Clinical Factors Associated with Progression to AIDS in the Italian Cohort of HIV-Positive Hemophiliacs

1994 ◽  
Vol 72 (01) ◽  
pp. 033-038 ◽  
Author(s):  
N Schinaia ◽  
A M G Ghirardini ◽  
M G Mazzucconi ◽  
G Tagariello ◽  
M Morfini ◽  
...  

SummaryThis study updates estimates of the cumulative incidence of AIDS among Italian patients with congenital coagulation disorders (mostly hemophiliacs), and elucidates the role of age at seroconversion, type and amount of replacement therapy, and HBV co-infection in progression. Information was collected both retrospectively and prospectively on 767 HIV-1 positive patients enrolled in the on-going national registry of patients with congenital coagulation disorders. The seroconversion date was estimated as the median point of each patient’s seroconversion interval, under a Weibull distribution applied to the overall interval. The independence of factors associated to faster progression was assessed by multivariate analysis. The cumulative incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 17.0% (95% Cl = 14.1-19.9%) over an 8-year period for Italian hemophiliacs. Patients with age greater than or equal to 35 years exhibited the highest cumulative incidence of AIDS over the same time period, 32.5% (95% Cl = 22.2-42.8%). Factor IX recipients (i.e. severe B hemophiliacs) had higher cumulative incidence of AIDS (23.3% vs 14.2%, p = 0.01) than factor VIII recipients (i.e. severe A hemophiliacs), as did severe A hemophiliacs on less-than-20,000 IU/yearly of plasma-derived clotting factor concentrates, as opposed to A hemophiliacs using an average of more than 20,000 IU (18.8% vs 10.9%, p = 0.02). No statistically significant difference in progression was observed between HBsAg-positive vs HBsAg-negative hemophiliacs (10.5% vs 16.4%, p = 0.10). Virological, immunological or both reasons can account for such findings, and should be investigated from the laboratory standpoint.

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi60-vi60
Author(s):  
Lilly Shen ◽  
Wee Loon Ong ◽  
Briana Farrugia ◽  
Anna Seeley ◽  
Carlos Augusto Gonzalvo ◽  
...  

Abstract INTRODUCTION Despite increasing use of stereotactic radiosurgery (SRS) for management of brain metastases (BM), published Australian data is scarce. We aim to report on the outcomes following SRS for limited BM in a single Australian institution. METHODS This is a retrospective cohort of patients with limited BM treated with SRS between August 2015 and March 2019. A dose of 24Gy/3# were prescribed to intact lesion, and 21Gy/3# to surgical cavity post-surgical resection. All patients were followed with 3-monthly surveillance MRI brain. Primary outcomes were: local failure (LF: increased in size of SRS-treated BM lesion/ recurrence in surgical cavity), distant failure (DF: intracranial progression outside of the SRS-treated lesion/ cavity), and overall survival (OS). LF, DF and OS were estimated using the Kaplan-Meier method. Multivariate Cox regressions were used to evaluate factors associated with outcomes of interest, with death as competing-risk events for LF and DF. RESULTS 76 courses of SRS were delivered in 65 patients (54 unresected BM lesions, and 22 surgical cavities). 43 (66%) patients were ECOG 0–1. 35 (54%) patients had solitary BM. 41 (63%) had symptomatic BM. Half of the patients had primary lung cancer. Median follow-up was 4.8 months (range:0.1–39 months). 10 LF were observed at a median of 3.5 month post-SRS, with 6- and 12-month LF cumulative incidence of 14% and 24% respectively. 30 DF were observed at a median of 3.3 months, with 6- and 12-month DF cumulative incidence of 38% and 63% respectively. The 12- and 24-month OS were 39% and 26% respectively. In multivariate analyses, better ECOG status, solitary BM lesion, resection of BM pre-SRS, and use of subsequent systemic therapy were independently associated with improved OS. CONCLUSION This is one of the few Australian series reporting on outcomes following SRS for limited BM, with comparable outcomes to published international series.


Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 492-495 ◽  
Author(s):  
JJ Goedert ◽  
MG Sarngadharan ◽  
ME Eyster ◽  
SH Weiss ◽  
AJ Bodner ◽  
...  

Abstract The third member of the family of T cell leukemia viruses (HTLV III) has been proposed as the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia, particularly those with factor VIII deficiency who receive commercial clotting factor concentrates. In a prevalence survey conducted between September 1982 and April 1984, initial serum samples from 74% of hemophiliacs who had ever been treated with commercial factor VIII concentrate, 90% of those frequently treated with factor VIII concentrate, and 50% of those treated with both factor VIII and factor IX concentrates had antibodies reactive against antigens of HTLV III, compared with none of the hemophiliacs treated only with factor IX concentrate or volunteer donor plasma or cryoprecipitate. Two of the seropositive patients have developed AIDS-related illnesses, and a third patient died of bacterial pneumonia. One initially seronegative patient developed antibodies against HTLV III during the study and is currently well. The predominant antibody specificities appear directed against p24 and p41, the presumed core and envelope antigens of HTLV III, suggesting that factor VIII concentrate may transmit the p24 and p41 antigens of HTLV III. However, the presence of infectious retroviruses in clotting factor concentrates and the effectiveness of screening and viral neutralization procedures remain to be determined.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S105-S107
Author(s):  
P Jenkinson ◽  
N Plevris ◽  
M Lyons ◽  
S Siakavellas ◽  
I Arnott ◽  
...  

Abstract Background Peri-anal Crohn’s disease (pCD) significantly affects quality of life in patients with CD. The natural history of pCD in the era of biologic therapy is poorly understood. Perianal surgery includes examination under anaesthesia (EUA), drainage of peri-anal sepsis, seton instertion and fistula manipulation. EUA forms part of the standard of care at diagnosis of pCD and therefore can be used as a proxy for incidence of pCD. Methods CD patients were identified from the Lothian IBD registry, a physician validated registry of all IBD cases within Lothian which has been shown to be 94.3% complete. Prospectively collected coding data was used to identify peri-anal surgery, which was validated by review of the electronic health record. Biologic prescription data was extracted from the Lothian biologics database; a physician validated, prospectively collected registry. Time trend analysis was performed for the period 2000 to 2017 by 1) calculating annual incidence rates of peri-anal interventions for all patients with CD and estimating annual percentage change and 2) by calculating cumulative incidence of pCD and biologic prescription in newly diagnosed CD and 3) stratifying by era of diagnosis (Cohort 1: 2000–2008 and Cohort 2: 2009–2017. Results 2937 patients with CD were identified in the study period, with 1108 operations for pCD performed on 381 patients. Rates of surgery fell from 5.1 to 2.0 operations per 100 CD patients per year between 2000 and 2017 (p<0.001) giving an annual percentage change of -3.4% (-4.9% to -1.9% 95% CI) (fig 1). 1753 new diagnoses of CD were made of whom 247 developed pCD. 5 year risk of pCD was 12.8% (9.5–16.6%) with no significant difference identified between cohort 1 (11.5%) and cohort 2 (13.8%) (p=0.116) (fig 2). The 5 year incidence of biologic prescription for patients with pCD increased from 11.2% in cohort 1 to 58.1% in cohort 2 (p<0.001) (fig 3). Figure 1: Number of peri-anal interventions per 100 CD patients per year (multiple procedures per patient included). Figure 2: Kaplan Meier curves showing cumulative incidence of pCD stratified by era of diagnosis. Figure 3: Kaplan Meier curves showing cumulative incidence of biologic prescription in patients with CD stratified by era of diagnosis and presence of pCD. Conclusion The incidence of pCD remains unchanged over time. Although we cannot ascribe causality, the overall decrease in surgery for pCD has been paralleled by a marked increase in the use of biologic medication.


Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1898-1902
Author(s):  
M Makris ◽  
JA Garson ◽  
CJ Ring ◽  
PW Tuke ◽  
RS Tedder ◽  
...  

The polymerase chain reaction (PCR) was used to detect hepatitis C (HCV) viral sequences (HCV-RNA) in clotting factor concentrates that had been stored at 4 degrees C for 1 to 16 years. A total of 43 concentrates were tested, comprising 31 batches of factor VIII, 6 of factor IX, 2 of antithrombin III, 3 of FEIBA, and 1 of factor VII. HCV- RNA was detected in 13 of the 43 batches (30.2%). Concentrates that had not undergone viral inactivation during manufacture were significantly more likely to contain detectable HCV-RNA than concentrates that had been virally inactivated (56.3% v 14.5%, P = .006). HCV sequences were more commonly detected in concentrates made from paid donor plasma than in those made from volunteer donor plasma (44% v 11%, P = .041), and more commonly in virally inactivated concentrates with pre-1989 than with post-1989 expiration dates (50% v 0%, P = .004). Of the four batches of heat-treated products that were HCV-RNA positive, at least three transmitted non-A, non-B hepatitis (NANBH). An association between the presence of HCV-RNA in concentrates and the development of NANBH was demonstrated in nine previously untreated patients on prospective follow-up. HCV-RNA was detected in the concentrates administered to the six patients whose alanine aminotransferase (ALT) abnormalities met the diagnostic criteria for NANBH and who later seroconverted for HCV, but it was not detected in the concentrates administered to the three patients whose ALT abnormalities failed to satisfy the diagnostic criteria and who did not seroconvert. We suggest that the use of this PCR technique to monitor clotting factor concentrates derived from pooled blood may potentially contribute to product safety.


Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 492-495
Author(s):  
JJ Goedert ◽  
MG Sarngadharan ◽  
ME Eyster ◽  
SH Weiss ◽  
AJ Bodner ◽  
...  

The third member of the family of T cell leukemia viruses (HTLV III) has been proposed as the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia, particularly those with factor VIII deficiency who receive commercial clotting factor concentrates. In a prevalence survey conducted between September 1982 and April 1984, initial serum samples from 74% of hemophiliacs who had ever been treated with commercial factor VIII concentrate, 90% of those frequently treated with factor VIII concentrate, and 50% of those treated with both factor VIII and factor IX concentrates had antibodies reactive against antigens of HTLV III, compared with none of the hemophiliacs treated only with factor IX concentrate or volunteer donor plasma or cryoprecipitate. Two of the seropositive patients have developed AIDS-related illnesses, and a third patient died of bacterial pneumonia. One initially seronegative patient developed antibodies against HTLV III during the study and is currently well. The predominant antibody specificities appear directed against p24 and p41, the presumed core and envelope antigens of HTLV III, suggesting that factor VIII concentrate may transmit the p24 and p41 antigens of HTLV III. However, the presence of infectious retroviruses in clotting factor concentrates and the effectiveness of screening and viral neutralization procedures remain to be determined.


2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 256-256
Author(s):  
Kenshiro Shiraishi ◽  
Tomohiro Shinozaki

256 Background: There is a growing body of evidence that vast majority of patients with early breast cancer who underwent breast conserving therapy (BCT) live their longer ‘cancer survivor’ lives through modern sophisticated treatment. Accordingly, second malignancies after BCT are on the rise, which are sticky dilemmas accompanied by additional anxiety and need for further medical care. Investigation of secondary malignancies should be made the first priority in Japan as the world's top country for longevity. Methods: In order to investigate the second malignancies after BCT, a cohort study was conducted based on our database from 1982 to mid-2015. Actuarial rates of second malignancies, overall (OS) and cause-specific survival (CSS), were calculated by using the Kaplan-Meier method. We calculated standardized incidence ratios (SIR) for each cancer type corresponding to the national registry. Results: 1,557 patients (49.5%) were followed-up for more than 10 years. At a median follow-up of 113 months, 180 patients had developed a second malignancy. The increases in risk were for leukemia (SIR: 3.89 (1.76–6.84)) and ovarian cancer (SIR: 3.65 (2.26–5.38)). Trends toward increased risk was seen in reno-ureteral cancer (SIR: 2.25 (0.96–4.08)) and endometrial cancer (SIR: 1.59 (0.92–2.43)) though it was not statistically significant. No increased risk was observed for other gastrointestinal and genitourinary cancer, malignant melanoma, lymphoma, thyroid or head and neck cancer. Overall 10-year cumulative incidence of OS was 93.3%, and overall 10-year cumulative incidence of CSS was 95.0%. Overall 10-year incidence of secondary cancer was 5.9%. A total number of secondary malignancies within 10 years was 157 and this number explained 84.4% of all cases observed during follow-up. Secondary cancers continued to occur afterward, and cumulative incidence at 15- and 20-years were 8.4% , and 9.6%, respectively. Conclusions: Secondary cancers after BCT continue to arise as long as patients survive. Given its nature of life-threatening to cancer survivors, attending care team must pay persistent attention to secondary malignancies especially in Japan with the longest life-span.


2021 ◽  
Author(s):  
Yuefan Shen ◽  
Anping Xiang ◽  
Sihi Shao

Abstract OBJECTIVES: Ureteral stenosis is a serious complication after flexible ureteroscopy. Other studies have confirmed that stone impaction and intraoperative ureteral injury are important factors causing stricture, and how to predict the occurrence of stricture before surgery may be an important topic. This study retrospectively studied the influence of preoperative hydronephrosis degree on ureteral stenosis after flexible ureteroscopy to explore whether preoperative hydronephrosis degree could predict postoperative ureteral stenosis. METHODS: A retrospective study was conducted on patients who received flexible ureteroscopy in our hospital for upper ureteral calculi from January 2015 to June 2018. The postoperative follow-up was performed for 36 months, and intraoperative and postoperative complications were recorded. According to the degree of hydronephrosis, the patients were divided into mild hydronephrosis group and moderate and severe hydronephrosis group. Preoperative clinical baseline data of the patients were adjusted by propensity matching score, and differences in intraoperative mucosal injury, operative time, incidence of postoperative ureteral stricture, and SFR 1 month after surgery were statistically analyzed. Kaplan-Meier method and Log-rank test were used to compare the differences in the cumulative incidence of ureteral stenosis between the two groups. Cox regression analysis was used to compare the hazard ratio of ureteral stenosis between the two groups. RESULTS: A total of 447 patients with 469 sides surgery were included, including 349 sides in the mild hydronephrosis group and 120 sides in the moderate and severe hydronephrosis group. 30 sides in 29 patients developed ureteral stenosis. The stenosis rate before propensity matching analysis was 6.4%, and 8% after propensity matching analysis. However, the SFR and operation time were not statistically consistent. Kaplan-Meier showed a significant difference in the cumulative incidence of ureteral stenosis between the two groups.CONCLUSIONS: Preoperative patients with moderate to severe hydronephrosis are more likely to have intraoperative mucosal injury, and the incidence of ureteral stricture is higher after flexible ureteroscopy. Preoperative hydronephrosis is an important predictor of ureteral stricture. Preoperative hydronephrosis is an important predictor of ureteral stricture.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Nakano ◽  
R Imai ◽  
M Yoshida ◽  
S Shimokata ◽  
S Adachi ◽  
...  

Abstract Background Venous thromboembolism (VTE) is the third frequent acute cardiovascular syndrome in the Europe and Japan. Since direct oral anticoagulants (DOACs) are widely used now, the morbidity and mortality of pulmonary embolism (PE) patients especially associated with cancer needs to be re-evaluated. Purpose We evaluated the clinical course of patients with PE mainly treated with DOACs. Methods This retrospective observational study was conducted in a single center. The data were collected from the medical record of consecutive patients who received inpatient treatment of PE. In this study, we have compared PE patients with cancer (cancer PE) to those without cancer (non-cancer PE) and evaluated the mortality, recurrent of VTE and major bleedings. Results In total, 140 patients were enrolled: 94 patients were cancer-related, and 46 patients were without cancer (Table). The type of the tumor in cancer PE patients were as follows: gastric 8 (9%), esophageal 5 (5%), pancreatic 12 (13%), lung 14 (15%), lymphoma 2 (2%), gynecologic 17 (18%), renal 2 (2%), bile duct 8 (9%), colon 12 (13%), and others 17 (18%). Kaplan-Meier curve showed that the cumulative all-cause mortality was significantly higher in the cancer PE group (35/94 (37%) vs. 2/46 (4%), P<0.001 (log rank), HR 10.3 [95% CI:2.5–43.3]). The cumulative incidence of recurrent VTE was significantly higher in the cancer PE group (7/94 (7%) vs. 0/46, P=0.03 (log rank)). There was no significant difference in the cumulative incidence of major bleeding between the cancer PE group and the non-cancer PE group (8/94 (9%) vs. 5/46 (11%)). Conclusions The risk of recurrent VTE was still higher in cancer PE patients compared to non-cancer PE patients, although DOACs were used. Meanwhile the incidence of major bleeding was comparable in both groups, the risk of bleeding might be acceptable with using DOACs especially in cancer PE patients. Figure 1 Funding Acknowledgement Type of funding source: None


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2277-2277
Author(s):  
Ru Zhang ◽  
Dena Yassin ◽  
Lingyun Ji ◽  
Robert Miller ◽  
Diane J. Nugent ◽  
...  

Abstract Thromboelastography (TEG) is a leading candidate for monitoring bypassing agent therapy in hemophilia. It is not clear, however, which pre-analytic methods provide the most sensitivity in assessing the response to clotting factor concentrates. Previous studies have utilized kaolin (K) or recombinant human tissue factor (TF) as activators, and native blood (NB) or citrated blood (CB) as the collection method. Utilizing blood samples from 16 hemophiliacs (8 with and 8 without inhibitors), we compared NB to CB and K to 2 dilutions of TF [1:17,000(TF1) and 1:42,000(TF2)] with and without ex vivo addition of recombinant FVIIa (rFVIIa) and recombinant factor VIII (rFVIII). For patients with inhibitors, 3 experiments were performed for each of the above comparisons: no added factor and addition of rFVIIa 1.5mcg/ml and 4.5 mcg/ml. For patients without inhibitors (all FVIII deficient), 5 experiments were performed: no added factor, rFVIII 0.5 units/ml, rFVIII 1 units/ml, and rFVIIa 1.5 and 4.5mcg/ml. This initial analysis focused on the R parameter (reaction time) which is the time to initial fibrin formation and is the parameter that is most sensitive to the addition of clotting factor concentrates. The R values were analyzed via log transformed random effects ANOVA. All R values are expressed as geometric means. See table for results. There was no significant difference in the R time of NB and CB for any of the experiments. For inhibitor patients following the addition of rFVIIa, the R time was significantly longer for K than for TF1 and TF2 allowing a clearer distinction in response to various concentrations of rFVIIa. This is demonstrated as a significant difference between the 2 concentrations of rFVIIa with the higher concentration demonstrating a shorter R. For patients without inhibitors, activation with K led to a significantly longer R relative to TF1 and TF2 as well with both placebo and rFVIIa. Importantly, when adding a non-activated factor such as rFVIII, R was equivalent for K and TF2 both of which were significantly longer than TF1. In conclusion, 1) we recommend CB as the collection method as it is more practical in clinical settings, and 2) activation with K demonstrates a longer R than TF1 or TF2, resulting in increased sensitivity to addition of 2 clinically relevant concentrations of rFVIIa in both the inhibitor and non-inhibitor patients. Thus we suggest that K is the best activator when analyzing response to rFVIIa in hemophilia patients. Observed (Predicted) Geometric Mean R (mins) for CB Patient Type Factor Kaolin TF1 TF2 *p<0.001 for K versus TF1, K versus TF2, and TF1 versus TF2. *p<0.001 for rFVIIa 1.5 mcg/ml versus 4.5 mcg/ml for all activation methods. #p<0.03 for K versus TF1 for all factors. #p<0.001 for K versus TF2 for placebo and both concentrations of rFVIIa Inhibitor* rFVIIa 1.5 mcg/ml 50.6 (50.1) 14.7 (14.7) 25.1 (25.3) rFVIIa 4.5 mcg/ml 37.3 (32.1) 11.1 (9.4) 19.4 (16.2) No Inhibitor # Placebo 18.2 (17.6) 9.1 (9.1) 13.6 (13.9) rFVIII 0.5 U/ml 7.7 (7.7) 6.0 (6.0) 8.1 (8.1) rFVIII 1.0 U/ml 7.1 (7.1) 5.8 (5.8) 7.6 (7.6) rFVIIa 1.5 mcg/ml 12.7 (11.3) 5.8 (5.9) 10.3 (8.9) rFVIIa 4.5 mcg/ml 9.8 (11.0) 5.8 (5.7) 8.3 (8.7)


1999 ◽  
Vol 82 (08) ◽  
pp. 572-575 ◽  
Author(s):  
Jeanne Lusher

IntroductionThe treatment of hemophilia A and B has improved considerably in recent years. The availability of hepatitis A and B vaccines, safer clotting factor concentrates (particularly recombinant factor VIII and recombinant factor IX concentrates), and synthetic agents, such as desmopressin,1 has resulted in earlier, more aggressive treatment and prophylactic regimens aimed at preventing chronic, debilitating joint disease.2-8There have been no new cases of human immunodeficiency virus (HIV) disease attributable to clotting factor in North America since 1987, and documented instances of hepatitis transmission by clotting factor concentrates have been rare in the 1990s. Concerns remain that certain nonenveloped viruses, such as human parvovirus B19 and hepatitis A virus, can still be transmitted by some plasma-derived clotting factor concentrates,9and questions linger as to whether the agents causing Creutzfeld-Jacob disease (CJD) and new variant CJD might also be transmitted. Overall, however, the products available to treat hemophilia today are safer than ever before.An increasing number of persons with hemophilia are receiving exclusively recombinant (r) products, and manufacturers are now producing new, second-generation r-factor VIII products that are stabilized with sugars, rather than albumin, or are smaller, truncated molecules.10 Scientists are now designing specific changes into the factor VIII genes in an attempt to derive unique and improved forms of r-factor VIII.11 The next logical areas of focus are to bring to fruition the promise of an “unlimited supply” of r-factor VIII and r-factor IX products, to meet the needs of persons with hemophilia, not only in developed countries, but throughout the world, and to be able to cure hemophilia through gene therapy.As gene therapy trials begin in humans with hemophilia, the scientists involved, the United States Food and Drug Administration (FDA), and perhaps most importantly, members of the hemophilia community must decide which categories of affected individuals should be entered in these trials, particularly the earliest, Phase I trials. Who is most likely to benefit if gene therapy proves to be both effective and safe? Who should be the first patients to be enrolled in each new trial? Who is at greatest risk if something unexpected happens? What would be considered a good outcome? Clearly, some of these questions are more difficult to answer than others.


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