This issue was addressed specifically within the framework of the Italian ITI Registry (the PROgnostic Factors in Immune Tolerance [PROFIT] study). The Italian ITI registry was established in 2005 by the Italian Association of Haemophilia Centres to monitor clinical practice in Italy and investigate predictors

of ITI outcome. In an era of randomized trials including the ITI setting, the new ITI Registry was planned for several reasons. Over the past two decades, Italian haemophilia centres have gained a wealth of experience with use of ITI but, for the most part, the data have not been collected systematically. Despite the introduction of randomized clinical trials in haemophilia, many patients who are candidates for ITI do not fulfil specific inclusion criteria for randomized clinical trials or refuse randomized treatment choices; data from these patients

IWR-1 are therefore omitted from such trials. Moreover, modern registries can provide useful information with regard to the definition of ITI success or failure in clinical practice as well as address new issues such as the role for genetic or immunological factors in ITI outcome. In this respect, the Ibrutinib PROFIT Registry consists of a retrospective analysis of ITI courses completed between 1996 and 2005 and a prospective study of ITI courses ongoing or started after approval of the Italian ITI registry (2005–2010). Coordinated in Naples and Milan, 25 Italian haemophilia centres from across the country participated in the study. A central genetics

laboratory in Foggia, Italy, assessed F8 gene mutations in individual patients. For study purposes, ITI outcomes were reviewed centrally and defined according to currently 上海皓元医药股份有限公司 accepted criteria [9, 12]. Specifically, success was defined as an inhibitor titre <0.5 BU mL−1, recovery ≥66% and half-life ≥6 h. Partial success was defined as an inhibitor titre <5 BU mL−1 and/or recovery <66% and/or half-life <6 h (a clinical response to FVIII). Failure was defined as an inhibitor decline <20% of peak titre on ITI (for any 6-month period after the first 3 months), with no success or partial success within 33 months. The first report from the Registry was published in 2009 [12], and an update of data analysis was more recently presented at the World Federation of Haemophilia Congress in 2012 [13]. Of 133 ITI courses in total, 23 were excluded from analysis for the following reasons: 12 courses were administered after previous ITI failure; four patients had low-responding inhibitors and two patients had mild/moderate haemophilia; ITI was ongoing in five patients. Therefore, this analysis focused on 110 patients with severe haemophilia and high-responding inhibitors who underwent a first ITI course, irrespective of regimen or type of FVIII concentrates used, according to the choice of the reporting physician. The demographic and clinical characteristics of patients at baseline and at the start of ITI therapy are summarized in Table 2.

This issue was addressed specifically within the framework of the Italian ITI Registry (the PROgnostic Factors in Immune Tolerance [PROFIT] study). The Italian ITI registry was established in 2005 by the Italian Association of Haemophilia Centres to monitor clinical practice in Italy and investigate predictors

of ITI outcome. In an era of randomized trials including the ITI setting, the new ITI Registry was planned for several reasons. Over the past two decades, Italian haemophilia centres have gained a wealth of experience with use of ITI but, for the most part, the data have not been collected systematically. Despite the introduction of randomized clinical trials in haemophilia, many patients who are candidates for ITI do not fulfil specific inclusion criteria for randomized clinical trials or refuse randomized treatment choices; data from these patients

Everolimus order are therefore omitted from such trials. Moreover, modern registries can provide useful information with regard to the definition of ITI success or failure in clinical practice as well as address new issues such as the role for genetic or immunological factors in ITI outcome. In this respect, the learn more PROFIT Registry consists of a retrospective analysis of ITI courses completed between 1996 and 2005 and a prospective study of ITI courses ongoing or started after approval of the Italian ITI registry (2005–2010). Coordinated in Naples and Milan, 25 Italian haemophilia centres from across the country participated in the study. A central genetics

laboratory in Foggia, Italy, assessed F8 gene mutations in individual patients. For study purposes, ITI outcomes were reviewed centrally and defined according to currently 上海皓元 accepted criteria [9, 12]. Specifically, success was defined as an inhibitor titre <0.5 BU mL−1, recovery ≥66% and half-life ≥6 h. Partial success was defined as an inhibitor titre <5 BU mL−1 and/or recovery <66% and/or half-life <6 h (a clinical response to FVIII). Failure was defined as an inhibitor decline <20% of peak titre on ITI (for any 6-month period after the first 3 months), with no success or partial success within 33 months. The first report from the Registry was published in 2009 [12], and an update of data analysis was more recently presented at the World Federation of Haemophilia Congress in 2012 [13]. Of 133 ITI courses in total, 23 were excluded from analysis for the following reasons: 12 courses were administered after previous ITI failure; four patients had low-responding inhibitors and two patients had mild/moderate haemophilia; ITI was ongoing in five patients. Therefore, this analysis focused on 110 patients with severe haemophilia and high-responding inhibitors who underwent a first ITI course, irrespective of regimen or type of FVIII concentrates used, according to the choice of the reporting physician. The demographic and clinical characteristics of patients at baseline and at the start of ITI therapy are summarized in Table 2.

2 (median, 33; IQR, 27-39). DILI was hepatocellular (R ≥ 5) in 98 (77.8%) subjects, a mixed reaction (2 < R < 5) in 12 (9.5%), and cholestatic (R ≤ 2) in 16 (12.6%). Data were missing in seven subjects. Sixty-one different agents, alone or in combination, were thought to cause DILI ALF (Table 1A-C). Causality assessment, by expert opinion, indicated that a selected agent was

highly likely in 108 (81.1%), probable in 20 (15.0%), and only possible in five (3.8%) cases. Four cases were considered only possible due to use of LY294002 research buy many compounds, unknown temporal associations, comorbid conditions, or use of agents of low DILI potential; the fifth case had taken atorvastatin as the only medication with DILI potential, for 36 months. In 27 (20.3%) cases, only one drug was used, including nine isoniazid cases. In three cases, a combination of two to four antituberculosis drugs (isoniazid, rifampin, pyrazinamide, and ethambutol) were the only medications used. The remaining 103 (77.4%) cases were taking several and sometimes many other agents besides the prime suspect(s), including drugs of varying hepatotoxic potential (Table 2). Antimicrobials were most commonly responsible for DILI ALF (Table 1A), among which antituberculosis therapies predominated. Isoniazid was the sole antituberculosis drug in 15 cases, and in six cases in combination. Sulfur drugs frequently selleck compound caused ALF, especially trimethoprim-sulfamethoxazole

(TMP-S) alone (nine cases); this agent was also implicated in combination with azithromycin, a statin, and/or antiretroviral compounds. Nitrofurantoin was implicated 12 times. Terbinafine and azole antifungal drugs were relatively common, but antiretroviral drugs were infrequent. CAM, nonprescription medications,

dietary supplements, weight loss treatments, and illicit substances—several of which carry FDA warnings24—were responsible for 14 (10.6%) cases. Of the neuropsychiatric drugs, phenytoin use (eight cases) was frequent, 上海皓元 along with other antiepileptics (n = 5), and psychotropic drugs (n = 4). Halogenated anesthetic hepatotoxicity occurred twice. Disulfiram for alcoholism, and propylthiouracil for thyrotoxicosis, accounted for nine cases each. Bromfenac was implicated in four cases, whereas other nonsteroidal anti-inflammatory drugs (NSAIDs), biological agents, and leukotriene inhibitors were infrequent hepatotoxins. One patient treated with gemtuzumab following bone marrow transplantation developed sinusoidal obstruction syndrome. Fifteen subjects were taking statins, in four of whom another drug was the likely cause of DILI ALF (TMP-S, nitrofurantoin, and cefopime, respectively, and one subject was treated with amoxicillin-clavulanic acid followed by amoxicillin). Cerivastatin was used in two cases, simvastatin in two (alone or with ezetemibe), and atorvastatin in two. In one subject taking nitrofurantoin, atorvastatin was changed after 1 month to simvastatin, which was used for 2 months.

2 (median, 33; IQR, 27-39). DILI was hepatocellular (R ≥ 5) in 98 (77.8%) subjects, a mixed reaction (2 < R < 5) in 12 (9.5%), and cholestatic (R ≤ 2) in 16 (12.6%). Data were missing in seven subjects. Sixty-one different agents, alone or in combination, were thought to cause DILI ALF (Table 1A-C). Causality assessment, by expert opinion, indicated that a selected agent was

highly likely in 108 (81.1%), probable in 20 (15.0%), and only possible in five (3.8%) cases. Four cases were considered only possible due to use of selleck products many compounds, unknown temporal associations, comorbid conditions, or use of agents of low DILI potential; the fifth case had taken atorvastatin as the only medication with DILI potential, for 36 months. In 27 (20.3%) cases, only one drug was used, including nine isoniazid cases. In three cases, a combination of two to four antituberculosis drugs (isoniazid, rifampin, pyrazinamide, and ethambutol) were the only medications used. The remaining 103 (77.4%) cases were taking several and sometimes many other agents besides the prime suspect(s), including drugs of varying hepatotoxic potential (Table 2). Antimicrobials were most commonly responsible for DILI ALF (Table 1A), among which antituberculosis therapies predominated. Isoniazid was the sole antituberculosis drug in 15 cases, and in six cases in combination. Sulfur drugs frequently APO866 caused ALF, especially trimethoprim-sulfamethoxazole

(TMP-S) alone (nine cases); this agent was also implicated in combination with azithromycin, a statin, and/or antiretroviral compounds. Nitrofurantoin was implicated 12 times. Terbinafine and azole antifungal drugs were relatively common, but antiretroviral drugs were infrequent. CAM, nonprescription medications,

dietary supplements, weight loss treatments, and illicit substances—several of which carry FDA warnings24—were responsible for 14 (10.6%) cases. Of the neuropsychiatric drugs, phenytoin use (eight cases) was frequent, medchemexpress along with other antiepileptics (n = 5), and psychotropic drugs (n = 4). Halogenated anesthetic hepatotoxicity occurred twice. Disulfiram for alcoholism, and propylthiouracil for thyrotoxicosis, accounted for nine cases each. Bromfenac was implicated in four cases, whereas other nonsteroidal anti-inflammatory drugs (NSAIDs), biological agents, and leukotriene inhibitors were infrequent hepatotoxins. One patient treated with gemtuzumab following bone marrow transplantation developed sinusoidal obstruction syndrome. Fifteen subjects were taking statins, in four of whom another drug was the likely cause of DILI ALF (TMP-S, nitrofurantoin, and cefopime, respectively, and one subject was treated with amoxicillin-clavulanic acid followed by amoxicillin). Cerivastatin was used in two cases, simvastatin in two (alone or with ezetemibe), and atorvastatin in two. In one subject taking nitrofurantoin, atorvastatin was changed after 1 month to simvastatin, which was used for 2 months.

Noteworthy, enrichment of miR-492-suppressed genes was most significantly overrepresented in functional clusters assorted by metal binding properties, by extracellular space occurrence, or by the more general category of developmental processes. They include, e.g., members of the copper and cadmium binding MT1 (metallothionein) gene family, which is instrumental to regulate aggressive neoplastic cell growth, prognosis, and/or resistance against radiation and chemotherapy Imatinib chemical structure in a variety of human neoplasias,

including HCC.34, 35 Moreover, the members of the ALB/AFP/AFM (albumin, alpha fetoprotein, afamin) multigene family were found, which belong to the earliest genes to be expressed in the fetal liver in mammals.36 Despite the limitations in transferring findings on regulatory circuits defined in HB cell culture to the HB tumor biology, it is tempting to speculate that KRT19-associated miR-492 overexpression could act as a regulatory component to counteract some gene expressions (e.g., MT1 or AFP) that might

otherwise drive the tumor toward an unfavorable phenotype. Within this set of suppressed genes we identified putative direct targets of miR-492 by using target prediction algorithms and quantitative PCR-based verification. They included BAAT, ST6GAL1, TCF21, HSD3B1, ALB, BID, GDA, and CDKN2A. Consistently, an inverse relationship to miR-492 expression was noted RXDX-106 manufacturer in HB tumors for most of these candidate targets. 上海皓元医药股份有限公司 However, the level of significance was reached only for BAAT, which might be due to the heterogeneous composition of tumor tissue. Because BAAT, ST6GAL1, ALB, and GDA are mainly expressed in the mature liver, these data suggest that high miR-492 levels in HB might indicate a rather immature stage of the tumor. Because miR-492 closely correlates with KRT19 expression and obviously influences genes involved in tumor progression and hepatocyte differentiation, we wondered whether this might be reflected in the clinicopathological features of HB. Indeed,

both markers were significantly higher expressed in metastatic stages compared to nonmetastatic stages, although only a small cohort of 26 HB tumor samples was available for this study. This observation would be consistent with data published by Cairo et al.18 demonstrating that HB tumors with high expression of KRT19 are attributed as a poor prognostic group. Metastasis-related miRNAs have also been discovered in HCC.24 MiR-492, however, did not show up as significantly out-regulated in HCC miRNA profiles.24, 25 Equally, a recently published list of miRNAs being potentially involved in HB genesis37 does not contain miR-492. This might be due to the relatively weak expression level of miR-492, which could result in a loss of this candidate by background corrections of miRNA arrays.

9, 24 In the present study, regardless of the dual combination of dynamic contrast imaging technique applied, no more than 13% of grade I tumors ≤2 cm were correctly identified on radiological examination, compared with >50% for grade II and grade III tumors of similar size. As a consequence, of the 29 radiologically identified tumors, only 7% were grade I HCC, which in turn accounted for the 48% of CH5424802 in vivo tumors that were not identified on radiological examination

(P = 0.0003). Altogether, these findings reinforce the relationship that exists between arterial vascularization of the tumor, cell grade, and detectability by dynamic contrast imaging that was only partially reported by previous studies.25-29 The fact that in our study multivariate analysis showed tumor cell grading and nodule size to be the only two independent predictors of a radiological diagnosis of HCC further reinforces the association between HCC grade and vascularization. The lack of any correlation between tumor

size and cell grading in our series of small HCC nodules does not contrast with the well-known correlation between tumor size and cell grading that has been reported in surgical HCC nodules. Medium to large tumors are known to be heterogeneous in cell grading and to be generally less differentiated than small HCC nodules. We were not surprised to find no correlation between tumor grade and serum AFP values, because this could reflect the selection of patients with small tumors that rarely circulate high serum levels of AFP. A correlation between serum AFP levels and tumor cell grade has been reported in other RAD001 supplier clinical settings,30 even though AFP synthesis in malignant hepatocytes does not merely reflect cell dedifferentiation, but it is a more complex phenomenon related to HCC heterogeneity.31

Gene expression studies have shown that HCC subgroups with consistent AFP overexpression are likely 上海皓元 related to a progenitor cell phenotype with up-regulation of developmental and imprinting genes mainly occurring in a hepatitis B virus–related background.32 Most of our patients were hepatitis C–related, and it has also been shown that AFP-negative subgroups are enriched in HCC with different prognosis (i.e., showing both excellent and poor survival).33 The grade I tumors that we could not classify as HCC by contrast imaging likely correspond to Barcelona Clinic Liver Cancer stage 0 tumors (very early HCC) originally described in Japan as <2 cm HCCs having a vaguely nodular appearance and an intact portal tract–based structure.34, 35 In the original report, all those tumors were grade I and had a favorable outcome following hepatic resection compared with tumors of similar size with a distinctly nodular pattern that were made out by contrast imaging techniques. The latter tumors were more often dedifferentiated and tended to recur after hepatic resection.

Patients with at least one GI symptom made up 70% (14/20) of the BA group, and heartburn and/or regurgitation were detected in 40% of patients. Endoscopic findings of GERD were mucosal breaks (n = 3). The IS of the control group was 0.389 ± 0.297 um, while the BA group was 0.806 ± 0.556 um (P = 0.001). The presence of GERD symptoms (P = 0.306) and a history of recent asthma

attacks (P = 0.710) did not show selleck inhibitor significant differences. Conclusions:  The BA group showed a significant difference in the dilatation of IS compared to the control group, suggesting a higher prevalence of GERD in BA patients and a close pathophysiological correlation. “
“Tumor cells escape host immunosurveillance and thus produce an advantageous environment for tumor progression. Recent studies have demonstrated that tumor-infiltrating lymphocytes

(TILs) play a principal role in the immune response to tumors. However, little is understood about numerical alterations in CD3+ TILs during tumor progression in patients with gastric cancer. The present study examines the density of CD3+ TILs to elucidate their clinical significance in gastric cancer. The numbers of CD3+ TILs in 120 resected specimens from patients with gastric cancer and 27 endoscopic resected specimens from patients with gastric adenoma were immunohistochemically assessed using a CD3 polyclonal antibody. The mean number of CD3+ TILs (± SD) in the patients with gastric cancer and adenoma was 87.5 ± 59.8 and 379.6 ± 128.1, respectively. Significantly more CD3+ TILs were found

in specimens from patients with gastric adenoma than with gastric cancer (P < 0.0001). Acalabrutinib research buy The numbers of CD3+ TILs significantly correlated with depth of tumor invasion, lymph node metastasis, and stage (P = 0.022, P = 0.0004, and P = 0.011, respectively). The 5-year survival rate was significantly poorer for patients with fewer CD3+ TILs (P = 0.004). Multivariate analysis selected the density of CD3+ TILs as an independent prognostic factor (P = 0.034). Our results demonstrated that the density of CD3+ TILs decreases during tumor progression. The density of CD3+ TILs is an immunological predictor of lymph node metastasis and disease outcome in patients with gastric cancer. “
“Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and 上海皓元医药股份有限公司 the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics.

Patients with at least one GI symptom made up 70% (14/20) of the BA group, and heartburn and/or regurgitation were detected in 40% of patients. Endoscopic findings of GERD were mucosal breaks (n = 3). The IS of the control group was 0.389 ± 0.297 um, while the BA group was 0.806 ± 0.556 um (P = 0.001). The presence of GERD symptoms (P = 0.306) and a history of recent asthma

attacks (P = 0.710) did not show R788 mouse significant differences. Conclusions:  The BA group showed a significant difference in the dilatation of IS compared to the control group, suggesting a higher prevalence of GERD in BA patients and a close pathophysiological correlation. “
“Tumor cells escape host immunosurveillance and thus produce an advantageous environment for tumor progression. Recent studies have demonstrated that tumor-infiltrating lymphocytes

(TILs) play a principal role in the immune response to tumors. However, little is understood about numerical alterations in CD3+ TILs during tumor progression in patients with gastric cancer. The present study examines the density of CD3+ TILs to elucidate their clinical significance in gastric cancer. The numbers of CD3+ TILs in 120 resected specimens from patients with gastric cancer and 27 endoscopic resected specimens from patients with gastric adenoma were immunohistochemically assessed using a CD3 polyclonal antibody. The mean number of CD3+ TILs (± SD) in the patients with gastric cancer and adenoma was 87.5 ± 59.8 and 379.6 ± 128.1, respectively. Significantly more CD3+ TILs were found

in specimens from patients with gastric adenoma than with gastric cancer (P < 0.0001). this website The numbers of CD3+ TILs significantly correlated with depth of tumor invasion, lymph node metastasis, and stage (P = 0.022, P = 0.0004, and P = 0.011, respectively). The 5-year survival rate was significantly poorer for patients with fewer CD3+ TILs (P = 0.004). Multivariate analysis selected the density of CD3+ TILs as an independent prognostic factor (P = 0.034). Our results demonstrated that the density of CD3+ TILs decreases during tumor progression. The density of CD3+ TILs is an immunological predictor of lymph node metastasis and disease outcome in patients with gastric cancer. “
“Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and 上海皓元医药股份有限公司 the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is based on 477 patients with HCC seen at Mayo Clinic Rochester between 1994 and 2008 (derivation cohort) and 904 patients at the Korean National Cancer Center between 2000 and 2003 (validation cohort). Multivariate proportional hazards models and corresponding risk score were created based on baseline demographic, clinical, and tumor characteristics.

“
“Chemokines learn more modulate inflammatory responses that are prerequisites for organ fibrosis upon liver injury. Monocyte-derived hepatic macrophages are critical

for the development, maintenance, and resolution of hepatic fibrosis. The specific role of monocyte-associated chemokine (C-X3-C motif) receptor 1 (CX3CR1) and its cognate ligand fractalkine [chemokine (C-X3-C motif) ligand 1)] in liver inflammation and fibrosis is currently unknown. We examined 169 patients with chronic liver diseases and 84 healthy controls; we found that CX3CL1 is significantly up-regulated in the circulation upon disease progression, whereas CX3CR1 is down-regulated intrahepatically in patients with advanced liver fibrosis or cirrhosis.

To analyze the functional relevance of this pathway, two models of experimental liver fibrosis were applied to wild-type (WT) click here and CX3CR1-deficient mice. Fractalkine expression was induced upon liver injury in mice, primarily in hepatocytes and hepatic stellate cells. CX3CR1−/− animals developed greater hepatic fibrosis than WT animals with carbon tetrachloride–induced and bile duct ligation–induced fibrosis. CX3CR1−/− mice displayed significantly increased numbers of monocyte-derived macrophages within the injured liver. Chimeric animals that underwent bone marrow transplantation revealed that CX3CR1 restricts hepatic fibrosis 上海皓元 progression and monocyte accumulation through mechanisms exerted by infiltrating immune cells.

In the absence of CX3CR1, intrahepatic monocytes develop preferentially into proinflammatory tumor necrosis factor–producing and inducible nitric oxide synthase–producing macrophages. CX3CR1 represents an essential survival signal for hepatic monocyte–derived macrophages by activating antiapoptotic bcl2 expression. Monocytes/macrophages lacking CX3CR1 undergo increased cell death after liver injury, which then perpetuates inflammation, promotes prolonged inflammatory monocyte infiltration into the liver, and results in enhanced liver fibrosis. Conclusion: CX3CR1 limits liver fibrosis in vivo by controlling the differentiation and survival of intrahepatic monocytes. The opposing regulation of CX3CR1 and fractalkine in patients suggests that pharmacological augmentation of this pathway may represent a possible therapeutic antifibrotic strategy. (HEPATOLOGY 2010;52:1769-1782) Sustained inflammation is a common characteristic of chronic liver injury in mice and men and induces the development of hepatic fibrosis.

We also excluded 517 patients randomized to peginterferon maintenance in order to eliminate a potential effect of maintenance peginterferon on clinical outcomes, although we found no effect of maintenance peginterferon on clinical outcomes in our prior analysis.9 Of the remaining 333 nonresponders who were randomized to the no-treatment (control) arm, 24 were excluded for the following reasons: 17 were not followed after randomization, six were treated with interferon outside of the HALT-C Y-27632 mouse Trial, and one had negative HCV RNA test results during the randomized phase of the HALT-C Trial. Thus,

the first comparison group consisted of 309 nonresponder patients randomized to the control arm of HALT-C Trial who were viremic and did not receive subsequent interferon. The second comparison group consisted of patients who had a breakthrough or relapse and who were randomized to the control arm

of the HALT-C Trial. Of the 80 patients in the BT/R group randomized to the control (untreated) arm, three were excluded for the following reasons: two were not followed after randomization, and one patient was treated with peginterferon and ribavirin outside of the HALT-C Trial. Thus, a total of 77 patients with BT/R who were randomized to the control arm and who remained viremic after randomization were included in this analysis. The beginning date for this analysis was Cabozantinib the day when patients began peginterferon and ribavirin treatment during the lead-in phase of the HALT-C Trial (August 2000

to January 2003). The end date for 上海皓元 determination of clinical outcomes for the SVR patients was the day of their amended protocol study visit or telephone contact (September 2008 to March 2009). The date for assessment of blood tests for SVR patients was the day of the amended protocol study visit or the most recent laboratory tests from the patient’s medical records (for patients participating by telephone). For the NR and BT/R groups, clinical outcome data were included for the first 7.5 years of participation in the HALT-C Trial. The blood test results from the Month 72 visit for the NR and the BT/R groups were used for analysis of changes in blood tests because a larger number of patients had reached that time point (239 of 386) compared with the number available at the Month 84 visit (144 of 386). The median follow-up time for patients in the SVR group was 86 months, patients in the BT/R group was 85 months, and patients in the NR group was 79 months. Follow-up rates through Month 72 were 60% (185/309) in the NR group and 70% (54/77) in the BT/R group. The survival status of all patients was evaluated by searching the online U.S. Social Security Death Index (SSDI) (http://ssdi.rootsweb.ancestry.com), which is generated from the U.S. Social Security Administration’s Death Master File.