Myelofibrosis-Associated Lymphoproliferative Disease: Retrospective Study of 16 Cases and Literature Review

Background. To better describe the clinical, biological, and the outcome of non-Hodgkin's lymphoma (NHL) with, at the initial presentation, bone marrow fibrosis (MF). Patients and Methods. From January 2001 to January 2007, 16 eligible patients with NHL and MF were retrieved from the Pathology Department of the University hospital of Amiens. Median age of patients was 62 years (range 16–74) with a sex ratio male/female of 3. Results. MF is associated with all types of lymphoma predominantly with B-cell phenotype and it seems to be more associated with low-grade NHL. B-symptoms are more frequent at diagnosis and more patients presented with an elevated LDH level. JAK-2 was negative in the 10 patients analysed. Two patients presented with features of primary MF with no evidence of lymphoma. Overall response rate was 94% after the first line of therapy with regression or improvement of MF. Relapse occurred in 8 patients (47%) with recurrence of MF in all of them. After a median follow-up of 42 months, 12 patients were alive with an overall survival rate for the entire group of 75%. Conclusions. MF-associated NHL is a rare manifestation which may be associated with all types of NHL and its presence does not seem to confer a poor prognosis. A search for lymphoproliferation should be considered when the cause of MF is not apparent

Aromatic L-Amino Acid Decarboxylase Deficiency Is a Cause of Long-Fasting Hypoglycemia

Objective/Context: Long-fasting hypoglycemia in children may be induced by neurotransmitter disorders. Case Report: A 5-year-old girl with a medical history of chronic diarrhea presented three episodes of severe hypoglycemia (20 mg/dL) between ages 3 and 5 years. She became pale and sweaty with hypothermia (33.5°C), bradycardia (45 bpm), and acidosis and presented a generalized seizure. During the 17-hour fast test performed to determine the etiology of her hypoglycemia, insulin and C-peptide were appropriately low, and human GH, IGF-I, cortisol, amino acids, and acylcarnitines were in the usual range for fasting duration. However, the presence of vanillactic and vanilpyruvic acids in urine led us to investigate the metabolism of dopamine and serotonin in the cerebrospinal fluid. Indeed, these results indicated an aromatic L-amino acid decarboxylase deficiency that impairs the synthesis of serotonin, dopamine, and catecholamines. The diagnosis was confirmed by the low aromatic L-amino acid decarboxylase (AADC) enzyme activity in plasma (5 pmol/min/mL; reference value, 20–130) and the presence of two heterozygous mutations, c.97G>C (p.V33L, inherited from her father) and c.1385G>C (p.R462P, inherited from her mother) in the DCC gene. She was supplemented with pyridoxine and raw cornstarch (1 g/kg) at evening dinner to reduce the night fast. The episodes of hypoglycemia and the chronic diarrhea were suppressed. Conclusion: Here is the first case report of long-fasting hypoglycemia due to a nontypical AADC deficiency. Hypoglycemia was severe, but the other neurological clinical hallmarks present in AADC-deficient patients were mild to moderate. Thus, neurotransmitter disorders should be considered in any patients presenting hypoglycemia with urine excretion of vanillactic acid

Efficacy of Anakinra for Various Types of Crystal-Induced Arthritis in Complex Hospitalized Patients: A Case Series and Review of the Literature

International audienceBackground. There are few data on anakinra use after failure of conventional medications for crystal-induced peripheral arthritis and/or crowned dens syndrome among complex hospitalized patients. Methods. We retrospectively analyzed the outcome of six patients affected with subacute crystal-induced arthritis who had received anakinra in second or third line therapy, including three patients with crowned dens syndrome and three others with gouty arthritis. Patients' comorbidities, reasons for anakinra use and associated drugs, and outcomes were recorded. Results. All patients presented with elevated inflammatory syndrome, systemic symptoms with poly/oligoarthritis. Except for absolute contraindications, all patients were previously treated with full or decreased dose of NSAID, colchicine, and/or glucocorticoids, with unsatisfactory response. All three gouty patients exhibited complete responses in all acute involvements under anakinra within 3 to 5 days, including one of them who needed the reintroduction of colchicine treatment that was previously unsuccessful. Crowned dens syndrome patients, including two with pseudogout and one with subacute hydroxyapatite deposition disease, needed 9 to 11 days to achieve complete response. Tolerance to anakinra was good. Conclusion. In case series of complex hospitalized patients, anakinra showed good activity in crowned dens syndrome and associated crystal-induced peripheral arthritis, with longer treatment duration than in gouty arthritis

Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P ¼ .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P ¼.007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT

N-Oleoyl-glycine reduces nicotine reward and withdrawal in mice.

Cigarette smokers with brain damage involving the insular cortex display cessation of tobacco smoking, suggesting that this region may contribute to nicotine addiction. In the present study, we speculated that molecules in the insular cortex that are sensitive to experimental traumatic brain injury (TBI) in mice might provide leads to ameliorate nicotine addiction. Using targeted lipidomics, we found that TBI elicited substantial increases of a largely uncharacterized lipid, N-acyl-glycine, N-oleoyl-glycine (OlGly), in the insular cortex of mice. We then evaluated whether intraperitoneal administration of OlGly would alter withdrawal responses in nicotine-dependent mice as well as the rewarding effects of nicotine, as assessed in the conditioned place preference paradigm (CPP). Systemic administration of OlGly reduced mecamylamine-precipitated withdrawal responses in nicotine-dependent mice and prevented nicotine CPP. However, OlGly did not affect morphine CPP, demonstrating a degree of selectivity. Our respective in vitro and in vivo observations that OlGly activated peroxisome proliferator-activated receptor alpha (PPAR-α) and the PPAR-α antagonist GW6471 prevented the OlGly-induced reduction of nicotine CPP in mice suggests that this lipid acts as a functional PPAR-α agonist to attenuate nicotine reward. These findings raise the possibility that the long chain fatty acid amide OlGly may possess efficacy in treating nicotine addiction

Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets.

International audienceno abstrac

Diacylglycerol lipase beta inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain

Background and PurposeInhibition of diacylglycerol lipase (DGL) prevents LPS-induced pro-inflammatory responses in mouse peritoneal macrophages. Thus, the present study tested whether DGL inhibition reverses allodynic responses of mice in the LPS model of inflammatory pain, as well as in neuropathic pain models. Experimental ApproachInitial experiments examined the cellular expression of DGL and inflammatory mediators within the LPS-injected paw pad. DAGL- (-/-) mice or wild-type mice treated with the DGL inhibitor KT109 were assessed in the LPS model of inflammatory pain. Additional studies examined the locus of action for KT109-induced antinociception, its efficacy in chronic constrictive injury (CCI) of sciatic nerve and chemotherapy-induced neuropathic pain (CINP) models. Key ResultsIntraplantar LPS evoked mechanical allodynia that was associated with increased expression of DGL, which was co-localized with increased TNF- and prostaglandins in paws. DAGL- (-/-) mice or KT109-treated wild-type mice displayed reductions in LPS-induced allodynia. Repeated KT109 administration prevented the expression of LPS-induced allodynia, without evidence of tolerance. Intraplantar injection of KT109 into the LPS-treated paw, but not the contralateral paw, reversed the allodynic responses. However, i.c.v. or i.t. administration of KT109 did not alter LPS-induced allodynia. Finally, KT109 also reversed allodynia in the CCI and CINP models and lacked discernible side effects (e.g. gross motor deficits, anxiogenic behaviour or gastric ulcers). Conclusions and ImplicationsThese findings suggest that local inhibition of DGL at the site of inflammation represents a novel avenue to treat pathological pain, with no apparent untoward side effects.United States Department of Health & Human Services - DA009789 - DA017259 - DA032933 - DA033934-01A1 DA035864 - DA038493-01A1National Institutes of Health (NIH) - USANIH-NINDS Center core grant - 5P30NS047463United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA - P30NS047463NIH National Institute of Neurological Disorders & Stroke (NINDS)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA - R01DA032933 - K99DA035864 - P01DA017259 - P01DA009789 - F32DA038493 - R00DA035864 - P30DA033934NIH National Institute on Drug Abuse (NIDA)European Commissio

Successful treatment of Candida parapsilosis mural endocarditis with combined caspofungin and voriconazole

BACKGROUND: Fungal mural endocarditis is a rare entity in which the antemortem diagnosis is seldom made. Seven cases of mural endocarditis caused by Candida spp. have been collected from literature and six of these patients died after treatment with amphotericin B. CASE PRESENTATION: We report a case of mural endocarditis diagnosed by transesophageal echocardiogram and positive blood cultures to Candida parapsilosis. Because blood cultures continued to yield C. parapsilosis despite caspofungin monotherapy, treatment with voriconazole was added. CONCLUSION: This is the first description of successful treatment of C. parapsilosis mural endocarditis with caspofungin and voriconazole

Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma

Bruton tyrosine kinase (BTK) inhibitors have greatly improved the spectrum of treatment options in mantle cell lymphoma (MCL) [1–4]. Acalabrutinib is a highly selective, orally administered, and potent BTK inhibitor with limited off-target activity [5]. Acalabrutinib was approved in 2017 by the US Food and Drug Administration for the treatment of relapsed/refractory MCL based on clinical data from the open-label, multicenter, phase 2 ACE-LY-004 study of acalabrutinib 100 mg twice daily [1]. Here, we present updated results from the ACE-LY-004 study after a median 26-month follow-up. Eligibility criteria and study design were published previously (Supplementary methods) [1]. Analysis of minimal residual disease (MRD) was conducted after complete response (CR) or partial response (PR) was achieved using the quantitative ClonoSEQ next-generation sequencing (5 × 10−6 ) assay (Adpative Biotechnologies, Seattle, WA, USA) in consenting patients with available paired archival tumor and whole blood samples. Data are updated as of February 12, 2018