Morphology of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPN) are a group of clonal haematological malignancies first described by Dameshek in 1957. The Philadelphia-negative MPN that will be described are polycythaemia vera (PV), essential thrombocythaemia (ET), pre-fibrotic myelofibrosis and primary myelofibrosis (PMF). The blood and bone marrow morphology are essential in diagnosis, for WHO classification, establishing a baseline, monitoring response to treatment and identifying changes that may indicate disease progression. The blood film changes may be in any of the cellular elements. The key bone marrow features are architecture and cellularity, relative complement of individual cell types, reticulin content and bony structure. Megakaryocytes are the most abnormal cell and key to classification, as their number, location, size and cytology are all disease-defining. Reticulin content and grade are integral to assignment of the diagnosis of myelofibrosis. Even with careful assessment of all these features, not all cases fit neatly into the diagnostic entities; there is frequent overlap reflecting the biological disease continuum rather than distinct entities. Notwithstanding this, an accurate morphologic diagnosis in MPN is crucial due to the significant differences in prognosis between different subtypes and the availability of different therapies in the era of novel agents. The distinction between “reactive” and MPN is also not always straightforward and caution needs to be exercised given the prevalence of “triple negative” MPN. Here we describe the morphology of MPN including comments on changes with disease evolution and with treatment.     

Mode of death in patients with newly diagnosed heart failure in the general population

BACKGROUND: Early prognosis for incident (new) heart failure (HF) patients in the general population is poor. Clinical trials suggest approximately half of chronic HF patients die suddenly but mode of death for incident HF cases in the general population has not been evaluated. AIMS: To describe mode of death in the first six months after a new diagnosis in the general population. METHODS: Two-centre UK population-based study. RESULTS: 396 incident HF patients were prospectively identified. Overall mortality rates were 6% [3-8%], 11% [8-14%] and 14% [11-18%] at 1, 3 and 6months respectively. There were 59 deaths over a median follow-up of 10months; 86% (n = 51) were cardiovascular (CV) deaths. Overall, the mode of death was progressive HF in 52% (n = 31), sudden death (SD) in 22% (n = 13), other CV death in 12% (n = 7), and non-CV death in 14% (n = 8). On multivariable analysis, progressive HF deaths were associated with older age, lower serum sodium, systolic hypotension, prolonged QRS duration at baseline and absence of ACE inhibitor therapy at the time of discharge or death. CONCLUSION: Early prognosis after a new diagnosis of HF in the general population is poor and progressive HF, rather than sudden death, accounts for the majority of deaths.     

Cardiovascular safety update of Tadalafil: retrospective analysis of data from placebo-controlled and open-label clinical trials of Tadalafil with as needed, three times-per-week or once-a-day dosing

Because most men with erectile dysfunction have underlying vascular disease, it is important to update the cardiovascular safety profile of medications used in the treatment of erectile dysfunction. This retrospective analysis evaluated serious cardiovascular treatment-emergent adverse events (CVTEAEs) reported in 36 clinical trials of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. A serious CVTEAE was defined as myocardial infarction, cardiovascular death, or cerebrovascular death. In the 36 trials, 12,487 men (mean age 55 years) with erectile dysfunction received tadalafil, with 5,771 patient-years (PYs) of exposure, and 2,047 men (mean age 56 years) received placebo, with 460 PYs of exposure. Tadalafil 2 to 50 mg was taken as needed, 3 times/week, or once a day. Co-morbidities at baseline included hypertension (31%), diabetes (21%), hyperlipidemia (17%), and coronary artery disease (5%). Across all trials, the incidence rate of serious CVTEAEs was 0.40/100 PYs in tadalafil-treated patients and 0.43/100 PYs in placebo-treated patients. In patients taking tadalafil as needed, 3 times/week, or once a day, the incidence rates of serious CVTEAEs ranged from 0.17 to 0.54/100 PYs across placebo-controlled and open-label trials. In conclusion, the incidence rates of serious CVTEAEs were comparable among men with erectile dysfunction taking tadalafil as needed, 3 times/week, or once a day, and these rates were also comparable with those in placebo-treated patients. In this clinical trial population of men with erectile dysfunction, tadalafil was not associated with an increased risk for serious cardiovascular adverse events.     

Long term follow up of 93 families with myeloproliferative neoplasms: life expectancy and implications of JAK2V617F in the occurrence of complications

The long-term evolution of familial myeloproliferative neoplasms was studied in 93 families with 227 subjects including 97 with polycythemia vera (PV), 105 essential thrombocythemia (ET), 14 primary myelofibrosis (PMF) and 11 chronic myeloid leukemia (CML). In PV patients, with 12years of median follow-up, overall survival was 83% at 10years and 37% at 20years. A high JAK2(V617F) allele burden was correlated with the transformation to myelofibrosis (p<0.0001), but not with the transformation to acute leukemia. Among the 105 ET, with 8years of median follow-up, overall survival was 83% at 10years and 57% at 20years. Progression to acute leukemia and progression to myelofibrosis were 10% and 13%. There was a trend toward a more frequent evolution to myelofibrosis when the JAK2(V617F) mutated allele burden was >50% (p=0.09), but not to AML. Hematologic transformation of the MPN was responsible for 69% of the deaths, cerebral stroke for 7% and 4% died of myocardial infarction. Eleven JAK2(V617F) mutated patients developed 13 deep splanchnic thromboses in PV and ET. Finally whereas patients with familial PV and ET have a comparable prognosis to non-familial MPN, the JAK2(V617F) mutation was associated with a more frequent occurrence of thrombosis in the entire population.     

Mortality among males with hemophilia: relations with source of medical care. The Hemophilia Surveillance System Project Investigators

Although persons with hemophilia are known to be at increased risk of death, no studies have examined the source of medical care and other personal characteristics for associations with mortality. To determine death rates and to identify causes of death and predictors of mortality, we studied a cohort comprised of all hemophilic males identified by a six-state surveillance system. Data were obtained by medical record review of contacts with physicians, hemophilia treatment centers (HTCs), and other sources of care during 1993-1995 and from death certificates. Factors examined included age, race, state of residence, health insurance type, medical care source, hemophilia type/severity, presence of inhibitor, liver disease, HIV infection, and AIDS. A total of 2950 subjects were followed for an average of 2.6 years. Their median age was 22 years; 73% were white, 79% had hemophilia A, 42% had severe disease, and 67% had visited an HTC. During 7575 person years (PYs) of observation, 236 persons died-an age-adjusted mortality rate of 40.4 deaths/1000 PYs; 65% of deaths were HIV related. In addition to age, factors independently associated with increased risk of death (relative risk, P value) were the following: AIDS (33.5, <.001); HIV infection (4.7, <.001); liver disease (2.4, <.001); and Medicare/Medicaid insurance (1.4,. 01). Those persons who had received care in an HTC had a significantly decreased risk of death (0.6,.002). Although HIV infection and the presence of severe liver disease remain strong predictors of mortality, survival is significantly greater among hemophilics who receive medical care in HTCs. (Blood. 2000;96:437-442)     

Fatal lactic acidosis associated with highly active antiretroviral therapy in patients with advanced human immunodeficiency virus infection in Taiwan

Lactic acidosis (LA), a rare but life-threatening adverse effect associated with antiretroviral therapy, has been reported with an increasing frequency since the mid-1990s. From June 1994 to June 2002, a total of six patients, four males and two females with a median age of 43 years (range, 30 to 74 years), had been diagnosed with LA. The estimated incidence of LA was 5.1 per 1000 patient-years (PYs) on highly active antiretroviral therapy (HAART) (95% confidence interval [95% CI], 4.5-5.5 per 1000 PYs) and 4.4 per 1000 PY on nucleoside analogues (NAs) (95% CI, 3.9-4.7 per 1000 PYs). Their median body mass index at diagnosis of LA was 17.6 kg/m(2) (range 16.3 to 22.6 kg/m(2)). The median CD4+ lymphocyte count at the initial diagnosis of HIV infection and at the onset of LA was 38 cells/ micro L (range, 4 to 103 cells/ micro L) and 108 cells/ micro L (range, 79 to 224 cells/ micro L), respectively. The most common symptoms were nausea, vomiting, and dyspnoea. All of the patients had findings suggestive of NA-related mitochondrial toxicity, such as myositis, pancreatitis, fatty hepatitis, peripheral neuropathy or lipodystrophy. The prescribed NA related to LA were stavudine in six patients, lamivudine, five, and didanosine, one. Despite treatment, all patients died of persistent circulatory collapse following LA. The median duration from diagnosis to death was eight days (range, 4-17 days). Our report highlights that clinicians caring for patients with AIDS should be alerted to the potentially fatal LA associated with antiretroviral therapy when patients present with low body mass index, lipodystrophy, unexplained abdominal symptoms, dyspnoea, or elevated aminotransferases.     

Long-term follow-up of children and adoles-cents with primary sclerosing cholangitis and autoimmune sclerosing cholangitis

BACKGROUND: Sclerosing cholangitis (SC) is a chronic cho-lestatic hepatobiliary disease with uncertain long-term prog-nosis in pediatric patients. This study aimed to evaluate long-term results in children with SC according to the types of SC.
METHODS: We retrospectively followed up 25 children with SC over a period of 4-17 years (median 12). The diagnosis of SC was based on biochemical, histological and cholangio-graphic ifndings. Patients fuliflling diagnostic criteria for probable or deifnite autoimmune hepatitis at the time of diag-nosis were deifned as having autoimmune sclerosing cholangi-tis (ASC); other patients were included in a group of primary sclerosing cholangitis (PSC). The incidence of the following complications was studied: obstructive cholangitis, portal hy-pertension, advanced liver disease and death associated with the primary disease.
RESULTS: Fourteen (56%) patients had PSC and 11 (44%) had ASC. Patients with ASC were signiifcantly younger at the time of diagnosis (12.3 vs 15.4 years,P=0.032) and had higher IgG levels (22.7 vs 17.2 g/L,P=0.003). The mentioned compli-cations occurred in 4 (16%) patients with SC, exclusively in the PSC group: one patient died from colorectal cancer, one patient underwent liver transplantation and two patients, in whom severe bile duct stenosis was present at diagnosis, were endoscopically treated for acute cholangitis. Furthermore, two other children with ASC and 2 children with PSC had elevated aminotransferase levels. The 10-year overall survival was 95.8% in all patients, 100% in patients without complicated liver disease, and 75.0% in patients with complications.
CONCLUSION: In children, ASC is a frequent type of SC, whose prognosis may be better than that in patients with PSC.     

Sepsis‐associated liver injury: Incidence,classification and the clinical significance

Aim: Although it is a common complication of sepsis, sepsis‐associated liver injury has not been substantially recognized, because its diagnostic criteria and clinical implications are unclear. We aimed to elucidate the incidence, manifestation, disease type classification and prognosis of sepsis‐associated liver injury. Methods: The subjects were 588 patients admitted to our hospital for sepsis between 2001 and 2010. They were classified into “normal liver function”, “sepsis‐associated liver injury” and “sepsis‐not‐associated liver injury” groups. Sepsis‐associated liver injury was classified as either “cholestatic”, “hepatocellular” or “shock liver.” Each of these three subgroups was further classified into “with jaundice” or “without jaundice”. The primary end‐point was the “poor prognosis ratio”, defined as the proportion of patients whose prognosis was “unchanged”, “worsened” or “died”. Results: Among the 449 subjects except for sepsis‐not‐associated liver injury (n = 139), the incidence of sepsis‐associated liver injury was 34.7% (156/449), including 75 cholestatic (48.1%), 34 hepatocellular (21.8%) and 47 shock liver (30.1%) cases. Jaundice was a complication in 25 (33%), six (17.6%) and four (8.5%) patients in each group, respectively. The poor prognosis ratio was higher in males (37.5%) and in the elderly (47.7%); it was 48.0%, 38.2% and 62.8% in the cholestatic, hepatocellular and shock liver groups, respectively, and higher than the normal liver function (18.4%) group (P < 0.0001). It was also higher in patients with jaundice (68.6%) than in those without (45.5%) (P < 0.0001). Conclusion: Sepsis‐associated liver injury, especially with jaundice, is a significant predictive sign of poor prognosis in patients with sepsis.     

Activating CBL mutations are associated with a distinct MDS/MPN phenotype

Activating point mutations in CBL have recently been identified in diverse subtypes of myeloid neoplasms. Because detailed clinical and hematological characteristics of CBL-mutated cases is lacking, we screened 156 BCR-ABL and JAK2 V617F negative patients with myeloproliferative neoplasms (MPN) and overlap syndromes between myelodysplastic syndrome (MDS) and MPN (MPS/MPN) for mutations in exons 8 and 9 of CBL by denaturing high-performance liquid chromatography and direct sequencing. CBL mutations were identified in 16/156 patients (10?%), of which five also carried mutations in EZH2 (n?=?3) and TET2 (n?=?2). Comprehensive clinical and hematological characteristics were available from 13/16 patients (81?%). In addition to splenomegaly (77?%), striking common hematological features were CML-like left-shifted leukocytosis (85?%) with monocytosis (85?%), anemia (100?%), and thrombocytopenia (62?%). Thrombocytosis was not observed in any patient. Relevant bone marrow features (n?=?12) included hypercellularity (92?%) with marked granulopoiesis (92?%), nonclustered microlobulated megakaryocytes (83?%), and marrow fibrosis (83?%). Nine deaths (progression to secondary acute myeloid leukemia/blast phase, n?=?7; cytopenia complications, n?=?2) were recorded. Three-year survival rate was 27?%, possibly indicating poor prognosis of CBL mutated MDS/MPN patients.     

Long-term prognosis after recovery from myocardial infarction: a community-based survey in Yamagata, Japan

OBJECTIVE: To assess the long-term prognosis after recovery from acute myocardial infarction (AMI) in the general population in Japan. PATIENTS AND METHODS: Among the 575,000 inhabitants of the Yamagata metropolitan area, a total of 117 patients suffered from first their AMI from April to December 1993. Thirteen patients (11%) died within four weeks after the onset. Of the remaining 104 patients, 101 (mean age, 69+/-12 years) were followed for an average of 65+/-5 months. RESULTS: Twenty-seven of the 101 patients (27%) died during the follow-up period. Compared with survivors, the patients who died were significantly older at the onset of AMI (74+/-12 vs. 67+/-12 years, p<0.01). More diabetic patients than non-diabetic patients died (42 vs. 21%, p<0.05) because of the higher frequency of non-cardiac deaths (29 vs. 11%, p<0.05). The total number of deaths of cardiac origin, including sudden deaths, was 11 (40%) and was lower than the number of definite non-cardiac deaths (n=15). The time from the onset of AMI to death was significantly shorter in cases of cardiac death than in cases of non-cardiac death (median, 16 vs. 45 months, p<0.01). Among non-cardiac deaths, deaths due to lung cancer and cerebral infarction were notable in men (standardized mortality ratio 278) and women (571), respectively. CONCLUSION: Non-cardiac death during long-term follow-up after AMI was more frequent than death of cardiac origin. Thus, preventive measures, including early treatment of complicating diseases, must be implemented to improve the long-term prognosis of patients with myocardial infarction.     

Comorbidities and sex differences in causes of death among mantle cell lymphoma patients – A nationwide population-based cohort study

The prognosis for mantle cell lymphoma (MCL) remains poor. Our aim was to assess the impact of comorbidities on survival and causes of death. For 1,385 MCL patients (1,009 males, 376 females) diagnosed in 2000–2014 (median age 71 years, range 22–96) comorbidities ≤ 10 years of diagnosis were classified according to the Charlson comorbidity index (CCI; 0, 1, 2+). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to compare lymphoma-specific and all-cause mortality rates. Model-based predictions were used to obtain probabilities of death. Overall, 44% had any comorbidity (CCI 1+) and 28% severe comorbidity (CCI 2+). Over a median follow-up of 3·7 years (range 0–16), 633 (46%) died, the majority (76%) from lymphoma. Severe comorbidity was independently associated with higher all-cause [hazard ratio (HR) = 1·52; 95% CI: 1·24–1·85) and lymphoma-specific mortality (HR = 1·31; 95% CI: 1·04–1·65). Particularly among patients with connective tissue, renal and psychiatric diseases, and dementia. Among females with any comorbidity, non-lymphoma deaths represented a larger proportion of all deaths, compared to males with any comorbidity. In general, more efficient lymphoma treatments need to be considered also for patients with severe comorbidity. However, among females with any comorbidity, the likelihood of non-lymphoma death was still considerable, perhaps favouring a more liberal use of a “wait and watch” approach.     

Survival of children with sickle cell disease

Contemporary survival data are not available for children with sickle cell disease (SCD). The few previous childhood SCD cohort studies do not reflect the benefits of modern therapy. We defined an inception cohort of newborns with sickle cell anemia (SS), sickle-beta degrees -thalassemia (S beta degrees ), sickle-hemoglobin C disease (SC), or sickle-beta(+)-thalassemia (Sbeta(+)) who were identified by newborn screening and followed for up to 18 years. The incidence of death and stroke were calculated. Overall survival, SCD-related survival (considering only SCD-related deaths), and strokefree survival were determined. The 711 subjects provided 5648 patient-years of observation. Twenty-five subjects died; mean age at death was 5.6 years. Five patients died from infection. Thirty had at least one stroke. Among SS and Sbeta degrees subjects (n = 448), the overall rates of death and stroke were 0.59 and 0.85/100 patient-years. Survival analysis of SS and Sbeta degrees subjects predicted the cumulative overall, SCD-related, and stroke-free survival to be 85.6%, 93.6%, and 88.5% by 18 years of age. No SCD-related deaths or strokes occurred in SC or Sbeta(+) subjects (n = 263). Childhood mortality from SCD is decreasing, the mean age at death is increasing, and a smaller proportion of deaths are from infection.     

Mortality and morbidity of HIV infected patients receiving HAART: a cohort study

HAART has substantially decreased mortality and morbidity among HIV-infected patients. We retrospectively analyzed morbidity and mortality in a cohort of HIV-infected adult patients with prolonged and frequent follow up (1987-2006). The study was divided in pre-HAART and HAART period for comparative reasons. In total, 615 HIV-infected patients (54 females) were included in our study. 144 died during the pre-HAART period (51.4 deaths per 100 patients). During the HAART period only 38 patients died from a total of 335 patients receiving HAART (11.3 deaths per 100 patients); the follow up in this part of the cohort was 2139 persons-years and the death incidence 1.77 deaths/per 100 person-years. The subanalysis excluding patients who died within 3 months from admission showed that death incidence among patients that have been receiving HAART from the time of diagnosis (1.2 deaths per 100 person-years) was slightly lower, compared to the death incidence of patients treated for some time with non-HAART as well (1.58 deaths per 100 persons-years). After the availability of HAART in this unit, the proportion of non-AIDS related deaths increased significantly from 8% to 40% (p<0.001); infections remained the leading cause of death in both groups of patients. Tauhe most common non-AIDS related causes of deaths were cancer and coronary disease. Our data from the studied cohort adds to the relevant literature regarding the dramatic reduction of morbidity and mortality that occurred after the availability of HAART.     

Mitral valve repair as an alternative treatment for heart failure patients

Heart failure is one of the leading causes of hospitalization worldwide. Mitral regurgitation (MR) is a known complication of end-stage cardiomyopathy and is associated with a poor prognosis. Historically, these patients were managed medically and frequently with mitral valve replacement, both of which have unfavorable long-term outcomes. Over a 10-year period, we studied 167 patients with cardiomyopathy and severe MR who underwent mitral valve repair. These patients with 4+ MR, a mean left ventricular ejection fraction (LVEF) of 14+/-6 and New York Heart Association (NYHA) class III or IV congestive heart failure (CHF) were prospectively studied. All patients underwent mitral valve repair with an undersized annuloplasty ring. There was one intra-operative death and eight 30-day mortalities. Intra-operative echocardiography revealed no MR in most patients and trivial to mild MR in seven patients. There were 26 late deaths; two of these patients had progression of CHF and underwent transplantation. The 1-, 2-, and 5-year actuarial survival rates were 82%, 71%, and 52%, respectively. NYHA class was improved for all patients from a pre-operative mean of 3.2+/-0.2 to 1.8+/-0.4 postoperatively. At 24-month follow-up, all patients demonstrated improvement in LVEF, cardiac output, and end-diastolic volume, with a reduction in sphericity index and regurgitant volume. Mitral valve repair utilizing an undersized annuloplasty ring is safe and effectively corrects MR in cardiomyopathic patients. All of the observed changes contribute to reverse remodeling and restoration of the normal LV geometric relationship. Mitral valve repair offers a new strategy for patients with MR and end-stage cardiomyopathy.     

Clinical Impact of Valvular Heart Disease in Elderly Patients Admitted for Acute Coronary Syndrome: Insights From the Elderly-ACS 2 Study

BackgroundElderly patients are under-represented in clinical trials and registries, and a gap of evidence exists for clinical decision making in the setting of acute coronary syndromes (ACS). We aimed to assess the prevalence and independent prognostic impact of valvular heart disease (VHD) diagnosed during the index hospitalization on clinical outcomes among elderly patients with ACS. Included VHDs were moderate-to-severe mitral regurgitation (MR), moderate-to-severe aortic stenosis (AS), or both combined.MethodsWe explored the Elderly-ACS 2 dataset, which includes patients older than 74 years of age diagnosed with ACS and managed invasively. The primary endpoint was a composite of all-cause death, myocardial infarction, disabling stroke, and rehospitalization for heart failure at 1 year; the secondary endpoint was death for cardiovascular causes. Patients were stratified into 4 groups: no VHD, moderate-to-severe MR, moderate-to-severe AS, and both moderate-to-severe MR and AS.ResultsOf the 1443 subjects enrolled, 190 (13.2%) had moderate-to-severe MR, 26 (1.8%) had moderate-to-severe AS, and 13 (0.9%) had both moderate-to-severe MR and AS. When compared with those with no VHD, patients with moderate-to-severe MR had hazard ratios (HRs) for the primary endpoint of 2.04 (95% confidence interval [CI], 1.36-3.07], those with moderate-to-severe AS had HRs of 3.10 (95% CI, 1.39-6.93), and those with both moderate-to-severe MR and AS had HRs of 4.00 (95% CI, 1.65-9.73] (all P < 0.01). Patients with moderate-to-severe MR also had increased risks of cardiovascular death (HR 3.17; 95% CI, 1.57-6.42; P < 0.01), whereas in those with moderate-to-severe AS or both moderate-to-severe MR and AS, a nonsignificant increased risk was observed.ConclusionsIn a contemporary cohort of elderly patients admitted for ACS, VHD was found in 1 of 5 subjects and had an independent, consistent impact on prognosis.     

A clinical prediction rule to identify patients with atrial fibrillation and a low risk for stroke while taking aspirin

BACKGROUND: We sought to derive and internally validate a simple and easily applied clinical prediction rule to identify patients with nonvalvular atrial fibrillation (AF) whose stroke risk while taking aspirin is, irrespective of age, low enough that oral anticoagulation therapy is unnecessary. METHODS: We included 2501 patients with AF treated with aspirin during participation in 6 clinical trials. Patients were randomly divided into derivation and validation sets. Recursive partitioning was used to identify patients in the derivation set whose risk for stroke (ischemic or hemorrhagic) or transient ischemic attack was comparable to that observed in an age- and sex-matched cohort from the Framingham Heart Study. The derived prediction rules were tested on the validation set. RESULTS: Overall, 166 patients (6.6%) had an event during 4688.6 person-years (PYs) of observation for an incident rate of 3.5 events per 100 PYs. Patients in the derivation set classified as low risk (no previous stroke or transient ischemic attack, no treated hypertension or systolic blood pressure equal to or exceeding 140 mm Hg, no symptomatic coronary artery disease, and no diabetes) experienced 1.0 events per 100 PYs, compared with an age- and sex-matched rate of 1.2 events per 100 PYs. In the validation set, low-risk patients experienced 1.1 events per 100 PYs (expected rate of 1.2 events per 100 PYs). Low-risk patients made up 24% of the cohort and 16% of patients older than 75 years. Low-risk patients who were randomized to therapeutic oral anticoagulation therapy experienced 1.5 events per 100 PYs. CONCLUSION: Irrespective of age, patients with AF and none of these 4 clinical features and who take aspirin have stroke rates comparable to those of age-matched community cohorts and would not benefit substantially from anticoagulation.     

Pregnancy outcomes in myeloproliferative neoplasms: UK prospective cohort study

The reported higher risk of maternal and fetal complications in women with myeloproliferative neoplasms (MPN) poses challenge during pregnancy. A national prospective study of maternal and fetal outcomes of pregnant women with a diagnosis of MPN was undertaken via the United Kingdom Obstetric Surveillance System between January 2010 and December 2012. Fifty‐eight women with a diagnosis of MPN were identified; 47 (81%) essential thrombocythaemia, five (9%) polycythaemia vera, five (9%) myelofibrosis and one (2%) MPN‐unclassified. There were 58 live births. The incidence of miscarriage was 1·7/100 (95% confidence interval [CI]: 0·04–9·24) and the perinatal mortality rate was 17/1000 (95% CI: 0·44–92·36) live and stillbirths. Incidence of maternal complications was 9% (5/57) pre‐eclampsia, 9% (5/57) post‐partum haemorrhage and 3·5% (2/57) post‐partum haematoma. There were no maternal deaths or thrombotic events. Delivery was induced in 45% (24/53) of women and the Caesarean section rate was 45% (24/53). The majority (85%, 45/53) delivered at term (>37 weeks gestation). Twenty‐two percent (12/54) of neonates were below the 10% centile for growth and 13% (7/54) required admission to a neonatal care‐unit; there were no neonatal deaths. The findings of this large, UK prospective study suggests women with MPN appear to have successful pregnancies with better outcomes than would be anticipated from the literature.     

Prevalence of right ventricular dysplasia-cardiomyopathy in a non-referral hospital

In a cardiological department of a non-referral hospital responsible for 80,000 inhabitants with 2500 in-hospital patients and 1500 out-hospital patients per year, the prevalence, symptoms and prognosis of arrhythmogenic right ventricular dysplasia-cardiomyopathy (ARVD/C) were examined retrospectively. From 1997 to 2002, ARVD/C was diagnosed in 35 females and 45 males (overall prevalence 1 in 1000 inhabitants) with a mean age of 45.6 years. Symptoms were chest pain (80%), palpitations (60%) and syncopes (30%), and clinical findings were repetitive ventricular premature beats (50%), supraventricular arrhythmias (30%), ventricular tachycardia (20%), aborted sudden death due to ventricular fibrillation (1%), right heart failure (4%), biventricular heart failure (1%) and high grade AV nodal block (4%). Endomyocardial biopsies were not performed. Aborted sudden death occurred in only one patient (0.3%) before the diagnosis was made, annual heart failure rate was 1%. No deaths appeared in a follow-up of 1-5 (mean 2.4) years with clinical assessment as the basis of diagnosis. The prevalence of ARVD/C is much higher and the prognosis better than expected from results of reference centers.     

Recurrent patterns and prognosis following resection of hepatocellular carcinoma

This report is based on an analysis of the recurrent patterns and post-treatment clinical outcome of 78 patients following hepatectomy for hepatocellular carcinoma (HCC). Patients with a single recurrent tumor (group A;n=41) often had multicentric carcinogenesis (41.7%) and were treated locally; i.e., by re-resection or by percutaneous ethanol injection therapy (PEIT). Many of them (42.9%) followed the “curative pattern,” with good prognosis (70.3% 5-year survival rate). Although 6 of the patients with two or three recurrent tumors (group B;n=19) had multicentric carcinogenesis that could be treated locally, 13 of the 19 followed the “non-curative pattern,” with a poor prognosis after recurrence (14.8% 3-year survival rate after recurrence). The primary tumors of the patients with multiple or infiltrating type (group C;n=18) were advanced and these patients had metastatic recurrence, thereby following the “early death pattern” (58.8%) with a poor prognosis (30% 5-year survival rate). For group C patients, hepatectomy was regarded as part of a multidisciplinary treatment regimen that included aggressive postoperative chemotherapy as a necessary component.     

199例肥厚型心肌病患者的长期随访研究

目的探讨肥厚型心肌病（HCM）患者的长期预后及其死亡的相关危险因素。方法回顾性分析1999年6月至2006年3月期间收入院的234例HCM患者的病史资料,并对其中获得随访的199例患者的随访结果采用SPSS13．0软件包进行统计学处理。结果234例患者中,199例（85％）获得随访,35例（15％）患者失访。平均随访时间为（31．7±22．6）个月,由确诊到随访结束时间中位数为35个月。随访中21例患者死亡,其中19例患者被确认为HCM相关性死亡,包括心脏骤停11例（57．9％）、心力衰竭死亡7例（36．8％）、脑卒中死亡1例,另有2例患者分别因意外事故和急性胰腺炎死亡。患者确诊后1、2、3、4、5年生存率分别为96．7％、94．7％、94．7％、93．6％、89．0％。单因素分析显示,男性、心功能Ⅲ及以上、心房颤动、持续或短阵室速、左心房增大、左心室流出道梗阻、HCM家族史7个变量与HCM预后相关。而多因素分析显示,仅持续或短阵室速（RR=2．234,P〈0．001）、心功能Ⅲ及以上（RR=1．964,P=0．003）是HCM的独立预后危险因素。心脑事件死亡患者中,超声心动图表现以MaronⅢ型为多见（73．7％）,仅1例患者表现为心尖肥厚型心肌病（5．2％）。对心脏骤停者和心力衰竭死亡者进行分析显示,7例（63．6％）心脏骤停者发生在60岁以下的患者中（P=0．12,但仅1例患者小于35岁）,5例（71．4％）心力衰竭死亡者发生在60岁以上的患者中（P=0．22）。仅2例心脏骤停者和1例心力衰竭死亡者存在静息状态下左心室流出道压差。7例（63．6％）心脏骤停者和2例（28．6％）心力衰竭死亡者合并阵发性室速。心脏骤停者与心力衰竭死亡者的室壁厚度分别为（20．4±4．7）mm和（22．7±6．3）mm。结论HCM患者的中长期预后相对较好,以心肌肥厚仅累及心尖部者预后最佳。持续或短阵室速、心功能Ⅲ级以上是发生HCM相关心脑血管不良事件的独立危险因素。心脏骤停可发生在各年龄段,对其的预防在年轻和中老年患者中同样重要。