RESUMO
OBJECTIVES: Improved survival after hematopoietic cell transplantation (HCT) and an increasingly comorbid transplant population may give rise to new trends in the causes of death. METHODS: This study includes all adult allogeneic HCT recipients transplanted at Rigshospitalet between January 1, 2010 and December 31, 2019. Underlying causes of death were determined using the Classification of Death Causes after Transplantation (CLASS) method. RESULTS: Among 802 HCT recipients, 289 died during the study period. The main causes of death were relapse (N = 133, 46.0%), graft-versus-host disease (GvHD) (N = 64, 22.1%) and infections (N = 35, 12.1%). Multivariable analyses showed that with increasing transplant calendar year, a decreased risk of all-cause mortality (HR 0.92, 95% CI 0.87-0.97) and death from GvHD (HR 0.87, 95% CI 0.78-0.97) was identified, but not for other specific causes. Standardized mortality ratios (SMRs) for all-cause mortality decreased from 23.8 (95% CI 19.1-28.5) to 18.4 (95% CI 15.0-21.9) for patients transplanted in 2010-2014 versus 2015-2019, while SMR for patients who died from GvHD decreased from 8.19 (95% CI 5.43-10.94) to 3.65 (95% CI 2.13-5.18). CONCLUSIONS: As risk of all-cause mortality and death from GvHD decreases, death from relapse remains the greatest obstacle in further improvement of survival after HCT.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Causas de Morte , Transplante Homólogo/efeitos adversos , Transplantados , Doença Enxerto-Hospedeiro/etiologia , Recidiva , Estudos RetrospectivosRESUMO
Antibiotic-resistant bacterial infections are increasingly an issue in allogenic hematopoietic stem cell transplant patients. How antibiotic treatment impacts antibiotic resistance in the human gut microbiome remains poorly understood in vivo. Here, a total of 577 fecal samples from 233 heavily antibiotic-treated transplant patients were examined using high-resolution prescription data and shotgun metagenomics. The 13 most frequently used antibiotics were significantly associated with 154 (40% of tested associations) microbiome features. Use of broad-spectrum ß-lactam antibiotics was most markedly associated with microbial disruption and increase in resistome features. The enterococcal vanA gene was positively associated with 8 of the 13 antibiotics, and in particular piperacillin/tazobactam and vancomycin. Here, we highlight the need for a high-resolution approach in understanding the development of antibiotic resistance in the gut microbiome. Our findings can be used to inform antibiotic stewardship and combat the increasing threat of antibiotic resistance.
Assuntos
Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Humanos , Microbioma Gastrointestinal/genética , Antibacterianos/efeitos adversos , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86-0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74-0.95) and death from infections (HR 0.86 per year, 95% CI 0.77-0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future.
Assuntos
Transplante de Órgãos , Causas de Morte , Rejeição de Enxerto , Humanos , Transplante de Órgãos/efeitos adversos , Estudos Retrospectivos , TransplantadosRESUMO
The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. During two 10-day courses of remdesivir starting 24 and 45 days after fever onset, pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/complicações , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Febre/tratamento farmacológico , Febre/virologia , Humanos , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/virologia , Fatores de Tempo , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
A 26-year-old woman developed fever, myalgias and headaches two weeks after having been scratched by a rat, which she kept as a pet. She had limited renal involvement and marginal pleocytosis in the cerebrospinal fluid (CSF). A 51-year-old man had just returned from a holiday with water sports activities and was admitted with fever, severe headaches, neck pain, myalgias and signs of acute renal failure and pleocytosis in the CSF. Both patients had positive Leptospira DNA polymerase chain reaction in their CSF and were treated to full remission.