Variation and heritability of Hb F and F-cells among beta-thalassemia heterozygotes in Hong Kong

Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with beta-thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult beta-thalassemia carriers in Hong Kong. They had wide variations in Hb F and F-cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT-allele in the (G)gamma-globin gene promoter had higher Hb F and more F-cells compared with those lacking the Xmn I T-allele. However, both groups exhibited a similarly wide spread of Hb F and F-cells. The correlation of Hb F and F-cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F-cells were calculated in 66 families (111 parents who were beta-thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F-cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults.     

Registration of interstitial lung diseases by 20 centres of respiratory medicine in Flanders

We report the results of a prospective registration of the prevalence of interstitial lung diseases by 20 centres of respiratory medicine in Flanders from January 1992 till July 1996. The 20 centres registered a total of 362 cases. Sarcoidosis (31% with inclusion of stage I, or 22% without stage I), idiopathic pulmonary fibrosis (20%), hypersensitivity pneumonitis (13%) and unclassified forms of interstitial lung diseases (9%) were the most often diagnosed diseases. The mean age of the patients was 52 +/- 17 (SD) years, but ranged from 32 +/- 10 years in histiocytosis X to 70 +/- 13 years in drug induced interstitial lung diseases. The male to female ratio was 1.3 but ranged from 2.3 in interstitial lung diseases due to inhalation of inorganic materials to 0.8 in interstitial lung diseases due to connective tissue disease. The diagnosis was considered certain in 60%, probable in 30% and possible in 10%. In 50% of the cases the diagnosis was proven by biopsy and the most often used biopsy technique was transbronchiolo-alveolar biopsy (40% of biopsies) followed by open lung biopsy (32%). At diagnosis vital capacity was 82 +/- 22% pred. (ranging from 92 +/- 19% in sarcoidosis to 71 +/- 24% in idiopathic pulmonary fibrosis) and CO-diffusing capacity was 77 +/- 19% pred. (ranging from 77 +/- 19% in sarcoidosis to 41 +/- 13% in drug induced pneumonitis). The regional frequency of interstitial lung diseases in Flanders varied widely and was not proportional to the regional distribution of the 20 contributing centres. In conclusion this registration provides interesting information on the occurrence and presentation of the different forms of interstitial lung diseases, although it may still underestimate the real prevalence and incidence of interstitial lung diseases.     

Lack of long-term adverse adrenal effects from inhaled triamcinolone: Lung Health Study II

STUDY OBJECTIVE: Inhaled corticosteroids (ICS) are widely used in the treatment of COPD. One of the potential adverse effects of their use is the development of adrenal suppression. Our study aimed to determine the effects of ICS on adrenal function over 3 years of use in patients with COPD. METHODS: Two hundred twenty-one subjects were recruited from the 1,116 patients already enrolled in Lung Health Study II and were randomized to receive either triamcinolone, 1,200 microg, or placebo daily. Basal cortisol levels and cortisol levels at 30 min and 60 min following cosyntropin injection were measured at study entry and after 1 year and 3 years of participation. RESULTS: Basal cortisol levels in the placebo group were higher than in those receiving active drug at all time points and rose through the study period. There was no suppression of cortisol levels after cosyntropin stimulation at any study point in any subgroup. CONCLUSION: Use of inhaled triamcinolone, 1,200 microg/d, over 3 years does not suppress baseline adrenal function or diminish adrenal responsiveness to cosyntropin stimulation.     

Effect of autologous blood donation on the central venous pressure, blood loss and blood transfusion during living donor left hepatectomy

AIM: Autologous blood donation (ABD) is mainly used to reduce the use of banked blood. In fact, ABD can be regarded as acute blood loss. Would ABD 2-3 d before operation affect the CVP level and subsequently result in less blood loss during liver resection was to be determined. METHODS: Eighty-four patients undergoing living donor left hepatectomy were retrospectively divided as group Ⅰ (GI) and group Ⅱ (Gil) according to have donated 250-300 mL blood 2-3 d before living donor hepatectomy or not. The changes of the intraoperative CVP, surgical blood loss, blood products used and the changes of perioperative hemoglobin (Hb) between groups were analyzed and compared by using Mann-Whitney U test. RESULTS: The results show that the intraoperative CVP changes between GI (n = 35) and GII (n = 49) up to graft procurement were the same, subsequently the blood loss, but ABD resulted in significantly lower perioperative Hb levels in GI. CONCLUSION: Since none of the patients required any blood products perioperatively, all the predonated bloods were discarded after the patients were discharged from the hospital. It indicates that ABD in current series had no any beneficial effects, in term of cost, lowering the CVP, blood loss and reduce the use of banked blood products, but resulted in significant lower Hb in perioperative period.     

Recommendations of the National Heart, Lung, and Blood Institute Nanotechnology Working Group

Recent rapid advances in nanotechnology and nanoscience offer a wealth of new opportunities for diagnosis and therapy of cardiovascular, pulmonary, and hematologic diseases and sleep disorders. To review the challenges and opportunities offered by these nascent fields, the National Heart, Lung, and Blood Institute convened a Working Group on Nanotechnology. Working Group participants discussed the various aspects of nanotechnology and its applications to heart, lung, blood, and sleep (HLBS) diseases. This report summarizes their discussions according to scientific opportunities, perceived needs and barriers, specific disease examples, and recommendations on facilitating research in the field. An overarching recommendation of the Working Group was to focus on translational applications of nanotechnology to solve clinical problems. The Working Group recommended the creation of multidisciplinary research centers capable of developing applications of nanotechnology and nanoscience to HLBS research and medicine. Centers would also disseminate technology, materials, and resources and train new investigators. Individual investigators outside these centers should be encouraged to conduct research on the application of nanotechnology to biological and clinical problems. Pilot programs and developmental research are needed to attract new investigators and to stimulate creative, high-impact research. Finally, encouragement of small businesses to develop nanotechnology-based approaches to clinical problems was considered important.     

Laparoscopic rectopexy for recurrent volvulus of J pouch after total proctocolectomy and ileal pouch anal anastomosis

Ileal‐pouch anal anastomosis (IPAA) is most commonly performed after total proctocolectomy for ulcerative colitis and familial adenomatous polyposis. Small‐bowel obstruction is one of the complications that can occur years after the operation, but intestinal obstruction due to volvulus of the J pouch is a rare condition. We report a case of recurrent volvulus in a patient who had undergone IPAA after total proctocolectomy for cancer of the rectum and multiple colonic polyps. The patient underwent laparoscopic rectopexy and had no recurrence of volvulus.     

A large real‐world cohort study examining the effects of long‐term entecavir on hepatocellular carcinoma and HBsAg seroclearance

Real‐world studies examining reduction in risk of hepatocellular carcinoma (HCC) in patients receiving antivirals are limited by the small size of the studies, or by data insufficiency and heterogeneity with short follow‐up duration. We aimed to examine the real‐world long‐term outcome of patients receiving entecavir treatment on HCC incidence and HBsAg seroclearance. The incidence of HCC in 1225 entecavir‐treated patients between 2002 and 2015 was compared with the HCC incidence estimated using the REACH‐B, GAG‐HCC and CU‐HCC scores. Standardized incidence ratios (SIR) were calculated. The impact of entecavir treatment on HBsAg seroclearance was also explored. The median follow‐up of the cohort was 6.6 years, with 66 cases of HCC development. Using the REACH‐B model, the reduction of HCC risk was significant from year 6 onwards with SIR of 0.68 (95% CI 0.535‐0.866) at year 10. In subgroup patients without cirrhosis, consistent risk reduction was observed from the fifth year and the SIR reached 0.51 (95% CI 0.271‐0.704) by year 10. Benefit in cirrhotic patients was demonstrated when using the GAG‐HCC and CU‐HCC score, with the SIR at year 10 being 0.38 (95% CI 0.259‐0.544) and 0.46 (95% CI 0.314‐0.659), respectively. The cumulative rate of HBsAg seroclearance was 5.2%. HBsAg level at third year of treatment and baseline‐to‐3‐year percentage reduction was predictive of subsequent HBsAg seroclearance. In conclusion, long‐term entecavir therapy was associated with significant reduction in the risk of HCC in the real world. However, HBsAg seroclearance rate remained low. Additional therapy may be considered in patients with adverse predictive factors for subsequent HBsAg seroclearance.