Spanish Registry of Patients With Alpha-1 Antitrypsin Deficiency; Comparison of the Characteristics of PISZ and PIZZ Individuals

Abstract

Alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of pulmonary emphysema and liver disease. The growing interest in this deficiency in Spain led to the development of the Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency (REDAAT) in 1993. At present, the REDAAT is a network of more than 350 health care professionals and the database includes a total of 511 individuals. The adult population included consists of 469 individuals (91.8% of the total) and their phenotype distribution is: 348 Pi*ZZ (74.2%), 100 Pi*SZ (21.3%) and 21 carriers of rare variants (4.5%). The most frequent diagnosis is lung disease (74.6%). Patients with chronic obstructive pulmonary disease (COPD) registered in the REDAAT constitute approximately 15% of the expected cases of AATD-related COPD in Spain. Pi*ZZ showed more severe impairment in lung function and younger age at baseline compared with Pi*SZ. The mean decline in FEV₁ in the Pi*ZZ subgroup was –23 ml/year (SD:142.8), being –18 ml/year (SD:108.8) in Pi*SZ. Forty-five percent of the Pi*ZZ individuals received augmentation therapy. A total of 61 deaths was recorded.

The characteristics of the REDAAT population demonstrate some differential trends compared to other series: distribution of phenotypes, inclusion of children and patients treated with replacement therapy. Patients with the Pi*SZ phenotype were older and had milder lung function impairment. The most important challenge of this registry is to collect good quality long-term data that will allow better understanding of the natural history of the disease in real life.     

Ongoing research in Europe: Alpha One International Registry (AIR) objectives and development.

In 1997, the World Health Organization recommended establishing an international registry of alpha1-antitrypsin deficiency. The objective of the present article is to describe the organisation of an international network of registries, the Alpha One International Registry (AIR), and the processes of enrolling and entering data. By the end of 2005, the registry included individuals from 21 countries (from four continents). The inclusion criterion was either phenotypes PiZZ, PiSZ or other severely deficient variants. Demographic and clinical information have been collected by a standardised questionnaire, translated for each country. Data are transferred to the AIR database at the Dept of Respiratory Medicine, University Hospital, Malm?, Sweden, either by e-mail or via two web-enabled questionnaires in HTML. All data are merged and checked for consistency and missing values. Collection of data started in 1999 and, by September 2005, data on 2,150 individual patients (1,180 male) had been submitted. Of these, 1,855 (84%) have phenotype PiZ, 181 (8%) PiSZ and 114 (5%) other rare Pi phenotypes. The mean age at inclusion was 49.8 yrs (SD = 13.3) and the majority were index cases (64.1%). The Alpha One International Registry is the largest specific alpha1-antitrypsin deficiency registry, fulfilling a major World Health Organization recommendation. The success related to the convergence of national registries into a common database creating a unique registry beyond geographic boundaries and encompassing alpha1-antitrypsin deficiency from various ethnic groups.     

Alpha-1 Antitrypsin Deficiency in Canada: Regional Disparities in Diagnosis and Management

Abstract

Background: Since 1999, as part of the Alpha1 International Registry (AIR), the Canadian Alpha-1 Antitrypsin Deficiency (AATD) Registry has maintained demographic and medical information volunteered by AATD individuals.

Methods: We undertook a retrospective chart review to describe the characteristics of registry participants. Inclusion criteria were ZZ phenotype or other severe deficiency and written consent. We reviewed baseline medical records and annual follow-ups, conducted by mail.

Results: The number of registrants ranged from 8.7 per million in British Columbia and Ontario to 1.3 per million in Quebec. Similarly, the rate of augmentation therapy use ranged from 7.7 per million in British Columbia to 0.1 per million in Quebec. 290 patients (146 males), most PiZZ, were enrolled by 2013. Patients with lung disease reported symptoms onset at (mean ± SD) 40 ± 11 years but were diagnosed as AATD at 47 ± 10 years. Typical patients were ex-smokers with respiratory symptoms, severely reduced FEV₁, an accelerated rate of FEV₁ decline, and minimal bronchodilator response. A subgroup diagnosed by liver disease or familial screening was younger and had better preserved lung function but a similar rate of FEV₁ decline. There were 63 deaths, of which 29 were lung-related and 6 were liver-related. Average age at death was 60.5 ± 11.2 years. 

Discussion: Most patients experience a diagnostic delay of seven years after symptom onset, a period during which lung health may deteriorate further. There is marked regional variation in the rate of diagnosis and specific therapy usage for AAT in Canada.     

Formation and current results of a patient-organized registry for alpha(1)-antitrypsin deficiency

BACKGROUND: Significant challenges exist to investigating uncommon illnesses because too few patients are seen at any single clinical center to permit appropriate research studies. Recognizing this impediment to clinical research in alpha(1)-antitrypsin deficiency, the Alpha One Foundation, a patient-organized research foundation, has collaborated with clinician-scientists to organize a voluntary registry of individuals with alpha(1)-antitrypsin deficiency. PURPOSE: To facilitate clinical research in alpha(1)-antitrypsin deficiency by organizing a registry of affected individuals willing to be approached to participate in clinical studies. METHODS: Elements of the Alpha One Foundation Research Network Registry include a Medical and Scientific Advisory Committee, composed of physician-investigators and patient advocates, designated clinical resource centers at medical institutions with expertise in the management of individuals with alpha(1)-antitrypsin deficiency, and a data coordinating center with responsibility for database management and analysis. Questionnaires requesting information about demographic features, alpha(1)-antitrypsin phenotype, smoking history, and health-care utilization were distributed to prospective registrants through the following channels: mailings from the Alpha One Foundation; mailings from the clinical resource centers; and distribution by home-care and pharmaceutical companies. Information from this questionnaire formed the basis of the initial registry database. RESULTS: Between May 1997 and June 1999, 7,789 forms were distributed, and forms were returned by 712 unique registrants. Registrants have the following characteristics: mean (+/- SD) age, 49.3+/-13.2 years; women, 47.7%; white, 96.2%; PI*ZZ phenotype, 70.7%; ex-smokers, 73.3%; COPD patients, 87.2% (emphysema patients, 54.2%; chronic bronchitis patients, 33%); and self-reported liver disease, 6.4%. The mean number of physician visits reported by registrants in the preceding 12 months was 7.8+/-9.4, 59% reported currently receiving IV augmentation therapy, and 35% reported using supplemental oxygen at home. Examples of ongoing research studies using this unique database include: (1) a case-control study to evaluate occupational risk factors for obstructive lung disease in individuals with alpha(1)-antitrypsin deficiency and (2) a study to evaluate the health-care costs for affected individuals. CONCLUSIONS: A registry currently including 712 individuals with alpha(1)-antitrypsin deficiency has been organized through a collaboration between physician-investigators and a patient-organized research foundation. Use of the registry has already facilitated studies that were previously difficult because of the paucity of identifiable study subjects. The registry cohort promises to provide an important resource for future clinical and epidemiologic studies.     

Implantable cardioverter defibrillators in Israel: utilization and implantation trends.

BACKGROUND: Since its introduction, the implantable cardioverter defibrillator (ICD) has evolved to its present status as the dominant therapeutic modality for patients with life-threatening arrhythmias. Several randomized studies have shown the benefit of ICD implantation as the first choice of treatment for primary as well as secondary indications for ventricular arrhythmias. Therefore, it is expected that the use of ICDs will increase further. The main objectives of this study were to analyze the Israeli experience with ICD implantation from 1993 to 1999, to examine the diffusion of ICD therapy in Israel and the evolution of implantation patterns and indications. METHODS: We conducted a retrospective review and analysis of an ICD registry for the period of January 1993-December 1999. Data collected included demographic, administrative, clinical and survival data. RESULTS: A total of 732 new implantations were identified and reviewed. The mean length of follow up of all patients was 30.7+/-21.1 months. 86% of patients were males and the mean age at implantation was 62.6+/-12.4 years. 79% of patients had CAD and the mean EF of all patients was 29.2+/-11.2%. 135 patients (18.4%) died during follow-up. One, two and three-year survival rates were calculated and were 92.7%, 87.8% and 82.0% respectively. A steady increase in implantation rate and in implanting centers was observed over the years. CONCLUSIONS: ICD therapy is relatively expensive; therefore a national registry which is continuously monitored may be the most expedient method to follow clinical and economic aspects of the utilization of this therapeutic modality.     

Italian Registry of Patients with Alpha-1 Antitrypsin Deficiency: General Data and Quality of Life Evaluation

Abstract

Alpha1-antitrypsin Deficiency (AATD) is a rare hereditary disorder with an estimated prevalence of about 1/5000 individuals in Italy. Deficient patients are at a higher risk of developing lung emphysema and chronic liver disease. The low estimated prevalence of AATD prompted the establishment of a registry with the aim of learning more about the natural history and the quality of care of these patients. The Italian registry for AATD was established in 1996. In this study, genetic and clinical findings of Italian AATD patients are presented. Moreover, we also evaluated the changes in health-related quality of life (HRQoL) in patients with COPD and AAT deficiency over a three-year period, in relation to augmentation therapy.

In a period spanning 18 years (1996–2014) a total of 422 adult subjects with severe AATD were enrolled, namely 258 PI*ZZ, 74 PI*SZ, 4 PI*SS and 86 patients with at least one rare deficient allele. The 21.3% frequency for AATD patients with at least one deficient rare variant is the highest so far recorded in national registries of AATD. The registry data allow a detailed characterization of the natural course of the disease and the level of patient care, as well as confirm the usefulness of early AATD detection.     

Alpha1-antitrypsin deficiency: current perspective on research, diagnosis, and management

The Alpha One International Registry (AIR), a multinational research program focused on alpha₁-antitrypsin (AAT) deficiency, was formed in response to a World Health Organization recommendation. Each of the nearly 20 participating countries maintains a national registry of patients with AAT deficiency and contributes to an international database located in Malmö, Sweden. This database is designed to increase understanding of AAT deficiency. Additionally, AIR members are engaged in active, wide-ranging investigations to improve the diagnosis, monitoring, and treatment of the disease and meet biennially to exchange views and research findings. The fourth biennial meeting was held in Copenhagen, Denmark, on 2–3 June 2005. This review covers the wide range of AAT deficiency-related topics that were addressed encompassing advances in genetic characterization, risk factor identification, clinical epidemiology, inflammatory and signalling processes, therapeutic advances, and lung imaging techniques.     

A model of an inflammatory bowel disease population-based registry: The Forlì experience (1993–2013)

Background and aimsThe article presents a population-based registry designed to estimate incidence and prevalence of inflammatory bowel disease (IBD) in the area of Forlì (north-eastern Italy).MethodsThe registry included all patients with IBD ulcerative colitis (UC) and Crohn’s disease (CD) in the Forlì area from 1993 to 2013. A data manager matched records from various sources.ResultsSeven hundred ninety-one patients were registered during the study period, 564 (71.3%) with UC and 227 (28.7%) with CD. The standardized annual incidence rate for UC was 12.8 per 100,000 females (95% CI 11.1–14.4) and 15.7 per 100,000 males (95% CI 13.9–17.5). That of CD was 7.0 per 100,000 for females (95% CI 5.7–8.3) and 5.4 per 100,000 males (95% CI 4.3–6.4). The prevalence of CD and UC on 1 January 2014 was 109.2 per 100,000 inhabitants (95% CI 94.3–124.2) and 266.4 per 100,000 inhabitants (95% CI 243.4–289.7), respectively.ConclusionsAlthough further studies are needed, the data suggest that incidence and prevalence of IBD in Italy are underestimated.     

Trends in incidence,treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989–2010

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989–2010 and mantle cell lymphoma in the period 2001–2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989–1993 and the period 1994–1998 [5-year relative survival 42% (95%CI: 39%–45%) and 41% (38%–44%), respectively], but increased to 46% (43%–48%) in the period 1999–2004 and to 58% (56%–61%) in the period 2005–2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice.     

全国第三次冠心病介入治疗病例注册登记资料分析

目的：分析1999－2001年我国冠心病介入治疗（PCI）的发展趋势。方法：凡开展冠心病介入治疗的医院，均填写由中华医学会心血管病学分会介入心脏病学组和中华心血管病杂志编辑部统一印发的表格，根据表格提供的资料对1999－2001年我国完成的PCI病例进行回顾性统计分析。结果：1999－2001年共注册PCI病例总数26098例，来自全国范围内112所医院，其中1999年8000例，2000年11753例，2001年16345例，总成功率97．0％。共扩张病变53695处，其中43304处（80．6％）病变置入支架，支架置入成功率90％。30339例择期PCI的主要并发症包括冠状动脉痉挛（2．4％）、严重冠状动脉夹层（2．2％）、冠状动脉急性闭塞（0．8％）、急性、亚急性血栓形成（0．6％）、急性心肌梗死（0．5％）、急诊冠状动脉旁路移植术（0．07％）、死亡（0．31％）。随访中靶血管重建术7．0％。急性心肌梗死急诊PCI较上次注册资料有较大增长，共5759例，其中直接PCI 4417例，补救性CI这1342例，总成功率96．3％。左主干PCI共完成551例，总成功率98．4％，手术死亡率0．9％，随访期中死亡8例（1．5％），靶血管重建术8．2％。此次参加注册的医院中，每年完成PCI＜75例的医院占46．0％，每年完成PCI＞200例的医院仅占20．1％。结论：近3年来我国PCI仍迅速发展，每年完成例数以40％左右的速率增长，PCI成功率及燕发症发生率与国外献报道相似。在严格选择的左主干病变，PCI也取得较好效果。但我国各地及各医院之间PCI发展仍极不平衡，继续加强技术培训及规范化管理，在今后一段时间内仍然是十分必要的。     

A Comparison of Two Short-Course Primaquine Regimens for the Treatment and Radical Cure of Plasmodium vivax Malaria in Thailand

Thai adult males (N = 85) with acute Plasmodium vivax malaria and normal glucose-6-phosphate dehydrogenase screening were randomized to receive 30 mg or 60 mg primaquine daily for 7 days (N = 43 and 42, respectively). The regimens were well tolerated and all patients recovered fully. Median fever clearance (47 hours; range 4 to 130 hours), mean ± SD parasite clearance times (87.7 ± 25.3 hours), gametocyte clearance, and adverse effects were similar in the 2 groups. Two patients, 1 from each group, had a 30% reduction in hematocrit. The cumulative 28 day relapse rate (95% confidence interval) by Kaplan Meier survival analysis was 29% (16–49%) in the 30 mg group compared with 7% (2–24%) in the 60 mg group; P = 0.027. Comparison with previous data obtained at this same site suggests that the recurrences comprised approximately 17% recrudescences and 12% relapses in the 30 mg/day group compared with 3% recrudescences and 4% relapses in the 60 mg/day group. These data suggest that the dose-response relationships for primaquine''s asexual stage and hypnozoitocidal activities in-vivo are different. A 1 week course of primaquine 60 mg daily is an effective treatment of vivax malaria in this region.     

Frailty syndrome and all-cause mortality in demented patients: the Italian Longitudinal Study on Aging

Cognition has already been considered as a component of frailty, and it has been demonstrated that it is associated with adverse health outcomes. We estimated the prevalence of frailty syndrome in an Italian older population and its predictive role on all-cause mortality and disability in nondemented subjects and in demented patients. We evaluated 2,581 individuals recruited from the Italian Longitudinal Study on Aging, a population-based sample of 5,632 subjects, aged 65–84 years old. Participants received identical baseline evaluation at the 1st survey (1992–1993) and were followed at 2nd (1995–1996) and 3rd survey (2000–2001). A phenotype of frailty according to partially modified measurement of Cardiovascular Health Study criteria was operationalized. The overall prevalence of frailty syndrome in this population-based study was 7.6% (95% confidence interval (CI) 6.55–8.57). Frail individuals noncomorbid or nondisable were 9.1% and 39.3%, respectively, confirming an overlap but not concordance in the co-occurrence among these conditions. Frailty was associated with a significantly increased risk of all-cause mortality over a 3-year follow-up (hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.52–2.60) and over a 7-year follow-up (HR 1.74, 95% CI 1.44–2.16), but with significant increased risk of disability only over a 3-year follow-up (HR 1.32, 95% CI 1.06–1.86 over a 3-year follow-up and HR 1.16, 95% CI 0.88–1.56 over a 7-year follow-up). Frail demented patients were at higher risk of all-cause mortality over 3- (HR 3.33, 95% CI 1.28–8.29) and 7-year follow-up periods (HR 1.89, 95% CI 1.10–3.44), but not of disability. Frailty syndrome was a short-term predictor of disability in nondemented older subjects and short- and long-term predictor of all-cause mortality in nondemented and demented patients.     

The Epidemiology of Dengue in the Americas Over the Last Three Decades: A Worrisome Reality

We have reported the epidemic patterns of dengue disease in the Region of the Americas from 1980 through 2007. Dengue cases reported to the Pan American Health Organization were analyzed from three periods: 1980–1989 (80s), 1990–1999 (90s), and 2000–2007 (2000–7). Age distribution data were examined from Brazil, Venezuela, Honduras, and Mexico. Cases increased over time: 1,033,417 (80s) to 2,725,405 (90s) to 4,759,007 (2000–7). The highest concentrations were reported in the Hispanic Caribbean (39.1%) in the 80s shifting to the Southern Cone in the 90s (55%) and 2000–7 (62.9%). From 1980 through 1987, 242 deaths were reported compared with 1,391 during 2000–7. The most frequently isolated serotypes were DENV-1 and DENV-2 (90s) and DENV-2 and DENV-3 (2000–7). The highest incidence was observed among adolescents and young adults; dengue hemorrhagic fever incidence was highest among infants in Venezuela. Increasing dengue morbidity/mortality was observed in the Americas in recent decades.     

Is Age of 80 Years a Threshold for Carotid Revascularization?

Background and purpose:

Carotid Angioplasty and Stenting (CAS) has emerged as an alternative to Carotid Endarterectomy (CEA) in treatment of carotid stenotic disease. With increasing life expectancy clinicians are more often confronted with patients of higher age. Octogenarians were often excluded from randomized trials comparing CAS to CEA because they were considered high-risk for revascularization. Conflicting results on the peri-procedural outcome of carotid revascularization in these patients have been reported. In order to objectively evaluate whether age above 80 years should be an upper limit for indicating carotid revascularization we systematically reviewed the currently available literature.

Methods:

Literature was systematically reviewed between January 2000 and June 2010 using Pubmed and Embase, to identify all relevant studies concerning CAS and CEA in octogenarians. Inclusion criteria were 1) reporting outcome on either CEA or CAS; and 2) data subanalysis on treatment outcome by age. The 30-day Major Adverse Event (MAE) rate (disabling stroke, myocardial infarction or death) was extracted as well as demographic features of included patients.

Results:

After exclusion of 23 articles, 46 studies were included in this review, 18 involving CAS and 28 involving CEA. A total of 2.963 CAS patients and 14.365 CEA patients with an age >80 years were reviewed. The MAE rate was 6.9% (range 1.6 - 24.0%) following CAS and 4.2% (range 0 – 8.8%) following CEA.A separate analysis in this review included the results of one major registry 140.376 patients) analyzing CEA in octogenarians only reporting on 30-day mortality and not on neurological or cardiac adverse events. When these data were included the MAE following CEA is 2.4% (range 0 – 8.8%)

Conclusions:

MAE rates after CEA in octogenarians are comparable with the results of large randomized trials in younger patients. Higher complication rates are described for CAS in octogenarians. In general, age > 80 years is not an absolute cut off point to exclude patients from carotid surgery. In our opinion, CEA should remain the golden standard in the treatment of significant carotid artery stenoses, even in the very elderly.     

Decreasing Disparities in Infant Survival using Surveillance Data from Burkina Faso

We assessed changes in the effect size of risk factors for infant mortality comparing a birth cohort from 2005 to 2010 with a birth cohort from 1993 to 1999 in the Nouna Health and Demographic Surveillance System (HDSS) in Burkina Faso. Single- and three-level Cox proportional hazards regression models were used for analysis. Independent variables among others included year of birth, ethnicity, religion, age of the mother, birth order, death of the mother, being a twin, and distance to the closest health facility. We observed an infant mortality rate of about 51/1,000 person-years. The strongest risk factors were death of the mother and being a twin, which were also the strongest risk factors from the previous analysis period. Compared with the period 1993–1999, the effect of most risk factors decreased, notably ethnicity, religious affiliation, distance to the closest health facility, birth order, and season of birth. The strongest reduction in mortality occurred in the groups with the previously highest infant mortality rates in 1993–1999.     

Pleural mesothelioma surveillance: Validity of cases from a tumour registry

BACKGROUND:

Pleural mesothelioma is a rare tumour associated with exposure to asbestos fibres. Fewer than than one-quarter of cases registered in the Quebec Tumour Registry (QTR) have been compensated as work-related. While establishing a surveillance system, this led to questioning as to whether there has been over-registration of cases that are not authentic pleural mesotheliomas in the QTR.

OBJECTIVE:

To assess whether registered cases of pleural mesothelioma could be confirmed.

METHODS:

A medical chart review was designed to assess the proportion of mesothelioma cases newly registered in the QTR in 2001/2002 that could be confirmed. For each registered case, clinical, medical imaging and pathology information were sought and, occasionally, additional immunohistochemistry staining was obtained. Three specialists – a chest physician, a radiologist and a pathologist – reviewed the available information and material, coding each mesothelioma case as to degree of certainty of the mesothelioma diagnosis.

RESULTS:

The QTR reported 190 incident cases of mesothelioma (81% males) for the period. The specialists classified 81% of charts as ‘certain/probable’or ‘possible’ mesotheliomas, 8% as ‘unlikely to be a mesothelioma’ and 11% as ‘not a mesothelioma’. After excluding chart summaries of unsatisfactory quality, 87% to 88% of the charts were classified as ‘certain/probable’ or ‘possible’ mesotheliomas, and 9% to 11% were still considered ‘not a mesothelioma’.

CONCLUSION:

Tumour registry data are a valid source of information for mesothelioma surveillance. While there is some over-registration of mesothelioma cases in the QTR, a significant majority of registered cases appeared to be authentic. Over-registration cannot explain the greater proportion of cases that were not compensated.     

Alpha-1 antitrypsin deficiency and the risk of hepatocellular carcinoma in end-stage liver disease

AIM: To evaluate the association between alpha-1 antitrypsin deficiency (A1ATD) and hepatocellular carcinoma (HCC) in patients with end-stage liver disease (ESLD).METHODS: Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study (N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension (ascites, variceal bleeding, thrombocytopenia, or hepatic encephalopathy). A1ATD was diagnosed using phenotype characterization (MZ or ZZ), liver biopsy detection of PAS-positive diastase-resistant (PAS+) globules, or both. Patients with other causes of liver diseases such as hepatitis C virus (HCV), alcoholic liver disease and non-alcoholic steatohepatitis (NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities, biopsy findings, or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma, or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-to-interval analysis for interval censored data.RESULTS: This study included 675 patients. 7% of subjects had A1ATD (n = 47). Out of all subjects who did not have A1ATD, 46% had HCV, 17% had alcoholic liver disease, 19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1ATD, 15 had a primary diagnosis of A1ATD (PI*ZZ phenotype and PAS+ globules), 8 had a PI*MZ phenotype alone, 14 had PAS+ alone, and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4 (25^th, 75^th percentiles: 1, 5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29% (n = 199). In the A1ATD group, the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis (P = 0.001). Patients with ESLD due to A1ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis, 1.5% in patients with NASH and 0.9% in alcohol-induced liver disease (P < 0.001).CONCLUSION: Within this group of patients with ESLD, there was no significant association between A1ATD and increased risk of HCC.     

Results of laparoscopic splenectomy for treatment of malignant conditions

BackgroundLaparoscopic splenectomy (LS) is widely accepted for treatment of benign diseases, but there are few reports of its use in cases of haematological malignancy. In addition, comparative studies with open operation are lacking. Malignant haematological diseases have specific clinical features-notably splenomegaly and impaired general health-which can impact on the immediate outcome after LS. The immediate outcome of LS comparing benign with malignant diagnoses has been analysed in a prospective series of 137 operations.Patients and methodsBetween February 1993 and April 2000, 137 patients with a wide range of splenic disorders received LS. Clinical data and immediate outcome were prospectively recorded,and age, diagnosis, operation time, perioperative transfusion requirement, spleen weight, conversion rate, accessory incision, hospital stay and complications were analysed.ResultsThe series included 100 benign cases and 37 suspected malignancies. In patients with malignant diseases the mean age was greater (37 years [3–85] vs 60 years [27–82], p<0.0l), LS took longer (138 min [60–400] vs 161 min [75–300], p<0.05) and an accessory incision for spleen retrieval was required more frequently (18% vs 93%, p<0.0l) because the spleen was larger (279 g [60–1640] vs 1210 g [248–3100], p <0.01). However, the rate of conversion to open operation (5% vs 14%), postoperative morbidity rate (13% vs 22%) and transfusion requirement (15% vs 26%) did not differ between benign and malignant cases. Hospital stay was longer in malignant cases (3.7 days [2–14] vs 5 days [2–14], p<0.05).ConclusionLS is a safe procedure in patients with malignant disease requiring splenectomy in spite of the longer operative time and the higher conversion rate.     

Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission

Background

Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known.

Design and Methods

We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005.

Results

T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46–75), 59% (95% CI 45–74) and 13% (95% CI 3–25), respectively. The incidences of grades II–IV and III–IV acute graft-versus-host disease were 27% (95% CI 16–44) and 10% (95% CI 4–25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13–38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27–71) vs. 68% (95% CI 44–84), p=0.045).

Conclusions

T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.     

Validation of a novel device to objectively measure adherence to long-term oxygen therapy

Rationale

We have developed a novel oxygen adherence monitor that objectively measures patient use of long-term oxygen therapy. The monitor attaches to the oxygen source and detects whether or not the patient is wearing the nasal cannula.

Objective

The study’s purpose was to validate the monitor’s performance in patients with chronic obstructive pulmonary disease during wakefulness and sleep.

Methods

Ten adult males with stable chronic obstructive pulmonary disease (mean ± SD FEV₁ 37.7 ± 14.9% of predicted) on long-term continuous oxygen therapy were tested in a sleep laboratory over a 12–13 hour period that included an overnight polysomnogram.

Measurements

The monitor’s measurements were obtained at 4-minute intervals and compared to actual oxygen use determined by review of time-synchronized video recordings.

Main results

The monitor made 1504/1888 (79.7%) correct detections (unprocessed data) across all participants: 957/1,118 (85.6%) correct detections during wakefulness and 546/770 (70.9%) during sleep. All errors were false negatives, ie, the monitor failed to detect that the participant was actually wearing the cannula. Application of a majority-vote filter to the raw data improved overall detection accuracy to 84.9%.

Conclusions

The results demonstrate the monitor’s ability to objectively measure whether or not men with chronic obstructive pulmonary disease are receiving their oxygen treatment. The ability to objectively measure oxygen delivery, rather than oxygen expended, may help improve the management of patients on long-term oxygen therapy.