Gabriele Di Comite - Academia.edu (original) (raw)

Papers by Gabriele Di Comite

Experimental Dermatology, Jun 5, 2023

Elsevier eBooks, 2011

Publisher Summary This chapter provides insight into the relevant clinical, pathogenetic, diagnos... more Publisher Summary This chapter provides insight into the relevant clinical, pathogenetic, diagnostic, and therapeutic aspects of the central nervous system (CNS) involvement in primary and secondary vasculitides. Vasculitides represent a group of highly heterogeneous disorders characterized by inflammation in the wall of blood vessels. Vasculitis, an immune-mediated mechanism, can occur as a primary process or can be secondary to an underlying condition, including infections, malignancies, connective tissue diseases, and drug use. The classification of vasculitides has been extremely challenging over the decades and several attempts have been made to classify them according to etiology, the clinical picture, or the underlying immunopathologic mechanism. In this regard, a major advance was achieved in 1990 when the American College of Rheumatology (ACR) published a set of classification criteria, grouping primary vasculitides according to the size of affected vessels. They identified three groups: small-vessel, medium-vessel, and large-vessel vasculitides. Overall, involvement of the CNS and peripheral nervous system (PNS) is common in primary systemic vasculitides. In contrast, such involvement is only occasionally observed in the setting of infectious diseases or malignancy or as a consequence of drug use. The pattern of PNS involvement in primary and secondary vasculitides is almost invariable, since it is related to occlusion of the vasa nervorum due to necrotizing small-vessel vasculitis. The ensuing picture is that of sensory axonal polyneuropathy or mononeuritis multiplex. The range of possible manifestations of CNS involvement is much wider, since several mechanisms can be implicated.

Journal of The European Academy of Dermatology and Venereology, Jan 7, 2020

Current word count: 4041 (Introduction to end of Discussion), excluding tables, figures, and refe... more Current word count: 4041 (Introduction to end of Discussion), excluding tables, figures, and references Number of tables: 3 Number of figures: 3 Submission version Funding: The development of review article was funded by Novartis Pharma AG

Journal of the American Academy of Dermatology, 2020

The Alday-Maldacena solution, relevant to the n = 4 gluon amplitude in N = 4 SYM at strong coupli... more The Alday-Maldacena solution, relevant to the n = 4 gluon amplitude in N = 4 SYM at strong coupling, was recently identified as a minimum of the regularized action in the moduli space of solutions of the AdS 5 σ-model equations of motion. Analogous solutions of the Nambu-Goto equations for the n = 4 case are presented and shown to form (modulo the reparametrization group) an equally large but different moduli space, with the Alday-Maldacena solution at the intersection of the σ-model and Nambu-Goto moduli spaces. We comment upon the possible form of the regularized action for n = 5. A function of moduli parameters z a is written, whose minimum reproduces the BDDK one-loop five-gluon amplitude. This function may thus be considered as some kind of Legendre transform of the BDDK formula and has its own value independently of the Alday-Maldacena approach.

Reumatismo, 2011

Objectives: Two evaluate the rate of different organs involvement in 50 patients with Wegener's G... more Objectives: Two evaluate the rate of different organs involvement in 50 patients with Wegener's Granulomatosis (GW), and to describe their clinical manifestations and their response to treatment. Methods: We evaluated 50 consecutive patients with GW, come to our attention from January 1987 to May 2003. 43 patients met the 1990 American College of Rheumatology (ACR) criteria for classification of GW; 7 patients the 1993 ELK criteria. Results: 82% of patients presented Ear/Nose/Throat (ENT) involvement, which is the most common site of inflammation. 22% of our patients had ENT-restricted disease; in 78% of cases disease extended to other organs. Lungs were involved in 72% of cases; kidney in 36%; eye in 24%; nervous system (NS) in 14% (central NS in 10% and peripheral NS in 4%); skin in 10%; heart in 8%; testis in 4%. Arthritis was present in 10% of patients. We discuss treatment of all patients and response to therapy of those 28 whose follow-up is available. Conclusions: Involvement of airways and kidney is by far the most common in GW, though potentially any other organ or system may be affected. The total rate of other organs involvement is 70%.

New England Journal of Medicine, 2007

Background Bisphosphonate therapy is the current standard of care for the prevention and treatmen... more Background Bisphosphonate therapy is the current standard of care for the prevention and treatment of glucocorticoid-induced osteoporosis. Studies of anabolic therapy in patients who are receiving long-term glucocorticoids and are at high risk for fracture are lacking. Methods In an 18-month randomized, double-blind, controlled trial, we compared teriparatide with alendronate in 428 women and men with osteoporosis (ages, 22 to 89 years) who had received glucocorticoids for at least 3 months (prednisone equivalent, 5 mg daily or more). A total of 214 patients received 20 μg of teriparatide once daily, and 214 received 10 mg of alendronate once daily. The primary outcome was the change in bone mineral density at the lumbar spine. Secondary outcomes included changes in bone mineral density at the total hip and in markers of bone turnover, the time to changes in bone mineral density, the incidence of fractures, and safety. Results At the last measurement, the mean (±SE) bone mineral density at the lumbar spine had increased more in the teriparatide group than in the alendronate group (7.2±0.7% vs. 3.4±0.7%, P<0.001). A significant difference between the groups was reached by 6 months (P<0.001). At 12 months, bone mineral density at the total hip had increased more in the teriparatide group. Fewer new vertebral fractures occurred in the teriparatide group than in the alendronate group (0.6% vs. 6.1%, P = 0.004); the incidence of nonvertebral fractures was similar in the two groups (5.6% vs. 3.7%, P = 0.36). Significantly more patients in the teriparatide group had at least one elevated measure of serum calcium. Conclusions Among patients with osteoporosis who were at high risk for fracture, bone mineral density increased more in patients receiving teriparatide than in those receiving alendronate. (ClinicalTrials.gov number, NCT00051558.

Neurology, 1997

MRI and CSF investigations revealed meningeal involvement in a 29-year-old patient with biopsy-co... more MRI and CSF investigations revealed meningeal involvement in a 29-year-old patient with biopsy-confirmed Wegener's granulomatosis. The intracranial manifestation of Wegener's granulomatosis was supported by the detection of pathologic circulating antineutrophil cytoplasm (c-ANCA) in the CSF. We monitored disease activity by c-ANCA measurement in the CSF. After repeated cycles of intrathecal administration of methotrexate and corticoids, progression of meningeal infiltration stopped, and CSF c-ANCA titers became negative.

Current Opinion in Neurology, 1988

Purpose of review: In the past decade, primary and secondary central nervous system (CNS) vasculi... more Purpose of review: In the past decade, primary and secondary central nervous system (CNS) vasculitides have been more commonly diagnosed and recognized than previously. With the increasing awareness of these disorders, it is crucial for the treating physician to ...

ESC Heart Failure, 2020

AimsIn May 2016, a new version of the European Society of Cardiology (ESC) Guidelines for the man... more AimsIn May 2016, a new version of the European Society of Cardiology (ESC) Guidelines for the management of heart failure (HF) was released. The aim of this study was to describe the management of HF with reduced ejection fraction after the publication of ESC Guidelines.Methods and resultsThe Linx registry is a multicentre, observational, cross‐sectional study from 14 Catalan hospitals that enrolled 1056 patients with HF and reduced left ventricular ejection fraction (≤40%) from 1 February to 30 April 2017 in outpatient cardiology clinics. Results were compared between hospitals according to their level of complexity in our own registry and compared with previously published registries similar to ours. Sacubitril/valsartan was prescribed to 23.9% of patients in our population, as a consequence, use of angiotensin‐converting enzyme inhibitor and angiotensin receptor blockers in monotherapy decreased to 48.1% and 16.9%, respectively, and prescription of beta‐blockers (91.8%), mineralo...

Journal of Clinical Microbiology, 2000

We report the case of a 69-year-old man with acute pulmonary echinococcosis. A computed tomograph... more We report the case of a 69-year-old man with acute pulmonary echinococcosis. A computed tomographic scan of the thorax revealed the presence of multiple nodules in both lungs, and laboratory tests showed eosinophilia and the presence of antibodies against Echinococcus granulosus. Therapy with albendazole led to resolution of the pulmonary nodules and a normalization of the white cell count. To our knowledge this is the first described case of acute echinococcosis, as the diagnosis of this disease is usually delayed to chronic phases. Therefore, finding unexplained eosinophilia, especially in association with pulmonary nodules, should lead one to suspect acute hydatid disease.

Leukemia & Lymphoma, 2002

Future Rheumatology, 2006

Considerable evidence supports the role of a deregulated clearance of dying cells in the pathogen... more Considerable evidence supports the role of a deregulated clearance of dying cells in the pathogenesis of lupus. The dissection of this event in mouse models has provided insight into the origin and persistence of the autoantibodies, which represent a hallmark of the disease, and other processes critical for chronic inflammation and tissue damage. The comparison with animals that do not develop autoimmunity has also led to the identification of specific events in the pathway to lupus. Recent advances have provided evidence for the feasibility of rational therapeutic procedures, aimed at preventing immune-mediated damage and restoring tissue homeostasis.

Neurological Sciences, 2005

Rheumatological diseases can involve the central and the peripheral nervous system in many ways. ... more Rheumatological diseases can involve the central and the peripheral nervous system in many ways. Every structure-the brain, meninges, spinal cord, cranial nerves, peripheral nerves-can be affected. Early recognition of neurological abnormality can help achieving diagnosis of the underlying condition and prevent permanent sensorimotor or cognitive function loss. This review focuses on the clinical presentation of the neurological involvement in rheumatological diseases.

Leukemia & Lymphoma, 2006

Myeloid sarcoma (MS) is a neoplastic growth of myeloblasts or immature myeloid cells arising in a... more Myeloid sarcoma (MS) is a neoplastic growth of myeloblasts or immature myeloid cells arising in an extra-medullary site or in the bone. MS may precede, occur simultaneously or follow acute or chronic myeloid leukemia, as well as other types of myeloproliferative disorders or myelodysplastic syndromes [1]. The WHO classification scheme recognizes three types of MS based on degree of myeloid maturation: blastic, immature and differentiated [1]. Additionally, sporadic cases differing from myeloid lineage, such as megakaryoblastic or erythroid differentiation, have been described. A 68 year-old man was referred to our Institution for a sudden worsening buttock pain extended to left thigh, that arose a month earlier in association with fever up to 398C. Infectious causes were ruled out and fever was treated with cortisone, taking into account a 7 year-history of symmetric polyarthritis. Five years prior to admission a diagnosis of Essential Thrombocythaemia (ET) based on clinical, laboratory and morphological criteria had been made. In particular, morphologic examination of bone marrow aspirate showed increased cellularity, normal-looking myeloid and erythroid lineages and a marked increase of megakaryocytes, which displayed a range of morphological abnormalities, including giant forms, albeit in the absence of bizarre nuclei. Blasts cell count was less than 2%. Therapy with hydroxyurea has been initiated. Physical examination disclosed left buttock enlargement and swelling. Laboratory tests revealed: hemoglobin 11.3 g L, white blood cell count 28.7610 L (N 77%, L 5%, M 3%, E 1%, B 2%), without any evidence of blasts, platelets count 862610 L, LDH 1235 U L and elevated acute phase reagents (ESR/1 h 120, Reactive C-protein 90 mg dl). Total body CT-scan revealed a left iliac bone osteolysis measuring 11 cm in diameter and locally infiltrating the posterior muscles, multiple iliac and inguinal lymphadenopathies and a mediastinal lesion measuring 4 cm. Bone scintigraphy showed increased uptake of Tc-99 m in the previously described areas, as well as in femurs and tibias. A 2.5 cm diameter inguinal lymph node was excised, formalin-fixed and paraffin-embedded. Histopathological analysis revealed almost complete effacement of lymph node architecture by a diffuse proliferation of large sized, immature-looking elements; these cells exhibited a high nuclear/cytoplasmic ratio with coarse chromatin and quite regular nuclear outline (Figure 1(a)). Within this population, scattered larger cells were readily visible: these cells showed irregular, polylobated nuclei and were similar to immature megakaryocytes (Figure 1(b)). These two types of neoplastic cells were both immunoreactive for CD43, CD45, CD34, focally for factor VIII (Figure 1(c)), CD61, vimentin and EMA (Figure 1(d)), with also a focal positivity for CD117 and CD68. The same elements did not stain for CD20, CD30, CD16, CD138, cytokeratin-pool, actin, desmin, S-100 protein, HMB45, ALK-1, myeloperoxydase and lysozyme. Fluorescence in-situ

Journal of the Neurological Sciences, 2009

Both the central nervous system (CNS) and the peripheral nervous system (PNS) are major target or... more Both the central nervous system (CNS) and the peripheral nervous system (PNS) are major target organs in primary vasculitides. They may either be affected in the setting of systemic vasculitis, potentially involving any other organ, or they may be the sole site of the inflammatory process. In both cases, the clinical pattern of PNS involvement is essentially uniform, presenting as sensory axonal polyneuropathy or mononeuritis multiplex. The damage is related to the ischemic occlusion of the vasanervorum due to small-vessel vasculitis. On the contrary, the range of manifestations of CNS vasculitis is much wider and several pathogenetic mechanisms are implicated, including angiitis of the hemispheres and spinal cord, thrombosis of dural sinuses, stenosis and aneurysms of medium and large arteries, granulomatous meningeal involvement and direct cytokine damage presenting with encephalopathy. Besides, even extracranial noninflammatory vascular disease may induce CNS symptoms, as is the case of carotid stenosis, vena cava syndrome and renovascular hypertension. In this paper we will review the broad spectrum of clinical manifestations of CNS and PNS neuropathy as they occur in primary systemic and non systemic vasculitides.

Journal of Leukocyte Biology, 2008

TNF-␣ plays an important role in the natural history of rheumatoid arthritis (RA), a systemic dis... more TNF-␣ plays an important role in the natural history of rheumatoid arthritis (RA), a systemic disease characterized by endothelial activation and synovial involvement with bone erosions. Neuroendocrine signals contribute as well to RA, but their role is poorly understood. We measured in 104 RA patients and in an equal number of sexand age-matched, healthy controls the blood levels of chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF-␣-mediated vascular inflammation. CgA levels were significantly higher in patients with RA and remained stable over time. High levels of CgA were significantly associated with severe extra-articular manifestations, namely pulmonary fibrosis, rheumatoid vasculitis, serositis, and peripheral neuropathy. RA sera curbed the response of human microvascular endothelial cells to TNF-␣, as assessed by the expression of ICAM-1, the release of MCP-1/CCL2, and the export of nuclear high-mobility group box 1; the effect abated in the presence of anti-CgA antibodies. The efficacy of the blockade was significantly correlated with the CgA concentration in the serum. The recombinant aminoterminal portion of CgA, corresponding to residues 1-78, had similar inhibitory effects on endothelial cells challenged with TNF-␣. Our results suggest that enhanced levels of CgA identify patients with extraarticular involvement and reveal a negative feedback loop that limits the activation of endothelial cells in RA.