Therapeutic aspects of Sydenham's Chorea: an update

Sydenham's Chorea (SC) is a hyperkinetic movement disorder associated with neuropsychiatric manifestations. It is believed to be caused by the autoimmune response following a group A beta-hemolytic streptococcal (GABHS) pharyngitis, and it is one of the major diagnostic criteria for Acute Rheumatic Fever (ARF) diagnosis. Despite having been known and studied for centuries, there are still no standardized therapies or official guidelines for SC treatment, so that it is necessarily left to physicians' clinical experience. Antibiotic treatment, symptomatic therapies, and immunomodulatory treatment are the three pillars upon which SC patients' management is currently based, but they still lack a solid scientific basis. The aim of this writing is precisely to review the state of the art of SC's treatment, with an overview of the advances made in the last 5 years. However, since the therapeutic uncertainties are a mere reflection of the severe gap of knowledge that concerns SC's pathogenesis and manifestations, the importance of high-quality research studies based on homogenized methodologies, instruments, and measured outcomes will also be stressed

Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham's Chorea: A Multicenter Prospective Study

Sydenham's chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12-15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC's onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset

Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham’s Chorea: a Multicenter Prospective Study

The aim of the study is to evaluate the presence of psychiatric conditions in patients with a previous diagnosis of rheumatic fever, with or without Sydenham’s chorea, several years after its clinical onset. Even though the clinical association between Sydenham’s chorea and neuropsychiatric disorders has already been studied, nature and timing of the latter still need to be clarified: neuropsychiatric symptoms are mainly reported in the acute phase of the disease, but there are numerous literature studies where they are showed to precede or follow the acute disease onset, even by years. Nevertheless, an extensive characterization of these symptoms is still lacking. To investigate this topic, we enrolled 48 patients with a previous diagnosis of rheumatic fever from 7 different centers located all over Italy. The overall population was divided in two groups: a group (SC) formed by those patients who had Sydenham’s chorea (n=21) and another group (nSC) consisting of patients with a history of rheumatic fever without Sydenham’s chorea. 7 different psychiatric questionnaires were administered to all participants to evaluate their work and social functioning and to assess the presence of mood disorders, anxiety disorders, psychotic disorders, personality disorders, PTSD, and other psychiatric disorders. Demographic variables, clinical data and information about diagnostic process, therapy and follow-up were also collected and compared between our two groups of patients. The data collected suggest a general higher frequency of psychiatric conditions among patients with a previous diagnosis of Sydenham’s chorea when compared with those who were diagnosed with rheumatic fever in absence of choreic symptoms, revealing that Sydenham’s chorea can exert a strong psychopathological impact on patients even years after the acute onset of symptoms. In particular, the administration of the Work and Social Adjustment Scale (WSAS) showed a significantly higher amount of work and social functioning difficulties in the SC group (mean=2.48, S.D.=0.512, mean rank=28.69) than in the nSC group (mean=2.19, S.D.=0.483, mean rank=21.24). Furthermore, 60,4% (n=29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p=0.00) in SC patients (95.2%) than in nSC patients (33.3%). The analysis of the data deriving by the other questionnaires also produced results indicating a higher psychopatological involvement for patients with a history of Sydenham’s chorea when compared to the nSC group, but further research involving more numerous populations of patients will be needed to reach statistical significance

Cardiovascular Disorders: Q153 - A157

Le pagine descrivono, attraverso un approccio clinico-radiologico, i più comuni scenari clinici ed i più comuni reperti radiologici, delle principali cardiopatie congenite di interesse chirurgic

Off-pump coronary artery bypass surgery versus standard linear or pulsatile cardiopulmonary bypass: endothelial activation and inflammatory response

OBJECTIVE: Poor outcomes after coronary artery bypass grafting (CABG) have been linked to perioperative endothelial activation and systemic inflammatory responses. The use of pulsatile cardiopulmonary bypass (PCPB) or off-pump CABG (OPCABG) may minimise these phenomena. We compared biochemical and clinical outcomes among patients who underwent CABG with PCPB, CABG with linear CPB (LCPB) or OPCABG. METHODS: Sixty consecutive patients undergoing isolated elective CABG were prospectively randomised trial to receive pulsatile CPB (group A, 20 patients), linear CPB (group B, 20 patients) or OPCABG (group C, 20 patients). Levels of proinflammatory cytokines (interleukins-2, -6, and -8), anti-inflammatory cytokines (interleukin-10) and endothelial markers (vascular endothelial growth factor (VEGF), monocyte chemo-attractant protein (MCP)-1) were measured before, during and after surgery. RESULTS: VEGF and MCP-1 levels increased significantly during surgery in all groups, but they increased the least and were the lowest overall with OPCABG. They rose most and peaked overall with LCPB. Interleukin-2 levels remained stable during OPCABG but decreased equally during PCPB and LCPB. Interleukin-6 and -8 levels rose significantly during both types of CPB versus OPCABG. Interleukin-10 levels increased significantly in all groups during surgery, but they rose least and were the lowest overall with OPCABG and rose most and were the highest overall with PCPB. Intubation times, intensive care unit (ICU) stay and hospital stay were significantly longer in the LCPB group than the other two groups. CONCLUSIONS: LCPB appears to promote endothelial activation and cytokine secretion, which may delay recovery. OPCABG was associated with slight endothelial activation and cytokine response. PCPB significantly attenuates endothelial/cytokine leakage, resulting in hospital outcomes comparable with those after OPCABG

Impact of endothelial activation on infective and inflammatory complications after cardiac surgery in type II diabetes mellitus

PURPOSE: Altered endothelial response has been described in diabetics after cardiac surgery. Infections and inflammatory organ damage often complicate the postoperative course. We evaluated endothelial/cytokine response (ECR) after cardiac surgery and its role on infective/inflammatory complications of type II diabetic patients. METHODS: Perioperative ECR of 60 diabetic patients (Group A) undergoing cardiopulmonary bypass was compared to that of 60 non-diabetics (Group B). Hemodynamics, endothelial markers [vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1)], pro-inflammatory (IL-2, IL-6, IL-8) and anti-inflammatory cytokines (IL-10) were analyzed preoperatively (T0), at time of aortic declamping (T1), at ITU admission (T2), at 12 h (T3) and 24 h (T4) postoperatively. Postoperative infective/inflammatory complications were registered, and the related ECR was analyzed. RESULTS: Hemodynamics were comparable. No differences were found in perioperative IL-6 (p = 0.776) and IL-8 (p=0.660) between the 2 groups. However, the diabetics showed significantly higher endothelial activation (VEGF p = 0.0001, p = 0.0001 since T1 to T3; MCP-1 p = 0.0001, p<0.007 at T1, T3 and T4) with lower IL-10 (p = 0.0001, p<0.05 at T2, T3, T4) and lower IL-2 secretion (p = 0.0001, p < 0.0001 at T1, T2). Infections developed in 23.3% of the diabetics; inflammatory complications in 13.3%. Those developing infections showed significantly lower IL-2 (p = 0.042; p = .021 at T1 and T2) than patients without infections, whereas those with complicated inflammatory lung or renal injury had higher MCP-1 leakage (p = 0.006) with lower IL-10 (p = 0.005). CONCLUSIONS: The diabetics showed higher endothelial activation and lower antiinflammatory response to CPB compared to non-diabetics. Infections in diabetic patients correlated with depressed IL-2, while inflammatory complications correlated to higher endothelial activation and lower anti-inflammatory cytokine secretion

Allogeneic Hemopoietic Stem Cell Transplants in Patients with Acute Myeloid Leukemia (AML) Prepared with Busulfan and Fludarabine (BUFLU) or Thiotepa, Busulfan, and Fludarabine (TBF): A Retrospective Study

: This is a multicenter retrospective comparison of 2 myeloablative conditioning regimens in 454 patients with acute myeloid leukemia (AML) in remission: busulfan (4 days) and fludarabine (BUFLU) versus thiotepa, busulfan, and fludarabine (TBF). Eligible for this study were patients allografted between January 2008 and December 2018 in 10 transplant centers, with AML in first or second remission: 201 patients received BUFLU, whereas 253 received TBF. The 2 groups (BUFLU and TBF) were comparable for age (P = .13) and adverse AML risk factors (P = .3). The TBF group had more second remissions and more haploidentical grafts. The donor type included HLA-identical siblings, unrelated donors, and family haploidentical donors. The 5-year cumulative incidence of nonrelapse mortality (NRM) was 19% for BUFLU and 22% for TBF (P = .8), and the 5-year cumulative incidence of relapse was 30% and 15%, respectively (P = .0004). The 5-year actuarial survival was 51% for BUFLU and 68% for TBF (P = .002). In a multivariate Cox analysis, after correcting for confounding factors, the use of TBF reduced the risk of relapse compared with BUFLU (P = .03) and the risk of death (P = .03). In a matched pair analysis of 108 BUFLU patients matched with 108 TBF patients, with the exclusion of haploidentical grafts, TBF reduced the risk of relapse (P = .006) and there was a trend for improved survival (P = .07). Superior survival of patients receiving TBF as compared with BUFLU is due to a reduced risk of relapse, with comparable NRM. The survival advantage is independent of donor type and AML risk factors

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors. A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (Gitmo)

Abstract PURPOSE: We performed a nationwide registry-based analysis to describe the clinical outcome of adults patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a TKI-based treatment. PATIENTS AND RESULTS: A total of 441 patients were included in the study. The median age at HSCT was 44 years (range 18-70). All the 441 patients (100%) received TKI before the HSCT (performed between 2005 and 2016). Of these patients, 404 (92%) were in cytologic complete remission (CR), while the remaining 37 (8%) had an active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of cases. The prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (TBI-based in 50%) and included ATG in 51% of cases. With a median follow-up after HSCT of 39.4 months (range: 1-145), the overall survival (OS) probability at 1, 2 and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2 and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients with CR and MRD-negative at the time of transplant compared with those of patients with CR but MRD-positive (50% OS not reached vs. 36 months, P=0.015; 50% PFS not reached vs. 26 months, P=0.003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5 years OS rate 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS and PFS of 7 and 5 months, respectively. The 5 years cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% vs. 35.4%, P=0.001). The non-relapse mortality (NRM) after 1, 2 and 5 years was 19.1% (95%CI: 15.5-22.9), 20.7% (95%CI: 17-24.7) and 24.1% (95%CI: 20-28.5), respectively. The NRM was significantly lower with a mEBMT risk score of 0-2 compared with mEBMT risk score of 65 3 (15% vs. 25%, P=0,016). CONCLUSIONS: The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allograft, in recent years at the GITMO Centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph+ ALL with an excellent outcome for the subgroup of patients MRD-negative both at HSCT and at 3 months after HSCT (5 year OS 70%)