Other Causes Research Articles

Characteristics of Cerebral Venous Sinus Thrombosis Due to Autoimmune Diseases: A Single-Center Retrospective Observational Study.

Cerebral venous sinus thrombosis (CVST) is a cerebrovascular disease characterized by thrombosis of the cerebral venous or dural sinuses. Autoimmune diseases (AD) are important causes of CVST. This study aims to reveal the differences between CVST associated with autoimmune diseases compared with other causes (OCs) and Behcet's syndrome (BS) compared with other ADs. This is a single-center retrospective study in which the medical records of 187 patients we followed with a diagnosis of CVST between 2008 and 2023 were collected retrospectively. Four neurologists collected data on initial symptoms, neurological examinations, and laboratory findings. Findings on magnetic resonance imaging and magnetic resonance venography performed on all patients (thrombosis localizations, hemorrhagic or ischemic complications, and collateralization) were re-evaluated by 2 radiologists. The results were compared with AD, other ADs, and OCs groups. There were 28 cases of CVST associated with AD. Of these, 18 were BS, and 10 were other AD. Subacute-chronic onset, headache, and transverse sinus involvement were more common in AD-related patients than in OCs. However, collateralization, venous infarction, hemorrhagic transformation, and bleeding were less common. BS-related patients had earlier age, more frequent transverse sinus, less frequent cortical vein thrombosis, and better collateralization than other ADs. CVST is one of the rare complications in autoimmune diseases. It has a more subacute-chronic onset. Since headaches are more common, it is essential to make a differential diagnosis of CVST in autoimmune diseases with chronic headaches. Transverse sinus thrombosis is more common. Collateralization, venous infarction, and hemorrhagic transformation are less.

Lethality among individuals infected with visceral leishmaniasis in Brazil: a retrospective study (2007-2018).

Visceral leishmaniasis (VL) is a public health problem with a high prevalence and lethality in Brazil. This study aims to estimate the lethality and associated factors in individuals with VL and assess survival time, emphasizing VL/HIV coinfection. This retrospective study has 37,583 individuals notified and confirmed with VL in the Sistema de Informação de Agravos de Notificação (SINAN) between 2007 and 2018 (Brazil). Lethality was evaluated considering VL deaths, deaths from other causes (OC), and non-deaths. We performed a multinomial logistic regression, with non-death as the benchmark category. We conducted a survival analysis (Kaplan-Meier method), emphasizing VL/HIV coinfection. Most individuals were young, male, mixed race, low schooling level, and urban dwellers. The lethality rate was 10.2% (VL and OC deaths) and 7.8% (VL deaths). The prevalence of HIV infection was 8.81%. A higher likelihood of VL and OC deaths was observed in older age groups, females, and with a higher number of symptoms. A higher likelihood of OC deaths was identified in individuals with HIV. A lower likelihood of VL and OC deaths was observed for individuals on VL therapy. The mean survival time was longer for VL/HIV individuals, who had a lower survival rate than those with VL. The data point to the need for attention to the timely diagnosis of VL and HIV and adequate pharmacological treatment in this population.

Left atrial mechanics for secondary prevention from embolic stroke of undetermined source.

Anticoagulation is not justified unless atrial fibrillation (AF) is detected in cryptogenic stroke (CS) patients. We sought to explore whether left atrial (LA) remodelling is associated with embolic stroke of undetermined source (ESUS). In this prospective study, we evaluated consecutively 186 patients in sinus rhythm who presented with an acute ischaemic stroke (embolic and non-embolic) and sex- and age-matched controls. We performed continuous electrocardiogram (ECG) monitoring to capture paroxysmal AF episodes as recommended by the guidelines. After 12 months of follow-up, continuous ECG monitoring was repeated in patients with undetected AF episodes. We quantified LA reservoir and contraction strain (LASr and LASct) by speckle-tracking, LA volumes by 3D echocardiography. Out of 186 patients, 149 were enrolled after comprehensive investigation for the source of ischaemic stroke and divided into other cause (OC) (n = 52) and CS (n = 97) groups. CS patients were also subdivided into AF (n = 39) and ESUS (n = 58) groups. Among CS patients, LA strain predicted AF independently from CHARGE-AF score and LA volume indices. ESUS group, despite no captured AF, had significantly worse LA metrics than OC and control groups. AF group had the worst LA metrics. Moreover, LASr predicted both CS (embolic stroke with and without AF) and ESUS (embolic stroke with no detected AF) independently from LAVImax and CHA2DS2-VASc score. LASr >26% yielded 86% sensitivity, 92% specificity, 92% positive, and 86% negative predictive values for the identification of ESUS (areas under curve: 0.915, P < 0.0001, 95% confidence interval: 0.86-0.97). Echocardiographic quantification of LA remodelling has great potential for secondary prevention from ESUS.

Mortality Secondary to Unintentional Poisoning after Inpatient Rehabilitation among Individuals with Moderate to Severe Traumatic Brain Injury.

Studies have shown reduced life expectancy following moderate-severe traumatic brain injury (TBI) with death from unintentional poisoning (UP) being 11 times higher following TBI than in the general population. The characteristics of those who die of unintentional poisoning are compared with the characteristics of those who die of other causes (OC) in a retrospective cohort who received inpatient rehabilitation following TBI and enrolled in the TBI Model Systems National Database between 1989 and 2017 (n = 15,835 cases with 2,238 deaths recorded). Seventy-eight cases (3.5%) of deaths were the result of UP, 76% were the result of OC, and 20.5% were from an unknown cause. Among the UP deaths, 90% involved drugs (of these, 67% involved narcotic drugs and 14% involved psychostimulants), and 8% involved alcohol. Age-adjusted risk for UP death was associated with: white/non-Hispanic race/ethnicity, living alone, non-institutionalization, pre- and post-injury illicit drug use and alcohol/drug problem use, any alcohol use at last follow-up, better Functional Independence MeasureTM (FIM) scores, history of arrest, moderate disability (vs. severe disability or good recovery), less supervision needed, and greater anxiety. Adults who receive inpatient rehabilitation for TBI who die from UP are distinguishable from those who die of OC. Factors such as pre-injury substance use in the context of functional independence may be regarded as targets for prevention and/or intervention to reduce substance use and substance-related mortality among survivors of moderate-severe TBI. The current findings may have implications for medical care, surveillance, prevention, and health promotion.

P358 Prevalence of suicide in a cohort of subjects submitted to exercise echocardiography: clinical characteristics and exercise echocardiography results

Abstract Patients with clinical symptoms and morbidities might be more prone to commit suicide. Suicidal rate reaches up to 25-30/100.000 subjects in the countries most affected by this problem. We aimed to establish the rate of suicides among a large cohort of patients submitted to Exercise echocardiography (ExE), and also to study their clinical and ExE results, to better understand possible explanations. Methods Retrospective analysis of prospectively collected data on 12,615 patients (age 62 ± 12 years, 63% men) with a first treadmill ExE performed in our center for known/suspected coronary artery disease. Exclusion criteria were significant valve disease, cardiomyopathy, congenital heart disease, and age &amp;lt;18 year-old. Ischemia was defined as the development of new wall motion abnormalities (WMAs) with exercise; abnormal ExE as ischemia or resting WMAs. Results During a follow-up of 4.7± 4.8 years (interquartil range 0.1-8.0 years) there were 2,578 deaths, including 21 due to suicide (rate 166/100.000 subjects). We compare clinical characteristics and ExE results between patients that committed suicide (S), patients that died of other causes (OC), and patients that survived (Surv). The worst clinical and ExE characteristics were found in patients that died of non-suicidal causes, whereas patients that committed suicide were in an intermediate risk position (Table). In conclusion, suicidal rate seems to be very high among patients with a clinically indicated ExE. Clinical characteristics and ExE results of suicidal subjects are worse than in survivor patients and could in part explain this event. Surv S OC P value Age, y 61 ± 12 65 ± 11 69 ± 9 &amp;lt;0.001 Male 60% 86% 72% &amp;lt;0.001 Diabetes Mellitus 17.5% 24% 31% &amp;lt;0.001 Achieved METS 9.7 ± 3.2 8.3 ± 3.6 7.6 ± 2.9 &amp;lt;0.001 Good functional capacity (≥10 METs) 55% 52% 29% &amp;lt;0.001 Symptoms during ExE 16% 14% 19% 0.01 Maximal double product 25.0 ± 5.9 22.5 ± 6.4 22.9 ± 6.0 &amp;lt;0.001 Submaximal test 20% 31% 32% &amp;lt;0.001 Ischemia 27% 38% 44% &amp;lt;0.001 ExE abnormal 37% 50% 63% &amp;lt;0.001 LVEF at rest 59 ± 7 53 ± 13 54 ± 11 &amp;lt;0.001 LVEF at peak 64 ± 11 60 ± 16 55 ± 15 &amp;lt;0.001

Can Fetuin-A, CRP, and WBC Levels Be Predictive Values in the Diagnosis of Acute Appendicitis in Children with Abdominal Pain?

Background: Acute appendicitis (AA) is the most common cause of emergency surgery. Therefore, perforation is common. Early diagnosis and new markers are needed. The aim of this study was to investigate the effects of plasma Fetuin-A (FA) levels in patients with an acute abdomen (AB). Material and Method: This prospective study included 107 patients younger than 16 years of age who were admitted to the emergency department for abdominal pain between January and December 2018. The patients who presented abdominal pain were divided into two groups as AA and other causes (OC) of AB. Patients with acute appendicitis; intraperitoneal, retrocolic/retrocecal, and appendicitis were divided into three groups. Additionally, the AA group was divided into two groups as perforated appendicitis and non-perforated appendicitis. Serum FA levels of the patients were evaluated in the emergency department. Results: In the AA group, C-reactive protein (CRP) and white blood cell (WBC) levels were higher, and FA levels were significantly lower than in the AB group. Intraperitoneal localization was 95.2% and perforation was frequent. When significant values in the univariate regression analysis for acute abdomen and perforation were compared in the multivariate regression analysis, CRP, WBC, and FA levels were found to be prognostic. Furthermore, decreased FA levels were associated with AA, while too greatly decreased FA levels were associated with the risk of perforation. Conclusion: Current diagnosis can be made by history, physical examination, laboratory, and imaging methods in appendicitis cases. While trying to diagnose AA in children, the FA, CRP, and WBC levels may be predictive values to identify risk factors.

External causes of death after severe traumatic brain injury in a multicentre inception cohort: clinical description and risk factors

ABSTRACTObjective: To characterize the clinical profile of patients dying from external causes (EC) following severe traumatic brain injury (TBI).Design and Methods: Data from 2545 patients forming the NSW-BIRP inception cohort discharged from post-acute inpatient rehabilitation between 1 July 1990 and 1 October 2007 were retrospectively reviewed. Standardized mortality ratios (SMRs) were calculated for EC sub-categories. Demographic, clinical and rehabilitation service factors were compared between deaths from EC, deaths from other causes (OC), and non-deceased. Clinical profiles of EC sub-categories were analysed descriptively.Results: Overall, patients with TBI were 5.2x more likely to die from EC relative to the general population. Risk of death was elevated in all EC sub-categories examined, with the largest risks relating to other accidental threats to breathing (SMR = 33.0; 95%CI = 13.79–60.45) and falls (SMR = 14.3; 95%CI = 5.01–28.39). The EC group were younger, more likely to have pre-injury psychiatric histories, less severe injuries, greater functional independence, and die earlier than the OC group. There was considerable heterogeneity in the clinical profiles of patients dying from different EC sub-categories.Conclusions: EC constitutes one of the largest causes of mortality following TBI in patients surviving beyond the post-acute phase. Potential implications for risk modification and prevention of premature and avoidable deaths are discussed.

Effect of iron status on fertility of woman in relation with certain hormones and other parameters

Seventy six subfertile women and thirty fertile women (control group) enrolled in this study. The subfertile women subdivided into two subgroups according to the cause of subfertility: first group ovarian dysfunction (OD) either due to polycystic ovary syndrom (PCOS) or due to other cause (OC) likes anovulation, hyperprolactenemia, premature ovarian failure. Second group: unexplained infertility, their age range (16-40) yr. At day 3 of menstrual cycle (MC) estimation of serum level of multiple hormones like luteinized (LH), follicle stimulating (FSH), estradiole (E2), prolactin (PRL), testosterone, iron status (serum iron, serum ferrtin and total iron binding capacity TIBC) , while at day 13 of MC, estimation of serum levels of LH, serum leptin, glutathione, iron status .Comparison of iron status between fertile and subfertile women at day 13 of MC revealed significant increase in serum ferritin level in women with PCOS. Assessment the serum levels of certain hormones in fertile and subfertile women in those having serum ferritin level less than normal value at day 3 of MC show the following: significantly higher serum testosterone level in PCOS group, also significantly higher serum prolactine level in group of OD due to O.C. as compared with fertile group. Assessment the serum levels of certain hormones in fertile and subfertile women in those having serum ferritin level higher than normal value at day 3 of MC show significantly higher serum prolactine level in group of OD due to O.C. as compared with fertile group. Assessment the serum levels of certain hormones in those having serum ferritin level less than normal value at day 13 of MC, shows significant decrease in LH in women with OD due to O.C. as compared with fertile group.Conclusions: It was concluded that the decrease in serum ferritin levels in the blood may be associated directly or indirectly with subfertility caused by ovarian dysfunction

Preoperative medical treatment in Cushing's syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN.

Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.

Long-term causes of relative excess mortality after diagnosis of testicular germ cell tumor.

4553 Background: Despite today’s excellent cure rates among testicular germ cell tumor (TGCT) patients, reduced long-term relative survival (RS) is an increasing concern. We recently reported a continuing decline in RS among TGCT patients diagnosed in Norway, even beyond 30 years of follow-up. Late effects of treatment is the main culprit. Although several reports describe increased mortality from second cancer (SC), cardiovascular disease (CVD), and other causes (OC) among TGCT survivors, data beyond 20 years of follow-up are scarce. The study aim was to analyze long-term relative risks (RR) and causes of death (CD) among TGCT patients diagnosed in Norway, 1953-2014. Methods: Data sources were the Cancer Registry of Norway and the Norwegian Cause of Death Registry. All men diagnosed with TGCT in Norway during 1953-2014 were included, except spermatocytic seminomas. End of follow-up was December 31st, 2014. Patients were classified by CD, histology, disease extent and age at diagnosis, as well as by decade of diagnosis and follow-up time. Standardized mortality ratios (SMR), compared with the general Norwegian male population, were computed. Results: At end of follow-up, 2359 of 9390 patients were deceased. CD was obtained for 2320 patients; 37.6 % TGCT, 24.5 % SC, 19.1 % CVD and 18.8 % OC. SMR for all SC were significant particularly after 20 years of follow-up (1.8 – 3.1), with similar findings in localized disease at diagnosis. SMR were most consistently elevated beyond 20-30 years for SC of the pancreas, large intestine and bladder. By contrast, SMR for CVD were significant among patients diagnosed 2000-14, both before and after one year of follow-up (2.6). There were no significant SMR for CVD beyond 20 years of follow-up. Several OC SMR were elevated, such as for digestive and genitourinary diseases beyond 20-30 years (2.2 – 5.1). Conclusions: TGCT patients have increased RR of SC and OC death even beyond 20-30 years of follow-up, while the increased RR of CVD death is mostly confined to the first decade. CVD deaths in patients diagnosed 2000-14 are a particular concern. Continuing optimization of TGCT treatment and follow-up schemes is required, including further research on toxicity mechanisms.

Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN.

To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing's syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. We analyzed data on the diagnostic tests performed in 1341 patients with Cushing's syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.

Competing risks of mortality by PAM50 intrinsic subtype: BC tamoxifen-treated cohort.

562 Background: We previously showed that baseline patient/tumour characteristics, or prior treatment affected cause of death in NCIC CTG endocrine therapy trials (MA.14, MA.17, MA.27), in particular older age was associated with non-breast cancer death. We now examine whether PAM50 intrinsic subtypes were differentially associated with cause of death in a cohort of British Columbia tamoxifen-treated patients. Methods: Patients were 718 post-menopausal women, treated with tamoxifen, without adjuvant chemotherapy who had tumours which were Luminal A, Luminal B, Basal, or HER2 intrinsic subtype and known cause of death [cancer-specific (BrCa); other cause (OC)]. We tested whether intrinsic subtype and other patient and tumour characteristics were associated with 1) all cause mortality, and if so, 2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. Results: Patients were followed a median of 11.7 years. In women <70 years of age, 138/425 (32% died of breast cancer) and ...

Competing risks of death in younger and older postmenopausal breast cancer patients

To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival (P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival (P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa) and other cause (OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1 (IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-hydroxy vitamin D were associated with (1) all cause mortality, and if so and (2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447 (82%) < 70 years and 120 (18%) ≥ 70 years. There were 170 deaths: 106 (62.3%) BrCa; 55 (32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9 (5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrCa and OC deaths were not significantly different by treatment arm (P = 0.40): tamoxifen patients experienced 50 BrCa and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 BrCa and 23 OC deaths. Proportionately more deaths (P = 0.004) were from BrCa for patients < 70 years, where 70% of deaths were due to BrCa, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index (BMI) (P = 0.02). Higher pathologic T and N were associated with more BrCa deaths (P < 0.0001 and 0.002, respectively). The cumulative hazard plot for BrCa and OC mortality indicated the concurrent accrual of both types of death throughout follow-up, that is the existence of competing risks of mortality. MA.14 therapy did not impact mortality (P = 0.77). Three baseline patient and tumor characteristics were differentially associated with cause of death: older patients experienced more OC (P = 0.01) mortality; patients with T1 tumors and hormone receptor positive tumors had less BrCa mortality (respectively, P = 0.01, P = 0.06). Additionally, step-wise cause-specific models indicated that patients with node negative disease experienced less BrCa mortality (P = 0.002); there was weak evidence that, lower C-peptide (P = 0.08) was associated with less BrCa mortality, while higher BMI (P = 0.01) was associated with worse OC mortality. We demonstrate here a new paradigm of simultaneous testing of therapeutics directed at multiple diseases for which postmenopausal women are concurrently at risk. Octreotide LAR did not significantly impact breast cancer or other cause mortality, although different baseline factors influenced type of death.

Abstract 2919: Do Premature Ventricular Contractions Play a Role in the Etiologic Subtypes of Ischemic Stroke?

Background The relationship between stroke and non-atrial fibrillation cardiac arrhythmias remains unclear. Frequent premature ventricular contractions (PVCs) are associated with impaired ventricular relaxation and may increase the risk of clot formation and subsequent embolization. This study investigated the relationship between frequency of PVCs and etiologic subtypes of ischemic stroke. Methods Consecutive ischemic stroke patients admitted within 7 days of onset who underwent 24-hour Holter monitoring were enrolled (n=451). Subtypes of ischemic stroke were defined according to the SSS-TOAST classification as Large artery atherosclerosis (LAD), cardioembolic stroke (CE), small vessel occlusion (SVO), other causes (OC), and cryptogenic stroke (CS). Risk factors, demographic information, and 24-hour Holter recordings were compared between the subtypes of ischemic stroke. Results There were 182 women and 269 men (191 LAD, 90 CE, 93 SVO, 13 OC, 64 CS), with a mean age of 66 years (median 68). PVCs were seen in 305 patients (67.5%) on 24-hour Holter monitoring (median 3, IQR 0-48). CE had a higher median number of PVCs (median 24, IQR 0-258) than LAD (median 2, p=0.01), SVO (median 1, p&lt;0.001), OC (median 0, p=0.013), and CS (median 4, p=0.2). The proportions of frequent PVCs (&gt;50 in a 24-hour Holter monitoring) were higher in CE (43.3%) compared with the other groups (20.9% in LAD, 15.1% in SVO, 15.4% in OC, and 23.4% in CS; p&lt;0.001). Compared with the SVO, the upper 3 quartiles of PVCs were associated with CE (OR 2.93; 95% CI, 1.69 to 5.06) and CS (OR 1.86; 95% CI, 1.07 to 3.2) in ordinal logistic regression analysis after adjustment for traditional risk factors. Conclusions The number of PVCs detected by 24-hour Holter monitoring is associated with CE and CS. The presence of high frequency of PVC may help in stratifying patients with different stroke subtypes, particularly embolic stroke. The role of these arrhythmias as a risk marker for ischemic stroke deserves further investigation.

Competing causes of death in NCIC CTG MA.17, a placebo-controlled trial of letrozole as extended adjuvant therapy for breast cancer patients

540 Background: Risk of death from other malignancies (OM) and other causes (OC) than breast cancer (BC) increases with age. Effects of baseline factors on type of death were assessed with competing risks analyses. Methods: In NCIC CTG MA.17, 5,187 women free of recurrent breast cancer after 5 years of tamoxifen were randomized to letrozole (L, 2,593 women) or placebo (P, 2,594 women). The primary endpoint was disease free survival (DFS), and secondary, overall survival (OS). Follow-up was to October 9, 2005: median 3.9 years, range &lt;0.1 to 7.0 years. Effects of competing risks were examined for endpoints of BC, OM, and OC for 11 baseline trial factors: treatment, age, menopausal status, duration of prior tamoxifen, adjuvant radiotherapy, bone fracture, osteoporosis, cardiovascular disease, hormone receptor status, nodal status, adjuvant chemotherapy. Lagakos’ hierarchical method (Lagakos, Appl. Statist. 1978; 27:235–241) was used to test for differential effects of baseline factors on type of death (BC, OM, OC). Results: Rate of censoring was 97.8%, with 256 deaths (BC, 102; OM, 50; OC, 100; unknown, 4). Non-breast cancer deaths accounted for 60% of known deaths; 72%, for those ≥70 years; and 48%, for those &lt;70 years. Two baseline factors differentially affected type of death. Women with cardiovascular disease were more likely to die from OC (p=0.02), while those with osteoporosis were more likely to die of OM (p=0.03). Age and nodal status had directionally similar effects. Older women had shorter survival from all 3 causes of death (p=0.01). Lymph node positivity was associated with worse survival (p=0.003). Conclusions: Extended L provides similar proportional benefit in improving DFS for all ages of women (Muss ref abstract SABCS 2006). However, the magnitude of competing non-breast cancer, and non-treatment related, causes of death needs to be considered more frequently, since with early detection and improved therapies, breast cancer patients may increasingly be expected to survive their disease to die from another cause. The novel association between baseline osteoporosis and other malignancies is being explored quantitatively. No significant financial relationships to disclose.

The worsening of left ventricular hypertrophy is the strongest predictor of sudden cardiac death in haemodialysis patients: a 10 year survey.

Although the incidence of sudden cardiac death (SCD) is high among haemodialysis (HD) patients, there are few papers available on this topic. The aim of this study on a single-centre HD population observed over a 10 year period was to identify patient- and HD-related specific factors that might be associated with a higher risk of SCD. The study included 123 patients (76 men; age 29-79 years) undergoing renal replacement therapy at our dialysis unit for at least 6 months. For each patient, routine laboratory tests were performed monthly, blood pressure was measured both at the start and the end of each dialysis session, haemoglobin and pre-dialysis serum K(+) were determined weekly, serum iPTH was assessed thrice yearly, and an echocardiographic study was performed annually to determine the left ventricular mass index (LVMi). The prevalence of cardiovascular (CV) co-morbidities, and the incidence of new events were also recorded. During the 10 years, 85 patients died-16 from SCD, 30 from cardiac causes (CC) other than SCD, and 39 from other causes (OC); 38 patients were still alive (AL) at the end of the observation period. Comparative analysis of SCD, CC, OC and AL, reveals that the male prevalence (13/3) was higher in SCD than in AL, while AL were younger than the deceased patients regardless of the cause of death (P<0.0001; ANOVA), the duration of arterial hypertension was higher in SCD (129+/-104 months; P = 0.0005; ANOVA), despite similar antihypertensive therapies, and the difference between LVMi at end-point and at inception (deltaLVMi) was significantly higher in SCD [+56+/-38 g/m(2) body surface area] compared with OC (-5+/-35), AL (-17+/-25) and even CC (7+/-30) (P<0.0001; ANOVA); finally, the prevalence of patients with ischaemic heart disease (IHD) was higher in the SCD group (11/5; P<0.0001, chi(2)). Univariate Cox regression analysis demonstrated that the factors increasing the risk of SCD were IHD (P = 0.002), the worsening of left ventricular hypertrophy (LVH) (P<0.0001), and the presence of long-lasting arterial hypertension (P = 0.001). An increase in LVH was the sole risk factor for SCD when comparing SCD with CC patients (P = 0.003). By multivariate Cox regression analysis deltaLVMi was identified as the strongest predictor of SCD (P<0.0001). While confirming the role of common CV risk factors for SCD in dialysis patients such as IHD and arterial hypertension, this study is the first to demonstrate that the worsening of LVH is the strongest predictor of sudden death.

Massive haemoptysis death and other morbidity associated with high dose rate intraluminal radiotherapy for carcinoma of the bronchus

Four hundred and six patients with primary non-small cell carcinoma of the bronchus causing symptoms due to endobronchial disease, were treated with intraluminal radiotherapy (ILT) using the microSelectron-HDR machine at the Christie Hospital, Manchester, between April 1988 and the end of 1992. An assessment of morbidity for this treatment is presented, particularly with regard to the risk factors and causes of massive haemoptysis death. The most common early side-effect was a mild transient exacerbation of cough which usually resolved within 2–3 weeks. At various times following ILT treatment 83 bronchoscopies were carried out randomly in 55 patients. In bronchoscopies carried out within the first 3 months following ILT, no tumour was visible in 80% of cases. A mucosal radiation reaction score (RRS) was used to grade bronchoscopic appearance after ILT treatment. Overall, 55% of bronchoscopic examinations showed some degree of mucosal radiation reaction. The majority of radiation reactions from 6 months onwards after ILT demonstrated a degree of fibrosis. A radiation reaction was seen more frequently after treatment with 2000 cGy as opposed to 1500 cGy at 1 cm from the central axis of the radiation source. Thirty-two patients were identified who had died from massive haemoptysis (MH) as a terminal event. A Cox multivariate regression analysis showed that the treatment-related factors of increased dose at first ILT ( P = 0.004), prior laser treatment at the site of ILT ( P = 0.020) and second ILT treatment in the same location as the first ILT treatment ( P = 0.047), all significantly increased the relative risk of MH death compared with their effect on the relative risk of death from other causes (OC). (In addition a fourth treatment-related factor, namely the concurrent use of ILT and external beam radiotherapy (EB) had a P value of 0.08). Twenty out of 25 assessable MH-death patients (80%) had evidence of recurrent or residual tumour before death but 5 patients (20%) did not. For surviving patients the instantaneous risk of death at any one time (the cause-specific death rate expressed as deaths per 100 cases per month), showed a sharp peak for MH deaths between 9 and 12 months post ILT in contradistinction to OC death where the peak was between 3 and 6 months post ILT. These findings may imply a role for late radiation reaction in the treatment-related risk factors identified as increasing the relative risk of MH death and possible mechanisms are discussed. The results have implications for treatment regimes that use a dose of 2000 cGy at 1 cm in a single fraction technique, that have a high frequency of previous laser treatment, that use multiple, repeated ILT treatments in the same location and that use ILT concurrently with EB.