Acute Kidney Injury Recovery Patterns in Critically Ill Patients: Results of a Retrospective Cohort Study.

OBJECTIVES: Acute kidney injury, acute kidney injury severity, and acute kidney injury duration are associated with both short- and long-term outcomes. Despite recent definitions, only few studies assessed pattern of renal recovery and time-dependent competing risks are usually disregarded. Our objective was to describe pattern of acute kidney injury recovery, change of transition probability over time and their risk factors. DESIGN: Monocenter retrospective cohort study. Acute kidney injury was defined according to Kidney Disease Improving Global Outcomes definition. Renal recovery was defined as normalization of both serum creatinine and urine output criteria. Competing risk analysis, time-inhomogeneous Markov model, and group-based trajectory modeling were performed. SETTING: Monocenter study. PATIENTS: Consecutive patients admitted in ICU from July 2018 to December 2018 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three-hundred fifty patients were included. Acute kidney injury occurred in 166 patients at ICU admission, including 64 patients (38.6%) classified as acute kidney disease according to Acute Disease Quality Initiative definition and 44 patients (26.5%) who could not be classified. Cumulative incidence of recovery was 25 % at day 2 (95% CI, 18-32%) and 35% at day 7 (95% CI, 28-42%). After adjustment, need for mechanical ventilation (subdistribution hazard ratio, 0.42; 95% CI, 0.23-0.74) and severity of the acute kidney injury (stage 3 vs stage 1 subdistribution hazard ratio, 0.11; 95% CI, 0.03-0.35) were associated with lack of recovery. Group-based trajectory modeling identified three clusters of temporal changes in this setting, associated with both acute kidney injury recovery and patients' outcomes. CONCLUSIONS: In this study, we demonstrate Acute Disease Quality Initiative to allow recovery pattern classification in 75% of critically ill patients. Our study underlines the need to take into account competing risk factors when assessing recovery pattern in critically ill patients.

Performance of Diagnostic Scores in Thrombotic Microangiopathy Patients in the Intensive Care Unit: A Monocentric Study.

Early thrombotic thrombocytopenic purpura (TTP) recognition is critical as this disease is almost always lethal if not treated promptly with therapeutic plasma exchanges. Currently, as ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity is not widely available in emergency, scores have been developed to help differentiating TTP from other thrombotic microangiopathies (TMAs). The aim of this work was to study the accuracy of these diagnostic scores in the intensive care unit (ICU) setting. Performance of both Coppo and PLASMIC scores was studied in a cohort of adult TMA patients requiring admission to one university hospital ICU from 2006 to 2017. Receiver operating characteristic (ROC) curves were established, and confidence intervals of the area under the curve (AUC) were determined. Multivariate logistic regression analysis was performed to identify parameters specifically associated with TTP, to compare diagnostic scores and to elaborate more accurate diagnostic models. During the study period, 154 TMA patients required ICU admission, including 99 (64.2%) TTP and 55 (35.7%) non-TTP patients. AUC under the ROC curve in predicting TTP was 0.86 (95% confidence interval [CI]: 0.81-0.92) for the Coppo score, 0.67 (95% CI: 0.58-0.76) for the PLASMIC score, and 0.86 (95% CI: 0.81-0.92) for platelet count alone. Platelet count ≤20 G/L, determined as the best cut-off rate for thrombocytopenia, performed similarly to the Coppo score and better than the PLASMIC score to differentiate TTP from non-TTP patients, both using AUC ROC curve and logistic regression. In a monocentric cohort of TMA patients requiring ICU admission, the PLASMIC score had limited performance for the diagnosis of TTP. The performance of the Coppo score was good but similar to a single highly discriminant item: platelet count ≤20 G/L at admission.

Trajectories of acute graft-versus-host disease and mortality in critically ill allogeneic-hematopoietic stem cell recipients: the Allo-GRRR-OH score.

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity mortality in critically ill hematopoietic stem cell transplantation recipients. We assessed aGVHD trajectories in 191 allogeneic-HSCT recipients (age 42 (27-46)) admitted to our ICU between 2005 and 2015. aGVHD affected 130 (68%) patients (including 90% who underwent steroid therapy at a dose of 2 (2-2) mg/kg) and was graded 3 or 4 in 31% of the patients. Trajectories of aGVHD were clustered in four groups: (1) no aGVHD, (2) controlled aGVHD, (3) uncontrolled aGVHD (active, stable, or worsening), and (4) newly diagnosed and untreated aGVHD. Patients with controlled aGVHD and those admitted at the onset of aGVHD had similar survival than patients who never experienced aGVHD. By multivariable analysis, the dynamic assessment of aGVHD was independently associated with 90-day mortality, in addition to the admission to the ICU for acute respiratory failure, acute kidney injury or acute liver failure, and sepsis-related organ failure assessment score at admission. In conclusion, these findings suggest that GVHD cannot be assessed as a binary variable and at a single time point. Patients in whom GVHD is not uncontrolled with corticosteroids should have the same goals of ICU care than patients without GVHD.

Epidemiology, clinical features, and management of severe hypercalcemia in critically ill patients.

BACKGROUND: Severe hypercalcemia (HCM) is a common reason for admission in intensive-care unit (ICU). This case series aims to describe the clinical and biological features, etiologies, treatments, and outcome associated with severe HCM. This study included all patients with a total calcemia above 12 mg/dL (3 mmol/L) admitted in two ICUs from January 2007 to February 2017. RESULTS: 131 patients with HCM were included. HCM was related to hematologic malignancy in 58 (44.3%), solid tumors in 29 (22.1%), endocrinopathies in 16 (12.2%), and other causes in 28 (21.3%) patients. 108 (82.4%) patients fulfilled acute kidney injury (AKI) criteria. Among them, 25 (19%) patients required renal replacement therapy (RRT). 51 (38.9%) patients presented with neurological symptoms, 73 (55.7%) patients had cardiovascular manifestations, and 50 (38.1%) patients had digestive manifestations. The use of bisphosphonates (HR, 0.42; 95% CI, 0.27-0.67; P < 0.001) was the only treatment significantly associated with a decrease of total calcemia below 12 mg/dL (3 mmol/L) at day 5. ICU and Hospital mortality rates were, respectively, 9.9% and 21.3%. Simplified Acute Physiologic Score (SAPS II) (OR, 1.05; 95% CI 1.01-1.1; P = 0.03) and an underlying solid tumor (OR, 13.83; 95% CI 2.24-141.25; P = 0.01) were two independent factors associated with hospital mortality in multivariate analysis. CONCLUSIONS: HCM is associated with high mortality rates, mainly due to underlying malignancies. The course of HCM may be complicated by organ failures which are most of the time reversible with early ICU management. Early ICU admission and prompt HCM management are crucial, especially in patients with an underlying solid tumor presenting with neurological symptoms.

Candidemia in critically ill immunocompromised patients: report of a retrospective multicenter cohort study.

BACKGROUND: Immunocompromised critically ill patients constitute a population with the high risk of candidemia. This retrospective study aimed to assess the outcome of immunocompromised critically ill patients with candidemia. Secondary objectives were to describe clinical phenotypes of these patients, Candida ecology, and factors associated with mortality. RESULTS: Overall, 121 patients were included in this study. Median delay from candidemia to first antifungal therapy was 3 days, in line with the observed delay of blood culture positivity. Candia albicans was the main Candida specie identified (54%), and susceptibility of Candida to fluconazole and echinocandins was of, respectively, 70% and 92%. Hospital mortality was of 60%. After adjustment for confounders, severity as assessed by the need for vasopressors (HR 1.8, CI95% 1.1-3.1), need for mechanical ventilation (HR 2.0, CI95% 1.1-3.8) and allogenic stem cell transplantation (HR 2.5, CI95% 1.1-6.0) were independently associated with poor outcome. Candida specie, susceptibility and treatment strategies were not associated with outcome. CONCLUSIONS: Candidemia in immunocompromised critically ill patients is associated with a grim outcome. Despite the high prevalence of Candida non-albicans species, neither C. species nor its susceptibility was associated with outcome. Conversely, severity and preexisting allogeneic stem cell transplantation were independently associated with poor outcome. Despite antifungal prophylaxis and use of preemptive antifungal therapy in neutropenic patients, antifungal therapy was initiated three days after symptoms onset suggesting needs for specific strategies aiming to reduce this delay.

Characteristics, outcome and treatments with cranial pachymeningitis: A multicenter French retrospective study of 60 patients.

The aim of this study was to determine the characteristics, treatment, and outcome according to each etiology of pachymeningitis.We conducted a retrospective multicenter French nationwide study between 2000 and 2016 to describe the characteristics, outcome, and treatment of pachymeningitis.We included 60 patients (median age 55.5 years; interquartile range [IQR] 30-80, female/male ratio 0.43). Neurologic signs were present in 59 patients (98%) and consisted of headache in 43 (72%), cranial nerve palsy in 33 (55%), confusion in 10 (17%), seizures in 7 (12%), and focal neurologic signs in 9 (15%). Fever and weight loss were present in 8 (13%) and 13 cases (22%), respectively. Cerebral venous thrombosis was present in 8 cases (13%). Analysis of cerebrospinal fluid showed moderate hyperproteinorachia (median 0.68 g/L; IQR 0.46-3.2) with or without pleiocytosis. Diagnosis included idiopathic pachymeningitis (n = 18; 30%); granulomatosis with polyangiitis (n = 13; 17%); Erdheim-Chester disease (n = 10; 17%); IgG4-related disease and tuberculosis (n = 3; 5% each); Rosai-Dofman disease, microscopic polyangiitis, and sarcoidosis (n = 2, 3% each); cryptococcal meningitis, Lyme disease, ear-nose-throat infection, postlumbar puncture, low spinal-fluid pressure syndrome, and lymphoma (n = 1 each). We found no difference in demographics and neurologic presentation among idiopathic pachymeningitis, Erdheim-Chester disease, and granulomatosis with polyangiitis. In contrast, frequencies were lower with idiopathic pachymeningitis than Erdheim-Chester disease for general signs (6% and 40%, respectively, P = .041) and complete neurologic response (0% vs 39%, P = .045).The detection of extraneurologic signs and routine screening are needed to classify the pachymeningitis origin. Prospective studies are warranted to determine the best treatment in each case.

First Report of CD4 Lymphopenia and Defective Neutrophil Functions in a Patient with Amebiasis Associated with CMV Reactivation and Severe Bacterial and Fungal Infections.

We report the case of a patient with acute necrotizing colitis due to invasive amebiasis associated with CD4 lymphopenia and impaired neutrophil responses. The course of the disease was characterized by CMV reactivation and severe and recurrent bacterial and fungal infections, which might be related to the decreased CD4 T cell count and the impaired functional capacities of neutrophils, respectively. The clinical outcome was positive with normalization of both CD4 cell count and neutrophil functions.

Digestive-tract sarcoidosis: French nationwide case-control study of 25 cases.

Digestive tract sarcoidosis (DTS) is rare and case-series are lacking. In this retrospective case-control study, we aimed to compare the characteristics, outcome, and treatment of patients with DTS, nondigestive tract sarcoidosis (NDTS), and Crohn disease.We included cases of confirmed sarcoidosis, symptomatic digestive tract involvement, and noncaseating granuloma in any digestive tract. Each case was compared with 2 controls with sarcoidoisis without digestive tract involvement and 4 with Crohn disease.We compared 25 cases of DTS to 50 controls with NDTS and 100 controls with Crohn disease. The major digestive clinical features were abdominal pain (56%), weight loss (52%), nausea/vomiting (48%), diarrhea (32%), and digestive bleeding (28%). On endoscopy of DTS, macroscopic lesions were observed in the esophagus (9%), stomach (78%), duodenum (9%), colon, (25%) and rectum (19%). As compared with NDTS, DTS was associated with weight loss (odds ratio [OR] 5.8; 95% confidence interval [CI] 1.44-23.3) and the absence of thoracic adenopathy (OR 5.0; 95% CI 1.03-25). As compared with Crohn disease, DTS was associated with Afro-Caribbean origin (OR 27; 95% CI 3.6-204) and the absence of ileum or colon macroscopic lesions (OR 62.5; 95% CI 10.3-500). On the last follow-up, patients with DTS showed no need for surgery (versus 31% for patients with Crohn disease; P = 0.0013), and clinical digestive remission was frequent (76% vs. 35% for patients with Crohn disease; P = 0.0002).The differential diagnosis with Crohn disease could be an issue with DTS. Nevertheless, the 2 diseases often have different clinical presentation and outcome.

The diffuse infiltrative lymphocytosis syndrome (DILS). A comprehensive review.

The Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare multisystemic syndrome described in HIV-infected patients. It is characterised by CD8(+) T-cell lymphocytosis associated with a CD8(+) T-cell infiltration of multiple organs. DILS is usually seen in uncontrolled or untreated HIV infection but can also manifest itself independently of CD4(+) T-cell counts. The syndrome may present as a Sjögren-like disease that generally associates sicca signs with bilateral parotiditis, lymphadenopathy, and extraglandular organ involvement. The latter may affect the lungs, nervous system, liver, kidneys, and digestive tract. Anomalies of the respiratory system are often identified as lymphocytic interstitial pneumonia. Facial nerve palsy, aseptic meningitis or polyneuropathy are among the more frequent neurological features. Hepatic lymphocytic infiltration, lymphocytic interstitial nephropathy and digestive tract lymphocytic infiltration account for more rarely noted complications. Sicca syndrome, organomegaly and/or organ dysfunction associated with polyclonal CD8(+) T-cell organ-infiltration are greatly suggestive of DILS in people living with HIV. Labial salivary gland biopsy is therefore helpful when the focus score is equal or greater than 1 (or Chisholm Score ≥ 3). Primary Sjögren syndrome, chronic HCV or HTLV1 infection, graft versus host disease, IgG4-related disease, and immune reconstitution inflammatory syndrome are among the differential diagnoses that need to be considered. Treatment consists in highly active anti-retroviral therapy (HAART), which is usually effective in resolving clinical signs and symptoms. Steroids, however, may also be occasionally required when organ infiltration does not respond to HAART. This review should provide an insight into this rare entity complicating the course of HIV infection.

The spectrum of chronic CD8+ T-cell expansions: clinical features in 14 patients.

Chronic CD8(+) T-cell expansions can result in parotid gland swelling and other organ infiltration in HIV-infected patients, or in persistent cytopenias. We report 14 patients with a CD8+ T-cell expansion to better characterize the clinical spectrum of this ill-defined entity. Patients (9 women/5 men) were 65 year-old (range, 25-74). Six patients had ≥ 1 symptomatic organ infiltration, and 9 had ≥ 1 cytopenia with a CD8(+) (>50% of total lymphocyte count) and/or a CD8(+)/CD57(+) (>30% of total lymphocyte count) T-cell expansion for at least 3 months. One patient had both manifestations. A STAT3 mutation, consistent with the diagnosis of large granular lymphocyte leukemia, was found in 2 patients with cytopenia. Organ infiltration involved lymph nodes, the liver, the colon, the kidneys, the skin and the central nervous system. Three patients had a HIV infection for 8 years (range, 0.5-20 years). Two non-HIV patients with hypogammaglobulinemia had been treated with a B-cell depleting monoclonal antibody (rituximab) for a lymphoma. One patient had a myelodysplastic syndrome with colon infiltration and agranulocytosis. The outcome was favorable with efficient antiretroviral therapy and steroids in HIV-infected patients and intravenous immunoglobulins in 2/3 non-HIV patients. Six patients had an agranulocytosis of favorable outcome with granulocyte-colony stimulating factor only (3 cases), cyclophosphamide, methotrexate and cyclosporine A, or no treatment (1 case each). Three patients had a pure red cell aplasia, of favorable outcome in 2 cases with methotrexate and cyclosporine A; one patient was unresponsive. Chronic CD8(+) T-cell expansions with organ infiltration in immunocompromised patients may involve other organs than parotid glands; they are non clonal and of favorable outcome after correction of the immune deficiency and/or steroids. In patients with bone marrow infiltration and unexplained cytopenia, CD8(+) T-cell expansions can be clonal or not; their identification suggests that cytopenias are immune-mediated. Our results extend the clinical spectrum of chronic CD8(+) T-cell expansions.

Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study.

OBJECTIVE: To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE). METHODS: We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes. RESULTS: Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9-82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1-0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2-21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1-113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01). CONCLUSION: GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.

Visualization of amyloid arthropathy in light-chain systemic amyloidosis on F-18 FDG PET/CT scan.

We report a case of 63-year-old man with symmetrical joint swelling of the interphalangeal and metacarpal joints, associated with isolated hypogammaglobulinemia. Accessory glands biopsy revealed the presence of amyloidal deposits. PET/CT showed increased F-18 FDG activity in thickened soft tissues corresponding to amyloid arthropathy. Like multiple myeloma, PET/CT could be an interesting imaging in light-chain amyloidosis.