary resections performed by video-assisted thoracoscopy in Brazil. Methods: Thoracic surgeons (members of the Brazilian Society of Thoracic Surgery) were invited, via e-mail, to participate in the study. Eighteen surgeons participated in the project by providing us with retrospective databases containing information related to anatomic pulmonary resections performed by video-assisted thoracoscopy. Demographic, surgical, and postoperative data were collected with a standardized instrument, after which they were compiled and analyzed. Results: The surgeons provided data related to a collective total of 786 patients (mean number of resections per surgeon, 43.6). However, 137 patients were excluded because some data were missing. Therefore, the study sample comprised 649 patients. The mean age of the patients was 61.7 years. Of the 649 patients, 295 (45.5%) were male. The majority-521 (89.8%)-had undergone surgery for neoplasia, which was most often classified as stage IA. The median duration of pleural drainage was 3 days, and the median hospital stay was 4 days. Of the 649 procedures evaluated, 598 (91.2%) were lobectomies. Conversion to thoracotomy was necessary in 30 cases (4.6%). Postoperative complications occurred in 124 patients (19.1%), the most common complications being pneumonia, prolonged air leaks, and atelectasis. The 30-day mortality rate was 2.0%, advanced age and diabetes being found to be predictors of mortality. Conclusions: Our analysis of this representative sample of patients undergoing pulmonary resection by video-assisted thoracoscopy in Brazil showed that the procedure is practicable and safe, as well as being comparable to those performed in other countries.

RESUMO Objetivo: O objetivo deste estudo foi descrever os resultados de ressecções pulmonares anatômicas por videotoracoscopia no Brasil. Métodos: Cirurgiões torácicos (membros da Sociedade Brasileira de Cirurgia Torácica) foram convidados, por correio eletrônico, a participar do estudo. Dezoito cirurgiões participaram do projeto enviando seus bancos de dados retrospectivos referentes a ressecções anatômicas de pulmão por videotoracoscopia. Dados demográficos, cirúrgicos e pós-operatórios foram coletados em um instrumento padronizado e posteriormente compilados e analisados. Resultados: Dados referentes a 786 pacientes foram encaminhados (média de 43,6 ressecções por cirurgião), sendo 137 excluídos por informações incompletas. Logo, 649 pacientes constituíram nossa população estudada. A média de idade dos pacientes foi de 61,7 anos, 295 eram homens (45,5%), e a maioria - 521 (89,8%) - foi submetida à cirurgia por neoplasia, mais frequentemente classificada como estádio IA. A mediana do tempo de drenagem pleural foi de 3 dias, e a do tempo de internação, 4 dias. Dos 649 procedimentos realizados, 598 (91,2%) foram lobectomias. A taxa de conversão para toracotomia foi de 4,6% (30 casos). Complicações pós-operatórias ocorreram em 124 pacientes (19,1%), sendo pneumonia, escape aéreo prolongado e atelectasia as mais frequentes. A mortalidade em 30 dias foi de 2,0%, tendo como preditores idade avançada e diabetes. Conclusões: A casuística brasileira mostra que as ressecções pulmonares por cirurgia torácica videoassistida são factíveis e seguras, além de comparáveis àquelas de registros internacionais.

Cell therapy in the treatment of bronchiolitis obliterans in a murine model.

OBJECTIVE: To evaluate the importance of stem cells derived from adipose tissue in reducing graft inflammation in a murine model of allogeneic heterotopic tracheal transplant. METHODS: We performed a heterotopic tracheal allografting in dorsal subcutaneous pouch and systemically injected 5x105 mesenchymal stem cells derived from adipose tissue. The animals were divided into two groups according to the time of sacrifice: T7 and T21. We also carried out histological analysis and digital morphometry. RESULTS: The T7 animals treated with cell therapy had median obstructed graft area of 0 versus 0.54 of controls (p = 0.635). The treated T21 subjects had median obstructed graft area of 0.25 versus 0 in controls (p = 0.041). CONCLUSION: The systemically injected cell therapy in experimental murine model of bronchiolitis obliterans did not reduce the severity of the allograft inflammation in a statistically significant way in seven days; Conversely, in 21 days, it increased the allograft inflammatory process.

Cell therapy in the treatment of bronchiolitis obliterans in a murine model / Terapia celular no tratamento da bronquiolite obliterante em modelo murino

OBJECTIVE: To evaluate the importance of stem cells derived from adipose tissue in reducing graft inflammation in a murine model of allogeneic heterotopic tracheal transplant. METHODS:We performed a heterotopic tracheal allografting in dorsal subcutaneous pouch and systemically injected 5x105 mesenchymal stem cells derived from adipose tissue. The animals were divided into two groups according to the time of sacrifice: T7 and T21. We also carried out histological analysis and digital morphometry. RESULTS:The T7 animals treated with cell therapy had median obstructed graft area of 0 versus 0.54 of controls (p = 0.635). The treated T21 subjects had median obstructed graft area of 0.25 versus 0 in controls (p = 0.041). CONCLUSION:The systemically injected cell therapy in experimental murine model of bronchiolitis obliterans did not reduce the severity of the allograft inflammation in a statistically significant way in seven days; Conversely, in 21 days, it increased the allograft inflammatory process.

OBJETIVO: Avaliar a importância das células-tronco derivadas de tecido adiposo na redução do processo inflamatório no enxerto em modelo murino de transplante traqueal heterotópico alogênico. MÉTODOS:Foi realizado alotransplante traqueal heterotópico em bolsa dorsal subcutânea e injetado 5x105 células-tronco mesenquimais, derivadas de tecido adiposo, sistemicamente. Os animais foram distribuídos em dois grupos, conforme o tempo de sacrifício: T7 e T21. Procedida a análise em HE e morfometria digital. RESULTADOS:Os T7 tratados com terapia celular apresentaram mediana de área obstruída do enxerto de 0 contra 0,54 dos controles (p=0,635). Os T21 tratados apresentaram mediana de área obstruída da luz do enxerto de 0,25 nos tratados e 0 nos controles (p=0,041). CONCLUSÃO: A terapia celular injetada sistemicamente em modelo experimental murino de bronquiolite obliterante não reduziu a gravidade do processo inflamatório no aloenxerto de forma estatisticamente significativa em sete dias; de modo contrário, em 21 dias, aumentou o processo inflamatório no aloenxerto.

Modelo experimental de estenose traqueal mediante ressecção cirúrgica submucosa de anéis traqueais combinada com instilações de hidróxido de sódio / Experimental model of tracheal stenosis with submucosal resection of cartilaginous rings combined with sodium hydroxide instillations

OBJETIVO: Desenvolver, experimentalmente, malácia e estenose traqueal para testar novos modelos de órteses traqueais. MÉTODOS: Ressecamos três anéis cartilaginosos da traqueia cervical de cães no grupo A (n=5) e seis anéis no grupo B (n=4) para produzir malácia. Logo após, a mucosa da região com malácia recebeu aplicações de uma solução de hidróxido de sódio (NaOH) a 23 por cento, e os animais eram acompanhados com exames broncoscópicos para observar o desenvolvimento de estreitamento da luz da via aérea. Quando a estenose era de mais de 50 por cento da luz, ou havia sinais mínimos de insuficiência ventilatória, os animais eram sacrificados. O segmento de via aérea estreitada foi então coletado para análise histológica e era calculada a área de luz residual do segmento traqueal com estenose e malácia. RESULTADOS: Na análise histológica, foi constatada fibrose na submucosa e adventícia, associada a granulomas na mucosa. A luz residual média dos segmentos com estenose foi de 9 por cento e 12 por cento nos grupos A e B, respectivamente, (p>0,05). CONCLUSÃO: A combinação da ressecção de anéis cartilaginosos e da aplicação de NaOH 23 por cento na mucosa respiratória promoveu uma estenose traqueal intensa, porém esteve associada à perda de animais. Novos estudos são necessários para verificar se o emprego isolado de uma das técnicas seria mais seguro e eficaz para desenvolver estenose traqueal.

OBJECTIVE: To experimentally develop tracheal stenosis and malacia to test new models of tracheal stents. METHODS: We resected three cartilaginous rings from the cervical trachea of dogs in group A (n = 5) and six rings in group B (n = 4) to produce malacia. The mucosa of the region with malacia then received applications of a solution of sodium hydroxide (NaOH) at 23 percent, and the animals were accompanied with bronchoscopic examinations to observe the development of luminal narrowing of the airway. When the stenosis was of more than 50 percent or there were minimal signs of ventilatory failure, the animals were sacrificed. The segment of narrowed airway was then collected for histological analysis and calculation of the area of residual lumen in the tracheal segment with stenosis and malacia. RESULTS: In histological analysis, fibrosis was found in the submucosa and adventitia, associated with granulomas in the mucosa. The average residual lumen of the segments with stenosis was 9 percent and 12 percent in groups A and B, respectively (p> 0.05). CONCLUSION: The combination of resection of the cartilaginous rings and the application of 23 percent NaOH in the respiratory mucosa promoted severe tracheal stenosis, but was associated with loss of animals. Further studies are needed to verify that the isolated use of one of the techniques would be safer and more effective to develop tracheal stenosis.

Urgent lung transplantation in cystic fibrosis patients: experience of a French center.

OBJECTIVE: We report preliminary results obtained with urgent lung transplantation (ULTx) in cystic fibrosis (CF) patients, based on a French high emergency lung allocation (HELA) system, and the impact of this system on waiting-list death. METHODS: The medical records of the first 15 CF patients receiving ULTx between June 2007 and May 2010 at Hôpital Européen Georges Pompidou, France, were retrospectively reviewed. ULTx patients (URG group, n=15) were compared with our entire cohort of CF patients receiving elective lung transplants (LTx) (ELT group, n=118). RESULTS: Both groups were similar in terms of use of cardiopulmonary bypass (CPB), length of stay in the intensive care unit (ICU), and intubation > 72 h. Incidence of primary graft dysfunction (PGD) and perioperative mortality was also similar in both groups, but graft ischemic time and severity of PGD were higher in the URG group. One-year and 2.5-year survival rates were, respectively, 73% and 54.5% for the URG group. Death on the waiting list and time to LTx (including all pulmonary diagnoses) decreased by 67% and 64%, respectively. CONCLUSIONS: Although still preliminary and with a short follow-up period, our results suggest that the allocation of LTx to CF patients based on the HELA criteria yielded acceptable outcomes and improved waiting-list death rate and time to LTx.