Hypercalcemia at diagnosis of diffuse large B-cell lymphoma is not uncommon and is associated with high-risk features and a short diagnosis-to-treatment interval

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event-free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high-risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, β2-microglobulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was significantly shorter for hypercalcemic patients (P = .001). These associations with adverse prognostic factors translated into lower rates of EFS24 (HR = 1.66; 95% CI, 1.08-2.54) and shorter PFS (P = .0059) and OS (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters. These data suggest that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL.     

Age impacts the pattern of care for elderly patients with rectal cancer

Purpose

This study analyzed the current approaches for rectal cancer treatment in elderly patients.

Methods

We retrospectively studied 240 rectal cancer patients who had undergone radiotherapy from 2000 to 2008. The ages of the patients ranged from 65 and 75 years (group A, n?=?127) and older than 75 years (group B, n?=?113). The distribution of the Charlson comorbidity index was similar between the two groups, but the ECOG performance status (PS) differed between the groups (66 % of the patients of group A were PS 0, and 40 % were PS 0 in group B (p?<?0.0001)). The tumor stages were comparable between groups.

Results

The median age of the patients was 74.3 years (range 65–90.6). Treatment was discussed during a multidisciplinary cancer team meeting before treatment for 55 % of the cases in group A and 73 % of the cases in group B (p?<?0.001), and treatment proposals were in accordance with guidelines in 96 % of the cases in group A and 76 % of the cases in group B (p?<?0.001). Group B patients received slightly less concurrent chemotherapy (35 vs. 30 % for group A; p?=?0.54), more hypofractionated radiotherapy (41 vs. 54 % for group A; p?=?0.064), less surgery (92 vs. 80 % for group A; p?=?0.014), and less adjuvant chemotherapy (34 vs. 10 % for group A; p?<?0.001). Finally, 80 % of the patients in group A and 60 % of the patients in group B received treatment in accordance with guidelines (p?=?0.007) and in the logistic regression model. Non-metastatic patients who were aged below 75 years were predicted for conformal management (HR?=?0.323; 95 % CI?=?0.152–0.684) irrespective of their performance status, comorbidity, or disease stage.

Conclusions

Treatment proposals and administered therapy differed according to age.     

Respiratory system mechanical behavior in the chicken

We evaluated whether the avian respiratory system displays the same fundamental mechanical behavior during external forcing as found in mammals. We measured airway flow and pressures in the trachea, air sacs and thoracoabdominal cavity in 4 anesthetized-paralyzed roosters during sinusoidal volume oscillations at the trachea in the normal range of euthermic breathing frequency, f(0.2 to 1.0 Hz), and tidal volume, VT (10-50 ml). From the pressure and flow waveforms, we calculated resistance (R) and elastance (E) of the total respiratory system and its major compartments (lungs, air sacs and chest wall). E of the chest wall was minimum (147 cmH2O.L-1 +/- 7 SE) at 0.2 Hz-50 ml and was consistently, slightly lower than E of the total respiratory system over the entire range studied. Both elastances showed the same dependence on f and VT, increasing slightly with increasing f and decreasing with increasing VT. R of the chest wall was maximum (35.6 cmH2O.L- 1.sec-1 +/- 2.2 SE) at 0.2 Hz-10 ml and decreased with increasing f and VT, although the VT effect diminished at the higher f. E and R of the air sacs were much smaller than those of the chest wall, but showed similar f and VT dependencies. R of the lungs, due to resistance of the airways, was minimum (6.8 cmH2O.L-1.sec-1 +/- 1.5 SE) at 0.2 Hz-10 ml and increased with both f and VT. Total respiratory R reflected R of the air sacs and chest wall at low f and R of the lungs at high f. The f and VT dependencies of E and R in the chicken were strikingly similar to those measured in various types of mammalian respiratory tissues (Stamenovi? et al. (1990) J. Appl. Physiol. 69: 973-988. We conclude that, despite important anatomical differences between species, avian and mammalian respiratory tissues exhibit fundamentally similar mechanical behavior.     

Le milieu urbain : un facteur de risque pour les troubles psychotiques ?

A growing body of evidence suggests that urbanicity contributes to the development of psychosis, with elevated risks being associated with growing up or living in environments with a higher level of urbanization. This article aims to provide a review of the scientific literature studying the link between urbanicity and psychosis in order to identify the concepts used so far to clarify this issue and the hypotheses that have emerged from them. Taken together, the findings reviewed in this paper confirm that urbanicity is associated with an increased risk of schizophrenia and other non-affective psychosis. However, the mechanisms underlying this phenomenon remain unclear. The impact of urbanicity may result from a wide range of factors from air pollution to stressful impact of social life leading to “urban stress”. Indeed, the main underlying putative causes explored that may underpin this association are the social environment and air pollution. The role of psychosocial stressors such as neighborhood fragmentation, low social cohesion and social capital, deprivation, social adversities have been singled out by several studies. These different factors could lead to several pathways, possibly unified by dopaminergic hyperactivity in mesocorticolimbic system. Urbanicity could also potentially be related, at least in part, to environmental pollution which has been largely neglected compared to some of the other non-genetic environmental risk factors. The findings from our review show that recent studies link environmental pollution and especially air pollution exposure, to an increased risk of schizophrenia. There are feasible biological mechanisms involving neuro-inflammation processes by which some of the specific pollutants could affect brain development in a way that could increase risk for schizophrenia. Further research – from the cellular to epidemiological levels – is clearly needed. To fully understand the causal role of the environmental risk factors, the integration of genomics with large-scale epidemiological studies is warranted. Moreover, new studies on urbanicity should therefore be more interdisciplinary, bridging knowledge from different disciplines (psychiatry, epidemiology, human geography, urbanism, etc.) in order to enrich research methods. The fact that more than 50% of the World population lives in cities, a proportion likely to increase in the future, makes the resolution of this question an urgent matter. If causation is proven, enhancements of policy intended to reduce human exposure to environmental stressors and pollution could reduce the burden of schizophrenia and possibly other mental illnesses.     

NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein

Membrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV types-1 and -2) is mediated by Gag’s N-terminally myristylated matrix (MA) domain and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P₂]. To determine if other lentiviruses employ a similar membrane targeting mechanism, we initiated studies of the feline immunodeficiency virus (FIV), a widespread feline pathogen with potential utility for development of human therapeutics. Bacterial co-translational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMA^Q5A/G6S). These substitutions did not affect virus assembly or release from transfected cells. NMR studies revealed that the myristyl group is buried within a hydrophobic pocket in a manner that is structurally similar to that observed for the myristylated HIV-1 protein. Comparisons with a recent crystal structure of the unmyristylated FIV protein [myr(-)MA] indicate that only small changes in helix orientation are required to accommodate the sequestered myr group. Depletion of PI(4,5)P₂ from the plasma membrane of FIV-infected CRFK cells inhibited production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5)P₂ cellular signaling system to direct intracellular Gag trafficking during virus assembly.     

Myocarditis in Patients With Antisynthetase Syndrome: Prevalence,Presentation, and Outcomes

Antisynthetase syndrome (aSS) corresponds to an overlapping inflammatory myopathy identified by various myositis-specific autoantibodies (directed against tRNA-synthetases). Myocardial involvement in this condition is poorly described.From a registry of 352 aSS patients, 12 cases of myocarditis were retrospectively identified on the basis of an unexplained increase in troponin T/I levels associated with either suggestive cardiac magnetic resonance imaging (MRI) findings, nonsignificant coronary artery abnormalities or positive endomyocardial biopsy.The prevalence of myocarditis in aSS is 3.4% and was not linked to any autoantibody specificity: anti-Jo1 (n = 8), anti-PL7 (n = 3), and anti-PL12 (n = 1). Myocarditis was a part of the first aSS manifestations in 42% of the cases and was asymptomatic (n = 2) or revealed by an acute (n = 4) or a subacute (n = 6) cardiac failure. It should be noted that myocarditis was always associated with an active myositis. When performed (n = 11), cardiac MRI revealed a late hypersignal in the T1-images in 73% of the cases (n = 8). Half of the patients required intensive care. Ten patients (83%) received dedicated cardiotropic drugs. Steroids and at least 1 immunosuppressive drug were given in all cases. After a median follow-up of 11 months (range 0–84) 9 (75%) patients recovered whereas 3 (25%) developed a chronic cardiac insufficiency. No patient died.The prevalence of myocarditis in aSS is similar to that of other inflammatory myopathies. Although the prognosis is relatively good, myocarditis is a severe condition and should be carefully considered as a possible manifestation in active aSS patients.     

Rigid spine syndrome associated with sensory‐motor axonal neuropathy resembling Charcot–Marie‐Tooth disease is characteristic of Bcl‐2‐associated athanogene‐3 gene mutations even without cardiac involvement

Introduction: Bcl‐2‐associated athanogene‐3 (BAG3) mutations have been described in rare cases of rapidly progressive myofibrillar myopathies. Symptoms begin in the first decade with axial involvement and contractures and are associated with cardiac and respiratory impairment in the second decade. Axonal neuropathy has been documented but usually not as a key clinical feature. Methods: We report a 24‐year‐old woman with severe rigid spine syndrome and sensory‐motor neuropathy resembling Charcot–Marie–Tooth disease (CMT). Results: Muscle MRI showed severe fat infiltration without any specific pattern. Deltoid muscle biopsy showed neurogenic changes and discrete myofibrillar abnormalities. Electrocardiogram and transthoracic echocardiography results were normal. Genetic analysis of a panel of 45 CMT genes showed no mutation. BAG3 gene screening identified the previously reported c.626C>T, pPro209Leu, mutation. Discussion: This case indicates that rigid spine syndrome and sensory‐motor axonal neuropathy are key clinical features of BAG3 mutations that should be considered even without cardiac involvement. Muscle Nerve, 57 : 330–334, 2018     

Reciprocal Influences of HIV and Cannabinoids on the Brain and Cognitive Function

Globally, cannabis is the most commonly used illicit drug, with disproportionately high use among persons with HIV. Despite advances in HIV care, nearly half of persons living with HIV continue to experience neurocognitive deficits or impairments that may have negative impacts on their daily function. Chronic cannabis use may play a role in the development or exacerbation of these impairments. Here we present a review summarizing existing research detailing the effect of cannabis use associated with the neuropathogenesis of HIV. We examine evidence for possible additive or synergistic effects of HIV infection and cannabis use on neuroHIV in both the preclinical and adult human literatures, including in vitro studies, animal models, clinical neuroimaging research, and studies examining the cognitive effects of cannabis. We discuss the limitations of existing research, including methodological challenges involved with clinical research with human subjects. We identify gaps in the field and propose critical research questions to advance our understanding of how cannabis use affects neuroHIV.

Graphical Abstract

     

Letter to the Editor: Radiofrequency Ablation for Benign Thyroid Nodules: 1-Year Follow-Up in 184 Patients

World Journal of Surgery -