Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis.

OBJECTIVE: Typically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. METHOD: We conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson's chi-square or Fisher's exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. RESULTS: We selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations. Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8--34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6- 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2--35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2--24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1--90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2--24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. CONCLUSIONS: In our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.

Long-term Outcome of Epilepsy and Cortical Malformations Due to Abnormal Migration and Postmigrational Development: A Cohort Study.

OBJECTIVE: To evaluate the long-term outcomes of patients with epilepsy and malformations of cortical development (MCD). METHODS: We conducted a historical cohort study of patients with epilepsy and MCD due to impaired neuronal migration and postmigration organization with a follow-up period of ≥5 years. For each patient, MCD was classified after accurate neuroimaging reappraisal by an expert neuroradiologist. The primary outcome was remission, defined as a period of seizure freedom ≥5 years at any time from epilepsy onset. We used Kaplan-Meier estimates for survival analysis and univariate and multivariate Cox regression analyses to evaluate baseline variables as possible factors associated with remission. RESULTS: The cohort included 71 patients (M/F 31/40) with a 17-year median follow-up (1,506 person-years). About half (49.3%) had heterotopia, 35.2% polymicrogyria, 7% lissencephaly, and 8.5% the combination of 2 MCD. The mean age at seizure onset was 12.4 ± 7.2 years. Intellectual disability and neurologic deficits were observed in 30.4% and 40.9%, respectively. More than 60% of patients had refractory epilepsy. In 3 patients who underwent epilepsy surgery, MCD diagnosis was confirmed by histology. At the last visit, 44% of patients had been seizure-free during the previous year, but none of them had stopped antiseizure medication. Thirty patients achieved remission (42.2%) at some point in their disease history, whereas 41 individuals (57.8%) had never been in remission for ≥5 years. The cumulative remission rate was 38% by 20 years from inclusion. In the Cox model, unilateral distribution of MCD (hazard ratio [HR] 2.68, 95% CI 1.04-6.92) and a low seizure frequency at onset (HR 5.01, 95% CI 1.12-22.5) were significantly associated with remission. DISCUSSION: Patients with epilepsy and MCD showed a remission rate of 38% by 20 years from onset. Unilateral distribution of the MCD is associated with a 3-fold probability of achieving remission. About 40% of patients showed a drug-sensitive condition with risk of relapse during their epilepsy course. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with epilepsy and MCD, unilateral MCD and low seizure frequency at onset are associated with achieving epilepsy remission.

Risk of Adverse Cardiac and Bleeding Events Following Cardiac and Noncardiac Surgery in Patients With Coronary Stent: How Important Is the Interplay Between Stent Type and Time From Stenting to Surgery?

BACKGROUND: Epidemiology and consequences of surgery in patients with coronary stents are not clearly defined, as well as the impact of different stent types in relationship with timing of surgery. METHODS AND RESULTS: Among 39 362 patients with previous coronary stenting enrolled in a multicenter prospective registry and followed for 5 years, 13 128 patients underwent 17 226 surgical procedures. The cumulative incidence of surgery at 30 days, 6 months, 1 year, and 5 years was 3.6%, 9.4%, 14.3%, and 40.0%, respectively, and of cardiac and noncardiac surgery was 0.8%, 2.1%, 2.6%, and 4.0% and 1.3%, 5.1%, 9.1%, and 31.7%, respectively. We assessed the incidence and the predictors of cardiac death, myocardial infarction, and serious bleeding event within 30 days from surgery. Cardiac death occurred in 438 patients (2.5%), myocardial infarction in 256 (1.5%), and serious bleeding event in 1099 (6.4%). Surgery increased 1.58× the risk of cardiac death during follow-up. Along with other risk factors, the interplay between stent type and time from percutaneous coronary intervention to surgery was independently associated with cardiac death/myocardial infarction. In comparison with bare-metal stent implanted >12 months before surgery, old-generation drug-eluting stent was associated with higher risk of events at any time point. Conversely, new-generation drug-eluting stent showed similar safety as bare-metal stent >12 months and between 6 and 12 months and appeared trendly safer between 0 and 6 months. CONCLUSIONS: Surgery is frequent in patients with coronary stents and carries a considerable risk of ischemic and bleeding events. Ischemic risk is inversely related with time from percutaneous coronary intervention to surgery and is influenced by stent type.

Clinical governance network for clinical audit to improve quality in epithelial ovarian cancer management.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several hospitals throughout the region provide primary treatment for these patients and it is well know that treatment quality is correlated to the hospital that delivers. The aim of this study was to investigate the management and treatment of EOC in a Region of the North Italy (Emilia-Romagna, Italy). METHODS: A multidisciplinary group made up of 11 physicians and 3 biostatisticians was formed in 2009 to perform clinical audits in order to identify quality indicators and to develop Region-wide workup in accordance with the principles of evidence-based medicine (EBM). The rationale was that, by setting up an oncogynecology network so as to achieve the best clinical practice, critical points would decrease or even be eliminated. Analysis of cases was based on the review of the medical records. RESULTS: 614 EOC patients treated between 2007 and 2008 were identified. We found only 2 high-volume hospitals (≥ 21 patients/year), 3 medium-volume hospitals (11-20 operated patients/year), and 7 low-volume hospitals (≤ 10 operated patients /year). Only 222 patients (76.3%) had a histological diagnosis, FIGO surgical staging was reported only in 206 patients (70.9%) but not all standard surgical procedures were always performed, residual disease were not reported in all patients. No standard number of neoadjuvant chemotherapy cycles was observed. CONCLUSIONS: The differences in terms of treatments provided led the multidisciplinary group to identify reference centers, to promote centralization, to ensure uniform and adequate treatment to patients treated in regional centers and to promote a new audit involving all regional hospitals to a complete review of the all the EOC patients.

Factors influencing surgical delay after hip fracture in hospitals of Emilia Romagna Region, Italy: a multilevel analysis.

Hip fracture is becoming a major public health concern, with associated mortality and morbidity particularly in the elderly. This study aims to investigate factors (i.e. patient factors and hospital variables) associated with increased risk for delaying surgery after hip fractures, and to assess whether and to what extent timing was associated with mortality risk. All patients aged 65 and over, resident in Emilia Romagna Region (Italy) and admitted to hospital for hip fracture (2009 - 2010) were selected. Data on surgical delay were adjusted using multilevel logistic regression model. A Cox proportional hazard model was fitted to a propensity score matched sample to assess mortality between delayed and early treated patients. Of the 10, 995 patients included (mean age: 83.3 years), 44.9% underwent surgery within 2 days. Significant risk factors for delayed surgery were: gender (OR: 1.16), comorbidity (OR: 1.29), anticoagulant (OR: 7.64) ,antiplatelet medication (OR: 2.43) , type of procedure (OR: 1.37) and day of admission (OR: Thu-Fri: 6.05; Sat-Sun: 1.17). Type of hospital and annual volume of hip fracture surgeries were not sufficient to explain hospital variability. A significant difference in mortality rate between early and delayed surgery emerged six months post surgery.

Acute type A aortic dissection: significance of multiorgan malperfusion.

OBJECTIVES: Acute type A aortic dissection (AAAD) remains one of the most challenging diseases in cardiothoracic surgery, and despite numerous innovations, early mortality still remains high. The aim of this study was to review the Emilia-Romagna experience in the treatment of AAAD and to evaluate the effect of malperfusion on mortality and morbidity. METHODS: We examined data of 502 patients between January 2000 and December 2008, from the Emilia-Romagna Regional Registry of AAAD. The mean age was 62.4 ± 13 years and 66.5% were male. At presentation, various types of malperfusion syndromes (cerebral, cardiac, ileo-femoral, renal, mesenteric and spinal cord) were present in 103 patients (20.5%; malperfusion [MPS] group). Three hundred ninety-nine patients (No-MPS group) did not have pre-operative malperfusion. Arterial access for cardiopulmonary bypass was usually via the femoral artery (81.9%), while the axillary artery was used only in 14.7%. The aortic repair was performed using the 'open technique' in 348 patients (69.3%) and with aortic cross-clamping without circulatory arrest in 154 patients (30.7%). RESULTS: Overall in-hospital mortality was 20.9%: 43.7% in the MPS group vs 15% in the No-MPS group (P = 0.001). The operative technique and the cannulation site did not influence post-operative outcomes. Multivariate regression analysis identified mesenteric (odds ratio [OR] 9.5, confidence interval [CI] 2.4-37.4; P = 0.0012), cardiac malperfusion (OR 3.7, CI 1.7-8.0; P < 0.0001) and shock (OR 2.1, CI 1.2-3.5; P = 0.007) as significant risk factors for in-hospital mortality after surgery for type A dissection. Patients who presented single-organ malperfusion had a mortality rate of 34.7%, which increased to 61.9% and to 85.7% if two or more than two organ systems were involved, respectively. CONCLUSIONS: The results of the surgical treatment of AAAD are acceptable and mainly influenced by patient's status at presentation. Malperfusion of more organ systems makes the prognosis unfavourable and immediate proximal aortic repair may be sub-optimal. In these situations, alternative management strategies should be considered.

Acute aortic dissection: epidemiology and outcomes.

BACKGROUND: Little epidemiological information on acute aortic dissection (AAD) is available in the literature. The objective of the present study was to determine the incidence and mortality rates of AAD in the general population and to analyze its clinical features. METHODS: Data from the Emilia-Romagna regional database of hospital admissions was analyzed. Urgent admissions with the diagnosis of dissection of the aorta, dissection of the thoracic aorta and dissection of the thoracoabdominal aorta were selected. RESULTS: Between January 2000 and December 2008, 1499 Emilia-Romagna residents were hospitalized with a diagnosis of AAD. The patients were divided into three groups: Group A, 617 patients (41.2%) surgically treated for type A AAD; Group B, 93 complicated patients (6.2%) with type B AAD treated by endovascular stent-grafting and Group C, 789 patients (52.6%) suffering from any type of AAD medically treated. The overall annual incidence rate was 4.7%/100,000 people and was higher for men than for women (6.7% vs 2.9%).Two hundred ninety-six patients (19.8%) were 80 years of age or older.The overall in-hospital mortality rate was 27.7%, with mortality rates of 21.1%, 26.9% and 33% in Groups A, B and C, respectively. CONCLUSION: The incidence of AAD is not negligible and a notable rate of patients is ultra-octogenarian. A large number of patients with AAD had no surgery or interventional treatment. The results of surgical treatment for patients with type A dissection are acceptable but the results obtained in patients with complicated type B dissection who were treated with an endoprosthesis are dismal.