Lenalidomide, Melphalan, and Prednisone Association Is an Effective Salvage Therapy in Relapsed Plasma Cell Leukaemia

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least 2 × 109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005). Thalidomide, bortezomib and lenalidomide (Revlimid) have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006). In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007), although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008). We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy

Linear-in-Complexity Computational Strategies for Modeling and Dosimetry at TeraHertz

This work presents a fast direct solver strategy allowing full-wave modeling and dosimetry at terahertz (THz) frequencies. The novel scheme leverages a preconditioned combined field integral equation together with a regularizer for its elliptic spectrum to enable its compression into a non-hierarchical skeleton, invertible in quasi-linear complexity. Numerical results will show the effectiveness of the new scheme in a realistic skin modeling scenario

Linear-in-Complexity Computational Strategies for Modeling and Dosimetry at TeraHertz

This work presents a fast direct solver strategy allowing full-wave modeling and dosimetry at terahertz (THz) frequencies. The novel scheme leverages a preconditioned combined field integral equation together with a regularizer for its elliptic spectrum to enable its compression into a non-hierarchical skeleton, invertible in quasi-linear complexity. Numerical results will show the effectiveness of the new scheme in a realistic skin modeling scenario

Role of In Vitro Stimulation with Lipopolysaccharide on T-Cell Activation in HIV-Infected Antiretroviral-Treated Patients

We investigated the effect of LPS in vitro stimulation on T-cell activation in HIV-infected patients with different CD4+ recovery on HAART. PBMCs from 30 HIV-positive, HAART-treated, aviremic individuals with different CD4+ reconstitution (Low Responders: CD4+ < 350/μL; Intermediate Responders: CD4+ 350–599/μL; High Responders: CD4+ ≥ 600/μL) were cultured with LPS and the proportion of HLA-DR/CD38- and Ki67-expressing CD4+/CD8+ T-cells was measured (flow cytometry). Upon LPS stimulation, significantly higher CD4+ and CD8+HLA-DR+ cells were shown in LR and IR versus HIV-negative controls. While no differences in the proportion of LPS-stimulated CD4+CD38+ cells were recorded amongst HIV-positive subgroups, CD8+CD38+ cells were more elevated in patients with lower CD4+ recovery on HAART (i.e., LR and IR). Upon in vitro LPS stimulation, HLA-DR and CD38 expression on T-cells are differentially regulated. While HLA-DR induction reflects impaired CD4+ reconstitution on HAART, cell-surface CD38 expression is increased only on CD8+ T-cells, allowing to speculate that the sole induction of CD38 on CD4+ cells may not be sufficient to depict LPS-driven immune activation in HIV

Congenital myopathy with hanging big toe due to homozygous myopalladin (MYPN) mutation

Background: Myopalladin (MYPN) is a component of the sarcomere that tethers nebulin in skeletal muscle and nebulette in cardiac muscle to alpha-actinin at the Z lines. Autosomal dominant MYPN mutations cause hypertrophic, dilated, or restrictive cardiomyopathy. Autosomal recessive MYPN mutations have been reported in only six families showing a mildly progressive nemaline or cap myopathy with cardiomyopathy in some patients. Case presentation: A consanguineous family with congenital to adult-onset muscle weakness and hanging big toe was reported. Muscle biopsy showed minimal changes with internal nuclei, type 1 fiber predominance, and ultrastructural defects of Z line. Muscle CT imaging showed marked hypodensity of the sartorius bilaterally and MRI scattered abnormal high-intensity areas in the internal tongue muscle and in the posterior cervical muscles. Cardiac involvement was demonstrated by magnetic resonance imaging and late gadolinium enhancement. Whole exome sequencing analysis identified a homozygous loss of function single nucleotide deletion in the exon 11 of the MYPN gene in two siblings. Full-length MYPN protein was undetectable on immunoblotting, and on immunofluorescence, its localization at the Z line was missed. Conclusions: This report extends the phenotypic spectrum of recessive MYPN-related myopathies showing: (1) the two patients had hanging big toe and the oldest one developed spine and hand contractures, none of these signs observed in the previously reported patients, (2) specific ultrastructural changes consisting in Z line fragmentation, but (3) no nemaline or caps on muscle pathology

Current models of care for the management of HIV patients with comorbidities in England: a survey

Introduction: The number of people aged ]50 living with HIV in the UK is rapidly increasing. Effective treatment means HIV is usually well controlled; however, there has been an increase in individuals experiencing comorbid conditions associated with ‘‘normal’’ ageing. This aim of this study was to find out what models of care are currently in place for the management of patients with comorbidities. Materials and methods: A link to an online questionnaire was sent via the British HIV Association (BHIVA) Audit Committee to one HIV clinician in each HIV unit in England. Results: Forty-four units responded. Only 11 units (25%) provided specialized clinics for the management of comorbidities. These included: 1) Specialist clinics for the management of a non-infectious comorbidity (any age) e.g. a liver or renal clinic (n10). These clinics utilized in-person appointments (n3), or a combination of virtual and in-person appointments (n7). They were managed by an HIV clinician and non-HIV clinician together (n8), HIV clinician with an interest in the specialist area (n4) or specialist with an interest in HIV (n4). 2) Services for HIV patients with multiple comorbidities (any age) (n2). 3) Dedicated clinics for older people (n5) with eligibility determined by age (]50 years) or the presence of a comorbidity. Additionally, two HIV units employed a GP on site and two had set up a locally enhanced service providing enhanced primary care for HIV-positive patients. Six HIV units ran nurse-led clinics for patients with comorbid conditions. Co-ordination of care for patients with comorbid conditions was conducted by an HIV specialist doctor (n27), the patient’s GP (n18), HIV specialist nurse (n11) or the patient themselves (n9). Eleven clinics reported using case management for patients with multiple comorbid conditions. Self-management support (e.g. nurse-led or as part of an expert patient programme) for patients with comorbid conditions was provided at 18 HIV units. Conclusions: Only a quarter of the clinics surveyed had set up clinics for the management of comorbidities in people living with HIV. While a variety of different approaches were used, services were usually focused on the management of one comorbidity, and few provided services for multiple comorbidities. This is an increasing priority in the context of an ageing population. P162 Th

Long-Term Follow-Up of Testicular Microlithiasis in Children and Adolescents: Multicenter Prospective Cohort Study of the Italian Society of Pediatric Urology.

Introduction Testicular microlithiasis (TM), characterized by the presence of intratubular calcifications in a single or both the gonads, is an uncommon entity with unknown etiology and outcome in pediatric and adolescent age. In this study, the results of a multicenter long-term survey are presented. Materials and Methods From 11 units of pediatric urology/surgery, patients with TM were identified and yearly, followed up in a 7-year period, adopting a specific database. The recorded items were: age at diagnosis, presenting symptoms/associated abnormalities, ultrasonographic finding, surgery and histology at biopsy, if performed. Results Out of 85 patients, 81 were evaluated yearly (4 patients lost to follow-up). TM was bilateral in 66.6% of the patients. Associate genital abnormalities were present in 90%, more frequently undescended/retractile testis (23.4%) and varicocele (22.2%). TM remained unchanged at 4.7 years follow-up in 77 patients (93.8%) and was reduced in 4 patients after 1 to 5 years of inguinoscrotal surgery. Orchiectomy was performed in three patients (3.7%), one for severe testicular hypoplasia and two for seminoma (2.5%), respectively, concurrent and metachronous to diagnosis of TM. Tumorectomy with parenchymal sparing surgery was performed in a teratoma associated with TM. Conclusion TM is a controversial entity, often associated with several inguinogenital features, which rarely can recover. Testicular malignancy, although present in TM, has not proven definitively associated to microliths. Proper counseling, yearly ultrasound, and self-examination are long-term recommended

Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study

BACKGROUND: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. METHODS: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. RESULTS: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. CONCLUSIONS: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition

Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy

Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient's functional autonomy negatively affects the patient's quality of life and requires increasing involvement of relatives in the patient's daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients' and relatives' socio-demographic variables, patients' clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives