Cohort Of Young Patients Research Articles

Abstract TP115: Carotid Endarterectomy in Young and Middle Aged Patients

Introduction: The increasing prevalence and earlier onset of risk factors has resulted in an expanding population of younger patients undergoing carotid endarterectomy (CEA) in recent times. Outcomes after CEA are largely unreported in these patients. In this study, we evaluate 30-day postoperative outcomes after CEA in an exclusive cohort of young and middle aged patients. Methods: We studied all patients aged 64 years and younger, who underwent CEA in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) from January 2005 to December, 2013. Univariate methods (Chi Square, ttest) were employed to compare patients’ characteristics. Multivariate regression adjusting for patient characteristics was used to identify predictors of adverse outcomes. Results: There were 15830 CEA’s performed in this cohort with a mean age of 58 (S.D:5.1) years. The majority of patients were male (59%), Caucasian (85%) and hypertensive (81%). Nearly half (46%) were symptomatic. Overall, 266 (1.7%) patients suffered stroke in the 30 day post-operative period, while mortality and myocardial infarction rates were 0.6% and 0.4% respectively. The significant predictors of stroke or death were female gender (OR: 1.49; 95%CI: 1.15-1.92; p=0.002), symptomatic status (OR: 1.69; 95%CI: 1.30-2.21; p<0.001), previous cardiac intervention (OR: 1.42; 95%CI: 1.04-1.93; p=0.026) and physical dependence (OR: 1.81; 95%CI: 1.16-2.82; p=0.01). The mean length of in-hospital stay was 3 (SD:5.6) days and complications within 30 days of surgery are shown in Table 1. Conclusions: Absolute stroke and mortality rates after CEA in young and middle aged patients are not different from those reported in the general population. Stroke and mortality are significantly higher in symptomatic, physically dependent patients and those with prior cardiac intervention. We recommend extra vigilance in the management of these patients in order to improve CEA outcomes.

Long-term follow up of ileal pouch anal anastomosis in a large cohort of pediatric and young adult patients with ulcerative colitis

AimThe study's aim is to determine long-term outcomes in a large cohort of pediatric and young adult patients who underwent proctocolectomy with ileal pouch anal anastomsis (IPAA) for ulcerative colitis (UC). MethodsPatients diagnosed with UC in childhood or adolescence (age≤21years) who underwent IPAA in childhood, adolescence, or young adulthood between 1982 and 1997 were contacted to determine pouch history, complications, and quality of life. ResultsData were obtained from 74 patients out of a previously reported cohort. Median age at diagnosis of UC was 15years and at surgery was 18years. Median follow-up was 20years. Complications during follow-up were pouchitis (45%), strictures (16%), fistulae (30%), obstruction (20%), and change of diagnosis to Crohn's (28%). Twenty-three percent reported no complications. Fourteen percent had pouch failure, with Crohn's and fistulae reported to be the most frequent complications. Seventy-nine percent reported being very satisfied at 20years follow-up. ConclusionTo our knowledge, this study represents the largest cohort with the longest follow-up of pediatric and young adult patients undergoing IPAA for UC. Change in diagnosis to Crohn's and development of fistulae are risk factors for pouch failure. Despite reported complications, IPAA remains an excellent option for pediatric patients with UC.

Coronary calcium scoring for long-term mortality prediction in patients with and without a family history of coronary disease

ObjectiveMinimal data are available regarding the long-term mortality risk of subclinical atherosclerosis using coronary artery calcium (CAC) scoring among patients with a family history (FH) of coronary artery disease (CAD)....

Favorable Outcome of Older Patients with AML and a Favorable Genotype NPM1mut FLT3-ITD Treated with Intensive Chemotherapy: A Subgroup Analysis of Cetlam Protocol 2003 & 2012

IntroductionYounger patients with acute myeloid leukemia and intermediate cytogenetic risk (AML-IR) harboring NPM1 mutation (NPM1mut) without FLT3 internal tandem duplication (FLT3-ITD) have a relatively favorable prognosis, and are not deemed as candidates to receive an allogeneic hematopoietic stem cell transplantation in first complete remission (CR1). However, it remains uncertain if this favorable prognosis is also maintained in older patients within the same molecular features with some conflicting results.Patients and methodsWe analyzed the cohort of patients ≥60 year-old considered fit for intensive chemotherapy and included in the CETLAM protocols LMA-2003 and LMA-2012 for patients up to 70, consisting of a standard induction chemotherapy, HiDAC post-remission therapy, followed by alloHSCT in selected patients with high-risk features. Overall we identified 192 patients between 60 and 71 year-old diagnosed with AML-IR with known NPM1 and FLT3 mutational status.ResultsWe identified 192 AML-IR patients (93♀, 99♂) aged >=60 (median age was 65 years old (range: 60-71)), with a median WBC count 10.6 x 109/L (range: 0.23-400 x 109/L), median bone marrow blasts 65% (range: 20-100%). Overall, CR rate was 78%, five-year overall survival (OS) was 30±4%, and leukemia-free survival (LFS) was 31±4%. Patients were classified in three molecular groups depending on NPM1mut and FLT3-ITD: 40 patients harbored NPM1mut/FLT3 without ITD (FAV group), 98 patients had NPM1wt/FLT3wt, and 54 had a FLT3-ITD. Five-year OS of these 3 groups were: 64±9%, 25±6%, and 19±6%, respectively (p<0.001). Since the two latter groups, NPM1wt/FLT3wt and FLT3-ITD, did not show significant differences, we decided to group them in a sole subgroup (UNFAV group). There were no differences in the complete remission rate between patients of FAV and UNFAV groups (88% vs 78%, p=ns), but the cumulative incidence of relapse was significantly higher for patients of the UNFAV group (54 vs. 17.5%, p=0.000654).Multivariate analysis for OS, including WBC count, bone marrow blasts and molecular group (NPM1mut/FLT3wt vs. the other groups) identified WBC and molecular subgroup showed significance for the WBC count (HR=1.003, 95% CI: 1-1.006) and the molecular group (FAV vs. UNFAV, HR=0.345, 95% CI: 0.192-0.621).Interestingly, when we compared the outcome of the FAV group with a cohort of younger patients (up to 60, n=99) with the same molecular features included in these 2 protocols, the outcome did not differ depending on age (5-year OS 69±5% for younger patients, and 64±9% for older patients, p=0.463, and 5-yr LFS 67±5% for younger patients, and 55±12% for older patients, p=0.567). Moreover, the outcome of a small cohort of FAV patients older than 65 years (n=16) included in these protocols was relatively favourable, with a 5-yr OS and LFS not differing substantially from that of younger patients allocated in the same molecular subgroup.ConclusionsThe favorable impact of NPM1mut/FLT3-ITDneg genotype was maintained in a cohort of patients >60 who received intensive chemotherapy, with a high proportion of long-standing responses after HiDAC-based post-remission therapy. DisclosuresNo relevant conflicts of interest to declare.

Novel Agents Versus Conventional Drugs for the Treatment of Relapsed Multiple Myeloma Patients: Experience of a Single Center over the Last 25 Years

Background: New active classes of drugs such as proteasome inhibitors (e.g., bortezomib) and immunomodulatory drugs-IMiDs (e.g., thalidomide and lenalidomide) are nowadays the standard treatment for multiple myeloma (MM) patients, alone or in association with old agents. The achievement of deeper responses, using novel agents instead of conventional treatment, is a significant prognostic factor for the outcome of these patients, resulting in an improved overall survival (OS) and progression-free survival (PFS). Here, we report the single center real life comparison between the outcome achieved with old agents with that obtained with novel agents in young MM patients treated at first relapse over a 25-year period.Patients and Methods: We analyzed a cohort of 258 young (median age 55 years; range 19-69) newly diagnosed MM patients treated at our Center between August 1989 and November 2014. All patients received old or novel agents followed by autologous hematopoietic stem cell transplantation (single or tandem) as first line treatment. Of the 258 patients, 144 experienced a progression of disease after a median of 34 months (range 7-195) and received old or novel agents as second line therapy. Old agents used as first and second line treatment were prevalently vincristine, doxorubicin and dexamethasone (VAD), melphalan and prednisone (MP) or cyclophosphamide and dexamethasone (CD); novel agents included velcade-based or IMiD-based regimens. Our cohort was divided into four different groups: 1) 51 patients treated with old agents as first and second line therapy (35.4%);2) 79 patients treated with old agents as first line therapy and novel agents as second line therapy (54.8%);3) 2 patients treated with novel agents in induction therapy and subsequently with old agents as second line therapy (1.4%);4) 12 patients treated with novel agents both in first and second line (8.3%). Our analysis focused on groups 1 and 2; group 3 was not considered for the small number of patients and because the choice of treatment was based exclusively on a worsening of the clinical condition; group 4 was not included for the small number of patients and because of the short follow-up. Our aim was to compare the results obtained in patients treated only with old agents both as first and second line treatment with the outcome of patients who received old agents as first treatment and novel agents as second line treatment, to assess the impact of novel agents in real life MM patients' management.Results: The OS at 5 years for patients of group 2 was significantly higher than that of group 1 patients (41.6% vs 14.1%); even at 10 years, the OS was significantly better for group 2 (20.4% vs 2.4%, p<0.0001); median OS was 4.1 years for group 2 and 1.4 years for group 1. The PFS was superior for patients treated with novel agents as second line treatment both at 5 years (12% vs 6.9%) and at 10 years (10% vs 2.3%) (p=0.02); median PFS was 1.4 years for group 2 and 0.7 for group 1. PFS2, considered as the interval from the start of first line treatment to the date of second relapse, showed also significantly better results for group 2 patients compared to group 1 patients both at 5 (61.8% vs 33.3%) and 10 years (25.7% vs 9.2%). Median PFS2 was 6.8 years for group 2 and 3.7 years for group 1(p=0.0002).Conclusions: We analyzed the effect of the introduction of novel agents in a cohort of young MM patients treated at our Center over a 25-year period, between 1989 and 2014. Patients treated in the earlier years received old agents both as first and second line treatment, while in more recent years all patients who experienced a relapse were treated with novel agents as second line treatment. Our analysis underlines that patients receiving novel agents witnessed a significantly better OS and PFS compared to patients treated only with old agents. When focusing on PFS2, we could determine that the duration of response obtained with proteasome inhibitors and IMiDs was significantly longer than that obtained with conventional chemotherapy. This currently ongoing study and a longer follow-up in a larger number of group 4 patients will allow to conclusively define the true real life impact of novel agents when used both as first and second line treatment for the management of young MM patients. DisclosuresPetrucci:Celgene, Janssen-Cilag, Amgen, Mundipharma, BMS: Honoraria.

Olfaction in Parkin single and compound heterozygotes in a cohort of young onset Parkinson's disease patients.

Parkin related Parkinson's disease (PD) is differentiated from idiopathic PD by absent or sparse Lewy bodies, and preserved olfaction. The significance of single Parkin mutations in the pathogenesis of PD is debated. To assess olfaction results according to Parkin mutation status. To compare the prevalence of Parkin single heterozygous mutations in patients diagnosed with PD to the rate in healthy controls in order to establish whether these single mutations could be a risk factor for developing PD. Parkin gene mutation testing was performed in young onset PD (diagnosed <50 years old) to identify three groups: Parkin homozygous or compound heterozygote mutation carriers, Parkin single heterozygote mutation carriers, and non-carriers of Parkin mutations. Olfaction was tested using the 40-item British version of the University of Pennsylvania smell identification test (UPSIT). Of 344 young onset PD cases tested, 8 (2.3%) were Parkin compound heterozygotes and 13 (3.8%) were Parkin single heterozygotes. Olfaction results were available in 282 cases (eight compound heterozygotes, nine single heterozygotes, and 265 non-carriers). In Parkin compound heterozygotes, the median UPSIT score was 33, interquartile range (IQR) 28.5-36.5, which was significantly better than in single Parkin heterozygotes (median 19, IQR 18-28) and non-carriers (median score 22, IQR 16-28) (ANOVA P < 0.001). These differences persisted after adjusting for age, disease duration, gender, and smoking (P < 0.001). There was no significant difference in UPSIT scores between single heterozygotes and non-carriers (P = 0.90). Patients with Parkin compound heterozygous mutations have relatively preserved olfaction compared to Parkin single heterozygotes and non-carriers. The prevalence of Parkin single heterozygosity is similar to the 3.7% rate reported in healthy controls.

Hypertrophic Cardiomyopathy in Children, Adolescents, and Young Adults Associated With Low Cardiovascular Mortality With Contemporary Management Strategies.

Youthful age has been considered the time of greatest risk for patients with hypertrophic cardiomyopathy (HCM), largely because of the possibility of sudden death. The last 2 decades have witnessed more reliable identification of at-risk patients and utilization of implantable cardioverter-defibrillators for prevention of sudden death, and other contemporary treatment options. Whether such management advances have significantly altered the considerable mortality rate for young HCM patients remains unresolved. We studied long-term outcome in 474 consecutive HCM patients between 7 and 29 years of age presenting at 2 referral institutions. Over 7.1±5.1 years of follow-up (6.0 [3.0, 10.0]), 452 patients (95%) survived, with 95% experiencing no or mild symptoms. HCM-related death occurred in 18 patients (3%; 0.54%/y): arrhythmic sudden death (n=12), progressive heart failure and heart transplant complications (n=5), or postoperatively (n=1). In contrast, aborted life-threatening events occurred in 63 other high-risk patients (13%) with implantable cardioverter-defibrillator interventions for ventricular tachyarrhythmias (n=31), resuscitated out-of-hospital cardiac arrest (n=20), or heart transplant for advanced heart failure (n=12), 1.8%/y, 3-fold higher than HCM mortality. Five- and 10-year survival (considering only HCM deaths) was high (97% and 94%, respectively), virtually identical to that reported in middle-aged adult HCM patients (98% and 94%, P=0.23). In a large hospital-based cohort of young HCM patients, representing an age group considered at greatest risk, low mortality rates can be achieved with the application of contemporary cardiovascular treatment strategies, largely because of reliable identification of high-risk patients who benefited from implantable cardioverter-defibrillators for sudden death prevention, thereby creating the opportunity for extended longevity and good quality of life.

Contraception counseling for young breast cancer patients: A practical needs assessment and a survey among medical oncologists

Background/methodsWe analyzed an unselected, consecutive cohort of young breast cancer (BC) patients (≤40 years, n = 100) with regard to the contraceptive methods used at the time of diagnosis. Based on this data, we assessed the individual need for contraceptive counseling before cancer therapy. Secondly, in a study-specific self-report questionnaire, we surveyed 101 medical oncologists with the aim of evaluating attitudes towards contraception and how young patients are being counseled in the practical clinical setting. ResultsIn 62% of our cohort of young BC patients, we identified situations in which contraceptive counseling was necessary at the time of BC diagnosis. The patients did not use contraception or used an ineffective method (TIER III/IV, 42%), or were using hormonal methods (12%) or IUDs (8%).Almost all respondents of the survey (99%) stated that contraception is an important aspect in the surveillance of young BC patients and the vast majority (90%) discussed this item before starting therapy. Only 20% of the respondents reported that they a) inform the patients that reliable contraception is necessary before starting therapy, b) ask whether contraceptive methods are used during ongoing therapy, and c) regularly refer their patients to specialist counseling by a gynecologist. ConclusionsA large proportion of young women require contraceptive counseling after newly diagnosed BC. Oncologists should be aware that the use of reliable contraceptive methods should not only be discussed before starting therapy, but also during ongoing therapy. Oncologists should consider actively referring their young patients to gynecologists to ensure proper contraceptive counseling.

New drugs and patient-centred end-points in old age: setting the wheels in motion

Older patients with various degrees of frailty and disability, a key population target of pharmacological interventions in acute and chronic disease states, are virtually neglected in pre-marketing studies assessing the efficacy and safety of investigational drugs. Moreover, aggressively pursuing established therapeutic targets in old age, e.g. blood pressure, serum glucose or cholesterol concentrations, is not necessarily associated with the beneficial effects, and the acceptable safety, reported in younger patient cohorts. Measures of self-reported health and functional status might represent additional, more meaningful, therapeutic end-points in the older population, particularly in patients with significant frailty and relatively short life expectancy, e.g. in the presence of cancer and/or neurodegenerative disease conditions. Strategies enhancing early knowledge about key pharmacological characteristics of investigational drugs targeting older adults are discussed, together with the rationale for incorporating non-traditional, patient-centred, end-points in this ever-increasing group.

Pulmonary ventilation and micro-structural findings in congenital diaphragmatic hernia.

With increasing survival of patients with more severe forms of congenital diaphragmatic hernia (CDH) and risk of long-term respiratory morbidity, studies on lung morphology are needed. We used hyperpolarised (3) He MRI and anatomical (1) H MRI in a cohort of young adult CDH patients to image regional lung ventilation and microstructure, focusing on morphological and micro-structural (alveolar) abnormalities. Nine patients with left-sided CDH, born 1975-1993, were studied. Regional ventilation was imaged with hyperpolarised (3) He MRI, and the (3) He apparent diffusion coefficient (ADC) was computed separately for the ipsilateral and contralateral lungs. (1) H MRI was used to image lung anatomy, total lung volume and motion during free-breathing. (3) He MRI showed ventilation abnormalities in six patients, ranging from a single ipsilateral ventilation defect (3 patients) to multiple ventilation defects in both lungs (one patient treated with extra corporeal membrane oxygenation). In eight patients, (3) He ADC values for the ipsilateral lung were significantly higher than those for the contralateral lung. Functional and micro-structural changes persist into adulthood in most CDH patients. Ipsilateral elevated (3) He ADC values are consistent with enlargement of mean dimensions of the confining lung micro-structure at the alveolar level.

In a young cohort of patients, number of embryos frozen indicates better prognosis for future frozen cycle

In a young cohort of patients, number of embryos frozen indicates better prognosis for future frozen cycle

A decision tool for whole-body CT in major trauma that safely reduces unnecessary scanning and associated radiation risks: An initial exploratory analysis.

Whole-body CT (WBCT) has become routine practice in the assessment of major trauma patients. Whilst this may be associated with increased survival, several studies report high rates of negative scans. As no national guideline exists, selection criteria for WBCT vary widely. This study aims to (1) produce a scoring system that improves patient selection for WBCT (2) quantify patient radiation doses and their concomitant risk of malignancy. Clinical notes were reviewed for all patients undergoing a WBCT for trauma over a 21-month period at a UK major trauma centre. Clinical and radiological findings were categorised according to body region. Univariate analysis was performed using Chi-squared testing, followed by multivariable logistic regression. Secondary regression analysis of patients with significant injuries that the model did not identify was performed. The model was optimised and used to develop a scoring system. Sensitivity and specificity were calculated using the same dataset as was used to derive the models. Radiation exposure was determined and the excess lifetime risk of malignancy calculated. 255 patients were included, with a mean age of 45 years. 16% of scans were positive for polytrauma, 42% demonstrated some injury and 42% showed no injury. The regression model identified independent predictors of polytrauma to be (1) clinical signs in more than one body region, (2) reduced Glasgow Coma Score, (3) haemodynamic abnormality, (4) respiratory abnormality, (5) mechanism of injury. The final model had a sensitivity of 95% (95% CI 86-99%) and specificity of 59% (95% CI 52-66%) for significant CT findings. Mean radiation exposure was 31.8 mSv, conferring a median excess malignancy risk of 1 in 474. After including neurological deficit, our scoring system had a sensitivity of 97% (95% CI 88-99%) and specificity of 56% (95% CI 49-64%) for significant injury. We propose this is used to stratify the use of trauma radiographs, focused CT and WBCT for major trauma patients. Although not intended to replace clinical judgement, our scoring system adds an objective component to decision-making. We believe this will safely reduce the number of unnecessary CT scans performed on a relatively young cohort of patients.

National Trends of Local Ablative Therapy Among Young Patients With Small Renal Masses in the United States

To assess national trends in the usage of local ablative therapy for small renal masses (SRMs) in a cohort of young patients. Ablation of SRMs has been shown to offer cancer control with limited follow-up. Although ablation is considered effective for patients with limited life expectancy, its use among younger patients may be considered controversial. We used the National Cancer Data Base to identify patients between the ages of 40 and 65 years who were diagnosed with SRMs from 2004 to 2011. The primary outcome was the use of local ablative therapy. Multivariable logistic regression analysis was used to identify patient and hospital factors associated with ablation therapies in this cohort. During the study period, we identified 49,441 patients with SRMs, of which 2789 (5.6%) were treated with ablative therapies. The proportion of patients undergoing ablation gradually rose from 2.2% in 2004 to 6.2% in 2011 (P < .001). On multivariable analysis, patients were more likely to receive local ablation at academic hospitals (odds ratio [OR]: 1.5; P < .001) compared with community hospitals, or primarily insured by Medicaid (OR: 1.4; P < .001) or Medicare (OR: 1.3; P < .001) compared with private insurance. The use of local ablative therapies is gradually rising but has so far been limited to a small fraction of young patients with SRMs. Patients treated at high-volume, academic hospitals or insured with Medicaid or Medicare were treated to a greater degree with ablation. These results have important implications for the adoption of ablation and the need for long-term surveillance.

Prevalence and risk factors for violent behavior in young people presenting with first-episode psychosis in Hong Kong: A 3-year follow-up study.

The aim of the current study was to examine the rates of violence prior to and 3 years following treatment initiation, and predictors of post-treatment violence in Chinese young people presenting with first-episode psychosis (FEP). Seven hundred patients aged 15-25 years consecutively enrolled in a territory-wide early intervention program for FEP in Hong Kong from July 2001 to August 2003 were studied. Socio-demographic, pre-treatment, baseline and 3-year follow-up variables were collected via systematic medical file review. Violent behavior was defined as physical aggression towards people and was further categorized at two levels of severity. After onset of psychosis, 6.7% (n = 47) patients exhibited violence before treatment. During 3-year treatment period, 9.4% (n = 66) committed violent behavior and 4.3% (n = 30) perpetrated serious violence. Two-fifths (40.4%) of patients who displayed pre-treatment violent behavior engaged in further act of violence after service contact. Multivariate regression analysis showed that previous violence, male gender and lower educational attainment were significantly associated with an increased risk of violence during 3-year follow-up. Comorbid substance, male gender, lower educational level and past history of violence were found to independently predict occurrence of serious violence after commencement of treatment for FEP. In a large representative cohort of Chinese young FEP patients, the rates of violent behavior before and after treatment were relatively lower than that reported in the literature. Risk factors for violence identified by the current study were comparable to the findings of previous research conducted in western populations. Close monitoring of patients with history of violence and specific treatments targeting at minimizing substance abuse may facilitate early identification and intervention of high-risk cases to reduce violence risk in the early course of illness.

Prevalence of degenerative changes of the spine on magnetic resonance images and radiographs in patients aged 16-45 years with chronic back pain of short duration in the Spondyloarthritis Caught Early (SPACE) cohort.

To determine the prevalence of degenerative changes (DCs) in the spine of young patients with back pain without axial spondyloarthritis (no-axSpA), with possible axSpA (poss-axSpA) and with definite axSpA (axSpA), as shown on MRI and radiographs. Whole-spine MRI and cervical and lumbar radiography were performed in patients ≥16 years of age with chronic back pain (≥3 months, ≤2 years, onset <45 years) and potential axSpA (Spondyloarthritis Caught Early cohort). Patients were classified as no-axSpA, poss-axSpA [not fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria] or axSpA (fulfilling ASAS axSpA criteria). Images (MRI and X-rays) were evaluated on the presence of DCs by two independent readers, blinded to clinical and laboratory information as well as to the results of the other imaging modality. In cases of disagreement, a third reader served as adjudicator. A Chi-square test was used to analyse differences between patient groups according to various selected cut-off points (1-3) of individual DCs. Of 274 patients (38% male, mean age: 29 years), 25 (9%) were classified as no-axSpA, 134 (48.9%) as poss-axSpA and 115 (42.0%) as axSpA. Two hundred and forty-five (89%) patients had DCs on MRI [21/25 (84%) no-axSpA, 121/134 (90%) poss-axSpA, 103/115 (90%) axSpA, P = 0.792], range 1-29 (median 5.5), and 121 (44%) patients had DCs on radiographs [13/25 (52%) no-axSpA, 62/134 (46%) poss-axSpA, 48/115 (42%) axSpA, P = 0.261], range 1-11 (median 2). Prevalence of DCs was similar between patient groups. DCs were predominantly found in the lumbar spine. Prevalence of DCs was high in this cohort of young patients with short-term chronic back pain, in accordance with the literature. Prevalence of DCs in no-axSpA patients, poss-axSpA patients and axSpA patients was found to be similar.

T-Tau is Associated with Objective Memory Decline Over Two Years in Persons Seeking Help for Subjective Cognitive Decline: A Report from the Gothenburg-Oslo MCI Study.

There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.

Resting 12-lead electrocardiogram reveals high-risk sources of cardioembolism in young adult ischemic stroke

BackgroundThe diagnostic work-up to reveal etiology in a young ischemic stroke (IS) patient includes evaluation for high-risk source of cardioembolism (HRCE), since this subtype associates with high early recurrence rate and mortality. We investigated the association of ECG findings with a final etiologic subgroup of HRCE in a cohort of young patients with first-ever IS. MethodsThe Helsinki Young Stroke Registry includes IS patients aged 15 to 49years admitted between 1994 and 2007. Blinded to other clinical data, we analyzed a 12-lead resting ECG obtained 1–14days after the onset of stroke symptoms in 690 patients. We then compared the ECG findings between a final diagnosis of HRCE (n=78) and other/undetermined causes (n=612). We used multivariate logistic regression to study the association between ECG parameters and HRCE. ResultsOf our cohort (63% male), 35% showed ECG abnormality, the most common being T-wave inversion (16%), left ventricular hypertrophy (14%), prolonged P-wave (13%), and prolonged QTc (12%). 3% had atrial fibrillation (AF), and 4% P-terminal force (PTF). Of the continuous parameters, longer QRS-duration, QTc, and wider QRS-T-angle independently associated with HRCE. After AF, PTF had the strongest independent association with HRCE (odds ratio=44.32, 95% confidence interval=[10.51–186.83]), followed by a QRS-T angle >110° (8.29 [3.55–19.32]), T-wave inversion (5.06, 2.54–10.05), and prolonged QTc (3.02 [1.39–6.56]). ConclusionRoutine ECG provides useful information for directing the work-up of a young IS patient. In addition to AF, PTF in particular showed a strong association with etiology of HRCE.

Long-Term Follow-Up of Chemotherapy-Induced Ovarian Failure in Young Breast Cancer Patients: The Role of Vascular Toxicity.

We previously reported that chemotherapy-induced ovarian toxicity may result from acute vascular insult, demonstrated by decreased ovarian blood flow and diminished post-treatment anti-Müllerian hormone (AMH) levels. In the present study, we report the continuous prospective evaluation of ovarian function in that cohort. Patients (aged <43 years) with localized breast cancer were evaluated by transvaginal ultrasound prior to initiation of chemotherapy, immediately at treatment completion, and at 6 and 12 months after treatment cessation. Doppler flow velocity indices of the ovarian vasculature (resistance index [RI], pulsatility index [PI]) were visualized. Hormone markers of ovarian reserve were assessed at the same time points. Twenty patients were enrolled in the study. Median age was 34 ± 5.24 years. Ovarian blood flow was significantly reduced immediately following chemotherapy (both RI and PI; p = .01). These parameters were partially recovered at later points of assessment (6 and 12 months after treatment); patients aged <35 years significantly regained ovarian blood flow compared with patients aged >35 years (p < .05). AMH dropped dramatically in all patients following treatment (p < .001) and recovered in only 10 patients. Hormone markers of ovarian reserve shortly after chemotherapy depicted a postmenopausal profile for most patients, accompanied by related symptoms. Follicle-stimulating hormone (FSH) levels recovered in 14 of 20 patients and significantly returned to the premenopausal range in patients aged <35 years (p = .04); 10 of 20 resumed menses at 12 months. The pattern of vascular impairment was lessened in patients treated with a trastuzumab-based protocol, although results did not reach statistical significance (p = .068). Continuous prospective evaluation of ovarian vasculature and function in a cohort of young patients during and after chemotherapy indicated that ovarian toxicity may derive from acute vascular insult. Age may affect whether patients regain ovarian function, whereas recovery of blood flow and premenopausal FSH levels at later assessment was notable in patients aged <35 years. This study explored the role of vascular toxicity in mediating ovarian impairment and recovery following chemotherapy. Continuous prospective evaluation of ovarian vasculature and function in a cohort of young patients during and after chemotherapy indicated that ovarian toxicity may derive from acute vascular insult. Future studies are warranted to further characterize patterns of vascular toxicity of various chemotherapies in clinical practice and to assess the role of chemotherapy-induced vascular toxicity for specific end organs such as the ovary with systemic vascular effect. Elucidating the cause of impairment may facilitate development of measures to minimize vascular toxicity and consequences of acute vascular insult.

Risk factors for lung function decline in a large cohort of young cystic fibrosis patients.

To identify novel risk factors and corroborate previously identified risk factors for mean annual decline in FEV1% predicted in a large, contemporary, United States cohort of young cystic fibrosis (CF) patients. Retrospective observational study of participants in the EPIC Observational Study, who were Pseudomonas-negative and ≤12 years of age at enrollment in 2004-2006. The associations between potential demographic, clinical, and environmental risk factors evaluated during the baseline year and subsequent mean annual decline in FEV1 percent predicted were evaluated using generalized estimating equations. The 946 participants in the current analysis were followed for a mean of 6.2 (SD 1.3) years. Mean annual decline in FEV1% predicted was 1.01% (95%CI 0.85-1.17%). Children with one or no F508del mutations had a significantly smaller annual decline in FEV1 compared to F508del homozygotes. In a multivariable model, risk factors during the baseline year associated with a larger subsequent mean annual lung function decline included female gender, frequent or productive cough, low BMI (<66th percentile, median in the cohort), ≥1 pulmonary exacerbation, high FEV1 (≥115% predicted, in the top quartile), and respiratory culture positive for methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus, or Stenotrophomonas maltophilia. We have identified a range of risk factors for FEV1 decline in a large cohort of young, CF patients who were Pa negative at enrollment, including novel as well as previously identified characteristics. These results could inform the design of a clinical trial in which rate of FEV1 decline is the primary endpoint and identify high-risk groups that may benefit from closer monitoring.

Outcomes of repair of left partial anomalous pulmonary venous connection in children

Herein, we report a case series of patients who underwent repair of left partial anomalous pulmonary venous connection (L-PAPVC) via anastomosing the anomalous pulmonary vein (PV) to the left atrial appendage. Fifteen children underwent repair of L-PAPVC between 1980 and 2014. The median age at surgery was 3.6 years (range: 5 days to 17.2 years). Concomitant anomalies were present in 87% (13/15). There were no early deaths. There was 1 late death occurring 63 days following surgical repair due to pneumococcal septicaemia in a patient with prior atrial septal defect closure and Ehlers-Danlos syndrome. The overall survival rate was 93.7% at 15 years. A single patient (1/15, 7%) required reoperation 1 year after L-PAPVC repair for PV stenosis due to several thrombi located throughout the PV. The rate of freedom from PV reoperation was 90% at 10 years. The follow-up was 100% complete with a median time of 11 years (range: 52 days to 20 years). To our knowledge, this is the youngest cohort of patients who have undergone surgical repair of L-PAPVC. Repair of L-PAPVC in children can be achieved via anastomosis of the anomalous vessel to the left atrial (LA) with excellent outcomes. The rate of anastomotic stenosis at the site of implantation on the LA is low.