Targeted caspofungin prophylaxis for invasive aspergillosis in high-risk liver transplant recipients, a single-center experience.

BACKGROUND: Invasive aspergillosis (IA) is a rare but highly lethal complication after orthotopic liver transplantation (OLT). Targeted antifungal prophylaxis has been proposed as a strategy to prevent IA among orthotopic liver transplant recipient (OLTr), but limited data are available to support its efficacy. METHOD: We conducted a single-center, retrospective, before and after cohort study, comparing IA incidences among OLTr who did not receive antifungal prophylaxis after transplantation (cohort 1) to OLTr who received targeted antifungal prophylaxis after liver transplantation (cohort 2). Patients in cohort 2 received caspofungin prophylaxis if they presented one of the following risk factors: retransplantation, acute liver failure, dialysis, or Aspergillus colonization prior to transplantation. The primary outcome was IA at 90 days after transplantation. RESULTS: A total of 391 OLTr were included in the study; 181 patients in the cohort 1 (no prophylaxis) and 210 patients in the cohort 2 (targeted prophylaxis). Among patients in cohort 2, 19% (40/ 210) were considered at high risk for IA and 85% (34/40) of those received caspofungin prophylaxis. The incidence of IA at 90 days was 3.3% (6/ 181) and 0.5% (1/ 210), in cohort 1 and 2, respectively (OR 0.14; 95%CI 0.01-0.83; P = .03). Ninety-day mortality was similar among the two cohorts (3.9% (7/181) and 2.4% (5/210) in cohort 1 and 2, respectively (OR 0.61; 95% 0.18-1.93; P = .40)). The 90-day mortality among the OLTs with IA was 71% (5/7). CONCLUSION: Targeted caspofungin prophylaxis was associated with lower rate of IA.

A real-world experience of SARS-CoV-2 infection in a tertiary referral centre of Montréal: Unexpected low prevalence and low mortality.

BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centre hospitalier de l'Université de Montréal (CHUM) during the first wave of the SARS-CoV-2 pandemic. METHODS: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection. Cases were considered positive as defined by the detection of SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. RESULTS: Between April 1 and July 31, 2020, 5,637 were admitted to our liver unit and/or seen as outpatient. Among them, 42 were positive for SARS-CoV-2. Twenty-two patients had CLD without cirrhosis while 16 patients had cirrhosis at the time of the infection (13, 2, and 1 with Child-Pugh A, B, and C scores, respectively). Four were LT recipients. Overall, 15 of 42 patients (35.7%) were hospitalized; among them, 7 of 42 (16.7%) required respiratory support and 4 of 42 (9.5%) were transferred to the intensive care unit. Only 4 of 42 (9.5%) patients died: 2 with CLD without cirrhosis and 2 with CLD with cirrhosis. Overall survival was 90.5%. CONCLUSION: This real-world study demonstrates an unexpectedly low prevalence and low mortality in the context of SARS-CoV-2 infection among patients with CLD with or without cirrhosis and LT recipients.

Severe immune thrombocytopenic purpura in critical COVID-19.

COVID-19 is a new disease with many undescribed clinical manifestations. We report herein a case of severe immune thrombocytopenic purpura (ITP) in a critical COVID-19 patient. A patient presented a severe episode of immune thrombocytopenia (< 10 × 109/L) 20 days after admission for a critical COVID-19. This thrombocytopenia was associated with a life-threatening bleeding. Response to first-line therapies was delayed as it took up to 13 days after initiation of intravenous immunoglobulin and high-dose dexamethasone to observe an increase in platelet count. COVID-19 may be associated with late presenting severe ITP. Such ITP may also be relatively resistant to first-line agents. Hematological manifestations of COVID-19, such as the ones associated with life-threatening bleeding, must be recognized.

First Canadian Case Report of Kidney Transplantation From an HIV-Positive Donor to an HIV-Positive Recipient.

RATIONALE: Kidney transplantation has become standard of care for carefully selected patients living with human immunodeficiency virus (HIV) and end-stage renal disease (ESRD) in the highly active antiretroviral therapy (HAART) era. American and European prospective cohort studies have reported similar patient and graft survival compared with HIV-negative kidney transplant recipients. Despite an increased rate of acute rejection, partially due to drug interactions, HIV immunovirologic parameter generally remains under control during immunosuppression. A few cases of kidney transplantation between HIV-infected patients were done in South Africa and showed favorable results. No cases of kidney transplantation from an HIV-positive donor in Canada have previously been reported. PRESENTING CONCERNS OF THE PATIENT: A 60-year-old Canadian man with HIV infection presented in 2007 with symptoms compatible with acute renal failure secondary to IgA nephropathy. Chronic kidney disease resulted after the acute episode. DIAGNOSES: Hemodialysis was started in 2012. The patient was referred for a kidney transplantation evaluation. INTERVENTIONS: The patient underwent kidney transplantation from an HIV-positive donor in January 2016. The recipient's antiretroviral regimen consisted of abacavir, lamivudine, and dolutegravir. No drug interactions have been reported between these antiretrovirals and the maintenance immunosuppressive regimen used. OUTCOMES: The outcome at 7 months post transplantation was excellent, with good graft function and adequate control of HIV replication, in the absence of opportunistic infections at a time when immunosuppression is at its highest intensity. No acute rejection was reported. An episode of bacteremic graft pyelonephritis due to Enterococcus faecalis was successfully treated after transplantation. NOVEL FINDING: With careful selection of patient, kidney transplantation between HIV-infected patients is a viable option. The use of antiretroviral drugs free of interactions simplified the dosing and management of the immunosuppressive drugs.

RAISONNEMENT: La transplantation rénale fait désormais partie des soins prodigués spécifiquement aux patients porteurs du VIH (virus de l'immunodéficience humaine) et présentant une insuffisance rénale terminale (IRT) à l'ère de la thérapie antirétrovirale. Des études de cohorte prospectives américaines et européennes ont rapporté une survie semblable du greffon et du receveur de la greffe chez ces patients, lorsque comparés aux receveurs d'une greffe non porteurs du VIH. En dépit d'un taux plus élevé de rejet aigu, attribuable en partie aux interactions médicamenteuses, les paramètres immunovirologiques du VIH sont demeurés stables sous traitement par les immunosuppresseurs. Quelques cas de transplantations rénales entre patients séropositifs ont été effectués en Afrique du Sud et ont montré des résultats favorables. À ce jour, on ne rapportait aucun cas de transplantation rénale provenant d'un donneur porteur du VIH au Canada. PRÉSENTATION DU CAS D'UN PATIENT: En 2007, un Canadien de 60 ans porteur du VIH s'est présenté avec des symptômes compatibles à l'insuffisance rénale aigüe secondaire à une néphropathie à IgA. Cet épisode aigu a par la suite évolué vers l'insuffisance rénale chronique. DIAGNOSTIC: L'insuffisance rénale terminale a été diagnostiquée en 2012. Dès lors, un traitement par hémodialyse a été initié et le patient a été recommandé pour une évaluation en vue d'une transplantation. INTERVENTIONS: Le patient a subi une greffe avec un rein provenant d'un donneur séropositif en janvier 2016. Le traitement antirétroviral du receveur était constitué d'abacavir, de lamivudine et de dolutégravir. Aucune interaction médicamenteuse n'a été rapportée entre ces antirétroviraux et le traitement immunosuppresseur de maintien administré. RÉSULTATS: En plus d'une bonne reprise de la fonction du greffon et du contrôle adéquat de la réplication du VIH, on a constaté la réussite de l'intervention lors du suivi du patient effectué 7 mois après la transplantation par l'absence d'infections opportunistes à un moment où l'immunosuppression est à son maximum. Aucun rejet aigu n'a été rapporté par contre, un épisode de pyélonéphrite bactérienne du greffon, attribuable à Enterococcus faecalis, est survenu à la suite de la transplantation, mais l'infection a été traitée avec succès. OBSERVATIONS NOUVELLES: On a constaté que la sélection rigoureuse des patients rendait possible la transplantation rénale entre patients porteurs du VIH. De plus, l'utilisation d'antirétroviraux qui ne causent aucune interaction médicamenteuse a simplifié l'ajustement de la posologie des immunosuppresseurs administrés. CAS DISCUTÉ: Nous rapportons le cas d'un Canadien de 60 ans porteur du VIH et ayant subi une greffe de rein provenant d'un donneur lui aussi séropositif. Le traitement antirétroviral du receveur était composé d'abacavir, de lamivudine et de dolutégravir. Aucune interaction médicamenteuse n'a été rapportée entre les antirétroviraux et le traitement immunosuppresseur de maintien. Sept mois après l'intervention, le patient se portait bien, comme en fait foi un taux de créatinine sérique de 155 µmol/L mesuré lors de la plus récente visite de suivi. La charge virale du patient (quantité d'ARN du VIH dans le sang) s'est avérée indétectable et le compte des lymphocytes T CD4 est demeuré au-dessus de 300 cellules/µl pendant toute la période de suivi. Le patient n'a présenté aucun signe indiquant la présence d'une maladie associée au SIDA, ni d'un rejet aigu du greffon. Enfin, un épisode de pyélonéphrite bactérienne du greffon, attribuable à Enterococcus faecalis, est survenu après la transplantation, mais l'infection a été traitée avec succès. CONCLUSIONS: Nous rapportons la première transplantation de rein réalisée au Canada entre un donneur séropositif et un receveur, lui aussi porteur du VIH. L'évolution du patient après l'intervention s'est avérée excellente, on a constaté une bonne reprise de la fonction du greffon et un contrôle adéquat de la réplication du VIH, une réussite confirmée par l'absence d'infections opportunistes à un moment où l'immunosuppression est à son maximum. De plus, l'utilisation d'antirétroviraux qui ne causent aucune interaction médicamenteuse a simplifié l'ajustement de la posologie des immunosuppresseurs administrés. DÉCOUVERTE: La sélection rigoureuse des patients rend possible la transplantation rénale entre patients séropositifs atteints d'IRT et donneurs eux aussi porteurs du VIH.

An Exception to the Rule or a Rule for the Exception? The Potential of Using HIV-Positive Donors in Canada.

Selected human immunodeficiency virus (HIV)-infected patients with end organ failure can safely receive an organ transplant from an HIV uninfected donor. Recent demonstration of the short term safety of organ transplantation between HIV-infected persons prompted a change in US American law to allow such transplantations. Prompted by the recent completion of the first organ transplantation between HIV-infected persons in Canada, we review Canadian law regarding the use of organs from HIV-infected donors, estimate the number of potential HIV-infected donors in Canada, and critically review considerations related to advancing organ transplantation from HIV-infected donors in Canada. Existing legislation allows organ transplantation from an HIV-infected donor under exceptional medical circumstances and therefore no change in legislation is required to increase utilization of organs from HIV-infected donors for transplantation in Canada. Among 335,793 hospital deaths between 2005 and 2009 in Canadian provinces excluding Quebec, 39 potential HIV-infected donors were identified. The actual number of HIV potential donors is estimated to be approximately 60% lower (3-5 potential donor per year), if the absence of viremia is required for transplantation. Although offering all Canadians the opportunity to donate organs is a laudable goal, further research to understand the need for HIV-positive donors and the willingness of HIV-positive recipients to accept organs from HIV-positive donors is needed to inform future policy regarding organ donation from HIV-infected persons in Canada.

Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome.

AIM: To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome (ARDS). METHODS: Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of iNO (20 ppm) or nebulized epoprostenol (10 µg/mL) was done in all patients. Thereafter, inhaled milrinone (1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide (iNO) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen (PaO2) were recorded before and after each inhaled therapy administration. RESULTS: The majority of ARDS were of pulmonary cause (n = 13) and pneumonia (n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass (n = 2), smoke inhalation injury (n = 1), thoracic trauma and pulmonary contusions (n = 2) and aspiration (n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and iNO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO2 from baseline was 8.8 mmHg [interquartile range (IQR) = 16.3], 6.0 mmHg (IQR = 18.4), 6 mmHg (IQR = 15.8) and 9.2 mmHg (IQR = 20.2) respectively with iNO, epoprostenol, inhaled milrinone, and iNO added to milrinone. Only iNO and the combination of inhaled milrinone and iNO had a statistically significant effect on PaO2. CONCLUSION: When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.

Ammonia clearance with haemofiltration in adults with liver disease.

BACKGROUND & AIMS: Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration. METHODS: Prospective study of adult patients with liver failure and arterial ammonia >100 µmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume. RESULTS: Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) µmol/L, (P ≤ 0.0001). CONCLUSION: Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration.