Search

BackgroundThymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone.MethodsWe compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period.ResultsA total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P

Fever of unknown origin (FUO) can be an unusual first clinical manifestation of pheochromocytoma. Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, several cases of IL-6-producing pheochromocytomas have been reported. This report describes a 45-year-old woman with pheochromocytoma who was admitted with FUO, normal blood pressure levels, microcytic and hypochromic anemia, thrombocytosis, hyperfibrinogenemia, hypoalbuminemia, and normal levels of urine and plasma metanephrines. After adrenalectomy, fever and all inflammatory findings disappeared.

Fever of unknown origin (FUO) can be an unusual first clinical manifestation of pheochromocytoma. Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, several cases of IL-6-producing pheochromocytomas have been reported. This report describes a 45-year-old woman with pheochromocytoma who was admitted with FUO, normal blood pressure levels, microcytic and hypochromic anemia, thrombocytosis, hyperfibrinogenemia, hypoalbuminemia, and normal levels of urine and plasma metanephrines. After adrenalectomy, fever and all inflammatory findings disappeared.

To evaluate the efficacy and the safety of repeated botulinum toxin type A (BT-A) injections in patients with severe acquired brain injury (ABI) and to gain a better knowledge of possible clinical or demographic characteristics associated with a better rehabilitation outcome.Prospective study with a 1-year follow-up period.Twenty-one patients with spasticity due to severe ABI and no further improving with rehabilitation treatment and oral anti-spastic drugs.Repeated BT-A injections associated to a rehabilitation programme.Barthel Index (BI), Modified Ashworth Score (MAS) and VAS score for pain subjective perception were recorded.At the end of the follow-up study, MAS, BI and VAS significantly improved. Despite the number of BT-A injections, a shorter interval between severe ABI onset and first BT-A treatment correlated to a better BI improvement. None of the patients experienced adverse events attributable to BT-A.BT-A was effective and safe in the treatment of spasticity in severe ABI patients, with a better functional outcome in those subjects treated earlier after spasticity onset. The lack of correlation between clinical outcome and number of injections suggests, in addition to a direct inhibition at the neuromuscular junction, a more distant BT-A long-term effect.

Background Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes in patients with S. aureus bacteremia. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies. To further elucidate the inflammatory correlates of poor clinical outcomes in patients with S. aureus bacteremia, we evaluated the association between a panel of blood proteins at initial presentation of bacteremia and disease severity outcomes. Methods We conducted an observational study (n = 32) to evaluate the prognostic value of circulating protein biomarkers for mortality and persistent bacteremia in patients with S. aureus bloodstream infections. A case–control study of 124 patients with complicated confirmed S. aureus bloodstream infections was used to validate our findings in the observational study. Results We identified 13 candidate proteins that were correlated with mortality and persistent bacteremia by multiple comparisons. Further statistical modeling identified IL-8 and CCL2 as the strongest individual predictors of mortality, with the combination of these biomarkers having the best power to classify fatal outcome. Baseline IL-17A levels were elevated in patients with persistent bacteremia, endovascular and metastatic tissue infections. Conclusion The results demonstrate the potential utility of selected biomarkers to distinguish patients with the highest risk for treatment failure and bacteremia-related complications, providing a valuable tool for clinicians in the management of S. aureus bacteremia. Additionally, these biomarkers could identify patients with the greatest potential to benefit from novel therapies in clinical trials. Disclosures All authors: No reported disclosures.

Staphylococcus aureus bacteremia is a leading cause of morbidity and mortality and yet tools to assess severity of infection and response to treatment are still lacking. This study aimed to establish a link between bacterial DNA quantified in blood and clinical severity in bacteremic patients. We developed a workflow coupled with a highly sensitive quantitative PCR method to quantify S. aureus bacterial DNA. This assay was used to measure whole blood S. aureus DNA (SA-DNA) and plasma-derived S. aureus cell-free DNA (SA-cfDNA) in a set of longitudinal samples from 45 patients with confirmed S. aureus bacteremia. SA-DNA was detectable at baseline and declined following treatment with antibiotics. Notably, baseline SA-DNA correlated with disease severity and levels were sustained in cases of complicated infections versus with non-complicated infections. In addition, plasma-derived S. aureus cell-free DNA could be readily detected in bacteremic patients and showed concordance with whole blood SA-DNA. High levels of SA-DNA and SA-cfDNA were associated with metrics of clinical severity, including longer durations of treatment, elevated white blood cell count, and positive blood cultures. Taken together, these data suggest that circulating bacterial DNA is more reflective of whole body bacterial load than blood culture and may aid in monitoring clearance of tissue reservoirs of infection during antibiotic therapy.

Mitoxantrone (MTX) is an antineoplastic agent approved for treatment of secondary progressive and rapidly worsening relapsing-remitting multiple sclerosis (MS). We designed a longitudinal open-label prospective study to evaluate the efficacy and toxicity of MTX over a 2-year treatment period with a further 3-year follow-up. Fifty consecutive MS patients were included and received MTX intravenously (8 mg/m(2) every 2 months for a total of 12 infusions). Efficacy was assessed clinically and by brain MRI performed before MTX therapy, at the end of treatment and at the end of each year of follow-up. Forty-nine patients completed the 5-year study, 44 (89.8%) completed the MTX course, five (10.2%) interrupted the treatment because of side effects. Fifteen (30.6%) patients showed Expanded Disability Status Scale (EDSS) progression on treatment and nine (18.4%) during follow-up. Seventeen (34.7%) patients had enhancing lesions at baseline, nine (18.4%) at the end of treatment, but none at the end of follow-up. In conclusion, we observed EDSS progression in about 1/3 of the patients during the treatment period and in 1/5 during the further 3-year follow-up period. This evidence suggests a delayed beneficial effect after MTX treatment is completed with only a minority of patients showing disability progression once the drug was suspended.

To assess factors related to residual dizziness (RD) in patients who underwent successful canalith repositioning procedures (CRPs) for benign paroxysmal positional vertigo (BPPV).Prospective cohort study.Academic center.Ninety-seven consecutive patients with BPPV of the posterior semicircular canal were initially enrolled. Diagnosis was assessed according to clinical history and bedside evaluation. All patients were treated with CRPs until nystagmus disappeared. Three days after the successful treatment, presence of RD was investigated. If RD was present, patients were monitored every 3 days until the symptoms disappeared. Subjects who required ≥4 CRPs or who failed to meet the follow-up visit were excluded. The Dizziness Handicap Inventory (DHI) was obtained from patients at the time of diagnosis and at every subsequent visit.At the end of selection, 86 patients were included; 33 (38.36%) reported RD after successful treatment. A significant difference in the incidence of RD was observed in consideration of the age of the subjects (P = .0003) and the DHI score at the time of diagnosis (P.001). A logistic regression analysis showed that the probability of RD occurrence increased with the increase of the emotional subdomain score of the DHI questionnaire.RD is a common self-limited disorder, more frequent in the elderly, which may occur after the physical treatment for BPPV. The DHI score at the time of BPPV diagnosis represents a useful tool to quantify the impact of this vestibular disorder on the quality of life and to estimate the risk of RD after CRPs.

©2015. American Geophysical Union. All Rights Reserved. The Jabal Qusaybah anticline is located at the western end of the Salakh Arch, a major salient in the foothills of the Oman Mountains. We performed a structural and petrographical-geochemical study of vein sets and fault zones associated with the development of this anticline. Our data illustrate a complex deformation pattern both in space and time, characterized by the unusual presence of widespread NE-SW left-lateral strike-slip fault zones trending oblique to the E-W fold axial strike, and of abundant and well-developed N-S fold-perpendicular extensional fault zones associated with axial bulging and dilation, well developed in the central region of the anticlinal crest. We propose a three-stage evolution for the Jabal Qusaybah anticline, starting with prefolding jointing in the foreland of the late Cretaceous Oman Mountains, and followed by development of extensional faulting in Campanian times. Positive inversion of the Qusaybah Fault, possibly in Miocene times, caused development of a layer-parallel shortening fabric and amplification the Jabal Qusaybah Anticline, in concomitance with the activity of NE-SW left-lateral strike-slip fault zones that triggered N-S, fold-perpendicular extensional faulting, particularly in the axial bump of the anticline. The final evolutionary stage was characterized by further amplification of the axial bump and related N-S extensional fracturing and by uplift and exhumation. To explain the complex noncylindrical fault-fold interactions in the study anticline, we tentatively propose that they were triggered by near foredeep-parallel tapering of the sedimentary/tectonic overburden of the Ara evaporites. ispartof: Tectonics vol:34 issue:3 pages:488-509 status: published

The objective of this study was to establish whether the time interval of 3 months is sufficient to detect whole-brain atrophy changes in patients with relapsing-remitting (RR) multiple sclerosis (MS). Another aim was to assess the value of monthly gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and of different Gd-enhancement patterns as predictors of brain atrophy. Thirty patients with RRMS (mean disease duration 4.9 years, mean age 34.4 years and mean Expanded Disability Status Scale [EDSS] 1.4) were assessed at baseline and monthly for a period of 3 months with clinical and MRI examinations. Calculations of baseline and monthly absolute and percent changes of MRI measures have been obtained using two semiautomated (Buffalo and Trieste) and one automated (SPM99) segmentation method. Changes of brain parenchymal fraction (BPF) were investigated according to Gd-enhancement patterns. Mean absolute and percent changes of BPF did not significantly differ at any time point in the study for any of the three methods. There was slight but not significant decrease of BPF from baseline to month 3: -0.0004 (0.05%), p=0.093 for Trieste; -0.0006 (0.07%), p=0.078 for Buffalo; and -0.0006 (0.08%), p=0.081 for SPM99 method. In ring-enhancement positive patients, there was a significant difference between baseline and month 3 changes of BPF, EDSS, and number of relapses. Over the study period, we did not demonstrate differences between changes of BPF according to the presence of Gd enhancement. Longitudinally, multiple regression analysis demonstrated that the only clinical or MRI parameter that predicted BPF decrease was the mean absolute change of ring-enhancing lesion load (R=0.62, p=0.003). The noteworthy findings of this study are (1) the observation that a significant brain atrophy progression cannot be detected over a 3-month period in RRMS; (2) the demonstration that the ring-enhancement pattern may contribute to more severe brain tissue loss in the short term; and (3) the lack of relationship between the presence and duration of Gd-enhancement activity and brain volume changes in the short term.

L’evoluzione a lungo termine dei prismi di accrezione è caratterizzata da interazioni complesse tra tettonica, forze di volume gravitazionali, e processi superficiali. E' influenzata da cambiamenti delle condizioni geodinamiche a grande scala, della configurazione geometrica dei margini di placca convergenti, delle proprietà meccaniche dei materiali coinvolti nella deformazione, e delle condizioni climatiche. In questo contesto, deformazioni contrazionali ed estensionali possono coesistere in porzioni diverse di uno stesso prisma o interessare ciclicamente la stessa area. Pulsi estensionali sviluppati durante la storia orogenica contrazionale di prismi di accrezione, in particolare, sono stati documentati in numerosi contesti e previsti dai modelli geo-meccanici. Le strutture deformative associate a tali pulsi estensionali contribuiscono all’evoluzione a scala regionale degli orogeni, influenzando la circolazione dei fluidi nella crosta superiore e modificando le proprietà meccaniche dei prismi di accrezione. I pulsi estensionali sin-contrazionali hanno perciò una notevole importanza scientifica ed economica. Nell’ambito di questa Tesi di Dottorato vengono investigate strutture deformative sviluppate durante la storia orogenica contrazionale di due prismi di accrezione: le Montagne dell'Oman e l'Appennino Settentrionale. Le attività di ricerca sono caratterizzate da un approccio multidisciplinare; l'evoluzione paleoidrologica delle strutture e i loro effetti sulla circolazione dei fluidi nella crosta superiore sono investigati con particolare attenzione. Il caso di studio di Jabal Qusaybah (Oman) offre la possibilità di studiare una struttura anticlinale sviluppata a livelli strutturali superficiali, al fronte del cuneo tettonico. Nonostante la sua posizione strutturale, l'evoluzione della piega è caratterizzata da interazioni tra deformazioni contrazionali, estensionali, e trascorrenti. I casi di studio nell'Appennino Settentrionale comprendono strutture estensionali chilometriche associate all'evoluzione di interi settori del prisma. Nel caso della Val di Lima, un sistema di faglie estensionali a basso angolo è univocamente inquadrato in un contesto contrazionale, essendo coinvolto in un piegamento successivo associato a sovrascorrimenti fuori sequenza. Nel caso di studio di Tellaro, il sistema di faglie estensionali taglia l'anticlinale di Punta Bianca, essendo associato all'assottigliamento tardo-orogenico del settore interno del prisma Appenninico. Il caso di Studio della Lunigiana include entrambi gli scenari precedenti. The long term evolution of orogenic wedges is characterized by complex interactions between tectonics, gravitational body forces, and surface processes. It is influenced by changes of large-scale geodynamic conditions, geometrical configuration of plate margins, mechanical properties of the materials involved in the deformation, and climate conditions. Within this framework, contractional and extensional deformations may coexist in different sectors of a thrust wedge or cyclically affect the same area. In particular, extensional pulses developed during the contractional orogenic history of thrust wedges have been documented in various contexts and predicted by geo-mechanical models. Deformation structures associated with such extensional events contribute to the regional-scale evolution of orogens, influencing fluid circulation within the upper crust and modifying mechanical properties of thrust wedges. Therefore, sin-contractional extension have remarkable scientific and economic significance. This Ph.D. thesis investigates extensional deformation structures developed during the orogenic contractional history of two thrust wedges: the Oman Mountains and the Northern Apennines. Research is done with a multidisciplinary approach, and close attention is paid to the palaehydrological evolution of the deformation structures and their influence on fluid circulation through the upper crust. The case study of the Jabal Qusaybah (Oman) allows investigating on an anticline developed at shallow structural levels, at the front of a thrust wedge. Despite this structural position, the evolution of the fold is characterized by interactions between contractional, extensional, and left-lateral strike-slip deformations. The Northern Apennines case studies involve km-scale extensional structures associated with the evolution of entire wedge sectors. In the Val di Lima case, a low-angle extensional fault system is unequivocally framed within the contractional orogenic history, being affected by superimposed folding due to out-of-sequence thrusting. In the Tellaro case, the extensional fault system cuts through the Punta Bianca anticline, being likely associated with the late orogenic thinning of the internal sector of the Northern Apennines. The Lunigiana case includes both the previous scenarios.

A low-angle extensional fault system affecting the non metamorphic rocks of the carbonate dominated Tuscan succession is exposed in the Lima valley (Northern Apennines, Italy). This fault system affects the right-side-up limb of a kilometric-scale recumbent isoclinal anticline and is, in turn, affected by superimposed folding and late-tectonic high-angle extensional faulting. The architecture of the low-angle fault system has been investigated through detailed structural mapping and damage zone characterization. Pressure-depth conditions and paleofluid evolution of the fault system have been studied through microstructural, mineralogical, petrographic, fluid inclusion and stable isotope analyses. Our results show that the low-angle fault system was active during exhumation of the Tuscan succession at about 180°C and 5 km depth, with the involvement of low-salinity fluids. Within this temperature - depth framework, the fault zone architecture shows important differences related to the different lithologies involved in the fault system and to the role played by the fluids during deformation. In places, footwall overpressuring influenced active deformation mechanisms and favored shear strain localization. Our observations indicate that extensional structures affected the central sector of the Northern Apennines thrust wedge during the orogenic contractional history, modifying the fluid circulation through the upper crust and influencing its mechanical behavior.

This multi-center Italian prospective observational study reports the 4 months follow-up data of 87 patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) shifted from intravenous to subcutaneous immunoglobulin treatment. A therapeutic shift from intravenous to subcutaneous immunoglobulin was performed in 87 patients (66 CIDP; 21 MMN) affected by immune-mediated peripheral neuropathies with evidence of a sustained clinical response to intravenous immunoglobulin. Patients were evaluated by means of the Overall Neuropathy Limitation Scale, Medical Research Council Scale and Life Quality Index questionnaire, both at the time of therapeutic shift and after 4 months of subcutaneous immunoglobulin treatment. A sustained clinical efficacy was observed after the switch to subcutaneous immunoglobulin: the Overall Neuropathy Limitation Scale score improved in the group of 66 CIDP patients (P = 0.018), with only one subject reporting a worsening of 1 point, and remained stable in the group of 21 MMN patients (P = 0.841), with one subject reporting a worsening of two points. An improvement in the patient's perception of therapeutic setting was reported in both groups. This large multi-center study confirms the short-term clinical equivalence of subcutaneous versus intravenous immunoglobulin and a possible improvement in the patient's perception of therapeutic setting with the subcutaneous administration. However, further studies are required to extend the results to a longer observational period.

Deformation mechanisms, long-term kinematics and evolution of fold and thrust belts subjected to erosion are studied through 2D analogue experiments involving large convergence. First-order parameters tested include (1) decollements and/or plastic layers interbedded at different locations within analogue materials and (2) synconvergence surface erosion. Weak layers, depending on their location in the model, favour deformation partitioning characterized by the simultaneous development of underplating domains in the inner part of the wedge (basal accretion) and frontal accretion where the wedge grows forward. Interaction between tectonics and surface processes influences this behaviour. Development of antiformal thrust stacks controlled by underplating shows small- and large-scale cyclicity. Thin plastic layers induce folding processes, which are studied at wedge scale. Recumbent and overturned folds, with large inverted limbs, develop in a shear-induced asymmetric deformation regime via progressive unrolling of synclinal hinges. Surface erosion and underplating at depth induce further rotation (passive tilting) and horizontalization of fold limbs. Model results give insights to discuss the mechanisms responsible for the large-scale structures (i.e. antiformal nappe stacks, klippen and kilometre-scale recumbent fold–nappes) encountered in several mountain belts such as the Montagne Noire (French Massif Central), the Galicia Variscan belt (Spain) and the northern Apennines (Italy). Supplementary material: Raw data of the experiments are available at www.geolsoc.org.uk/SUP18658.

Objectives: To investigate whether clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) who required a reduction of administration frequency of interferon-beta (IFNB) were similar to those of patients who did not. Methods: We identified three subgroups of patients under treatment for 24 months with subcutaneous (sc) high-frequency IFNB-1a or -1b: those continuing to receive IFNB according to the drug label (recommended frequency group), those reducing the administration frequency of sc IFNB-1a or -1b (reduced frequency group), and those switched to once weekly intramuscular (im) IFNB (switched group). All patients were followed for further 24 months. The occurrence of relapse, MRI activity and disability worsening were considered as outcome measures. Results: We identified 308 patients, 201 in the recommended frequency group, 70 in the reduced frequency group, and 37 in the switched group. Patients in the reduced frequency group had increased risk for relapses (HR = 1.95, p < 0.001) and MRI activity (HR = 1.41, p < 0.001), while patients in the switched group had increased risk for relapses (HR = 1.67, p = 0.012), but not for MRI activity (HR = 1.26, p = 0.08) than those in the recommended frequency group. Predictors for disease activity re-start after the reduction of IFNB administration frequency were younger age, higher pre-IFNB relapse rate, and reducing sc IFNB frequency to twice weekly rather than switching to im IFNB-1a once weekly. Conclusion: Our findings discourage the reduction of sc IFNB administration frequency, especially in younger patients with a higher pre-IFNB relapse rate. However, switching to im IFNB-1a may be considered in some selected cases.

Context Luminal bleeding after pancreaticoduodenectomy can be present in various degrees of acuity in up to 30% of patients. Case report In this report, we describe a rare and uncommon cause of gastrointestinal bleeding after pancreaticoduodenectomy and review of the literature. Conclusions Multiple biliary procedures with common complications increase the difficulty making the correct diagnosis and therefore all possible etiologies of a complication must be evaluated., JOP. Journal of the Pancreas, Vol 13, N° 2 (2012): March - p. 124-251

There are other options open to patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are non-responders to conventional treatment, including immunosuppressive and immunomodulatory agents (IA). The aim of this study was to assess whether the use of IA is able to increase the number of responders.Clinical and electrophysiological data of patients with refractory CIDP, followed at 10 Italian centres, were collected, and the clinical outcome (Rankin Scale) and drug side effects (SE) for the different therapies were analysed.A total of 110 patients were included. These patients underwent 158 different therapeutic procedures with IA. Seventy-seven patients were treated with azathioprine, 18 rituximab, 13 cyclophosphamide, 12 mycophenolate mofetil, 12 cyclosporine, 12 methotrexate, 11 interferon-alpha and three interferon beta-1a. The percentage of patients who responded to azathioprine (27%) was comparable to the percentage of responders to other therapies, after the exclusion of interferon beta-1a that was not effective in any of the three patients treated. The percentage of SE ranges from 8% (methotrexate) to 50% (cyclosporine).One-fourth of patients, refractory to conventional treatment, showed an improvement in their disability with IA. Methotrexate had the lowest SE; cyclosporine was associated with severe SE and often led to drug discontinuation.

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case–control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).