Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.

[Knowledge of chronic venous disease among healthcare professionals in Spain]. / Conocimiento de la enfermedad venosa crónica en los profesionales sanitarios en España.

INTRODUCTION: Chronic venous disease (CVD) is classified as the most prevalent vascular disease in humans. It has been associated with an increased incidence of cardiovascular diseases and is a strong predictor of all-cause mortality, representing a public health problem of the first magnitude. The objective of this study was to analyze the actions in the management of CVD in the daily clinical practice of health professionals in Spain. MATERIAL AND METHODS: Observational, descriptive and cross-sectional study with data collection through an opinion survey of 22 questions completed electronically through a Google® form for professionals involved in chronic venous disease care. Three hundred surveys were analyzed. The quantitative variables were represented with means and standard deviation and the qualitative ones with percentages and confidence intervals. RESULTS: Three hundred surveys analyzed. 65.3% were women. The most participatory age group was over 55 years of age. 85% of those surveyed considered that CVD is an underdiagnosed and undertreated disease, with an added negative impact in terms of follow-up during the Covid-19 pandemic, since 91.7% considered that it had not been adequate. 47% of the participants did not know the CEAP classification and 56.3% did not know the venous clinical severity scale (VCSS). 92.7% of physicians prescribed compression stockings and 74.7% phlebotonic drugs. Hidrosmine was the best known and most prescribed venoactive drug (51.7%). 73% of the doctors recognized that they did not use any algorithm or protocol for the diagnosis, treatment and monitoring of CVD in their usual clinical practice and 91% stated that they were not trained in their workplaces. 54.3% of the physicians believed that one of the main limitations that made follow-up of the disease difficult was the lack of coordination with the vascular surgeons. CONCLUSIONS: Updating and responding to the training needs of professionals regarding CVD is essential to guarantee quality care continuity in the care of our patients.

Infective endocarditis treated in a secondary hospital: epidemiological, clinical, microbiological characteristics and prognosis, with special reference to patients transferred to a third level hospital.

OBJECTIVE: To analyse the clinical and epidemiological characteristics and mortality-related factors of patients admitted to a secondary hospital with Infective Endocarditis (IE). METHODS: Observational study of a cohort of patients who have been diagnosed with IE in a secondary hospital and evaluated in accordance with a pre-established protocol. RESULTS: A total of 101 cases were evaluated (years 2000-2017), with an average age of 64 years and a male-to-female ratio of 2:1. 76% of the cases had an age-adjusted Charlson comorbidity index of >6, with 21% having had a dental procedure and 36% with a history of heart valve disease. The most common microorganism was methicillin-susceptible S. aureus (36%), with bacterial focus of unknown origin in 54%. The diagnostic delay time was 12 days in patients who were transferred, compared to 8 days in patients who were not transferred (p=0.07); the median surgery indication delay time was 5 days (IQR 13.5). The in-hospital mortality rate was 34.6% and the prognostic factors independently associated with mortality were: cerebrovascular events (OR 98.7%, 95% CI, 70.9-164.4); heart failure (OR 27.3, 95% CI, 10.2-149.1); and unsuitable antibiotic treatment (OR 7.2, 95% CI, 1.5-10.5). The mortality rate of the patients who were transferred and who therefore underwent surgery was 20% (5/25). CONCLUSIONS: The onset of cerebrovascular events, heart failure and unsuitable antibiotic treatment are independently and significantly associated with in-hospital mortality. The mortality rate was higher than the published average (35%); the diagnostic delay was greater in patients for whom surgery was indicated.

[Malignant hypertension and pheochromocytoma: a case report]. / Hipertensión maligna y feocromocitoma: reporte de un caso.

Malignant arterial hypertension is defined by extremely high levels of pressure associated with organ damage. It is a cause of hypertensive emergency and is defined by the coexistence of high blood pressure and bilateral retinal haemorrhage or exudates (grade III hypertensive retinopathy), with or without papilloedema (grade IV hypertensive retinopathy) currently associated with organ damage such as renal or cardiac failure. Around 1% of malignant arterial hypertension is secondary to endocrinological causes, including the most common: pheochromocytoma, which is classically characterized by the triad: headache, sweating and palpitations. However, there is no single clinical finding that is of significant value in its diagnosis. We now present the case of a 23-year-old patient with a hypertensive emergency, an adrenal mass associated with grade IV hypertensive retinopathy.

SEOM clinical guidelines for anaemia treatment in cancer patients (2020).

Anaemia is defined by the presence of haemoglobin (Hb) levels < 13 g/dL in men and 12 g/dL in women. Up to 39% of cancer patients present it at the time of diagnosis and up to 40% have iron deficiency. Anaemia causes fatigue, functional deterioration and a reduction in the quality of life; it has also been associated with a poorer response to anti-tumour treatment and lower survival. Basic diagnostic tests for anaemia are simple and should be a routine part of clinical practice. These guidelines review the available evidence on the use of different therapies for treating anaemia: erythropoiesis-stimulating agents, iron supplements, and transfusion of blood products.

Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.

Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions.

Leishmaniasis visceral en paciente infectado con VIH / VISCERAL LEISHMANIASIS IN PATIENTS INFECTED WITH AIDS

La coinfección entre el virus de la inmunodeficiencia humana (VIH) y la Leishmaniosis visceral (LV) ha sido descripta de manera reciente, en especial en Brasil y en ciertas áreas de la Europa del Mediterráneo. Los pacientes VIH positivos con fiebre de origen desconocido y/o citopenias tienen indicación de punción aspirativa de médula ósea para estudios microbiológicos e histopatológicos, estos últimos para descartar un síndrome linfoproliferativo. El diagnóstico de leishmaniosis visceral puede confirmarse por diversas técnicas microbiológicas y serológicas: detección de amastigotes de Leishmania en aspirados de médula ósea con tinción de Giemsa, detección de anticuerpos por aglutinación directa, inmunofluorescencia indirecta, detección del antígeno rK39, reacción en cadena de la polimerasa en extendidos de médula ósea y prueba de aglutinación del látex. La LV puede ser la primera manifestación del sida o ser una complicación grave en pacientes ya diagnosticados con VIH e inmunodeficiencia severa. La LV es una complicación grave y potencialmente fatal y debe sospecharse en todo sujeto VIH positivo con fiebre de etiología desconocida y/o citopenias.

The association between visceral leishmaniasis (VL) and HIV is recent and has an increasing number of cases in Brazil and worldwide - especially in the Mediterranean region of Europe. HIV patients with cytopenias and/or fever of an unknown etiology, have indication of bone marrow aspirate for microbiological cultures and histopathological examination to rule out lymphoproliferative disorders. Diagnosis of VL can be confirmed by the following examinations: Leishmania amastigotes detection in bone marrow aspirate with Giemsa smear, direct agglutination test, indirect immunofluorescence, rK39 dipstick test, polymerase chain reaction and latex agglutination test. VL may be the first infection related with HIV or patients can be diagnosed with VL concomitantly with AIDS. HIV/AIDS-associated VL is an aggressive complication with a potentially fatal evolution in advanced HIV/AIDS patients, without specific symptoms, that should be suspected in all HIV subjects with fever of unknown etiology and cytopenias.

What is the association between price and economic activity with cigarette consumption in Cuba from 1980 to 2014?

OBJECTIVES: Cuba is a tobacco-producing country that has been economically isolated as a consequence of an embargo imposed by the USA. It has also experienced a severe economic depression in the 1990s after the withdrawal of support by the former Soviet Union. These characteristics provide a unique opportunity to study the relation between large changes in economic activity, cigarette price and demand for cigarettes in a relatively isolated socialist economy. STUDY DESIGN: This is an observational epidemiological study. METHODS: Data were obtained on the annual price of a packet of cigarettes and the mean number of cigarettes consumed per adult living in Cuba from 1980 to 2014. Descriptive and regression analysis were used to explore the relationship between cigarette consumption and price in Cuba. RESULTS: In 1980, the mean price of a packet of cigarettes was 1.53 Cuban peso (CUP) in 1997 prices and the mean annual per capita consumption was 2237 cigarettes. In 2014, the mean price had increased to 5.57 CUP (1997 prices) per packet of cigarettes, and consumption had fallen to 1527 cigarettes per capita. There were significant negative associations between annual cigarette consumption and both price and living through an economic depression. The elasticity was approximately -0.31 with price, and living through an economic depression was also associated with lower consumption of cigarettes (a reduction of 9%, 95% confidence intervals -0.18 to -0.001). CONCLUSIONS: Higher cigarette pricing, along with other public health interventions, are required to protect the national population from the adverse effects of tobacco smoke exposure.

SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018).

Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.

Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.

Modelo de gestión para la aplicación del control metrológico legal y la evaluación de la conformidad en equipos biomédicos / Management model for the application of legal metrological control and conformity assessment in biomedical equipment / Modelo de gestão para o aplicativo do controle metrológico legal e a avaliação da conformidade em equipamentos biomédicos

En la actualidad el país enfrenta grandes cambios referentes a las normas orientadas a la gestión tecnológica que se debe aplicar a los equipos biomédicos, además de grandes cambios que hoy el Subsistema Nacional de Calidad ha presentado, orientados al control metrológico legal que se debe aplicar a algunos equipos que prestan sus servicios en el área de la salud. Dado lo anterior, este trabajo pretende presentar una propuesta basada en un modelo de gestión que integra los requerimientos del control metrológico legal aplicado a los equipos biomédicos, y a su vez la aplicación de procesos de medición para las actividades asociadas a la evaluación de la conformidad, utilizando como metodología un proceso de caracterización de las exigencias establecidas en las normas de Colombia. Estas normas están asociadas al control metrológico legal y a lo establecido en diferentes normas orientadas al aseguramiento de las mediciones en equipos; esto orientado a la evaluación de la conformidad, obteniendo como resultado más significativo una propuesta de estructura de gestión que le permitirá a las unidades de ingeniería de las entidades prestadoras de servicios de salud, no solo cumplir con lo exigido en las normas actuales sino a prestar unos servicios de alta calidad basados en confiabilidad como apoyo a los actividades encaminadas a la seguridad del paciente.

At present, the country faces major changes regarding regulations oriented toward technological management to be applied to biomedical equipment. In addition to those significant changes today, the National Quality System has introduced others regarding metrological control that need to be applied to some equipment in health services. As such, this paper aims to present a proposal based on a management model which integrates legal metrological controls applied to biomedical equipment, along with the application of measurement processes for activities associated to conformity evaluation. This model also uses a method of characterization of requirements established in different regulations aimed at ensuring equipment measurements also oriented toward conformity evaluation. The most significant expected result will be the proposal of a management structure enabling engineering units of health service providers to not only comply with said regulations, but also to offer high quality services based on trustworthiness, as support for activities aimed at patient safety.

Na atualidade o país enfrenta grandes mudanças referentes às normas orientadas à gestão tecnológica que se deve aplicar aos equipamentos biomédicos, além de grandes mudanças que hoje o subsistema nacional de qualidade a apresentado e orientado ao controle metrológico legal que se deve aplicar a alguns equipamentos que prestam seus serviços na área da saúde, dado o anterior este trabalho pretende apresentar uma proposta baseada num modelo de gestão que integra os requerimentos do controle metrológico legal aplicado às equipamentos biomédicos e a sua vez o aplicativo de processos de medida para as atividades associadas à avaliação da conformidade, utilizando como metodologia um processo de caracterização das exigências estabelecidas nas normas da Colômbia associadas ao controle metrológico legal e ao estabelecido em diferentes normas orientadas à garantia das medidas em equipamentos, isto orientado à avaliação da conformidade, obtendo como resultado mais significativo uma proposta de estrutura de gestão que lhe permitirá às unidades de engenharia das entidades prestadoras de serviço de saúde, não só cumprir com o exigido nas normas atuais senão também a emprestar uns serviços de alta qualidade baseados em fiabilidade como apoio às atividades encaminhadas à segurança do paciente.

The fusogenic peptide HA2 impairs selectivity of CXCR4-targeted protein nanoparticles.

We demonstrate here that the genetic incorporation of the fusogenic peptide HA2 into a CXCR4-targeted protein nanoparticle dramatically reduces the specificity of the interaction between nanoparticles and cell receptors, a factor to be considered when designing tumor-homing drug vehicles displaying endosomal-escape agents. The loss of specificity is concomitant with enhanced cell penetrability.

Ethical imperatives of timely access to orphan drugs: is possible to reconcile economic incentives and patients' health needs?

BACKGROUND: More than 6,800 rare diseases and conditions have been identified in the US, which affect 25-30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the effectiveness of incentives for the development of treatments for rare diseases, and reflected on the ethical imperatives for timely access to orphan drugs. METHODS: Study data were derived from the Food and Drug Administration (FDA) Orange Book and the Office of Orphan Drugs Development. A search was conducted to assess literature on the ethical principles and economic incentives for the development of orphan drugs. RESULTS: In the period 1983-2015, the FDA granted 3,647 orphan drug designations and 554 orphan drug approvals. The orphan drug approvals corresponded to 438 different brand names. Cancer was the therapeutic area with the highest number of approvals. The increased number of patients with rare diseases and the growth in the cost of orphan drugs pose a significant economic burden for patients, public programs and private third party payers. Regulatory differences to qualify for orphan designation and various population thresholds employed by the FDA and the European Medicines Agency lead to further unmet health needs for patients with rare diseases and aggravate health inequities. There is no societal consensus on the population and economic thresholds, the drug effectiveness indicator(s), or the societal value to be placed for the approval and reimbursement of orphan drugs. CONCLUSION: Orphan drug development and marketing in the US concentrate in few therapeutic areas. Despite the increase in the number of FDA approved orphan drugs, the unmet needs of patients with rare diseases evidence that the current incentives are not efficiently stimulating orphan drug development. There is need to balance economic incentives to stimulate the development and marketing of orphan drugs without jeopardizing patients' access to treatment. Thus, aligning pharmaceutical companies' incentives with societal budgetary constraints is necessary and the ethical imperatives of timely access to orphan drugs need to be agreed upon.

Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer.

BACKGROUND: Opioid effectiveness to treat cancer pain is often compromised by the development of tolerance and the occurrence of undesirable side effects, particularly during long-term treatment. Hence, the search for more efficient analgesics remains a necessity. The main goal of this study was to relieve neuropathic symptoms associated with tumour growth by administering the non-opioid analgesic dipyrone (DIP) alone or in combination with magnesium chloride (MgCl2 ), an adjuvant that blocks the NMDA receptor channel. METHODS: Mice were inoculated with a melanoma cell line (B16-BL6) in the left thigh and two protocols were used to evaluate the effect of DIP (270 mg/kg), MgCl2 (200 mg/kg), or the combination DIP-MgCl2 . In the therapeutic protocol the drugs, alone or combined, were administered once tumour had promoted increased nociception. In the preventive protocol, drugs were administered prior to the appearance of the primary tumour. Tumour growth was assessed with a caliper and nociception was determined using behavioural tests. RESULTS: DIP promoted antinociception only at the beginning of both protocols due to the development of tolerance. The combination DIP-MgCl2 improved the antinociceptive effect, avoiding tolerance and reducing tumour growth in the preventive treatment, more efficiently than each compound alone. CONCLUSIONS: These results suggest that DIP-MgCl2 may represent a safe, affordable and accessible option to reduce tumour growth and to treat cancer pain avoiding the risk of tolerance, without the typical complications of opioids agents, particularly when long-term treatment is required. SIGNIFICANCE: This study shows a non-opioid analgesic combined with an adjuvant as a therapeutic option to treat cancer pain. The avoidance of antinociceptive tolerance when repeated administration is required, as well as tumor growth reduction, are additional advantages to be considered.

Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) cause neurodevelopmental abnormalities. However, publications about epilepsy and electroencephalographic features are scarce. In this study, we prospectively performed electroencephalography (EEG) and brain magnetic resonance (MR) imaging in 61 patients with diagnosis of FASD. One patient had multiple febrile seizures with normal EEGs. Fourteen children showed EEG anomalies, including slow background activity and interictal epileptiform discharges, focal and/or generalized, and 3 of them had epilepsy. In one patient, seizures were first detected during the EEG recording and one case had an encephalopathy with electrical status epilepticus during slow sleep (ESES). Focal interictal discharges in our patients did not imply the presence of underlying visible focal brain lesions in the neuroimaging studies, such as cortical dysplasia or polymicrogyria. However, they had nonspecific brain MR abnormalities, including corpus callosum hypoplasia, vermis hypoplasia or cavum septum pellucidum. The latter was significantly more frequent in the group with EEG abnormal findings (p < 0.01).

Correlation between morphological MRI findings and specific diagnostic categories in fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) include physical and neurodevelopmental abnormalities related to prenatal alcohol exposure. Some neuroimaging findings have been clearly related to FASD, including corpus callosum and cerebellar anomalies. However, detailed studies correlating with specific FASD categories, that is, the fetal alcohol syndrome (FAS), partial FAS (pFAS) and alcohol related neurodevelopmental disorders (ARND), are lacking. We prospectively performed clinical assessment and brain MR imaging to 72 patients with suspected FASD, and diagnosis was confirmed in 62. The most frequent findings were hypoplasia of the corpus callosum and/or of the cerebellar vermis. Additional findings were vascular anomalies, gliosis, prominent perivascular spaces, occipito-cervical junction and cervical vertebral anomalies, pituitary hypoplasia, arachnoid cysts, and cavum septum pellucidum.

HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is being described for the first time in this study. A combination of O6-methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a possible biomarker in therapy choice. Interestingly, survival data shows a similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen methylation rates of different genes and evaluate the association between genes methylation and clinicopathologic variables. Our study is the first of its kind to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of methylated ones) and could be new markers in the study of GBM prognosis, especially in the therapy selection.

Dysregulated microRNAs involved in contrast-induced acute kidney injury in rat and human.

BACKGROUND: Contrast-induced nephropathy (CIN) is a complex syndrome of acute nephropathy that occurs following infusion of intravascular contrast agents, and is associated with an increased risk for adverse cardiovascular events. While there is no ideal biomarker for making an early diagnosis of CIN, we hypothesized that levels of specific circulating microRNA (miRNA) species might serve such a role. METHODS: miRNA microarray assays were used to detect miRNAs in the kidney tissue of rats studied as an animal model of CIN. Real-time PCR was performed to validate results of the microarray assays. Kidney-enriched miRNAs detected in rat plasma were used as biomarkers to screen for CIN. Results obtained from the rat model of CIN were further validated in human patients with CIN. RESULTS: Fifty-one miRNAs were aberrantly expressed in the kidney tissues between CIN and control rats; and among these, 17 miRNAs showed a >2-fold change of expression in the kidney tissues of CIN rats when compared with their expressions in non-CIN control rats. Among the 17 miRNAs aberrantly-expressed miRNAs screened from kidney tissue, only six also showed significantly different expression in the plasma of CIN rats. When compared with their levels in non-CIN control rats, the levels of three miR-30 family members (miR-30a, miR-30c, and miR-30e), as well as miR-320, were significantly increased in the plasma of CIN rats, while the plasma levels of miRNAs let-7a and miR-200a were significantly decreased. In a validation study of these results conducted with human plasma samples, only miR-30a, miR-30c, and miR-30e showed > 2-fold increases in CIN patients when compared with non-CIN patients. Receiver operating curves constructed to examine the abilities of miR-30a, miR-30c, and miR-30e to discriminate CIN patients from non-CIN patients showed AUCs of 0.954, 0.888, and 0.835, respectively. CONCLUSIONS: Our study provides the first evidence that plasma miRNAs, and especially three miR-30 family members (miR-30a, miR-30c, and miR-30e), might serve as early biomarkers and (or) target candidates for CIN.

Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study.

There are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2-63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made.