Ketamine restriction correlates with reduced cholestatic liver injury and improved outcomes in critically ill patients with burn injury.

Background & Aims: Ketamine-associated cholestatic liver injury is reported in patients with severe burn injury, but its association with patient outcome is unclear. We investigated the relationship between ketamine exposure, cholestatic liver injury, and outcome of critically ill patients with burn injury. Methods: In a retrospective study, patients with severe burn injury were analysed across two periods: unrestricted ketamine prescription (ketamine-liberal) and capped ketamine dosage (ketamine-restricted). The primary endpoint was cholestatic liver injury, and the secondary endpoint was 3-month mortality. Binary logistic regression models and the revised electronic causality assessment method were used to measure the strength of associations and causality assessment, respectively. Results: Of 279 patients (median age 51 [IQR 31-67] years; 63.1% men; burned surface area 28.5%, IQR 20-45%), 155 (56%) were in the ketamine-liberal group, and 124 (44%) were in the ketamine-restricted group, with comparable clinical characteristics, except for ketamine exposure (median doses 265.0 [IQR 0-8,021] mg and 20 [IQR 0-105] mg, respectively; p <0.001). A dose- and time-dependent relationship was observed between ketamine exposure and cholestatic liver injury. Ketamine restriction was associated with a reduced risk of cholestatic liver injury (adjusted odds ratio 0.16, 95% CI 0.04-0.50; p = 0.003) and with a higher probability of 3-month survival (p = 0.035). The revised electronic causality assessment method indicated that ketamine was probably and possibly the cause of cholestatic liver injury for 14 and 10 patients, respectively. Cholangitis was not observed in the ketamine-restricted group. In propensity-matched patients, the risk of 3-month mortality was higher (adjusted odds ratio 9.92, 95% CI 2.76-39.05; p = 0.001) in patients with cholestatic liver injury and ketamine exposure ≥10,000 mg. Other sedative drugs were not associated with liver and patient outcome. Conclusions: In this cohort, ketamine restriction was associated with less cholestatic liver injury and reduced 3-month mortality. Impact and implications: In a cohort of 279 critically ill patients with burn injury, ketamine was associated with a risk of liver bile duct toxicity. The risk was found to be dependent on both the dosage and duration of ketamine use. A restriction policy of ketamine prescription was associated with a risk reduction of liver injury and 3-month mortality. These findings have implications for the analgesia and sedation of critically ill patients with ketamine, with higher doses raising safety concerns.

Emergency computed tomography evaluation of caustic ingestion.

Computed tomography (CT) is used increasingly for the emergency assessment of caustic injuries and the need for emergency endoscopy has been challenged. The study evaluates outcomes of caustic ingestion in the modern era and the feasibility of abandoning emergency endoscopy. Between 2013 and 2019, 414 patients (197 men, median age 42 years) were admitted for caustic ingestion. Emergency and long-term outcomes of patients managed by CT and endoscopy (n = 120) and by CT alone (n = 294) were compared. Propensity score-based analysis was performed to limit bias of between-group comparison. A standard mortality ratio (SMR) was used to compare the observed mortality with the expected mortality in the general French population. Complications occurred in 97 (23%) patients and 17 (4.1%) patients died within 90 days of ingestion. Among 359 patients who underwent nonoperative management, 51 (14%) experienced complications and 7 (2%) died. Of 55 patients who underwent emergency surgery, 46 (84%) experienced complications and 10 (18%) died. The SMR was 8.4 for whole cohort, 5.5 after nonoperative management, and 19.3 after emergency surgery. On multivariate analysis, intentional ingestion (P < 0.016), age (P < 0.0001) and the CT grade of esophageal injuries (P < 0.0001) were independent predictors of survival. The CT grade of esophageal injuries was the only independent predictor of success (P < 0.0001). Crude and propensity match analysis showed similar survival in patients managed with and without endoscopy. CT evaluation alone can be safely used for the emergency management of caustic ingestion.

Development of a New Index to Assess Small Bowel Inflammation Severity in Crohn's Disease Using Magnetic Resonance Enterography.

Background: The severity of small bowel (SB) inflammation in Crohn's disease (CD) patients is a key component of the therapeutic choice. We aimed to develop a SB-CD Magnetic Resonance Enterography (MRE) index of Inflammation Severity (CDMRIS). Methods: Each gastroenterologist/radiologist pair in 13 centers selected MREs from 6 patients with SB-CD stratified on their perceived MRE inflammation severity. The 78 blinded MREs were allocated through balanced incomplete block design per severity stratum to these 13 pairs for rating the presence/severity of 13 preselected items for each SB 20-cm diseased segment. Global inflammation severity was evaluated using a 100-cm visual analog scale. Reproducibility of recorded items was evaluated. The CDMRIS was determined through linear mixed modeling as a combination of the numbers of segments with lesions highly correlated to global inflammation severity. Results: Four hundred and forty-two readings were available. Global inflammation severity mean ± SD was 21.0 ± 16.2. The independent predictors explaining 54% of the global inflammation severity variance were the numbers of segments with T1 mild-moderate and severe intensity of enhancement, deep ulceration without fistula, comb sign, fistula, and abscess. Unbiased correlation between CDMRIS and global inflammation severity was 0.76. Conclusions: The CDMRIS is now available to evaluate the severity of SB-CD inflammation. External validation and sensitivity-to-change are mandatory next steps.

Elastography improves accuracy of early hepato-biliary complications diagnosis after allogeneic stem cell transplantation.

Significant morbidity and mortality have been associated with liver complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Causes and consequences of these hepato-biliary complications are various and might be life-threatening. A high misdiagnosis rate has been reported because of a weak correlation between clinical, laboratory and imaging data. Liver elastography, a liver stiffness measure, is able to assess liver fibrosis and portal hypertension in most liver diseases, but data after allo-HSCT are scarce. Our aim was to determine the interest of sequential liver stiffness measurements for the diagnosis of early hepatic complications after allo-HSCT. Over a two years period of time, 161 consecutive adult patients were included and 146 were analyzed. Ultrasonography and elastography measurements were performed before transplantation, at day+7 and day+14 by three different experienced radiologists unaware of patients'clinical status. Eighty-one (55%) patients had liver involvements within the first 100 days after allo-HSCT. Baseline elastography was not predictive for the occurrence of overall liver abnormalities. A significant increase in 2D real-time shearwave elastography (2D-SWE) was found in patients with sinusoidal obstruction syndrome (SOS). Fifteen patients (10%) fulfilled EBMT score criteria and twelve (8%) reached Baltimore criteria for SOS diagnosis, but only six (4%) had a confirmed SOS. 2D-SWE at day+14 allowed early detection of SOS (AUROC=0.84, p=0.004) and improved sensibility (75%), specificity (99%) and positive predictive value (60%) over the Seattle, Baltimore or EBMT scores. A 2D-SWE measurement above 8.1kPa at day+14 after allo-HSCT seems a promising, non-invasive, and reproducible tool for early and accurate diagnosis of SOS.

Contributing factors and outcomes of burn-associated cholestasis.

BACKGROUND & AIMS: Cholestasis often occurs after burn injuries. However, the prevalence of cholestasis and its effect on outcomes in patients with severe burn injuries are unknown. The aim of this study was to describe the course and the burden of cholestasis in a cohort of severely burned adult patients. METHODS: We investigated the relationship between burn-associated cholestasis (BAC) and clinical outcomes in a retrospective cohort of patients admitted to our unit for severe burn injuries between 2012 and 2015. BAC was defined as an increased level of serum alkaline phosphatase (ALP) ≥1.5x the upper limit of normal (ULN) with an increased level of gamma-glutamyltransferase (GGT) ≥3x ULN, or as an increased level of total bilirubin ≥2x ULN. RESULTS: A total of 214 patients were included: 111 (52%) patients developed BAC after a median (IQR) stay of 9 (5-16) days. At 90 days, the mortality rate was 20%, including 34 and 9 patients with and without BAC (p <0.001), respectively, which corresponded to a 2.5-fold higher (95% CI 1.2-5.2, p = 0.012) risk of 90-day mortality for patients with BAC. After being adjusted for severity of illness, patients with BAC, hyperbilirubinemia and without elevated ALP and GGT levels had a hazard ratio of 4.51 (95% CI 1.87-10.87) for 90-day mortality. BAC was associated with the severity of the burn injury, shock and bacteraemia. BAC was present in 38 (51%) patients at discharge, and 7 (18%) patients had secondary sclerosing cholangitis. These patients maintained elevated levels of ALP and GGT that were 5.8x (1.7-15) the ULN and 11x the ULN (4.5-22), respectively, 20 months (3.5-35) after discharge. CONCLUSION: BAC is prevalent among patients with severe burn injuries and is associated with worse short-term outcomes, especially when total bilirubin levels were increased without elevated ALP and GGT levels. BAC survivors are at risk of developing sclerosing cholangitis. LAY SUMMARY: Cholestasis is common after burn injuries and is associated with burn severity, sepsis, organ failure and mortality. Patients with hyperbilirubinemia without elevated alkaline phosphatase and gamma-glutamyltransferase levels after the burn injury have a poor prognosis. Patients with burn-associated cholestasis may develop sclerosing cholangitis and secondary biliary cirrhosis.

Risk Factors for Acute Mesenteric Ischemia in Critically Ill Burns Patients-A Matched Case-Control Study.

OBJECTIVE: Burn-induced shock can lead to tissue hypoperfusion, including the gut. We performed this study to describe burn patients at risk of acute mesenteric ischemia (AMI) with the aim to identify potential modifiable risk factors. METHODS: Retrospective case-control study including adult severely burned patients between August 2012 and March 2017. Patients who developed AMI were matched to severely burned patients without AMI at a ratio of 1:3 (same year of admission, Abbreviated Burn Severity Index [ABSI], and Simplified Acute Physiology Score II [SAPSII]). Univariate and multiple regression analyses were performed. RESULTS: Of 282 severely burned patients, 15 (5%) were diagnosed with AMI. In the AMI group, patients had a median (interquartile range) total body surface area (TBSA), SAPSII, and ABSI of 55 (25-63)%, 53 (39-70), and 11 (8-13), respectively. The AMI mechanism in all patients was nonocclusive. Decreased cardiac index within the first 24 h (H24 CI), higher sequential organ failure assessment score on day 1 (D1 SOFA), and hydroxocobalamin use were associated with AMI. Odds ratios were 0.18 (95% confidence interval [CI], 0.03-0.94), 1.6 (95% CI, 1.2-2.1), and 4.6 (95% CI, 1.3-15.9), respectively, after matching. Multiple regression analysis showed that only decreased H24 CI and higher D1 SOFA were independently associated with AMI. Ninety-day mortality was higher in the AMI group (93% vs. 46% [P = 0.001]). CONCLUSIONS: Burns patients with initial low cardiac output and early multiple organ dysfunction are at high risk of nonocclusive AMI.

Emergency Computed Tomography Predicts Caustic Esophageal Stricture Formation.

BACKGROUND: Endoscopy is the best predictor of stricture formation after caustic ingestion. OBJECTIVE: Our aim was to compare the accuracy of emergency computed tomography (CT) and endoscopy in predicting risks of esophageal stricture. METHODS: We describe a CT classification of esophageal caustic injuries: Grade I show normal esophagus; Grade IIa display internal enhancement of the esophageal mucosa and enhancement of the outer wall conferring a "target" aspect; Grade IIb present as a fine rim of external esophageal wall enhancement. In 152 patients (56 males, median age 45) who underwent esophageal preservation after caustic ingestion we compared the accuracy of the CT and endoscopic (Zargar) classifications in predicting esophageal stricture. RESULTS: On endoscopy esophageal injuries were classified as grade 1 (n = 50; 33%), grade 2a (n = 11; 7%), grade 2b (n = 19; 13%), grade 3a (n = 14; 9%), and grade 3b (n = 58; 38%). On CT, 47 (31%) patients had grade I, 47 (31%) had grade IIa and 58 (38%) had grade IIb esophageal injuries. Fifty-six (37%) patients developed esophageal strictures. The risk of esophageal stricture formation was 0%, 17%, and 83%, for grade I, IIa, and IIb CT injuries and 0, 0, 28, 50, and 76% for endoscopic grade 1, 2a, 2b, and 3a and 3b injuries, respectively. ROC curve analysis at 120 days after ingestion showed that CT outperformed endoscopy in predicting stricture formation (AUC: 85.1 [95% CI, 74.9-95.3] vs 77.8 [95% CI, 66.5-89.0], P = 0.047) and did just as well as a combined CT-endoscopy algorithm (AUC: 85.8 [95% CI, 76.5-95.0] vs 85.1 [95% CI, 74.9-95.3], P = 0.73). CONCLUSION: Emergency CT outperforms endoscopy in predicting esophageal stricture formation after caustic ingestion. Emergency endoscopy evaluation after caustic ingestion is not indispensable.

Transient pituitary ACTH-dependent Cushing syndrome caused by an immune checkpoint inhibitor combination.

Immune checkpoint inhibitors have improved survival in numerous advanced malignancies, but are associated with a number of immune-related adverse events, including endocrinopathies. Endogenous Cushing's syndrome (CS) is a rare disorder resulting from exposure to high levels of circulating cortisol. CS can be caused either by adrenal cortex tumors or hyperplasia or by pituitary or extra-pituitary tumors over-secreting ACTH (known as ACTH-dependent CS). We report the first case of transient ACTH-dependent CS, which appeared after combined ipilimumab and nivolumab therapy. Our patient presented typical clinical features of CS after three infusions of combined therapy, high serum and daily urinary free cortisol, and high serum ACTH levels. Pituitary MRI showed an enlargement of the pituitary gland suggesting ACTH secretion of pituitary origin, which was confirmed by inferior petrosal sinus sampling. The pituitary findings were preceded by thyroiditis. The evolution was characterized by spontaneous CS regression and subsequent appearance of severe corticotroph deficiency consistent with destructive hypophysitis. Immunotherapy is a novel cause of CS.

Renal Arterial Mycotic Aneurysm After Kidney Transplantation.

Mycotic aneurysm is a rare condition mostly attributable to Candida or Aspergillus species. About 20 cases of Candida-related arteritis have been reported in kidney transplant patients. Herein, we report the case of a 40-year-old man who received a kidney from a deceased donor in whom an accidental digestive wound was made during organ retrieval. He presented with sudden anuria 47 days after renal transplantation, revealing a large mycotic aneurysm of the kidney graft renal artery. Organs derived from donors in whom a digestive breach is noticed should be used with caution.

Anoperineal disease in Hidradenitis Suppurativa : MR imaging distinction from perianal Crohn's disease.

OBJECTIVE: To determine whether Hidradenitis suppurativa (HS)-related anoperineal disease can be distinguished from Crohn's disease (CD) using MRI. METHODS: Pelvic MRI of 23 HS and 46 CD patients with anoperineal disease between 2007 and 2014 were independently analysed by two radiologists. For diagnosis of HS, sensitivity, specificity and positive likelihood ratios (LRs) of inflammatory features and of their anatomical distribution were calculated and compared to those of CD. RESULTS: In HS, fistulae were less present (P = .033) and less frequently involved the sphincters (P = .001) than in CD. Granulomas were more frequent (P = .0005). For anterior/inguinal and posterior localizations, sensitivity, specificity and LR for diagnosis of HS were 70% (49.1, 84.4), 87% (74.3, 93.9), 5.3 (2.41, 11.79) and 57% (36.8, 74.4), 93% (82.5, 97.8), 8.67 (2.74, 27.41), respectively. Combination of signs including posterior involvement, absence of rectal wall thickening and bilaterality of features yielded specificity of 100% (95% CI: 92.3-100) for HS. CONCLUSION: Although MRI presentations of anoperineal disease may overlap between CD and HS, specific diagnosis of HS is possible with a combination of three features: absence of features' predominance in perianal area, absence of rectal wall thickening and bilaterality of features. KEY POINTS: • Spectrum of MRI features of HS-related anoperineal disease is wide. • Specific diagnosis of HS-related anoperineal disease is possible using MR imaging. • A combination of three MR signs allows distinction between HS and CD.

Computed Tomography Evaluation of Esophagogastric Necrosis After Caustic Ingestion.

BACKGROUND: Endoscopy is the standard of care for emergency patient evaluation after caustic ingestion. However, the inaccuracy of endoscopy in determining the depth of intramural necrosis may lead to inappropriate decision-making with devastating consequences. Our aim was to evaluate the use of computed tomography (CT) for the emergency diagnostic workup of patients with caustic injuries. METHODS: In a prospective study, we used a combined endoscopy-CT decision-making algorithm. The primary outcome was pathology-confirmed digestive necrosis. The respective utility of CT and endoscopy in the decision-making process were compared. Transmural endoscopic necrosis was defined as grade 3b injuries; signs of transmural CT necrosis included absence of postcontrast gastric/ esophageal-wall enhancement, esophageal-wall blurring, and periesophageal-fat blurring. RESULTS: We included 120 patients (59 men, median age 44 years). Emergency surgery was performed in 24 patients (20%) and digestive resection was completed in 16. Three patients (3%) died and 28 patients (23%) experienced complications. Pathology revealed transmural necrosis in 9/11 esophagectomy and 16/16 gastrectomy specimens. Severe oropharyngeal injuries (P = 0.015), increased levels of blood lactate (P = 0.007), alanine aminotransferase (P = 0.027), bilirubin (P = 0.005), and low platelet counts (P > 0.0001) were predictive of digestive necrosis. Decision-making relying on CT alone or on a combined CT-endoscopy algorithm was similar and would have spared 19 unnecessary esophagectomies and 16 explorative laparotomies compared with an endoscopy-alone algorithm. Endoscopy did never rectify a wrong CT decision. CONCLUSIONS: Emergency decision-making after caustic injuries can rely on CT alone.

Computed tomography evaluation of high-grade esophageal necrosis after corrosive ingestion to avoid unnecessary esophagectomy.

BACKGROUND: Esophagectomy is the standard of care for high-grade corrosive esophageal necrosis as assessed endoscopically. However, the inaccuracy of endoscopy in determining the depth of intramural necrosis may lead to unnecessary esophageal resection, with devastating consequences. Our aim was to evaluate the use of computed tomography (CT) for the emergency diagnostic workup of endoscopic high-grade corrosive esophageal necrosis. METHODS: In a before (2000-2007)/after (2007-2012) study of patients with grade 3b endoscopic esophageal necrosis, we compared outcomes after routine emergency esophagectomy versus selection for emergency esophagectomy based on CT evidence of transmural necrosis, defined as at least two of the following: esophageal-wall blurring, periesophageal-fat blurring, and the absence of esophageal-wall enhancement. Survival estimated using the Kaplan-Meier method was the primary outcome. RESULTS: Compared to the routine-esophagectomy group (n = 125), the CT group (n = 72) had better overall survival in the crude analysis (hazard ratio [HR], 0.43; 95 % confidence interval [95 %CI], 0.21-0.85; P = 0.015) and in the analysis matched on gender, age, and ingested agent (HR, 0.36; 95 %CI, 0.16-0.79; P = 0.011). No deaths occurred among patients managed without emergency esophagectomy based on CT findings, and one-third of CT-group patients had their functioning native esophagus at last follow-up. Self-sufficiency for eating and breathing was more common (84 % vs. 65 %; relative risk [RR], 1.27; 95 %CI, 1.04-1.55; P = 0.016) and repeat suicide less common (4 % vs. 15 %; RR, 0.27; 95 %CI, 0.09-0.82; P = 0.019) in the CT group. CONCLUSION: The decision to perform emergency esophagectomy for endoscopic high-grade corrosive esophageal injury should rely on CT findings.

Development of the Lémann index to assess digestive tract damage in patients with Crohn's disease.

BACKGROUND & AIMS: There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn's disease (CD). METHODS: We performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1-3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods. RESULTS: Data from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall. CONCLUSIONS: In a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment.

Autoimmune hemolytic anemia and nodular lymphocyte-predominant hodgkin lymphoma: a rare association.

Autoimmune hemolytic anemia (AIHA) has been associated with chronic lymphocytic leukemia, non-Hodgkin lymphoma, and classical Hodgkin lymphoma, but to the best of our knowledge, the association of AIHA and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) has not been reported previously. A 20-year-old woman presented with conjunctival jaundice, fever, asthenia, and hemoglobin 9.2 g/dL revealing IgG-mediated warm antibody AIHA. Computed tomography (CT) scan and positron-emission tomography (PET) scan showed mediastinal and axillary lymph nodes with increased [(18)F]-fluorodeoxyglucose uptake. A mediastinal lymph node was biopsied during mediastinoscopy, and NLPHL was diagnosed by an expert hematopathologist. The hemoglobin level declined to 4.6 g/dL. The treatment consisted of four 28-day cycles of R-ABVD (rituximab 375 mg/m(2) IV, adriamycin 25 mg/m(2) IV, bleomycin 10 mg/m(2) IV, vinblastine 6 mg/m(2) IV, and dacarbazine 375 mg/m(2) IV, each on days 1 and 15). Prednisone was progressively tapered over 10 weeks. After the first chemotherapy cycle, the hemoglobin level rose to 12 g/dL. After the four cycles, PET and CT scans showed complete remission (CR). At the last followup (4 years), AIHA and NLPHL were in sustained CR.

Gastroenterology review and perspective: the role of cross-sectional imaging in evaluating bowel damage in Crohn disease.

OBJECTIVE: This article will review the performance and limitations of cross-sectional imaging methods to detect and display critical features of Crohn disease (CD)-related bowel damage, including stenosis and penetrating complications (i.e., fistula, abscess). International efforts to incorporate cross-sectional imaging findings along with endoscopic and surgical findings to create a global bowel damage score over the length of the gastrointestinal tract are summarized along with the rationale for these efforts. CONCLUSION: The first digestive damage score, the Lémann score, will incorporate surgical history, endoscopic findings, and imaging findings of stenosis and penetrating complications to provide a global assessment of CD-related destruction of the gastrointestinal tract. It is anticipated that the score will permit better understanding of the impact of modern therapeutics on the natural history of CD. Because CT is a technique that involves ionizing radiation and accuracy of ultrasound is highly related to CD location, MRI is proposed as first choice for nonemergent follow-up of CD patients.

JC virus variant associated with cerebellar atrophy in a patient with AIDS.

The human polyomavirus JC virus (JCV) is the agent of progressive multifocal leukoencephalopathy (PML). It has also recently been involved in cerebellar atrophy. Factors involved in this entity are elusive. We present a case of a human immunodeficiency virus (HIV)-infected patient with PML and cerebellar atrophy. In addition to a compartmentalization of JCV strains between urine, cerebrospinal fluid, and cerebellum, specific rearrangements in the JCV regulatory region were observed in the cerebellum, resulting in alterations of transcription factor binding sites. Our data underline the importance of searching for JCV in HIV-infected patients with cerebellar disorders and suggest that mutations in the regulatory region may be involved in cerebellar degeneration.