FIP1L1-PDGFRA-Associated Hypereosinophilic Syndrome as a Treatable Cause of Watershed Infarction.

Background and Purpose: Ischemic stroke has been reported in various conditions associated with eosinophilia. FIP1L1-PDGFRA fusion ([Fip1-like 1-platelet-derived growth factor receptor alpha]; F/P) leads to the proliferation of the eosinophilic lineage and thus to a clonal hypereosinophilic syndrome that is highly responsive to imatinib. Methods: We previously reported on a nationwide retrospective study of 151 patients with F/P-associated clonal hypereosinophilic syndrome. Patients from this cohort with a clinical history of ischemic stroke (as well as 2 additional cases) were further analyzed to better define their clinical picture and outcomes. Results: Sixteen male patients (median age, 51 [43­59] years) with low-to-intermediate cardiovascular risk were included. Median National Institutes of Health Stroke Scale was 4 (range, 1­6). Most cerebral imaging disclosed multiple bilateral infarctions of watershed distribution (69%). Despite frequent cardiac involvement (50%), cardiac thrombus was evidenced in a single patient and, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment), 62.5% of strokes were presumably of undetermined etiology. Among the 15 patients treated with imatinib, and after a median follow-up of 4.5 years, stroke recurred in only 3 patients (consisting of either cardio embolic or hemorrhagic events, unrelated to the first episode). Conclusions: F/P+ clonal hypereosinophilic syndrome is a diagnosis to consider in patients with unexplained ischemic stroke and hypereosinophilia (especially in the setting of multiple cortical borderzone distribution) and warrants prompt initiation of imatinib.

Inherited Thrombotic Thrombocytopenic Purpura Revealed by Recurrent Strokes in a Male Adult: Case Report and Literature Review.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy related to a severe deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). In this article, we describe the first case of a young male adult suffering from a hereditary TTP revealed by recurrent strokes, relapsing despite antiplatelet and anticoagulant therapy. Because of the persistent moderate thrombocytopenia, plasmatic ADAMTS13 activity was investigated and was found lower than 5% in the absence of anti-ADAMTS13 IgG. Direct sequencing of ADAMTS13 gene led to the diagnosis of Upschaw-Schulman syndrome (USS). Inherited TTP or USS is a rare autosomal recessive inherited disease leading to a severe deficiency of ADAMTS13 mostly beginning in childhood or in young female adult during pregnancy. Our patient was treated with fresh frozen plasma every 2 weeks. One year after diagnosis, he was free of neurological symptoms. Around 12 cases of inherited TTP diagnosed in adults (outside pregnancy) are described in literature. Only 4 of them exhibited a stroke. This case is the first late onset genetic TTP revealed by recurrent strokes, moderate thrombocytopenia without anemia.

Evaluation of quality of life and emotional distress in endometrial cancer patients: a 2-year prospective, longitudinal study.

OBJECTIVES: The aim of the study was to prospectively, and longitudinally assess Quality of Life (QoL) and emotional distress in a large series of endometrial cancer (EC) patients. METHODS: Global Health Status of the EORTC QLQ-C30 (GHS), the EORTC QLQ-CX24 (CX24), and the Hospital Anxiety and Depression Scale (HADS) questionnaires were administered at diagnosis, and after 3, 6, 12, and 24months since surgery. The Generalized Linear Model and the Between Subject test were used to analyze QoL changes over time, and the association between factors and patient QoL. RESULTS: GHS scores improved over time, although the statistical significance was not reached. Worse lymphedema scores were documented worsened over time with a trend to recover at the 12- and 24month evaluation (p-value=0.028). Scores for Menopausal Symptoms (MS) dramatically worsened over time reaching a 38.5 difference of mean±SE compared to baseline (p-value=0.011). Sexual Activity (SxA) scores improved until the 12-month evaluation (p-value=0.048), and showed a return to baseline levels at the last assessment (p-value=0.025). A significant improvement of anxiety scores was documented at the 3-month evaluation, and persisted over time. In multivariate analysis, unmarried status was associated with poor scores for sexual activity, while living with someone was associated with worse MS scores. CONCLUSIONS: Menopausal and lymphedema symptoms heavily affect QoL in EC patients. Since socio-demographic features play a major role in deteriorating SxA and MS, psycho-social intervention and patient education should be considered as an integral part of EC patient treatment.

Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome.

BACKGROUND & PURPOSE: In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. RESULTS: We identified 166 patients with neurological symptoms appearing in less than 1 month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50 years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1 year follow-up. One patient died, and 15% of patients relapsed. Age > 70 years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12 months. No predictors of relapse were identified. CONCLUSION: This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.

Long-term prospective longitudinal evaluation of emotional distress and quality of life in cervical cancer patients who remained disease-free 2-years from diagnosis.

BACKGROUND: A long-term prospective assessment of QoL in cervical cancer patients is still lacking. Here, we provide the first 2-years prospective, longitudinal study evaluating emotional distress and QoL in early stage (ECC) and locally advanced (LACC) cervical cancer patients who remained disease-free 2-years from diagnosis. METHODS: The questionnaires: Hospital Anxiety and Depression Scale (HADS), Global Health Status items of EORTC QLQ-C30 (GHS), and EORTC QLQ-CX24 (CX24) have been administered by a dedicated team of psycho-oncologists, administered at baseline, and after 3, 6, 12 and 24 months from surgery The Generalized Linear Model for repeated measure was used to analyze modifications of QoL measures over time. RESULTS: In both groups, an early reduction of the percentage of patients with anxiety levels ≥11 was observed at the 3-month evaluation (ECC: 25.7% at baseline Vs 14.7% after 3 months, p value=0.001; LACC: 22.2% at baseline Vs 15.4% after 3 months, p value=0.001). Despite this favorable trend, after 2 years from diagnosis, 11.9% of ECC and 15.6% of LACC patients still showed an anxiety score ≥11. No significant changes over time were observed in term of Depression levels. Focusing on QoL issues, mean GHS and Sexual Activity scores showed an improvement over time in both groups compared to baseline (GHS: 5.7% difference for ECC, p value=0.001, and 11.0% in LACC, p value=0.001; SXA: 13.9% difference for ECC, p value=0.001; and 6.1% in LACC, p value=0.008). On the other hand, Body Image mean scores were significantly impaired by chemoradiation administration in LACC patients, without long-term recovery (7.5% difference, p value=0.001). Finally, in both groups, lymphedema (LY) and menopausal symptoms (MS) showed an early worsening which persisted 2-year after surgery (LY: 19.5% difference for ECC, p value=0.014, and 27.3% in LACC, p value=0.001; MS: 14.4% difference for ECC, p value=0.004, and 16.0% in LACC, p value=0.002). CONCLUSIONS: Despite a significant improvement over time, elevated anxiety levels are still detectable at 24 months after surgery in approximately 10% of cervical cancer patients. Much more attention should be focused on surgical/medical approaches able to minimize the negative impact of lymphedema and menopausal symptoms on QoL.

Pre-treatment risk markers for hemorrhagic transformation in posterior circulation acute ischemic stroke treated with reperfusion therapy.

BACKGROUND: Hemorrhagic transformation (HT) is an uncommon complication of posterior circulation acute ischemic stroke (PCS) compared to anterior circulation stroke. Nevertheless, it remains a major concern especially following reperfusion therapy. This study aimed at identifying potential predictive factors associated with HT in PCS. METHODS: Consecutive patients, from a multicenter cohort, with PCS treated by IVT or EVT or the combination of both, were included from December 2015 to May 2019. The European Cooperative Acute Stroke Study criteria was used to identify HT. Potential risk factors were analyzed using univariate and multivariable testing models. RESULTS: A total of 96 patients were included in our study. Median age was 66 (57-83) years, 54 patients (56%) were male and median baseline NIHSS was 8 (4-14). 77 patients (80%) received IVT and 54 patients (56%) benefited from EVT. HT occurred in 19 patients (20%), while sHT occurred in 3 patients (3%). HT was found to be associated with poor functional status at 3 months in univariate analysis (p = 0.0084). Multivariable analysis confirmed that higher baseline NIHSS (OR 1.1008; 95% CI [1.0216-1.1862]; p = 0.0117) and lobar topography of ischemia (OR 4.4275; 95% CI [1.3732-14.2753]; p = 0.0127) were independent predictors of the occurrence of HT. DISCUSSION: HT is associated with increased morbidity in patients with PCS; higher NIHSS and lobar ischemia were independent predictors of HT in our population. Easy-to-use predictive markers may help to tailor therapeutic management of patients with PCS.

Quality of life and emotional distress in early stage and locally advanced cervical cancer patients: a prospective, longitudinal study.

OBJECTIVES: This prospective, longitudinal study investigates QoL issues and emotional distress in early stage cervical cancer (ECC) patients undergoing radical surgery (RS) and in locally advanced cervical cancer (LACC) patients triaged to chemoradiation (CT/RT) followed by RS. METHODS: The Global Health Status scale of EORTC QLQ-C30 (GHS), the EORTC QLQ-CX24 (CX24) and the Hospital Anxiety and Depression Scale (HADS) questionnaire were administered at baseline, and after 3, 6, and 12 months from surgery. For LACC patients QoL assessment was also performed after CT/RT. Statistical analysis was performed by the ANOVA for repeated measures and the Between Subject test. RESULTS: In ECC and LACC patients, the GHS scores improved over time (5.5% difference in mean scores compared to baseline in ECC, and 7.0% difference in mean score compared to baseline in LACC patients). An early worsening of lymphedema scores was documented in ECC cases (14.6% difference in mean values compared to baseline, p value=0.001), and in LACC patients (difference up to 28.3% of mean values, value=0.0001). Menopausal symptoms persistently worsened over time reaching >15% difference of mean values compared to baseline in both groups. Sexual activity scores markedly improved both in ECC and LACC patients (difference of mean score values compared to baseline was 16.5% in ECC, and 6.7% in LACC patients). Both ECC and LACC patients experienced an improvement of anxiety scores. CONCLUSIONS: Lymphedema and menopausal symptoms were the most disabling treatment-related sequelae; the amount of QoL issues and their multifaceted aspects require the cooperation of multidisciplinary teams.

Reperfusion therapy for acute ischemic stroke in older people: An observational real-life study.

BACKGROUND: While randomized clinical trials have shown the benefit of thrombolysis and endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), we aimed to describe in a real-life study the differences between older (>80 years old) and younger patients treated for AIS. METHODS: Thousand patients treated with thrombolysis and/or EVT were consecutively included in a prospective monocentric database (admitted from December 2015 to May 2019 in our comprehensive stroke center). Demographic data with detailed history, baseline physical examinations and treatments, laboratory and imaging data, prestroke functional status, and outcome 3 months after stroke were analyzed. RESULTS: Older patients (n = 357) had more baseline comorbidities and lower levels of prestroke independence (modified Rankin scale ≤2; 67.2% vs. 96.1%) and more severe strokes (median National Institute of Health Stroke Score [NIHSS] 15 vs. 12; p < 0.001) than younger patients (n = 643). There was no difference in the reperfusion treatments used or treatment timelines. In older patients, good functional status at 3 months was less common (29.7% vs. 61.3%) and mortality was higher (37.1% vs. 11.4%) than in younger patients. Younger age was independently associated with better prognosis (odds ratio [OR] 0.37, 95% confidence interval [CI]: 0.20-0.67; p = 0.001) and lower mortality (OR 4.38, 95% CI: 2.11-9.09; p < 0.001). Among older adults, features associated with good outcome at 3 months were age (OR 0.89, 95% CI: 0.81-0.97; p = 0.01), initial NIHSS (OR 0.89, 95% CI: 0.83-0.94; p < 0.0001), and absence of severe leukoaraiosis, anticoagulant treatment, and symptomatic intracerebral hemorrhage following reperfusion therapy (respectively, OR 0.42, 95% CI: 0.19-0.93; p = 0.03; OR = 0.07, 95% CI: 0.01-0.70; p = 0.02; and OR = 0.07, 95% CI: 0.01-0.61; p = 0.02). CONCLUSION: Although reperfusion therapy was less successful in older patients, these patients may benefit from acute recanalization despite their age. With an increasing older adult population, high-quality prospective studies are still required to better predict functional outcome and clarify the criteria that would allow better selection of appropriate treatment.

Pre-procedural predictive factors of symptomatic intracranial hemorrhage after thrombectomy in stroke.

OBJECTIVE: Symptomatic intracerebral hemorrhage (sICH) is a common complication of acute ischemic stroke (AIS) associated with limited treatments and poor outcomes. We aimed to identify predictive factors of sICH in patients with AIS following mechanical thrombectomy (MT) in a real-world setting. METHODS: Patients with large vessel occlusion of the anterior circulation treated with MT were consecutively included in a prospective monocentric cohort. Clinical, biological, and radiological parameters were collected to identify pre-procedural predictors for sICH. RESULTS: 637 patients were included in our study. Magnetic resonance imaging was performed on most patients (86.7%). sICH occurred in 55 patients (8.6%). 428 patients (67.2%) were treated with intravenous thrombolysis. After multivariate analysis, prior use of antiplatelet therapies (odd ratio (OR) 1.84, 95% confidence interval (CI) 1.01-3.32), high C-reactive protein (OR per standard deviation (SD) increase 1.28, 95% 1.01-1.63), elevated mean arterial blood pressure (OR per 10 mmHg increase 1.22, 95% CI 1.03-1.44), hyperglycemia (OR per one SD-log increase 1.38, 95% CI 1.02-1.87), and low ASPECTS (OR per 1-point decrease 1.42, 95% CI 1.12-1.80) were found to be independent predictive factors of sICH. The pre-procedural predictors did not change when the absence of successful recanalization was considered as a covariate. Patients with strokes of unknown onset time were not especially vulnerable for sICH. CONCLUSION: sICH after MT was associated with several pre-procedural risk factors: prior use of antiplatelet therapies, high C-reactive protein and hyperglycemia at baseline, elevated mean arterial blood pressure, and low ASPECTS.

Economic evaluation of breast cancer treatment: considering the value of patient choice.

PURPOSE: To use 5 years of primary data to compare the incremental cost-effectiveness of breast conservation and radiation versus mastectomy with the restriction of choice to a single therapy versus providing a choice of either therapy. PATIENTS AND METHODS: We evaluated a random retrospective cohort of 2,517 Medicare beneficiaries treated for newly diagnosed stage I or II breast cancer from 1992 through 1994. The outcome measures were quality-adjusted life-years (QALYs) and 5-year medical costs. Risk and propensity score adjustments were used in the analysis. RESULTS: A breast conservation and radiation regimen has significantly higher costs than mastectomy in the first year after surgery; the adjusted 5-year costs are $14,054 (95% confidence interval, $9,791 to $18,312) greater than those of mastectomy. The adjusted incremental cost-effectiveness ratio comparing breast conservation and radiation to mastectomy was $219,594 per QALY for the comparison of the two strategies. If the possibility of patient choice from maintaining the availability of multiple treatments versus restricting choice to mastectomy alone provides a quality-of-life gain of 0.031 QALYs, then the cost-effectiveness ratio of this choice option is $80,440 per QALY. CONCLUSION: The current system of providing a choice between mastectomy and breast conservation surgery is economically attractive when the economic analysis includes the benefit of patient choice of treatment.

Newborn screening by tandem mass spectrometry for medium-chain Acyl-CoA dehydrogenase deficiency: a cost-effectiveness analysis.

OBJECTIVE: To determine whether newborn screening by tandem mass spectrometry (MS/MS) for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is cost-effective versus not screening and to define the contributions of disease, test, and population parameters on the decision. METHODS: A decision-analytic Markov model was designed to perform cost-effectiveness and cost-utility analyses measuring the discounted, incremental cost per life-year saved and per quality-adjusted life-year saved of newborn screening for MCADD compared with not screening. A hypothetical cohort of neonates made transitions among a set of health states that reflected clinical status, morbidity, and cost. Outcomes were estimated for time horizons of 20 and 70 years. Probabilities and costs were derived from a retrospective chart review of a 32-patient cohort treated over the past 30 years at the Children's Hospital of Philadelphia, clinical experience with MCADD patient management, patient-family interviews, cost surveys, state sources, and published studies. In addition to older patients who came to medical attention by symptomatic presentation, our patient group included 6 individuals whose MCADD had been diagnosed by supplemental newborn screening. Estimates of the expected net changes in costs and life expectancy for MCADD screening were used to compute the incremental cost-effectiveness ratios. Sensitivity analyses were performed on key input variables, and 95% confidence intervals (CIs) were computed through second-order Monte Carlo simulations. RESULTS: In our base-case analysis over the first 20 years of life, the cost of newborn screening for MCADD was approximately 11,000 dollars(2001 US dollars; 95% CI: <0-33,800 dollars) per life-year saved, or 5600 dollars (95% CI: <0-17,100 dollars) per quality-adjusted life-year saved compared with not screening. Over a 70-year horizon, the respective ratios were approximately 300 dollars (95% CI: <0-13,000 dollars) and 100 dollars (95% CI: <0-6900 dollars). The results were robust when tested over plausible ranges for diagnostic test sensitivity and specificity, MCADD prevalence, asymptomatic rate, and screening cost. CONCLUSIONS: Simulation modeling indicates that newborn screening for MCADD reduces morbidity and mortality at an incremental cost below the range for accepted health care interventions. At the 70-year horizon, the model predicts that almost all of the additional costs of screening would be offset by avoided sequelae.