The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed ...to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy.
Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide.
An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3–4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long-term results were achieved in patients who received stem-cell transplantation after bortezomib induction.
Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival.
Overviews the use of of granulocyte colony-stimulating factors (G-CSF), and in particular pegfilgrastim and lipegfilgrastim, in reducing the incidence of severe neutropenia and febrile neutropenia ...(FN), both frequent and potentially fatal toxicities of myelosuppressive anticancer treatments, in patients with cancer receiving chemotherapy. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Volcanic‐intrusive complexes often formed along lateral slab edges as a consequence of subduction‐induced mantle flow. We investigate this process in the southern Tyrrhenian Sea by integrating ...multibeam bathymetry, seismic‐reflection data, regional magnetic anomalies data, and seismological data. The interpretation of the data highlights the presence of magmatic intrusions that locally reach the seafloor forming volcanic edifices. Chimneys, lava flows, and laccoliths are observed beneath and surrounding the volcanoes. The emplacement and cooling of the magma occurred during the Brunhes Chron. The volcanoes are not active even if the hydrothermal activity occurs. The volcanic‐intrusive complex can be subdivided in a western domain (Diamante and Enotrio seamounts) where strike‐slip transpressional faults deform the volcanic edifices and an eastern domain (Ovidio volcanic seamounts) characterized by flat‐topped volcanic edifices. The flat‐topped morphology is the result of the interplay between volcanism, erosion, sedimentation, and sea‐level change. The Ovidio volcanic seamounts formed in an area that experienced at least 60 m of subsidence. Magnetic signatures over the northern side of the Ovidio and Diamante seamounts highlight the presence of a deep‐rooted, magnetized feeding system remnant. Volcanic edifices extend above a magma feeding system, characterized by low Vp/Vs ratios. The Diamante‐Enotrio‐Ovidio volcanic‐intrusive complex formed as a consequence of the ascent of subduction‐induced mantle flow originated in the northern‐western edge of the retreating Ionian slab. We speculate that the magma ascent was controlled by a strike‐slip deformation belt, which accommodated the bulk of the shear strain resulting from the formation of a roughly E‐W trending, Subduction‐Transform Edges Propagator fault.
Key Points
An unknown volcanic‐intrusive complex is identified in an area located about 15 km off the Tyrrhenian coast of northern Calabria
The volcanic edifices formed in correspondence of a shallower crustal volume characterized by low Vp/Vs ratios
The volcanic‐intrusive complex is originated by the decompression melting of mantle material at the northern edge of the Ionian slab
In the Tyrrhenian back‐arc basin, the Ventotene Volcanic Ridge (VR) represents a NW‐SE‐oriented morphological high, located 25 km north of Ventotene Island in the Eastern Pontine Islands. It is ...considered part of an alignment of volcanic edifices developed in the central‐eastern Tyrrhenian Sea, from the western Pontine Islands (WPI) to the Campanian Volcanic Region. The samples dredged along the VR are basalts to trachybasalts belonging to the transitional (TR) rock‐series, with a 40Ar‐39Ar age of 2.760 ± 0.039 Ma. Petrological and geochronological data link the VR basalts to the TR peralkaline rhyolites cropping out at the WPI (∼1.6‐1.1 Ma); here, during a time span of ∼4.5‐1.0 Ma highly differentiated products of high‐potassium calc‐alkaline (HKCA, ∼4.5‐2.9 Ma) and K‐alkaline (KA, ∼1 Ma) series were also erupted. Notably, the parental melts of the three rock‐series were recognized in the continental slope close to the WPI (TR, HKCA) and eastward, namely in eastern Pontine Islands (KA), at the VR (TR), and in the Campanian Plain (HKCA). All the parental melts show typical orogenic geochemical signatures being originated from a similar heterogeneous suprasubduction mantle source, without the involvement of anorogenic sources. Tectonically, the faults bordering the VR, associated to the Pliocene E‐W directed rifting stage of the Tyrrhenian back‐arc basin were characterized by a more intense activity during the time span ∼5.0‐2.0 Ma (the emplacement time of HKCA and TR series), while KA products are related to a later stage of extension deformation (<∼2.0 Ma) when the extensional direction changed to NW‐SE and the VR fault activity decreased.
Key Points
Under‐investigated seafloor sectors controlled by complex geodynamic processes
The Ventotene Volcanic Ridge emplacement in a context of extensional deformations related to the opening of the Tyrrhenian back‐arc basin
Coexistence in space and time of high‐K calc‐alkaline, transitional and K‐alkaline rock‐series sharing orogenic‐type signatures
The burden perceived by caregivers of patients with dementia is a fundamental prognostic aspect in the history of the disease. The aim of this study was to demonstrate the internal consistency of the ...Caregiver Burden Inventory (CBI), a scale used to quantify burdens in different aspects of a caregiver's life, and the influence of patients' and caregivers' characteristics on its different dimensions.
In this cross-sectional study, 419 demented patients and their caregivers were evaluated in 16 geriatric centers in Italy. Cognitive status and behavioral disturbances were assessed by the Mini Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI), respectively. Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were also evaluated. Comorbidity was assessed by the Cumulative Illness Rating Scale (CIRS). The severity of dementia was evaluated by the Clinical Dementia Rating (CDR) score. Caregiver distress due to the behavioral problems of the patient was assessed by the Neuropsychiatric Inventory-Distress, a subscale of the NPI which evaluates stress caused by each behavioral disturbance of the patient, and by the Brief Symptom Inventory which evaluates anxiety and depression. Burden was evaluated by the CBI.
The CBI showed very high internal consistency (Cronbach's alpha value > 0.80). Factor analysis showed that the items clustered into four dimensions, and not five as originally proposed. Multiple regression analysis revealed that patients' behavioral disturbances and disability were the major predictors of the time-dependent burden; the psychophysical burden was explained mainly by caregiver anxiety and depression.
The CBI proved to be an effective multidimensional tool for evaluating the impact of burden on many aspects of caregivers' lives.
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•The genus Riggia Szidat, 1948 includes five species, all parasites of freshwater fish distributed in South America.•The new species has developed eyes and a large size.•Riggia ...puyensis sp. n. was found in C. breve and C. microps from the Puyo and Bobonaza rivers in Ecuador.•The prevalence of infection is 1.9% in C. breve, intensity 1 and 2.2% in C. microps, intensity 1.
A new isopod was found parasitizing Chaetostoma breve and Chaetostoma microps from the Puyo and Bobonaza rivers. The parasite found belongs to the Cymothoidae family and could be located within the genus Riggia instead of Artystone by the presence of abdominal plates fused with the telson. The specimens found represent a new species, Riggia puyensis n. sp., and could be distinguished from Riggia cryptocularis by the presence of developed eyes. The main difference of the new specie from Riggia nana and Riggia brasiliensis is the size, bigger compared with the first and smaller compared with the last species. Riggia acuticaudata have the maxilliped with simple setae, the palp without spination, and maxillule with five spines (two terminal and three subterminal) instead in R. puyensis n. sp. the maxilliped have plumose setae, the palp have spination (with one apical spine, two setae on middle article and one in the basal article) and the maxillule have five spines: two terminal, two subterminal and other spine lower to the others. Riggia paranaensis have similar size, same number of segments in the antena, and similar maxilla to R. puyensis n. sp., but the antennule in the new specie have seven segments instead 6 in R. paranaensis, the antennule and antenna present spines not mentioned in R. paranaensis. Besides, the relative position of the mandible in R. puyensis n. sp. is different compared with R. paranaensis, the maxillule have the same number of spines but with different disposition, and the maxilliped have simple setae in R. paranaensis but those are plumose in the new specie.
In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to ...chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the very-late-activation-4 integrin, a well-known key regulator of microenviromental interactions, and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P<0.0001), occurring also outside the trisomy 12 CLL subset. Using both the MEC-1 CLL-like cells stably transfected with the NOTCH1 intracellular domain and primary CLL cells bearing a mutated or wild-type NOTCH1 gene configuration, we provide evidence that triggering of the NOTCH1 pathway resulted in a positive CD49d expression regulation, which was driven by a NOTCH1-dependent activation of nuclear factot-κB (NF-κB). Consistently, pharmacological inhibition of the NOTCH1 and/or of the NF-κB pathways resulted in impaired NF-κB nuclear translocation with consequent down-modulation of CD49d expression. Altogether, our data link for the first time NOTCH1 mutations to CD49d expression regulation through the involvement of the NF-κB pathway in CLL.
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