Transient Lactic Acidosis and Elevation of Transaminases after the Introduction of Remdesivir in a Patient with Acute Kidney Injury.

A 56-year-old woman was transferred to the intensive care unit (ICU) two days after an allogeneic stem cell transplantation (ASCT) when she presented acute respiratory distress due to the relapse of a SARS-CoV-2 infection. Following that, she received two intravenous doses of 100 mg remdesivir. Subsequently, the patient developed multiple instances of diarrhea, progressing to oliguria and acute kidney injury, necessitating continuous venovenous hemofiltration (CVVH). Despite the absence of signs of hypoxemia or cardiocirculatory failure requiring vasopressor intervention, a progressive lactic acidosis emerged. Two days after the onset of lactic acidosis, a significant rise in aminotransferases and lactate dehydrogenase occurred, in the absence of encephalopathy and coagulation disorders. Remdesivir therapy had been interrupted upon the initial signs of lactic acidosis. Despite an improvement in liver function tests and lactic acidosis, the patient's condition deteriorated, ultimately leading to her demise on day 29 due to newly arising hematological complications.

Lactic acidosis after allogeneic haematopoietic stem cell transplantation potentially related to letermovir.

A 53-year-old woman with a history of acute myeloid leukaemia received a second allogeneic haematopoietic stem cell transplant and was prescribed, among other medications, acyclovir and letermovir (480-mg daily oral dose) for prophylaxis of, respectively, herpes simplex and cytomegalovirus infection. The patient was admitted in the intensive care unit for dyspnoea and oliguria. Laboratory investigations revealed acute kidney injury but also a severe and progressive lactic acidosis. Liver function tests were within normal range. The combination of lactic acidosis, hypoglycaemia and acylcarnitine profile in plasma raised the suspicion of mitochondrial toxicity. Letermovir therapy was interrupted, and determination of plasma letermovir pharmacokinetics revealed a prolonged terminal half-life (38.7 h) that was not significantly influenced by continuous venovenous haemofiltration. Exploration for genetic polymorphisms revealed that the patient was SLCO1B1*5/*15 (c.521T>C homozygous carrier and c.388A>G heterozygous carrier) with a predicted nonfunctional organic anion transporting polypeptide 1B1 protein. The relationship between letermovir accumulation and development of lactic acidosis requires further observations.

Flecainide-induced pneumonitis: a case report.

BACKGROUND: We report a case of acute respiratory distress associated with a histological pattern of acute fibrinous and organizing pneumonia, and discuss the possible responsibility of flecainide therapy. CASE PRESENTATION: A 61-year-old African woman developed a rapidly progressive dyspnea and required admission in the intensive care unit for orotracheal intubation and mechanical ventilation. Chest X-ray examination revealed bilateral infiltrates predominating in the basal part of both lungs. Lung computed tomography disclosed bilateral ground-glass opacities and septal thickening. After exclusion of the most common causes of infectious or immune pneumonia, a toxic origin was investigated and flecainide toxicity was considered. Lung biopsy was consistent with the unusual pattern of acute fibrinous and organizing pneumonia. Clinical and radiological improvement was noted after corticosteroid therapy, but the patient died from septic complications. CONCLUSION: Flecainide-induced lung injury has rarely been reported in the literature and remains a diagnosis of exclusion. The histological pattern of acute fibrinous and organizing pneumonia has been previously observed with amiodarone. There are no firm guidelines for the treatment of acute fibrinous and organizing pneumonia, but some patients may positively respond to corticosteroids.

Platypnea-orthodeoxia syndrome in a postoperative patient: a case report.

BACKGROUND: We report a case of platypnea-orthodeoxia syndrome observed in a complex clinical situation associating a bilateral pleural effusion, lobar pulmonary embolism, and a partial anomalous pulmonary venous return. CASE PRESENTATION: A 57-year-old Caucasian woman developed acute dyspnea in the postoperative course of an elective gynecological surgery for advanced stage ovarian cancer. Preoperative evaluation had failed to reveal any respiratory or cardiac problem. After evidence of a low arterial oxygen saturation, blood gas analysis from the central venous line correctly inserted in the right internal jugular vein revealed a higher oxygen saturation than in the arterial compartment. A thoracic computed tomography showed bilateral pleural effusion, lobar pulmonary embolism, and a drainage of a left pulmonary vein into the left innominate vein. This unique combination resulted in an uncommon cause of platypnea-orthodeoxia syndrome. CONCLUSION: Often associated with right-to-left shunting, platypnea-orthodeoxia syndrome may be observed in complex clinical conditions with several factors influencing the ventilation/perfusion ratio. The paradoxical finding of a higher oxygen saturation in a central venous line than in an arterial line should prompt the clinician to look at the possibility of partial anomalous pulmonary venous return. No specific treatment is required in asymptomatic adults, except for an echocardiographic follow-up to detect the onset of pulmonary hypertension.

Pulmonary tumor thrombotic microangiopathy in a patient with a metastatic urothelial carcinoma.

A 78-year-old woman was admitted for acute dyspnoea. One year before, she had been treated with cisplatin and gemcitabine for a high grade urothelial carcinoma. Immunotherapy was discussed 9 months later due the progression of bone metastases but could not be administered before this episode of respiratory distress. There was a major discrepancy between the findings of a limited pulmonary embolism at thoracic tomodensitometry and the severity of a recently developed pulmonary hypertension at echocardiography. The patient presented cardiac arrest on day 6 and post-mortem findings were consistent with diffuse pulmonary tumor thrombotic microangiopathy, a rare complication of urothelial carcinoma.

The causal relationship between O2:K7:H6 extra-intestinal pathogenic Escherichia coli (ExPEC) and native valve endocarditis: a case report.

BACKGROUND: Native valves infective endocarditis due to Escherichia coli is still a rare disease and a particular virulence of some E.coli isolate may be suspected. CASE PRESENTATION: A 79-year-old woman presented during the post-operative period of an orthopedic surgery a urinary tract infection following obstructive ureteral lithiasis. E. coli was isolated from a pure culture of urine and blood sampled simultaneously. After evidence of sustained E.coli septicemia, further investigations revealed acute cholecystitis with the same micro-organism in biliary drainage and a native valve mitral endocarditis. E.coli was identified as O2:K7:H6, phylogenetic group B2, ST141, and presented several putative and proven virulence genes. The present isolate can be classified as both extra-intestinal pathogenic E.coli (ExPECJJ) and uropathogenic E. coli (UPECHM). CONCLUSIONS: The relationship between the virulent factors present in ExPEC strains and some serotypes of E. coli that could facilitate the adherence to cardiac valves warrants further investigation.

Rhabdomyolysis and acute kidney injury induced by the association of rosuvastatin and abiraterone: A case report and review of the literature.

INTRODUCTION: Abiraterone acetate is an inhibitor of androgens biosynthesis, approved as first-line treatment in castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone has been rarely associated with severe rhabdomyolysis, but the mechanism of muscle toxicity is unknown. CASE REPORT: We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin. MANAGEMENT AND OUTCOME: Rhabdomyolysis was resolutive after rosuvastatin and abiraterone discontinuation, and kidney function recovered. There was no recurrence of muscle toxicity after re-initiation of abiraterone alone. DISCUSSION: Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided.

Hepatic portal venous gas and combined colchicine-bortezomib toxicity.

Hepatic portal venous gas was found at the abdomen CT of a patient who presented abdomonal pain and ileus in the course of colchine-bortezomib therapy. Drug toxicity was suspected as there was no evidence of intestinal ischemia at laparatomy.

Fulminant Hepatic Failure in the Course of an Outpatient Anesthetic Procedure: Sevoflurane among Other High-Risk Factors.

A 20-year-old man underwent an outpatient general anesthetic procedure with sevoflurane for the correction of a bilateral gynecomastia. The patient had been first exposed to sevoflurane two years before, without any complication. He presented an overweight with a body mass index (BMI) of 31.4 kg/m2 and had an episode of "binge" drinking a few days before anesthesia. He became icteric from postoperative day 9, and after the worsening of liver function tests, the liver biopsy revealed centrilobular necrosis. The patient became encephalopathic and required urgent liver transplantation on postoperative day 30. The possibility of a sevoflurane-related fulminant hepatic failure is discussed.

Refractory shock during the anesthetic and surgical management of an intrahepatic tumor arising from the adrenal cortex: A case report.

INTRODUCTION: Adrenocortical carcinoma is a rare type of malignant adrenal tumor with a possibility of delayed metastases. Diagnosis may be delayed with a non-secreting tumor or metastasis, and even in this case, surgical management may be complicate. PRESENTATION OF CASE: A 55-year-old man underwent elective surgery for the resection of a large intra-hepatic mass from an undetermined type according to a recent liver biopsy. He had a previous history of a non-secreting adrenal tumor that was operated ten years before. Pre-operatively, he was poorly symptomatic, with a normal arterial blood pressure. Anesthesia induction was uneventful, but at the time of tumor resection and removal, he developed extreme vasoplegia and shock with anuric renal failure, lactic acidosis, four-limb and abdominal compartment syndrome. The patient died on day 9 from delayed septic complications. According to the pathological findings, the tumor was a non-secreting adrenocortical carcinoma. DISCUSSION: Adrenocortical carcinoma (ACC) is rare condition with diverse clinical manifestations due to excessive hormonal production when the tumor is secreting and mimicking pheochromocytoma. Our patient underwent the resection a large intrahepatic non-secreting metastasis more than ten years after the initial lesion. Peri-operative and post-operative management was complicated by a refractory shock with the characteristics of a secondary systemic capillary leak syndrome. The role of endothelial lesions may be discussed. CONCLUSION: Surgery of metastatic adrenocortical carcinoma may be complicated by severe hemodynamic complications, even in the absence of hormonal secretion.

Fatal Idiopathic Hyperammonemia after Induction Chemotherapy for Acute Myeloid Leukemia.

Idiopathic hyperammonemia is a rare but potentially fatal complication occurring in patients with acute leukemia or bone marrow transplantation. The role of some specific anticancer drugs may be discussed, but the etiology of hyperammonemia is often multifactorial. We report the case of a 40-year-old woman who developed fatal idiopathic hyperammonemia two weeks after induction chemotherapy with idarubicin-aracytine for acute myeloid leukemia. Despite intensive care management and extrarenal epuration, the patient was declared brain dead two days after hyperammonemia onset.

Regional citrate anticoagulation and influence of recirculation on ionized calcium levels in the circuit.

Regional citrate anticoagulation is now widely used during continuous renal replacement therapy (CRRT), and especially in patients at risk for hemorrhagic complications. A close monitoring is required to avoid citrate overload, leading to metabolic alkalosis or citrate intoxication causing metabolic acidosis. This case report describes a dysfunction of the regional citrate anticoagulation due to the development of a deep vein thrombosis close to the site of insertion of the venous CRRT catheter. The result was a local recirculation in the circuit with a local citrate overload (acidosis and non-measurable calcium). In the patient's blood samples, the [calciumtotal/Ca2+systemic] ratio remained normal as a proof of local citrate accumulation without systemic effects. Initially, CRRT remained effective, but due to the progressive decrease of serum creatinine and cystatin C clearance, the site of catheter insertion was changed.

Prognostic factors of acute mesenteric ischemia in ICU patients.

BACKGROUND: The primary endpoint was to investigate the prognostic factors of acute mesenteric ischemia (AMI) in ICU patients. METHODS: Retrospective observational, non-interventional, monocentric study of a cohort of 214 ICU patients with a confirmed diagnosis of arterial AMI. RESULTS: We collected demographics, mortality, hospital stay, prior medical history, comorbidities, reasons for ICU admission, laboratory investigations, diagnostic procedures, therapy, severity scores. The 30-day mortality rate was 71% for the 214 patients with arterial AMI. The incidence of nonocclusive mesenteric ischemia was particularly high. AMI was a secondary diagnosis in 58% of patients. Half of the population was represented by surgical patients who mostly required an urgent procedure. The mortality rate was not different in the subgroup with aortic surgery. Three factors were associated with an increase or decrease in mortality: the maximal dose of vasopressors (VP) administered to the patient (OR = 1.20; 95%CI = 1.08-1.33; p <  0.001), arterial change in lactate values within the first 24 h of admission (OR = 1.24; 95%CI = 1.05-1.48; p = 0.012) and anticoagulation (OR = 0.19; 95%CI = 0.043-0.84; p = 0.029). CONCLUSIONS: Fatalities after AMI were related to a high incidence of multi-organ failure. The monitoring of arterial lactate appeared helpful to identify the patients with a poor prognosis.

Influence of hemodialysis on pramipexole pharmacokinetics: Lessons from two cases and literature review.

BACKGROUND: Restless legs syndrome (RLS) is not a rare condition in patients on long-term dialysis. Pramipexole is a small molecule used in the treatment of idiopathic and uremic RLS. Although some information concerning the efficacy and safety of pramipexole in uremic patients is available, data concerning the pharmacokinetics of pramipexole in hemodialysis (HD) are lacking. Following the occurrence of accidental pramipexole intoxication in a chronic HD patient, we were concerned about the efficacy of HD in removing pramipexole. Our aim was thus to assess plasma pramipexole concentrations and pramipexole clearance in a stable chronic HD patient without any residual kidney function. MATERIALS AND METHODS: Our patient was a 63-year-old man on chronic HD for 5 years who had been treated uneventfully with oral pramipexole for uremic RLS since then. During a routine 4-hour high-flux HD session, blood, ultrafiltrate, and dialysate samples were collected every hour to determine pramipexole concentrations over time. RESULTS: Pramipexole blood concentrations ranged from 12.1 to 23.9 µg/L. Pramipexole reduction ratio was 32.5%. Mean dialytic clearance of pramipexole was 76.8 mL/min. Postdialysis rebound was 5.6%. CONCLUSION: In the absence of any side effect, pramipexole blood concentrations at steady state were 2- to 4-fold higher than those observed in subjects with normal kidney function. Like other drugs with a high volume of distribution, pramipexole was poorly removed by HD. Therefore, HD is not recommended as a treatment option for pramipexole intoxication in patients with a glomerular filtration rate superior to 30 mL/min/1.73m².

Mechanisms of toxic cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy is a frequent disease responsible for 40-50% of cases of heart failure. Idiopathic cardiomyopathy is a primary disorder often related to familial/genetic predisposition. Before the diagnosis of idiopathic cardiomyopathy is made, clinicians must not only rule out viral and immune causes, but also toxic causes such as drugs, environmental agents, illicit substances and natural toxins. OBJECTIVE: The objective of this review is to present recent data on the mechanisms underlying toxic cardiomyopathy. METHODS: The US National Library of Medicine Pubmed database was searched from 1980 to December 2017 utilizing the combinations of the search terms "toxic cardiomyopathy", "drugs", "anticancer drugs", "azidothymidine", "rosiglitazone", "carbon monoxide", "alcohol", "illicit drugs", "cocaine", "metamfetamine", "metals", "venom". A total of 339 articles were screened and papers that dealt with the pathophysiology of toxic cardiomyopathy, either in animal models or in clinical practice were selected, with preference being given to more recently published papers, which left 92 articles. Anticancer drugs: The mechanisms of anthracycline-induced cardiotoxicity are primarily related to their mechanisms of action as anticancer drugs, mainly the inhibition of topoisomerase II ß and DNA cleavage. Additional metabolic or oxidative stress factors may play a part, together with interference with iron metabolism. The more recent drugs, trastuzumab and imatinib, also influence stress pathways. Antiretroviral agents: Azidothymidine is cardiotoxic as a result of mitochondrial toxicity. In addition to energy depletion, azidothymidine also increases the production of mitochondrial reactive oxygen species (ROS). Antidiabetic drugs: The cardiotoxicity of thiazolidinedione antidiabetic drugs is still under investigation, though interference with mitochondrial respiration or oxidative stress is suspected. Cocaine: Among the multiple mechanisms involved in cocaine-related cardiotoxicity, excessive sympathetic stimulation with increased myocardial oxygen consumption is well documented in the acute form of left ventricular dysfunction. As for cocaine-related cardiomyopathy, the role of apoptosis and ROS is under investigation. Ethanol: The aetiology of ethanol-related cardiotoxicity is multifactorial, with individual susceptibility being important. It involves apoptosis, alterations of the excitation-contraction coupling in cardiac myocytes, structural and functional alterations of the mitochondria and sarcoplasmic reticulum, changes in cytosolic calcium flows, changes in calcium sensitivity of myofilaments, alterations of mitochondrial oxidation, deregulation of protein synthesis, decrease of contractile proteins and disproportion between the different types of myofibrils, changes in the regulation of myosin ATPase, up-regulation of the L-type calcium channels, increase of oxidative stress, and induction of ANP and p21 mRNA expression in ventricular myocardium. Metamfetamines: Catecholamine-mediated toxicity is the probable cause, with a possible role for genetic susceptibility. Carbon monoxide: In addition to hypoxic injury, carbon monoxide is also directly toxic to the mitochondria, with impairment of mitochondrial respiratory chain at the cytochrome c oxidase level, decrease of glutathione concentrations and of ATP production. There is no evidence for a delayed dilated cardiomyopathy in survivors of an acute exposure. Metals: Cobalt-related cardiomyopathy probably results from interference with energy production and contractile mechanisms, but additional factors (nutrition, hypothyroidism) are often required. Antimony may cause lethal oxidative stress and cell death mediated by elevation in intra-cellular calcium. Proposed mechanisms for mercury toxicity include glutathione depletion, production of ROS, and interruption in selenium-dependent endogenous enzymatic reactions. The existence of a lithium-induced cardiomyopathy is still debated. Scorpion venom: Catecholamine release is the probable cause of acute cardiomyopathy following scorpion envenomation. CONCLUSIONS: The mechanisms behind toxic cardiomyopathy are complex and multifactorial but include interference with myocardial cell bioenergetics and intracellular calcium handling, the generation of ROS, neurohormonal stress, and induction of apoptosis.

Hypothermia with Extreme Bradycardia following Spinal Cord Infarction of Septic Origin.

Among other autonomic dysfunctions complicating acute spinal cord injury, deep hypothermia is rare but may induce serious cardiovascular complications. There are few pharmacological options to influence hypothermia. A 66-year-old woman was transferred to the intensive care unit (ICU) for serious cardiac arrhythmias (atrial fibrillation and asystole) in the context of a deep hypothermia (axillary temperature below 32°C). She had been admitted to the hospital two months before for an acute L4-L5 infectious spondylodiscitis without any initial neurological deficit. After surgery for epidural abscess drainage, she became paraplegic due to spinal cord infarction (from C7 to T6 levels) in the upper territory of the anterior spinal artery. In the ICU, the patient experienced several episodes of asystole and hypotension associated with a core body temperature below 35°C. Common causes of hypothermia (drugs, hypothyroidism, etc.) were excluded. A definitive pacemaker had to be inserted, but hypotension persisted. The prescription of oral progesterone (200 mg·d-1) helped to maintain a core temperature higher than 35°C, with a withdrawal of vasopressors. This case report illustrates that patients with incomplete spinal cord injury may present with delayed and deep hypothermia leading to serious cardiovascular complications. Progesterone could be able to influence positively central and peripheral thermal regulation.

Coronary vasospasm complicating cannabinoid hyperemesis syndrome.

Cannabinoid hyperemesis syndrome (CHS) is a clinical condition that was first described in 2004. The syndrome may occasionally be observed in long-term cannabis users and is characterized by a set of features: severe cyclic nausea and vomiting, recurrent epigastric or periumbilical pain, relief of symptoms with hot baths, and cannabis use cessation. The pathophysiology is not fully understood but is probably related to Cannabinoid-1 (CB-1) receptors dysregulation. On the other hand, there is also growing epidemiological evidence that cannabis smoking may trigger acute coronary syndrome (ACS) in young men. We describe the case of 41-year-old man with a long history of cannabis smoking who not only complained of recurrent epigastric but also of retrosternal pain. He had undergone several negative radiological or endoscopic investigations. During the last episode, electrocardiographic and echocardiographic changes were consistent with takotsubo cardiomyopathy. However, the patient was readmitted very soon with a ST-elevation myocardial infarction related to coronary vasospasm. While the link between CHS and ACS is not established, CHS patients with atypical pain should be investigated carefully to exclude any serious cardiac event. .