User login
Novel inhibitor proves ‘potent’ in hematologic malignancies
BOSTON—A pair of preclinical studies suggest the FLT3/BTK inhibitor CG’806 is active in a range of hematologic malignancies.
In one of the studies, CG’806 proved particularly effective against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3, and the compound was able to eradicate AML in mice.
In another study, researchers found CG’806 exhibited “broad potency” against leukemias, lymphomas, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs).
Both studies were presented as posters at Hematologic Malignancies: Translating Discoveries to Novel Therapies (poster 25 and poster 44).
Both studies involved researchers from Aptose Biosciences, the company developing CG’806.
Poster 25
Weiguo Zhang, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented poster 25, “CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3.”
The researchers tested CG’806 and other FLT3 inhibitors in human or murine leukemia cell lines with wild-type (WT) FLT3, FLT3-ITD mutations, FLT3 TKD domain mutations, or ITD plus TKD mutations.
Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with ITD mutations, D835 mutations, ITD plus F691I/Y842D/D835 mutations, or in FLT3 WT cells.
With CG’086, the IC50s in human AML cell lines were 0.17 nM for MV4-11 (FLT3-ITD) and 0.82 nM for MOLM13 (FLT3-ITD).
The IC50s in the murine leukemia cell lines were 9.49 nM for Ba/F3 (FLT3-WT), 0.30 nM for Ba/F3 (FLT3-ITD), 8.26 nM for Ba/F3 (FLT3-D835Y), 9.72 nM for Ba/F3 (FLT3-ITD+D835Y), and 0.43 nM for Ba/F3 (FLT3-ITD+F691L).
The researchers also found that CG’806 “triggers marked apoptosis” in FLT3-ITD-mutated primary AML samples but minimal apoptosis in normal bone marrow cells.
Another finding was that once-daily oral dosing of CG’806 in a murine model of AML (MV4-11) resulted in sustained micromolar plasma concentration over a 24-hour period.
This was accompanied by complete elimination of AML FLT3-ITD tumors without toxicity, the researchers said.
Poster 44
Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented poster 44, “CG’806, a First-in-Class FLT3/BTK Inhibitor, Exhibits Potent Activity against AML Patient Samples with Mutant or Wild-Type FLT3, as well as Other Hematologic Malignancy Subtypes.”
The researchers tested CG’806 in samples from patients with AML (n=82), MDS/MPNs (n=15), acute lymphoblastic leukemia (ALL, n=17), chronic lymphocytic leukemia (CLL, n=58), and chronic myeloid leukemia (CML, n=4).
The team observed “broad sensitivity” to CG’806, with 59% (48/82) of AML, 53% (8/15) of MDS/MPN, 40% (23/58) of CLL, 29% (5/17) of ALL, and 25% (1/4) of CML cases exhibiting an IC50 of less than 100 nM.
Among the 38 tested AML samples with known FLT3 mutational status, the FLT3-ITD+ AML samples tended to have enhanced sensitivity to CG’806 (median IC50 = 20 nM, n=8) relative to the FLT3-WT samples (median IC50 = 120 nM, n=30).
The researchers also found that CG’806 exerted potent anti-proliferative activity against human AML, B-ALL, mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cell lines.
“The analyses of CG’806 against primary hematologic malignancy patient samples and cultured cell lines show evidence of potent and broad drug activity in AML and other disease subtypes and support further development of this agent for hematologic malignancies,” Dr Kurtz said. 
BOSTON—A pair of preclinical studies suggest the FLT3/BTK inhibitor CG’806 is active in a range of hematologic malignancies.
In one of the studies, CG’806 proved particularly effective against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3, and the compound was able to eradicate AML in mice.
In another study, researchers found CG’806 exhibited “broad potency” against leukemias, lymphomas, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs).
Both studies were presented as posters at Hematologic Malignancies: Translating Discoveries to Novel Therapies (poster 25 and poster 44).
Both studies involved researchers from Aptose Biosciences, the company developing CG’806.
Poster 25
Weiguo Zhang, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented poster 25, “CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3.”
The researchers tested CG’806 and other FLT3 inhibitors in human or murine leukemia cell lines with wild-type (WT) FLT3, FLT3-ITD mutations, FLT3 TKD domain mutations, or ITD plus TKD mutations.
Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with ITD mutations, D835 mutations, ITD plus F691I/Y842D/D835 mutations, or in FLT3 WT cells.
With CG’086, the IC50s in human AML cell lines were 0.17 nM for MV4-11 (FLT3-ITD) and 0.82 nM for MOLM13 (FLT3-ITD).
The IC50s in the murine leukemia cell lines were 9.49 nM for Ba/F3 (FLT3-WT), 0.30 nM for Ba/F3 (FLT3-ITD), 8.26 nM for Ba/F3 (FLT3-D835Y), 9.72 nM for Ba/F3 (FLT3-ITD+D835Y), and 0.43 nM for Ba/F3 (FLT3-ITD+F691L).
The researchers also found that CG’806 “triggers marked apoptosis” in FLT3-ITD-mutated primary AML samples but minimal apoptosis in normal bone marrow cells.
Another finding was that once-daily oral dosing of CG’806 in a murine model of AML (MV4-11) resulted in sustained micromolar plasma concentration over a 24-hour period.
This was accompanied by complete elimination of AML FLT3-ITD tumors without toxicity, the researchers said.
Poster 44
Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented poster 44, “CG’806, a First-in-Class FLT3/BTK Inhibitor, Exhibits Potent Activity against AML Patient Samples with Mutant or Wild-Type FLT3, as well as Other Hematologic Malignancy Subtypes.”
The researchers tested CG’806 in samples from patients with AML (n=82), MDS/MPNs (n=15), acute lymphoblastic leukemia (ALL, n=17), chronic lymphocytic leukemia (CLL, n=58), and chronic myeloid leukemia (CML, n=4).
The team observed “broad sensitivity” to CG’806, with 59% (48/82) of AML, 53% (8/15) of MDS/MPN, 40% (23/58) of CLL, 29% (5/17) of ALL, and 25% (1/4) of CML cases exhibiting an IC50 of less than 100 nM.
Among the 38 tested AML samples with known FLT3 mutational status, the FLT3-ITD+ AML samples tended to have enhanced sensitivity to CG’806 (median IC50 = 20 nM, n=8) relative to the FLT3-WT samples (median IC50 = 120 nM, n=30).
The researchers also found that CG’806 exerted potent anti-proliferative activity against human AML, B-ALL, mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cell lines.
“The analyses of CG’806 against primary hematologic malignancy patient samples and cultured cell lines show evidence of potent and broad drug activity in AML and other disease subtypes and support further development of this agent for hematologic malignancies,” Dr Kurtz said.
BOSTON—A pair of preclinical studies suggest the FLT3/BTK inhibitor CG’806 is active in a range of hematologic malignancies.
In one of the studies, CG’806 proved particularly effective against acute myeloid leukemia (AML) cells harboring mutant forms of FLT3, and the compound was able to eradicate AML in mice.
In another study, researchers found CG’806 exhibited “broad potency” against leukemias, lymphomas, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs).
Both studies were presented as posters at Hematologic Malignancies: Translating Discoveries to Novel Therapies (poster 25 and poster 44).
Both studies involved researchers from Aptose Biosciences, the company developing CG’806.
Poster 25
Weiguo Zhang, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues presented poster 25, “CG’806, a first-in-class FLT3/BTK inhibitor, exerts superior potency against AML cells harboring ITD, TKD and gatekeeper mutated FLT3 or wild-type FLT3.”
The researchers tested CG’806 and other FLT3 inhibitors in human or murine leukemia cell lines with wild-type (WT) FLT3, FLT3-ITD mutations, FLT3 TKD domain mutations, or ITD plus TKD mutations.
Compared to second-generation FLT3 inhibitors (quizartinib, gilteritinib, or crenolanib), CG’806 showed more pronounced anti-proliferative effects in leukemia cells with ITD mutations, D835 mutations, ITD plus F691I/Y842D/D835 mutations, or in FLT3 WT cells.
With CG’086, the IC50s in human AML cell lines were 0.17 nM for MV4-11 (FLT3-ITD) and 0.82 nM for MOLM13 (FLT3-ITD).
The IC50s in the murine leukemia cell lines were 9.49 nM for Ba/F3 (FLT3-WT), 0.30 nM for Ba/F3 (FLT3-ITD), 8.26 nM for Ba/F3 (FLT3-D835Y), 9.72 nM for Ba/F3 (FLT3-ITD+D835Y), and 0.43 nM for Ba/F3 (FLT3-ITD+F691L).
The researchers also found that CG’806 “triggers marked apoptosis” in FLT3-ITD-mutated primary AML samples but minimal apoptosis in normal bone marrow cells.
Another finding was that once-daily oral dosing of CG’806 in a murine model of AML (MV4-11) resulted in sustained micromolar plasma concentration over a 24-hour period.
This was accompanied by complete elimination of AML FLT3-ITD tumors without toxicity, the researchers said.
Poster 44
Stephen E. Kurtz, PhD, of Oregon Health & Science University in Portland, and his colleagues presented poster 44, “CG’806, a First-in-Class FLT3/BTK Inhibitor, Exhibits Potent Activity against AML Patient Samples with Mutant or Wild-Type FLT3, as well as Other Hematologic Malignancy Subtypes.”
The researchers tested CG’806 in samples from patients with AML (n=82), MDS/MPNs (n=15), acute lymphoblastic leukemia (ALL, n=17), chronic lymphocytic leukemia (CLL, n=58), and chronic myeloid leukemia (CML, n=4).
The team observed “broad sensitivity” to CG’806, with 59% (48/82) of AML, 53% (8/15) of MDS/MPN, 40% (23/58) of CLL, 29% (5/17) of ALL, and 25% (1/4) of CML cases exhibiting an IC50 of less than 100 nM.
Among the 38 tested AML samples with known FLT3 mutational status, the FLT3-ITD+ AML samples tended to have enhanced sensitivity to CG’806 (median IC50 = 20 nM, n=8) relative to the FLT3-WT samples (median IC50 = 120 nM, n=30).
The researchers also found that CG’806 exerted potent anti-proliferative activity against human AML, B-ALL, mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cell lines.
“The analyses of CG’806 against primary hematologic malignancy patient samples and cultured cell lines show evidence of potent and broad drug activity in AML and other disease subtypes and support further development of this agent for hematologic malignancies,” Dr Kurtz said.
IV and SC rituximab produce similar results in FL
In a phase 3 trial, subcutaneous (SC) and intravenous (IV) rituximab produced comparable results as part of a first-line treatment regimen for follicular lymphoma (FL).
Overall response rates (ORR) were similar in patients who received SC rituximab and those who received IV rituximab, first in combination with chemotherapy and then alone as maintenance therapy.
Although patients who received SC rituximab had administration-related reactions that weren’t observed in the IV rituximab group, these events were largely mild-to-moderate local injection-site reactions.
Andrew Davies, PhD, of the University of Southampton in the UK, and his colleagues reported these results in The Lancet Haematology.
Data from stage 1 of this study, known as SABRINA, were previously published in The Lancet Oncology. The current publication includes stage 2 data.
The study was funded by Roche, which markets rituximab as Rituxan and MabThera.
The trial enrolled 410 patients with previously untreated, grade 1-3a, CD20-positive FL.
Patients were randomized to receive IV rituximab at 375 mg/m2 (n=205) or SC rituximab at 1400 mg (n=205) plus chemotherapy.
Chemotherapy consisted of 6 to 8 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) every 3 weeks during induction.
Patients then received rituximab maintenance every 8 weeks.
The researchers said baseline characteristics were balanced between the treatment arms, although there were more females in the SC arm than the IV arm—120 (59%) and 99 (48%), respectively.
Efficacy
In stage 1 of this study, the primary endpoint was the ratio of observed rituximab serum trough concentrations (Ctrough) between the treatment arms at cycle 7.
The results suggested SC rituximab was non-inferior to the IV formulation. The geometric mean Ctrough was 83.13 μg/mL in the IV arm and 134.58 μg/mL in the SC arm (ratio=1.62).
In stage 2, the primary endpoint was efficacy, or ORR, at the end of induction based on the researchers’ assessments and confirmed by an independent review panel of radiologists.
At the end of induction, the ORR was 84.9% (174/205) in the IV arm and 84.4% (173/205) in the SC arm. The complete response rate was 32.2% (n=66) in both arms.
At the end of maintenance therapy, the ORR was 78.1% (139/178) in the IV arm and 77.9% (134/172) in the SC arm. The complete response rates were 56.2% (n=100) and 50.6% (n=87), respectively.
At a median follow-up of 37 months, there was no significant difference between the arms with regard to progression-free survival (hazard ratio[HR]=0.84), event-free survival (HR=0.91), or overall survival (HR=0.81).
Safety
The incidence of adverse events (AEs) was similar between the treatment arms—95% in the IV arm and 96% in the SC arm. The incidence of grade 3 or higher AEs was 55% and 56%, respectively, and the incidence of serious AEs was 34% and 37%, respectively.
Overall, the most common AEs were gastrointestinal disorders (60% in the IV arm and 66% in the SC arm), infections and infestations (64% and 67%, respectively), and general or administration site conditions (50% and 60%, respectively).
Administration-related reactions were more common in the SC arm than the IV arm—48% and 35%, respectively. The most common of these reactions were chills (7%) and pruritus (6%) in the IV arm and injection-site erythema (11%), pruritus (6%), rash (5%), and injection-site pain (5%) in the SC arm.
Neutropenia was the most common grade 3 or higher AE, occurring in 34% of patients in the IV arm and 37% in the SC arm. Febrile neutropenia was the most frequent serious AE, occurring in 5% and 6%, respectively.
The researchers said these results suggest the SC formulation of rituximab has similar efficacy and a similar safety profile as IV rituximab in the first-line treatment of FL.
In a phase 3 trial, subcutaneous (SC) and intravenous (IV) rituximab produced comparable results as part of a first-line treatment regimen for follicular lymphoma (FL).
Overall response rates (ORR) were similar in patients who received SC rituximab and those who received IV rituximab, first in combination with chemotherapy and then alone as maintenance therapy.
Although patients who received SC rituximab had administration-related reactions that weren’t observed in the IV rituximab group, these events were largely mild-to-moderate local injection-site reactions.
Andrew Davies, PhD, of the University of Southampton in the UK, and his colleagues reported these results in The Lancet Haematology.
Data from stage 1 of this study, known as SABRINA, were previously published in The Lancet Oncology. The current publication includes stage 2 data.
The study was funded by Roche, which markets rituximab as Rituxan and MabThera.
The trial enrolled 410 patients with previously untreated, grade 1-3a, CD20-positive FL.
Patients were randomized to receive IV rituximab at 375 mg/m2 (n=205) or SC rituximab at 1400 mg (n=205) plus chemotherapy.
Chemotherapy consisted of 6 to 8 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) every 3 weeks during induction.
Patients then received rituximab maintenance every 8 weeks.
The researchers said baseline characteristics were balanced between the treatment arms, although there were more females in the SC arm than the IV arm—120 (59%) and 99 (48%), respectively.
Efficacy
In stage 1 of this study, the primary endpoint was the ratio of observed rituximab serum trough concentrations (Ctrough) between the treatment arms at cycle 7.
The results suggested SC rituximab was non-inferior to the IV formulation. The geometric mean Ctrough was 83.13 μg/mL in the IV arm and 134.58 μg/mL in the SC arm (ratio=1.62).
In stage 2, the primary endpoint was efficacy, or ORR, at the end of induction based on the researchers’ assessments and confirmed by an independent review panel of radiologists.
At the end of induction, the ORR was 84.9% (174/205) in the IV arm and 84.4% (173/205) in the SC arm. The complete response rate was 32.2% (n=66) in both arms.
At the end of maintenance therapy, the ORR was 78.1% (139/178) in the IV arm and 77.9% (134/172) in the SC arm. The complete response rates were 56.2% (n=100) and 50.6% (n=87), respectively.
At a median follow-up of 37 months, there was no significant difference between the arms with regard to progression-free survival (hazard ratio[HR]=0.84), event-free survival (HR=0.91), or overall survival (HR=0.81).
Safety
The incidence of adverse events (AEs) was similar between the treatment arms—95% in the IV arm and 96% in the SC arm. The incidence of grade 3 or higher AEs was 55% and 56%, respectively, and the incidence of serious AEs was 34% and 37%, respectively.
Overall, the most common AEs were gastrointestinal disorders (60% in the IV arm and 66% in the SC arm), infections and infestations (64% and 67%, respectively), and general or administration site conditions (50% and 60%, respectively).
Administration-related reactions were more common in the SC arm than the IV arm—48% and 35%, respectively. The most common of these reactions were chills (7%) and pruritus (6%) in the IV arm and injection-site erythema (11%), pruritus (6%), rash (5%), and injection-site pain (5%) in the SC arm.
Neutropenia was the most common grade 3 or higher AE, occurring in 34% of patients in the IV arm and 37% in the SC arm. Febrile neutropenia was the most frequent serious AE, occurring in 5% and 6%, respectively.
The researchers said these results suggest the SC formulation of rituximab has similar efficacy and a similar safety profile as IV rituximab in the first-line treatment of FL.
In a phase 3 trial, subcutaneous (SC) and intravenous (IV) rituximab produced comparable results as part of a first-line treatment regimen for follicular lymphoma (FL).
Overall response rates (ORR) were similar in patients who received SC rituximab and those who received IV rituximab, first in combination with chemotherapy and then alone as maintenance therapy.
Although patients who received SC rituximab had administration-related reactions that weren’t observed in the IV rituximab group, these events were largely mild-to-moderate local injection-site reactions.
Andrew Davies, PhD, of the University of Southampton in the UK, and his colleagues reported these results in The Lancet Haematology.
Data from stage 1 of this study, known as SABRINA, were previously published in The Lancet Oncology. The current publication includes stage 2 data.
The study was funded by Roche, which markets rituximab as Rituxan and MabThera.
The trial enrolled 410 patients with previously untreated, grade 1-3a, CD20-positive FL.
Patients were randomized to receive IV rituximab at 375 mg/m2 (n=205) or SC rituximab at 1400 mg (n=205) plus chemotherapy.
Chemotherapy consisted of 6 to 8 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) every 3 weeks during induction.
Patients then received rituximab maintenance every 8 weeks.
The researchers said baseline characteristics were balanced between the treatment arms, although there were more females in the SC arm than the IV arm—120 (59%) and 99 (48%), respectively.
Efficacy
In stage 1 of this study, the primary endpoint was the ratio of observed rituximab serum trough concentrations (Ctrough) between the treatment arms at cycle 7.
The results suggested SC rituximab was non-inferior to the IV formulation. The geometric mean Ctrough was 83.13 μg/mL in the IV arm and 134.58 μg/mL in the SC arm (ratio=1.62).
In stage 2, the primary endpoint was efficacy, or ORR, at the end of induction based on the researchers’ assessments and confirmed by an independent review panel of radiologists.
At the end of induction, the ORR was 84.9% (174/205) in the IV arm and 84.4% (173/205) in the SC arm. The complete response rate was 32.2% (n=66) in both arms.
At the end of maintenance therapy, the ORR was 78.1% (139/178) in the IV arm and 77.9% (134/172) in the SC arm. The complete response rates were 56.2% (n=100) and 50.6% (n=87), respectively.
At a median follow-up of 37 months, there was no significant difference between the arms with regard to progression-free survival (hazard ratio[HR]=0.84), event-free survival (HR=0.91), or overall survival (HR=0.81).
Safety
The incidence of adverse events (AEs) was similar between the treatment arms—95% in the IV arm and 96% in the SC arm. The incidence of grade 3 or higher AEs was 55% and 56%, respectively, and the incidence of serious AEs was 34% and 37%, respectively.
Overall, the most common AEs were gastrointestinal disorders (60% in the IV arm and 66% in the SC arm), infections and infestations (64% and 67%, respectively), and general or administration site conditions (50% and 60%, respectively).
Administration-related reactions were more common in the SC arm than the IV arm—48% and 35%, respectively. The most common of these reactions were chills (7%) and pruritus (6%) in the IV arm and injection-site erythema (11%), pruritus (6%), rash (5%), and injection-site pain (5%) in the SC arm.
Neutropenia was the most common grade 3 or higher AE, occurring in 34% of patients in the IV arm and 37% in the SC arm. Febrile neutropenia was the most frequent serious AE, occurring in 5% and 6%, respectively.
The researchers said these results suggest the SC formulation of rituximab has similar efficacy and a similar safety profile as IV rituximab in the first-line treatment of FL.
Study provides new insight into HSC dormancy
Preclinical research has revealed new insights regarding hematopoietic stem cells’ (HSCs) transition from a dormant state to an active one.
Investigators said they found the transition to be “a continuous developmental path” that is different for each individual cell, rather than a stepwise progression, as researchers previously believed.
The team also found the transition was characterized by low levels of Myc and high expression of retinoic acid.
In fact, the group’s experiments suggested that a diet lacking vitamin A can have a detrimental effect on HSCs.
Nina Cabezas-Wallscheid, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, Germany, and her colleagues conducted this research and reported their findings in Cell.
The investigators used single-cell RNA sequencing to show that HSCs’ transition from dormant to active cells is “a continuous stream-like progression of steadily increasing metabolic activity and preparation for cell-cycle entry without the apparent presence of accumulating cellular intermediates.”
The team said they observed robust downregulation of biosynthetic processes in dormant HSCs (compared to active HSCs) that was associated with the downregulation of Myc target genes.
The investigators also found that retinoic acid-induced signaling was “highly enriched” in dormant HSCs, and all-trans retinoic acid (ATRA) treatment maintained dormant HSCs in vitro.
In mice, ATRA protected dormant HSCs from activation.
The investigators exposed mice to a few different HSC activation conditions, including bacterial liposaccharide, the double-stranded RNA analog polyI:polyC, and the chemotherapeutic agent 5-fluorouracil. But pre-treatment with ATRA allowed HSCs to maintain a quiescent state in all 3 cases.
Finally, the investigators evaluated the effects of a vitamin A-free diet on HSCs. Adult mice fed a vitamin A-free diet for 14 to 17 weeks lost HSCs, particularly dormant HSCs. And without vitamin A, active HSCs were unable to return to a dormant state.
“Thus, we can prove, for the first time, that vitamin A has a direct impact on blood stem cells,” Dr Cabezas-Wallscheid said. “This shows how vitally important it is to have a sufficient intake of vitamin A from a balanced diet.”
The investigators also believe these findings could be applied in cancer research, as there is evidence to suggest that cancer cells rest in a state of dormancy, which makes them resistant to chemotherapy.
“Once we understand in detail how vitamin A or retinoic acid, respectively, sends normal and malignant stem cells into dormancy, we can try to turn the tables,” said study author Andreas Trumpp, PhD, also of DKFZ.
“If we could make cancer cells temporarily enter an active state, we could thus make them vulnerable to modern therapies.”
Preclinical research has revealed new insights regarding hematopoietic stem cells’ (HSCs) transition from a dormant state to an active one.
Investigators said they found the transition to be “a continuous developmental path” that is different for each individual cell, rather than a stepwise progression, as researchers previously believed.
The team also found the transition was characterized by low levels of Myc and high expression of retinoic acid.
In fact, the group’s experiments suggested that a diet lacking vitamin A can have a detrimental effect on HSCs.
Nina Cabezas-Wallscheid, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, Germany, and her colleagues conducted this research and reported their findings in Cell.
The investigators used single-cell RNA sequencing to show that HSCs’ transition from dormant to active cells is “a continuous stream-like progression of steadily increasing metabolic activity and preparation for cell-cycle entry without the apparent presence of accumulating cellular intermediates.”
The team said they observed robust downregulation of biosynthetic processes in dormant HSCs (compared to active HSCs) that was associated with the downregulation of Myc target genes.
The investigators also found that retinoic acid-induced signaling was “highly enriched” in dormant HSCs, and all-trans retinoic acid (ATRA) treatment maintained dormant HSCs in vitro.
In mice, ATRA protected dormant HSCs from activation.
The investigators exposed mice to a few different HSC activation conditions, including bacterial liposaccharide, the double-stranded RNA analog polyI:polyC, and the chemotherapeutic agent 5-fluorouracil. But pre-treatment with ATRA allowed HSCs to maintain a quiescent state in all 3 cases.
Finally, the investigators evaluated the effects of a vitamin A-free diet on HSCs. Adult mice fed a vitamin A-free diet for 14 to 17 weeks lost HSCs, particularly dormant HSCs. And without vitamin A, active HSCs were unable to return to a dormant state.
“Thus, we can prove, for the first time, that vitamin A has a direct impact on blood stem cells,” Dr Cabezas-Wallscheid said. “This shows how vitally important it is to have a sufficient intake of vitamin A from a balanced diet.”
The investigators also believe these findings could be applied in cancer research, as there is evidence to suggest that cancer cells rest in a state of dormancy, which makes them resistant to chemotherapy.
“Once we understand in detail how vitamin A or retinoic acid, respectively, sends normal and malignant stem cells into dormancy, we can try to turn the tables,” said study author Andreas Trumpp, PhD, also of DKFZ.
“If we could make cancer cells temporarily enter an active state, we could thus make them vulnerable to modern therapies.”
Preclinical research has revealed new insights regarding hematopoietic stem cells’ (HSCs) transition from a dormant state to an active one.
Investigators said they found the transition to be “a continuous developmental path” that is different for each individual cell, rather than a stepwise progression, as researchers previously believed.
The team also found the transition was characterized by low levels of Myc and high expression of retinoic acid.
In fact, the group’s experiments suggested that a diet lacking vitamin A can have a detrimental effect on HSCs.
Nina Cabezas-Wallscheid, PhD, of the German Cancer Research Center (DKFZ) in Heidelberg, Germany, and her colleagues conducted this research and reported their findings in Cell.
The investigators used single-cell RNA sequencing to show that HSCs’ transition from dormant to active cells is “a continuous stream-like progression of steadily increasing metabolic activity and preparation for cell-cycle entry without the apparent presence of accumulating cellular intermediates.”
The team said they observed robust downregulation of biosynthetic processes in dormant HSCs (compared to active HSCs) that was associated with the downregulation of Myc target genes.
The investigators also found that retinoic acid-induced signaling was “highly enriched” in dormant HSCs, and all-trans retinoic acid (ATRA) treatment maintained dormant HSCs in vitro.
In mice, ATRA protected dormant HSCs from activation.
The investigators exposed mice to a few different HSC activation conditions, including bacterial liposaccharide, the double-stranded RNA analog polyI:polyC, and the chemotherapeutic agent 5-fluorouracil. But pre-treatment with ATRA allowed HSCs to maintain a quiescent state in all 3 cases.
Finally, the investigators evaluated the effects of a vitamin A-free diet on HSCs. Adult mice fed a vitamin A-free diet for 14 to 17 weeks lost HSCs, particularly dormant HSCs. And without vitamin A, active HSCs were unable to return to a dormant state.
“Thus, we can prove, for the first time, that vitamin A has a direct impact on blood stem cells,” Dr Cabezas-Wallscheid said. “This shows how vitally important it is to have a sufficient intake of vitamin A from a balanced diet.”
The investigators also believe these findings could be applied in cancer research, as there is evidence to suggest that cancer cells rest in a state of dormancy, which makes them resistant to chemotherapy.
“Once we understand in detail how vitamin A or retinoic acid, respectively, sends normal and malignant stem cells into dormancy, we can try to turn the tables,” said study author Andreas Trumpp, PhD, also of DKFZ.
“If we could make cancer cells temporarily enter an active state, we could thus make them vulnerable to modern therapies.”
Woman’s Weakness is Worsening
ANSWER
The radiograph shows a large, hyperdense mass within the left hilum. A second hyperdense mass is seen within the left upper lobe. Both are concerning for neoplastic processes and warrant further evaluation with contrast-enhanced CT.
Although thorough work-up and biopsy is needed, the presumptive diagnosis is a primary lung mass with likely metastasis to the brain.
ANSWER
The radiograph shows a large, hyperdense mass within the left hilum. A second hyperdense mass is seen within the left upper lobe. Both are concerning for neoplastic processes and warrant further evaluation with contrast-enhanced CT.
Although thorough work-up and biopsy is needed, the presumptive diagnosis is a primary lung mass with likely metastasis to the brain.
ANSWER
The radiograph shows a large, hyperdense mass within the left hilum. A second hyperdense mass is seen within the left upper lobe. Both are concerning for neoplastic processes and warrant further evaluation with contrast-enhanced CT.
Although thorough work-up and biopsy is needed, the presumptive diagnosis is a primary lung mass with likely metastasis to the brain.
A 65-year-old woman is transferred to your facility for evaluation of left-side weakness she has been experiencing for more than two months. She states that it is worsening with time but denies any other symptoms. Outpatient MRI of the brain, obtained by the referring provider, is reported to show a right parietal mass with surrounding edema.
Medical history is significant for hypertension, diabetes, and hypercholesterolemia, which are controlled with medication. The patient reports smoking nearly two packs of cigarettes daily for at least 30 years.
Physical examination reveals normal vital signs and no apparent distress. The patient does have left hemiparesis; her left upper extremity is approximately 4/5 throughout, and her left lower extremity is approximately 2/5 throughout. The exam is otherwise normal.
As you review her admission lab results, you note that a chest radiograph was obtained (shown). What is your impression?
Using shock index in the ED to predict hospital admission and inpatient mortality
CLINICAL QUESTION: Can shock index (SI) in the ED predict the likelihood for hospital admission and inpatient mortality?
STUDY DESIGN: Retrospective chart review.
SETTING: Academic tertiary care center.
SYNOPSIS: All ED patients over 18 years of age over a 12-month period were included in the study for a total of 58,633 charts. Charts were excluded if the patient presented in cardiac arrest, left prior to full evaluation in the ED, or had an incomplete or absent first set of vital signs. Likelihood ratio (LR) values of greater than 5 and 10 were considered moderate and large increases in the outcomes, respectively. Authors found SI greater than 1.2 had a positive LR of 11.69 for admission to the hospital and a positive LR of 5.82 for inpatient mortality.
This study identified potential thresholds for SI but did not validate them. Whether SI would be a useful tool for triage remains unanswered.
BOTTOM LINE: Initial SI greater than 1.2 at presentation to the ED was associated with increased likelihood of hospital admission and inpatient mortality.
CITATIONS: Balhara KS, Hsieh YH, Hamade B, et al. Clinical metrics in emergency medicine: the shock index and the probability of hospital admission and inpatient mortality. Emerg Med J. 2017 Feb;34(2):89-94.
Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: Can shock index (SI) in the ED predict the likelihood for hospital admission and inpatient mortality?
STUDY DESIGN: Retrospective chart review.
SETTING: Academic tertiary care center.
SYNOPSIS: All ED patients over 18 years of age over a 12-month period were included in the study for a total of 58,633 charts. Charts were excluded if the patient presented in cardiac arrest, left prior to full evaluation in the ED, or had an incomplete or absent first set of vital signs. Likelihood ratio (LR) values of greater than 5 and 10 were considered moderate and large increases in the outcomes, respectively. Authors found SI greater than 1.2 had a positive LR of 11.69 for admission to the hospital and a positive LR of 5.82 for inpatient mortality.
This study identified potential thresholds for SI but did not validate them. Whether SI would be a useful tool for triage remains unanswered.
BOTTOM LINE: Initial SI greater than 1.2 at presentation to the ED was associated with increased likelihood of hospital admission and inpatient mortality.
CITATIONS: Balhara KS, Hsieh YH, Hamade B, et al. Clinical metrics in emergency medicine: the shock index and the probability of hospital admission and inpatient mortality. Emerg Med J. 2017 Feb;34(2):89-94.
Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: Can shock index (SI) in the ED predict the likelihood for hospital admission and inpatient mortality?
STUDY DESIGN: Retrospective chart review.
SETTING: Academic tertiary care center.
SYNOPSIS: All ED patients over 18 years of age over a 12-month period were included in the study for a total of 58,633 charts. Charts were excluded if the patient presented in cardiac arrest, left prior to full evaluation in the ED, or had an incomplete or absent first set of vital signs. Likelihood ratio (LR) values of greater than 5 and 10 were considered moderate and large increases in the outcomes, respectively. Authors found SI greater than 1.2 had a positive LR of 11.69 for admission to the hospital and a positive LR of 5.82 for inpatient mortality.
This study identified potential thresholds for SI but did not validate them. Whether SI would be a useful tool for triage remains unanswered.
BOTTOM LINE: Initial SI greater than 1.2 at presentation to the ED was associated with increased likelihood of hospital admission and inpatient mortality.
CITATIONS: Balhara KS, Hsieh YH, Hamade B, et al. Clinical metrics in emergency medicine: the shock index and the probability of hospital admission and inpatient mortality. Emerg Med J. 2017 Feb;34(2):89-94.
Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
Perioperative statin associated with reduction in all-cause perioperative mortality in noncardiac surgery
CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?
BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.
STUDY DESIGN: Retrospective, observational cohort analysis.
SYNOPSIS: Using the Veterans Affairs Surgical Quality Improvement Program database, 96,486 patients were studied who were undergoing elective or emergent noncardiac surgery (vascular, general, orthopedic, neurosurgery, otolaryngology, and urology). 96.3% were men. Patients who died the day of the surgery or the day after were excluded, as were patients with multiple surgeries during the assessment period. Statin exposure on the day of or the day after surgery was compared with no statin use. The primary outcome was 30-day mortality and the secondary outcomes were significant reduction in any other complication.
Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.
Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.
BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.
CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.
Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?
BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.
STUDY DESIGN: Retrospective, observational cohort analysis.
SYNOPSIS: Using the Veterans Affairs Surgical Quality Improvement Program database, 96,486 patients were studied who were undergoing elective or emergent noncardiac surgery (vascular, general, orthopedic, neurosurgery, otolaryngology, and urology). 96.3% were men. Patients who died the day of the surgery or the day after were excluded, as were patients with multiple surgeries during the assessment period. Statin exposure on the day of or the day after surgery was compared with no statin use. The primary outcome was 30-day mortality and the secondary outcomes were significant reduction in any other complication.
Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.
Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.
BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.
CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.
Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
CLINICAL QUESTION: Does perioperative statin use reduce 30-day mortality in noncardiac surgery?
BACKGROUND: Current perioperative guidelines focus on continuation of existing therapy in long-term statin users with weak recommendations of potential efficacy in reducing perioperative complications.
STUDY DESIGN: Retrospective, observational cohort analysis.
SYNOPSIS: Using the Veterans Affairs Surgical Quality Improvement Program database, 96,486 patients were studied who were undergoing elective or emergent noncardiac surgery (vascular, general, orthopedic, neurosurgery, otolaryngology, and urology). 96.3% were men. Patients who died the day of the surgery or the day after were excluded, as were patients with multiple surgeries during the assessment period. Statin exposure on the day of or the day after surgery was compared with no statin use. The primary outcome was 30-day mortality and the secondary outcomes were significant reduction in any other complication.
Statin exposure was associated with reduced 30-day all-cause mortality with a marginally favorable effect with longer-term statin use (6 months to 1 year before admission). For the secondary outcomes, there was significant risk reduction in cardiac, infectious, respiratory, and renal complications but no significant change in central nervous system or nonatherosclerotic thrombotic complications.
Statin exposure may be associated with adherence to medical treatment and follow-up thus causing a selection bias.
BOTTOM LINE: Perioperative statin use was associated with a reduction in 30-day mortality and other complications.
CITATIONS: London MJ, Schwartz GG, Hur K, Henderson WG. Association of perioperative statin use with mortality and morbidity after major noncardiac surgery. JAMA Intern Med. 2017 Feb 1;177(2):231-42.
Dr. Dietsche is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.
Anti-TNF drugs reduce mortality in Crohn’s disease
CHICAGO – As compared with prolonged use of corticosteroids, the use of anti–tumor necrosis factor (TNF) drugs was associated with reduced mortality in patients with Crohn’s disease, according to new findings presented here at Digestive Disease Week®.
The reduced mortality seen in this population may be secondary to the lower rates of major adverse cardiovascular events and hip fracture that are associated with anti-TNF use as compared to corticosteroid use. However, the same reduction in mortality risk was not observed in patients with ulcerative colitis using anti-TNF drugs.
Anti-TNF therapy has become a cornerstone in the management of inflammatory bowel disease (IBD), and Dr. Lewis noted that these agents have been shown to be useful for induction, maintenance, and remission, and to reduce surgical and hospitalization rates.
“However, fear of adverse events and cost has deterred greater use of these agents,” he told attendees.
In their study, Dr. Lewis and his colleagues compared the mortality risk with prolonged corticosteroids use versus anti-TNF drugs in patients with IBD.
They conducted a retrospective cohort study using data from 2006-2013 of a population of Medicaid and Medicare beneficiaries in the United States. The cohort included individuals who had received treatment with corticosteroids within the prior year and subsequently had been treated with either additional corticosteroid therapy for a total of greater than 3,000 mg of prednisone or equivalent within 12 months or newly initiated anti-TNF therapy.
The primary outcome of the study was all-cause mortality and secondary outcomes included common causes of death.
Dr. Lewis explained that 57 potential confounding variables were thought to be associated with the choice between corticosteroid use or anti-TNF therapy. These variables, which included demographic characteristics, medications, diagnostic tests, and comorbidities, were measured.
Among Crohn’s disease patients, 7,694 who were prolonged corticosteroid users and 1,879 were new to anti-TNF therapy. Among patients with ulcerative colitis, 3,224 were long-term corticosteroid users and 459 were new anti-TNF users.
The researchers found that the weighted annual incidences of death per 1,000 Crohn’s disease treated patients were 21.4 for those using anti-TNF therapy and 30.1 for those with prolonged corticosteroid use. For those with ulcerative colitis, these figures were 23.0 and 30.9, respectively.
The risk of death was statistically significantly reduced in Crohn’s disease patients who used anti-TNF therapy (odds ratio, 0.78; 95% confidence interval, 0.65-0.93). However, the benefit was not as pronounced in ulcerative colitis.
“We did not see the same effect for ulcerative colitis but for mortality, it was in the same direction, with a hazard ratio of 0.87,” he said.
Among the Crohn’s disease patients, anti-TNF therapy was associated with lower rates of major adverse cardiovascular events (OR, 0.68; 95% CI, 0.55-0.85) and hip fracture (OR, 0.5; 95% CI, 0.34-0.83), which were statistically significant. The use of anti-TNF therapy also reduced the risk of stroke in Crohn’s disease patients (OR, 0.72; 95% CI, 0.51-1.03), but there was also an increase in the risk of cancer (OR, 0.27; 95% CI, 0.98-1.65). Both of these findings nearly reached statistical significance.
In the model that censored for any of the secondary outcomes, the lower mortality risk was attenuated and very close to a null result (OR, 0.97; 95% CI 0.63-1.47).
Dr. Lewis also pointed out that in some of their models, the magnitude of benefit with anti-TNF therapy appears to be greatest in the patients with the most comorbidities.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
CHICAGO – As compared with prolonged use of corticosteroids, the use of anti–tumor necrosis factor (TNF) drugs was associated with reduced mortality in patients with Crohn’s disease, according to new findings presented here at Digestive Disease Week®.
The reduced mortality seen in this population may be secondary to the lower rates of major adverse cardiovascular events and hip fracture that are associated with anti-TNF use as compared to corticosteroid use. However, the same reduction in mortality risk was not observed in patients with ulcerative colitis using anti-TNF drugs.
Anti-TNF therapy has become a cornerstone in the management of inflammatory bowel disease (IBD), and Dr. Lewis noted that these agents have been shown to be useful for induction, maintenance, and remission, and to reduce surgical and hospitalization rates.
“However, fear of adverse events and cost has deterred greater use of these agents,” he told attendees.
In their study, Dr. Lewis and his colleagues compared the mortality risk with prolonged corticosteroids use versus anti-TNF drugs in patients with IBD.
They conducted a retrospective cohort study using data from 2006-2013 of a population of Medicaid and Medicare beneficiaries in the United States. The cohort included individuals who had received treatment with corticosteroids within the prior year and subsequently had been treated with either additional corticosteroid therapy for a total of greater than 3,000 mg of prednisone or equivalent within 12 months or newly initiated anti-TNF therapy.
The primary outcome of the study was all-cause mortality and secondary outcomes included common causes of death.
Dr. Lewis explained that 57 potential confounding variables were thought to be associated with the choice between corticosteroid use or anti-TNF therapy. These variables, which included demographic characteristics, medications, diagnostic tests, and comorbidities, were measured.
Among Crohn’s disease patients, 7,694 who were prolonged corticosteroid users and 1,879 were new to anti-TNF therapy. Among patients with ulcerative colitis, 3,224 were long-term corticosteroid users and 459 were new anti-TNF users.
The researchers found that the weighted annual incidences of death per 1,000 Crohn’s disease treated patients were 21.4 for those using anti-TNF therapy and 30.1 for those with prolonged corticosteroid use. For those with ulcerative colitis, these figures were 23.0 and 30.9, respectively.
The risk of death was statistically significantly reduced in Crohn’s disease patients who used anti-TNF therapy (odds ratio, 0.78; 95% confidence interval, 0.65-0.93). However, the benefit was not as pronounced in ulcerative colitis.
“We did not see the same effect for ulcerative colitis but for mortality, it was in the same direction, with a hazard ratio of 0.87,” he said.
Among the Crohn’s disease patients, anti-TNF therapy was associated with lower rates of major adverse cardiovascular events (OR, 0.68; 95% CI, 0.55-0.85) and hip fracture (OR, 0.5; 95% CI, 0.34-0.83), which were statistically significant. The use of anti-TNF therapy also reduced the risk of stroke in Crohn’s disease patients (OR, 0.72; 95% CI, 0.51-1.03), but there was also an increase in the risk of cancer (OR, 0.27; 95% CI, 0.98-1.65). Both of these findings nearly reached statistical significance.
In the model that censored for any of the secondary outcomes, the lower mortality risk was attenuated and very close to a null result (OR, 0.97; 95% CI 0.63-1.47).
Dr. Lewis also pointed out that in some of their models, the magnitude of benefit with anti-TNF therapy appears to be greatest in the patients with the most comorbidities.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
CHICAGO – As compared with prolonged use of corticosteroids, the use of anti–tumor necrosis factor (TNF) drugs was associated with reduced mortality in patients with Crohn’s disease, according to new findings presented here at Digestive Disease Week®.
The reduced mortality seen in this population may be secondary to the lower rates of major adverse cardiovascular events and hip fracture that are associated with anti-TNF use as compared to corticosteroid use. However, the same reduction in mortality risk was not observed in patients with ulcerative colitis using anti-TNF drugs.
Anti-TNF therapy has become a cornerstone in the management of inflammatory bowel disease (IBD), and Dr. Lewis noted that these agents have been shown to be useful for induction, maintenance, and remission, and to reduce surgical and hospitalization rates.
“However, fear of adverse events and cost has deterred greater use of these agents,” he told attendees.
In their study, Dr. Lewis and his colleagues compared the mortality risk with prolonged corticosteroids use versus anti-TNF drugs in patients with IBD.
They conducted a retrospective cohort study using data from 2006-2013 of a population of Medicaid and Medicare beneficiaries in the United States. The cohort included individuals who had received treatment with corticosteroids within the prior year and subsequently had been treated with either additional corticosteroid therapy for a total of greater than 3,000 mg of prednisone or equivalent within 12 months or newly initiated anti-TNF therapy.
The primary outcome of the study was all-cause mortality and secondary outcomes included common causes of death.
Dr. Lewis explained that 57 potential confounding variables were thought to be associated with the choice between corticosteroid use or anti-TNF therapy. These variables, which included demographic characteristics, medications, diagnostic tests, and comorbidities, were measured.
Among Crohn’s disease patients, 7,694 who were prolonged corticosteroid users and 1,879 were new to anti-TNF therapy. Among patients with ulcerative colitis, 3,224 were long-term corticosteroid users and 459 were new anti-TNF users.
The researchers found that the weighted annual incidences of death per 1,000 Crohn’s disease treated patients were 21.4 for those using anti-TNF therapy and 30.1 for those with prolonged corticosteroid use. For those with ulcerative colitis, these figures were 23.0 and 30.9, respectively.
The risk of death was statistically significantly reduced in Crohn’s disease patients who used anti-TNF therapy (odds ratio, 0.78; 95% confidence interval, 0.65-0.93). However, the benefit was not as pronounced in ulcerative colitis.
“We did not see the same effect for ulcerative colitis but for mortality, it was in the same direction, with a hazard ratio of 0.87,” he said.
Among the Crohn’s disease patients, anti-TNF therapy was associated with lower rates of major adverse cardiovascular events (OR, 0.68; 95% CI, 0.55-0.85) and hip fracture (OR, 0.5; 95% CI, 0.34-0.83), which were statistically significant. The use of anti-TNF therapy also reduced the risk of stroke in Crohn’s disease patients (OR, 0.72; 95% CI, 0.51-1.03), but there was also an increase in the risk of cancer (OR, 0.27; 95% CI, 0.98-1.65). Both of these findings nearly reached statistical significance.
In the model that censored for any of the secondary outcomes, the lower mortality risk was attenuated and very close to a null result (OR, 0.97; 95% CI 0.63-1.47).
Dr. Lewis also pointed out that in some of their models, the magnitude of benefit with anti-TNF therapy appears to be greatest in the patients with the most comorbidities.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
AT DDW
Key clinical point:
Major finding: Anti-TNF drugs were associated with reduced mortality in patients with Crohn’s disease (OR, 0.78) but to a much lesser extent in ulcerative colitis (OR, 0.87).
Data source: Database of Medicare and Medicaid recipients with 9,573 patients with Crohn’s disease and 3,683 with ulcerative colitis.
Disclosures: Dr. Lewis has disclosed financial relationships with Takeda, Pfizer, Lilly, Gilead, Johnson and Johnson, Samsung Bioepis, AbbVie, and Dark Canyon Laboratories.
VIDEO: Registry study will follow 4,000 fecal transplant patients for 10 years
CHICAGO – A 10-year registry study aims to gather clinical and patient-reported outcomes on 4,000 adult and pediatric patients who undergo fecal microbiota transplant in the United States, officials of the American Gastroenterological Association announced during Digestive Disease Week®.
The AGA Fecal Microbiota Transplantation National Registry will be the first study to assess both short- and long-term patient outcomes associated with fecal microbiota transplant (FMT) in both adults and children, Colleen Kelly, MD, said in an video interview. Most subjects will have received FMT for recurrent or refractory Clostridium difficile infections – the only indication for which Food and Drug Administration currently allows independent clinician action. But the investigational uses of FMT are expanding rapidly, and patients who undergo the procedure during any registered study will be eligible for enrollment, said Dr. Kelly, co-chair of the study’s steering committee.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The study’s primary objectives are short- and long-term safety outcomes, said Dr. Kelly of Brown University, Providence, R.I. While generally considered quite safe, short-term adverse events have been reported with FMT, and some of them have been serious – including one death from aspiration pneumonia in a patient who received donor stool via nasogastric tube (Clin Infect Dis. 2015 Mar;61[1]:136-7). Other adverse events are usually self-limited but can include low-grade fever, abdominal pain, distention, bloating, and diarrhea.
Researchers seek to illuminate many of the unknowns associated with this relatively new procedure. Scientists are only now beginning to unravel the myriad ways the human microbiome promotes both health and disease. Specific alterations, for example, have been associated with obesity and other conditions; there is concern that transplanting a new microbial population could induce a disease phenotype in a recipient who might not have otherwise been at risk.
With the planned cohort size and follow-up period, the study should be able to detect any unanticipated adverse events that occur in more than 1% of the population, Dr. Kelly said. It will include a comparator group of patients with recurrent or refractory C. difficile infection from a large insurance claims database to allow comparison between patients treated with FMT and those treated with antibiotics only.
The registry study also aims to discover which method or methods of transplant material delivery are best, she said. Right now, there are a number of methods (colonoscopy/sigmoidoscopy, enema, upper gastrointestinal endoscopy, nasogastric or nasoduodenal tube, and capsules), and no consensus on which is the best. As indications for FMT expand, there may be no single best method. The approach will probably be matched to the disorder being treated, and the study may help illuminate this as well.
For the first 2 years after a transplant, clinicians will follow patients and enter data into the registry. After that, an electronic patient-reported outcomes system will automatically contact the patient annually for follow-up information by email or text message. When patients enter their data, they can access educational material that will help keep them up-to-date on potential adverse events.
The study will also include a biobank of stool samples obtained during the procedures, hosted by the American Gut Project and the Microbiome Initiative at the University of California, San Diego. This arm of the project will analyze the microbiome of 3,000 stool samples from recipients, both before and after their transplant, as well as the corresponding donors whose material was used in the fecal transplant.
The registry study, a project of the AGA Center for Gut Microbiome Research and Education, is funded by a $3.3 million grant from the National Institute of Allergy and Infectious Diseases. It will be conducted in partnership with the Crohn’s and Colitis Foundation, Infectious Diseases Society, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
The registry study currently is accepting applications. Physicians who perform FMT for C. difficile infections, and centers that conduct FMT research for other potential indications, can fill out a short survey to indicate their interest.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT).
This article was updated June 8, 2017.
[email protected]
On Twitter @Alz_gal
CHICAGO – A 10-year registry study aims to gather clinical and patient-reported outcomes on 4,000 adult and pediatric patients who undergo fecal microbiota transplant in the United States, officials of the American Gastroenterological Association announced during Digestive Disease Week®.
The AGA Fecal Microbiota Transplantation National Registry will be the first study to assess both short- and long-term patient outcomes associated with fecal microbiota transplant (FMT) in both adults and children, Colleen Kelly, MD, said in an video interview. Most subjects will have received FMT for recurrent or refractory Clostridium difficile infections – the only indication for which Food and Drug Administration currently allows independent clinician action. But the investigational uses of FMT are expanding rapidly, and patients who undergo the procedure during any registered study will be eligible for enrollment, said Dr. Kelly, co-chair of the study’s steering committee.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The study’s primary objectives are short- and long-term safety outcomes, said Dr. Kelly of Brown University, Providence, R.I. While generally considered quite safe, short-term adverse events have been reported with FMT, and some of them have been serious – including one death from aspiration pneumonia in a patient who received donor stool via nasogastric tube (Clin Infect Dis. 2015 Mar;61[1]:136-7). Other adverse events are usually self-limited but can include low-grade fever, abdominal pain, distention, bloating, and diarrhea.
Researchers seek to illuminate many of the unknowns associated with this relatively new procedure. Scientists are only now beginning to unravel the myriad ways the human microbiome promotes both health and disease. Specific alterations, for example, have been associated with obesity and other conditions; there is concern that transplanting a new microbial population could induce a disease phenotype in a recipient who might not have otherwise been at risk.
With the planned cohort size and follow-up period, the study should be able to detect any unanticipated adverse events that occur in more than 1% of the population, Dr. Kelly said. It will include a comparator group of patients with recurrent or refractory C. difficile infection from a large insurance claims database to allow comparison between patients treated with FMT and those treated with antibiotics only.
The registry study also aims to discover which method or methods of transplant material delivery are best, she said. Right now, there are a number of methods (colonoscopy/sigmoidoscopy, enema, upper gastrointestinal endoscopy, nasogastric or nasoduodenal tube, and capsules), and no consensus on which is the best. As indications for FMT expand, there may be no single best method. The approach will probably be matched to the disorder being treated, and the study may help illuminate this as well.
For the first 2 years after a transplant, clinicians will follow patients and enter data into the registry. After that, an electronic patient-reported outcomes system will automatically contact the patient annually for follow-up information by email or text message. When patients enter their data, they can access educational material that will help keep them up-to-date on potential adverse events.
The study will also include a biobank of stool samples obtained during the procedures, hosted by the American Gut Project and the Microbiome Initiative at the University of California, San Diego. This arm of the project will analyze the microbiome of 3,000 stool samples from recipients, both before and after their transplant, as well as the corresponding donors whose material was used in the fecal transplant.
The registry study, a project of the AGA Center for Gut Microbiome Research and Education, is funded by a $3.3 million grant from the National Institute of Allergy and Infectious Diseases. It will be conducted in partnership with the Crohn’s and Colitis Foundation, Infectious Diseases Society, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
The registry study currently is accepting applications. Physicians who perform FMT for C. difficile infections, and centers that conduct FMT research for other potential indications, can fill out a short survey to indicate their interest.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT).
This article was updated June 8, 2017.
[email protected]
On Twitter @Alz_gal
CHICAGO – A 10-year registry study aims to gather clinical and patient-reported outcomes on 4,000 adult and pediatric patients who undergo fecal microbiota transplant in the United States, officials of the American Gastroenterological Association announced during Digestive Disease Week®.
The AGA Fecal Microbiota Transplantation National Registry will be the first study to assess both short- and long-term patient outcomes associated with fecal microbiota transplant (FMT) in both adults and children, Colleen Kelly, MD, said in an video interview. Most subjects will have received FMT for recurrent or refractory Clostridium difficile infections – the only indication for which Food and Drug Administration currently allows independent clinician action. But the investigational uses of FMT are expanding rapidly, and patients who undergo the procedure during any registered study will be eligible for enrollment, said Dr. Kelly, co-chair of the study’s steering committee.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The study’s primary objectives are short- and long-term safety outcomes, said Dr. Kelly of Brown University, Providence, R.I. While generally considered quite safe, short-term adverse events have been reported with FMT, and some of them have been serious – including one death from aspiration pneumonia in a patient who received donor stool via nasogastric tube (Clin Infect Dis. 2015 Mar;61[1]:136-7). Other adverse events are usually self-limited but can include low-grade fever, abdominal pain, distention, bloating, and diarrhea.
Researchers seek to illuminate many of the unknowns associated with this relatively new procedure. Scientists are only now beginning to unravel the myriad ways the human microbiome promotes both health and disease. Specific alterations, for example, have been associated with obesity and other conditions; there is concern that transplanting a new microbial population could induce a disease phenotype in a recipient who might not have otherwise been at risk.
With the planned cohort size and follow-up period, the study should be able to detect any unanticipated adverse events that occur in more than 1% of the population, Dr. Kelly said. It will include a comparator group of patients with recurrent or refractory C. difficile infection from a large insurance claims database to allow comparison between patients treated with FMT and those treated with antibiotics only.
The registry study also aims to discover which method or methods of transplant material delivery are best, she said. Right now, there are a number of methods (colonoscopy/sigmoidoscopy, enema, upper gastrointestinal endoscopy, nasogastric or nasoduodenal tube, and capsules), and no consensus on which is the best. As indications for FMT expand, there may be no single best method. The approach will probably be matched to the disorder being treated, and the study may help illuminate this as well.
For the first 2 years after a transplant, clinicians will follow patients and enter data into the registry. After that, an electronic patient-reported outcomes system will automatically contact the patient annually for follow-up information by email or text message. When patients enter their data, they can access educational material that will help keep them up-to-date on potential adverse events.
The study will also include a biobank of stool samples obtained during the procedures, hosted by the American Gut Project and the Microbiome Initiative at the University of California, San Diego. This arm of the project will analyze the microbiome of 3,000 stool samples from recipients, both before and after their transplant, as well as the corresponding donors whose material was used in the fecal transplant.
The registry study, a project of the AGA Center for Gut Microbiome Research and Education, is funded by a $3.3 million grant from the National Institute of Allergy and Infectious Diseases. It will be conducted in partnership with the Crohn’s and Colitis Foundation, Infectious Diseases Society, and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
The registry study currently is accepting applications. Physicians who perform FMT for C. difficile infections, and centers that conduct FMT research for other potential indications, can fill out a short survey to indicate their interest.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT).
This article was updated June 8, 2017.
[email protected]
On Twitter @Alz_gal
AT DDW
Updated osteoporosis guideline advocates bisphosphonates, nixes estrogens
The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.
The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.
The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.
Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.
Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).
Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.
One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.
Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”
The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.
The most important recommendation in this updated ACP guideline is for clinicians to offer bisphosphonates or denosumab to women with osteoporosis.
Even though large, well-designed, randomized controlled trials amply demonstrate the effectiveness of these drugs in preventing fractures, undertreatment is rampant and is actually increasing. It appears that patients and perhaps some clinicians have the mistaken impression that bisphosphonates frequently cause serious adverse effects.
In truth, the rate of adverse effects and of serious adverse events with bisphosphonates is very low. Clinicians should educate patients about the safety of these agents.
Eric S. Orwoll, MD, is at Oregon Health and Science University, Portland. Dr. Orwoll made these remarks in an editorial accompanying the updated guideline (Ann. Intern. Med. 2017 May 8. doi: 10.7326/M17-0957). His financial disclosures are available at www.acponline.org
The most important recommendation in this updated ACP guideline is for clinicians to offer bisphosphonates or denosumab to women with osteoporosis.
Even though large, well-designed, randomized controlled trials amply demonstrate the effectiveness of these drugs in preventing fractures, undertreatment is rampant and is actually increasing. It appears that patients and perhaps some clinicians have the mistaken impression that bisphosphonates frequently cause serious adverse effects.
In truth, the rate of adverse effects and of serious adverse events with bisphosphonates is very low. Clinicians should educate patients about the safety of these agents.
Eric S. Orwoll, MD, is at Oregon Health and Science University, Portland. Dr. Orwoll made these remarks in an editorial accompanying the updated guideline (Ann. Intern. Med. 2017 May 8. doi: 10.7326/M17-0957). His financial disclosures are available at www.acponline.org
The most important recommendation in this updated ACP guideline is for clinicians to offer bisphosphonates or denosumab to women with osteoporosis.
Even though large, well-designed, randomized controlled trials amply demonstrate the effectiveness of these drugs in preventing fractures, undertreatment is rampant and is actually increasing. It appears that patients and perhaps some clinicians have the mistaken impression that bisphosphonates frequently cause serious adverse effects.
In truth, the rate of adverse effects and of serious adverse events with bisphosphonates is very low. Clinicians should educate patients about the safety of these agents.
Eric S. Orwoll, MD, is at Oregon Health and Science University, Portland. Dr. Orwoll made these remarks in an editorial accompanying the updated guideline (Ann. Intern. Med. 2017 May 8. doi: 10.7326/M17-0957). His financial disclosures are available at www.acponline.org
The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.
The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.
The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.
Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.
Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).
Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.
One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.
Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”
The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.
The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.
The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.
The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.
Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.
Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).
Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.
One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.
Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”
The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point:
Major finding: The guideline offers six main recommendations and several additional pointers for clinicians and for those over age 50 years who are at risk for osteoporotic fracture.
Data source: A review of the evidence since the previous (2008) ACP guideline for treating osteoporosis.
Disclosures: This work was supported exclusively by the American College of Physicians. The authors’ financial disclosures are available at www.acponline.org
HCV incidence in young women doubled from 2006 to 2014
The incidence of hepatitis C virus infection in reproductive-age women has doubled between 2006 and 2014 while the number of acute cases increased more than threefold, according to data published in the Annals of Internal Medicine.
Researchers analyzed data from the National Notifiable Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014, finding 425,322 women with confirmed HCV infection, 40.4% of whom were aged 15 to 44 years.
Around half of all acute infections were in non-Hispanic white women, and of the 2,069 women with available risk information, 63% acknowledged injection drug use (Ann Intern Med. 2017 May 8. doi:10.7326/M16-2350).
The analysis also found 1,859 cases of hepatitis C infection in children aged 2-13 years. According to the Quest data, the proportion of children with current hepatitis C infection was 3.2-fold higher in children aged 2-3 years than in those aged 12-13 years.
Commenting on this age difference, Kathleen N. Ly, MPH, from the Centers for Disease Control and Prevention, and her coauthors noted that it may have been the result of decreased testing over time in children already known to have chronic hepatitis C infection, or could be caused by spontaneous remission of infection, which is more common in infants and children than in adults.
The rate of infection among pregnant women tested for hepatitis C virus between 2011 and 2014 was 0.73%, which the authors calculated would mean that overall, 29,000 women with hepatitis C virus infection gave birth during that period across the United States. Based on data from a recent systematic review and meta-analysis, which found a likely mother-to-child transmission rate of 5.8/100 live births, they estimated that 1,700 infants were born with hepatitis C infection during that period.
“In contrast, only about 200 childhood cases per year are reported to the NNDSS, which may suggest a need for wider screening for HCV in pregnant women and their infants, as is recommended for HIV and hepatitis B virus,” the authors wrote. “However, recommendations for screening in pregnant women and clearer testing guidelines for infants born to HCV-infected mothers do not exist at this time.”
The study was supported by the CDC. One author was an employee of Quest Diagnostics, but no other conflicts of interest were declared.
Recognizing hepatitis C infection in pregnant women and neonates is possible, and clinical trials of antiviral therapy may show safety and efficacy in pregnant women and in children. Rather than silence, HCV infection calls out for public health action directed at all aspects of the epidemic, including consideration of screening pregnant women. At the very least, screening of pregnant women for HCV infection risk factors, as well as risk-based testing, requires more emphasis. Another issue in need of attention is the lack of authoritative, consensus-based recommendations for the identification, testing, and case management of newborns of infected mothers.
Much work lies ahead to eradicate HCV, starting with resources for public health surveillance to monitor incidence and prevalence and to fully characterize the infection in the population. Strategies to effectively prevent or cure infection in reproductive-aged women and their sexual and needle-sharing partners are critical.
Alfred DeMaria Jr., MD, is from the Massachusetts Department of Public Health. These comments are taken from an accompanying editorial (Ann Intern Med. 2017 May 8. doi:10.7326/M17-0927). No conflicts of interest were declared.
Recognizing hepatitis C infection in pregnant women and neonates is possible, and clinical trials of antiviral therapy may show safety and efficacy in pregnant women and in children. Rather than silence, HCV infection calls out for public health action directed at all aspects of the epidemic, including consideration of screening pregnant women. At the very least, screening of pregnant women for HCV infection risk factors, as well as risk-based testing, requires more emphasis. Another issue in need of attention is the lack of authoritative, consensus-based recommendations for the identification, testing, and case management of newborns of infected mothers.
Much work lies ahead to eradicate HCV, starting with resources for public health surveillance to monitor incidence and prevalence and to fully characterize the infection in the population. Strategies to effectively prevent or cure infection in reproductive-aged women and their sexual and needle-sharing partners are critical.
Alfred DeMaria Jr., MD, is from the Massachusetts Department of Public Health. These comments are taken from an accompanying editorial (Ann Intern Med. 2017 May 8. doi:10.7326/M17-0927). No conflicts of interest were declared.
Recognizing hepatitis C infection in pregnant women and neonates is possible, and clinical trials of antiviral therapy may show safety and efficacy in pregnant women and in children. Rather than silence, HCV infection calls out for public health action directed at all aspects of the epidemic, including consideration of screening pregnant women. At the very least, screening of pregnant women for HCV infection risk factors, as well as risk-based testing, requires more emphasis. Another issue in need of attention is the lack of authoritative, consensus-based recommendations for the identification, testing, and case management of newborns of infected mothers.
Much work lies ahead to eradicate HCV, starting with resources for public health surveillance to monitor incidence and prevalence and to fully characterize the infection in the population. Strategies to effectively prevent or cure infection in reproductive-aged women and their sexual and needle-sharing partners are critical.
Alfred DeMaria Jr., MD, is from the Massachusetts Department of Public Health. These comments are taken from an accompanying editorial (Ann Intern Med. 2017 May 8. doi:10.7326/M17-0927). No conflicts of interest were declared.
The incidence of hepatitis C virus infection in reproductive-age women has doubled between 2006 and 2014 while the number of acute cases increased more than threefold, according to data published in the Annals of Internal Medicine.
Researchers analyzed data from the National Notifiable Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014, finding 425,322 women with confirmed HCV infection, 40.4% of whom were aged 15 to 44 years.
Around half of all acute infections were in non-Hispanic white women, and of the 2,069 women with available risk information, 63% acknowledged injection drug use (Ann Intern Med. 2017 May 8. doi:10.7326/M16-2350).
The analysis also found 1,859 cases of hepatitis C infection in children aged 2-13 years. According to the Quest data, the proportion of children with current hepatitis C infection was 3.2-fold higher in children aged 2-3 years than in those aged 12-13 years.
Commenting on this age difference, Kathleen N. Ly, MPH, from the Centers for Disease Control and Prevention, and her coauthors noted that it may have been the result of decreased testing over time in children already known to have chronic hepatitis C infection, or could be caused by spontaneous remission of infection, which is more common in infants and children than in adults.
The rate of infection among pregnant women tested for hepatitis C virus between 2011 and 2014 was 0.73%, which the authors calculated would mean that overall, 29,000 women with hepatitis C virus infection gave birth during that period across the United States. Based on data from a recent systematic review and meta-analysis, which found a likely mother-to-child transmission rate of 5.8/100 live births, they estimated that 1,700 infants were born with hepatitis C infection during that period.
“In contrast, only about 200 childhood cases per year are reported to the NNDSS, which may suggest a need for wider screening for HCV in pregnant women and their infants, as is recommended for HIV and hepatitis B virus,” the authors wrote. “However, recommendations for screening in pregnant women and clearer testing guidelines for infants born to HCV-infected mothers do not exist at this time.”
The study was supported by the CDC. One author was an employee of Quest Diagnostics, but no other conflicts of interest were declared.
The incidence of hepatitis C virus infection in reproductive-age women has doubled between 2006 and 2014 while the number of acute cases increased more than threefold, according to data published in the Annals of Internal Medicine.
Researchers analyzed data from the National Notifiable Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014, finding 425,322 women with confirmed HCV infection, 40.4% of whom were aged 15 to 44 years.
Around half of all acute infections were in non-Hispanic white women, and of the 2,069 women with available risk information, 63% acknowledged injection drug use (Ann Intern Med. 2017 May 8. doi:10.7326/M16-2350).
The analysis also found 1,859 cases of hepatitis C infection in children aged 2-13 years. According to the Quest data, the proportion of children with current hepatitis C infection was 3.2-fold higher in children aged 2-3 years than in those aged 12-13 years.
Commenting on this age difference, Kathleen N. Ly, MPH, from the Centers for Disease Control and Prevention, and her coauthors noted that it may have been the result of decreased testing over time in children already known to have chronic hepatitis C infection, or could be caused by spontaneous remission of infection, which is more common in infants and children than in adults.
The rate of infection among pregnant women tested for hepatitis C virus between 2011 and 2014 was 0.73%, which the authors calculated would mean that overall, 29,000 women with hepatitis C virus infection gave birth during that period across the United States. Based on data from a recent systematic review and meta-analysis, which found a likely mother-to-child transmission rate of 5.8/100 live births, they estimated that 1,700 infants were born with hepatitis C infection during that period.
“In contrast, only about 200 childhood cases per year are reported to the NNDSS, which may suggest a need for wider screening for HCV in pregnant women and their infants, as is recommended for HIV and hepatitis B virus,” the authors wrote. “However, recommendations for screening in pregnant women and clearer testing guidelines for infants born to HCV-infected mothers do not exist at this time.”
The study was supported by the CDC. One author was an employee of Quest Diagnostics, but no other conflicts of interest were declared.
FROM THE ANNALS OF INTERNAL MEDICINE
Key clinical point: The incidence of hepatitis C infection increased significantly in reproductive age women during 2006-2014.
Major finding: The incidence of hepatitis C infection in reproductive-age women doubled during 2006-2014 while the number of acute cases increased more than threefold.
Data source: Analysis of data from the National Notifiable Diseases Surveillance System from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014.
Disclosures: The study was supported by the Centers for Disease Control and Prevention. One author was an employee of Quest Diagnostics, but no other conflicts of interest were declared.