Cannabinoid hyperemesis syndrome in two French emergency departments: a prospective cohort

Chronic cannabis use can be associated with uncontrollable vomiting and abdominal pain. Diagnostic criteria for cannabinoid hyperemesis syndrome (CHS) were defined in 2012 by Simonetto et al. The objectives of this study were to describe the prevalence of CHS, the patients' epidemiological characteristics, and to show the difficulties encountered in caring for these patients in emergency departments, the extent of health care and an unsuitable follow‐up in general practices. A prospective cohort of patients with CHS was recruited among a target population of patients leaving the adult emergency services of the Marseille hospitals Nord and La Timone between October 2017 and July 2018, with abdominal pain syndrome of unidentified etiology. Inclusion criteria for the CHS cohort were chronic cannabis use associated with nausea and vomiting. There were 48 patients included in the CHS cohort who took cannabis daily, in a target population of 2 848 patients (i.e. 1.6%). A hot shower was the most effective symptomatic treatment in 54.2% of cases. Patients suffering from CHS spent significantly more hours in emergency departments (11 vs. 6.5), and, on average, visits were more frequent (4.9 vs. 3). 20.3% of them were hospitalized to continue pain medication. Once out of hospital, follow‐up was limited, and weaning off cannabis, the only etiological treatment, was difficult to set up. Informing patients about CHS is essential, and a hot shower could be systematically proposed, thus limiting an unnecessary extent of health care. CHS is genuine, medical staff should be made aware of it in occupational training, and it should be seriously considered in health policies.     

Tacrolimus overexposure in kidney transplant recipients during the first post‐operative week: caution is required in older patients

In liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus overexposure during the first week post‐transplantation on the kidney function (KF) of KT recipients. In this retrospective study, 105 KT recipients were attributed to overexposure group (OG) or normal group according to their Cmin during the first week of treatment. KF was evaluated by comparing the rate of delayed graft function (DGF) and by collecting plasma creatinine from day 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 and at 1 year. Risk factors for developing DGF were also investigated using a multivariate model. DGF was more frequent in OG (43% of patients; P = 0.027) which has higher plasma creatinine on day 7, 14, and 21. OG patients were older with more extended criteria donor's grafts. In the multivariate analysis, only cold ischemia time (CIT) remained associated with DGF (OR = 1.003), while TAC overexposure did not reach significance (P = 0.06; OR = 3.9). In this study, we confirmed the predominant role of CIT as a risk factor for the onset of DGF in kidney transplantation. 43% of KT recipients were overexposed with more DGF, especially older patients.     

Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity.     

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.     

Can radiomics improve the prediction of metastatic relapse of myxoid/round cell liposarcomas?

European Radiology - The strongest adverse prognostic factor in myxoid/round cell liposarcomas (MRC-LPS) is the presence of a round cell component above 5% within the tumor bulk. Its identification...     

Optical coherence tomography angiography for marginal corneal vascular remodelling after pterygium surgery with limbal-conjunctival autograft

PurposeTo demonstrate the marginal corneal vascular remodelling using optical coherence tomography angiography (OCTA) after pterygium surgery.MethodsTwenty-two eyes of 19 patients (8 males, 11 females; age, 58.68 ± 0.34 years) with primary grade-T3 nasal pterygium were enroled in this study. The eyes underwent excision of the pterygium followed by a free limbal-conjunctival autograft. OCTA was performed in the nasal limbal area before surgery and at 10 days, 1 month, and 3 months after surgery. The scans were analyzed in terms of postoperative vascular remodelling of the autograft and marginal corneal vascular arcades (MCAs).ResultsPreoperatively, the pterygium presented as abnormal centripetal vascular growth in OCTA scans. The conjunctival vessel density in the nasal quadrant was 29.26% ± 1.00%, 15.80% ± 0.83%, 19.80% ± 0.88%, and 20.26% ± 0.89% before and 10 days, 1 month, and 3 months, respectively, after surgery (F = 1.55, P < 0.01). The vessel density of MCAs was 28.33% ± 0.88%, 42.09% ± 0.41%, and 42.46% ± 0.31% 10 days, 1 month, and 3 months, respectively, after surgery (F = 188.2, P < 0.01).ConclusionsWe describe a new application of OCTA for MCA vasculature imaging. Vascular remodelling of the graft and MCAs appeared at 1 month and continued for 3 months after surgery.Subject terms: Conjunctival diseases, Corneal diseases