Is rosacea a red flag for more dangerous conditions? MedPAC wants to curb low-value care. Statins cut sepsis patients’ risk of death. And why reading aloud to kids can cut hyperactivity.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Is rosacea a red flag for more dangerous conditions? MedPAC wants to curb low-value care. Statins cut sepsis patients’ risk of death. And why reading aloud to kids can cut hyperactivity.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Is rosacea a red flag for more dangerous conditions? MedPAC wants to curb low-value care. Statins cut sepsis patients’ risk of death. And why reading aloud to kids can cut hyperactivity.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.

The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.

One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.

As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.

The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.

One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.

As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.

The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.

One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.

Micrograph showing DLBCL

New research helps explain why some patients with diffuse large B-cell lymphoma (DLBCL) respond well to immunochemotherapy and others do not.

Researchers analyzed samples from nearly 600 DLBCL patients and identified 4 new genetic subtypes of the disease.

Patients with 2 of these subtypes had overall survival (OS) rates that were roughly twice as high as OS rates in patients with the other 2 subtypes.

Louis M. Staudt, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues described these findings in NEJM.

The researchers noted that the current subtypes of DLBCL—germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL—are associated with OS after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients with ABC DLBCL have a much lower OS rate, on average, than patients with GCB DLBCL. However, even in the GCB subgroup, many patients relapse after treatment.

“The first question we wanted to tackle was whether there were other molecular features of the tumors that could help us explain why some people were well-served by chemotherapy,” Dr Staudt said.

“And the second, related question was, if we could understand who was not responding well to treatment, could we understand the genetics of these tumors to suggest new potential therapies beyond chemotherapy? The answer to both questions was ‘yes.’”

Dr Staudt and his colleagues analyzed tumor samples from 574 patients with DLBCL, performing exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to find recurrent aberrations.

The team also developed an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations.

In this way, they identified 4 genetic subtypes:

• MCD, which was named based on the co-occurrence of MYD88L265P and CD79B mutations
• BN2, whose name was based on the presence of BCL6 fusions and NOTCH2 mutations
• N1, named for NOTCH1 mutations
• EZB, named for EZH2 mutations and BCL2 translocations.

The researchers said aberrations in multiple genes distinguished each of these subtypes from other DLBCLs, and the subtypes differed phenotypically.

Patients with BN2 or EZB subtypes had much higher OS rates after receiving R-CHOP than patients with MCD or N1 subtypes. The predicted 5-year OS rates were 26% for MCD patients, 36% for N1 patients, 65% for BN2 patients, and 68% for EZB patients.

The researchers said they found evidence to suggest that MCD and BN2 DLBCLs rely on chronic active B-cell receptor signaling that is amenable to therapeutic inhibition.

The team also noted that some of the subtypes they identified can be found in both ABC and GCB DLBCLs. For example, a patient could have ABC DLBCL, which is associated with a lower OS rate after R-CHOP, but also have the BN2 genetic subtype that responds well to R-CHOP.

“This shows we’ve gone beyond where we were,” Dr Staudt said. “Before, even with our most advanced molecular diagnosis, we would have said all ABC tumors are the ‘bad’ type, and they need to be treated aggressively.”

“Now, we can implement this kind of classification and say that, even if a patient has the ‘bad’ ABC type, they have the ‘good’ genetic type, BN2. So there’s a much better chance of chemotherapy curing the disease.”

Data from this study will be shared through the National Cancer Institute’s Genomic Data Commons to make it available for future research.

Dr Staudt said he and his colleagues hope their new molecular classification will be used in clinical trials so that DLBCL treatment can move toward more targeted therapies.

“The goal is to find the right drug for the right person at the right time,” Dr Staudt said. “And we feel this genetic understanding of diffuse lymphoma is a step forward in precision therapy.”

Micrograph showing DLBCL

New research helps explain why some patients with diffuse large B-cell lymphoma (DLBCL) respond well to immunochemotherapy and others do not.

Researchers analyzed samples from nearly 600 DLBCL patients and identified 4 new genetic subtypes of the disease.

Patients with 2 of these subtypes had overall survival (OS) rates that were roughly twice as high as OS rates in patients with the other 2 subtypes.

Louis M. Staudt, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues described these findings in NEJM.

The researchers noted that the current subtypes of DLBCL—germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL—are associated with OS after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients with ABC DLBCL have a much lower OS rate, on average, than patients with GCB DLBCL. However, even in the GCB subgroup, many patients relapse after treatment.

“The first question we wanted to tackle was whether there were other molecular features of the tumors that could help us explain why some people were well-served by chemotherapy,” Dr Staudt said.

“And the second, related question was, if we could understand who was not responding well to treatment, could we understand the genetics of these tumors to suggest new potential therapies beyond chemotherapy? The answer to both questions was ‘yes.’”

Dr Staudt and his colleagues analyzed tumor samples from 574 patients with DLBCL, performing exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to find recurrent aberrations.

The team also developed an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations.

In this way, they identified 4 genetic subtypes:

• MCD, which was named based on the co-occurrence of MYD88L265P and CD79B mutations
• BN2, whose name was based on the presence of BCL6 fusions and NOTCH2 mutations
• N1, named for NOTCH1 mutations
• EZB, named for EZH2 mutations and BCL2 translocations.

The researchers said aberrations in multiple genes distinguished each of these subtypes from other DLBCLs, and the subtypes differed phenotypically.

Patients with BN2 or EZB subtypes had much higher OS rates after receiving R-CHOP than patients with MCD or N1 subtypes. The predicted 5-year OS rates were 26% for MCD patients, 36% for N1 patients, 65% for BN2 patients, and 68% for EZB patients.

The researchers said they found evidence to suggest that MCD and BN2 DLBCLs rely on chronic active B-cell receptor signaling that is amenable to therapeutic inhibition.

The team also noted that some of the subtypes they identified can be found in both ABC and GCB DLBCLs. For example, a patient could have ABC DLBCL, which is associated with a lower OS rate after R-CHOP, but also have the BN2 genetic subtype that responds well to R-CHOP.

“This shows we’ve gone beyond where we were,” Dr Staudt said. “Before, even with our most advanced molecular diagnosis, we would have said all ABC tumors are the ‘bad’ type, and they need to be treated aggressively.”

“Now, we can implement this kind of classification and say that, even if a patient has the ‘bad’ ABC type, they have the ‘good’ genetic type, BN2. So there’s a much better chance of chemotherapy curing the disease.”

Data from this study will be shared through the National Cancer Institute’s Genomic Data Commons to make it available for future research.

Dr Staudt said he and his colleagues hope their new molecular classification will be used in clinical trials so that DLBCL treatment can move toward more targeted therapies.

“The goal is to find the right drug for the right person at the right time,” Dr Staudt said. “And we feel this genetic understanding of diffuse lymphoma is a step forward in precision therapy.”

Micrograph showing DLBCL

New research helps explain why some patients with diffuse large B-cell lymphoma (DLBCL) respond well to immunochemotherapy and others do not.

Researchers analyzed samples from nearly 600 DLBCL patients and identified 4 new genetic subtypes of the disease.

Patients with 2 of these subtypes had overall survival (OS) rates that were roughly twice as high as OS rates in patients with the other 2 subtypes.

Louis M. Staudt, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues described these findings in NEJM.

The researchers noted that the current subtypes of DLBCL—germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL—are associated with OS after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients with ABC DLBCL have a much lower OS rate, on average, than patients with GCB DLBCL. However, even in the GCB subgroup, many patients relapse after treatment.

“The first question we wanted to tackle was whether there were other molecular features of the tumors that could help us explain why some people were well-served by chemotherapy,” Dr Staudt said.

“And the second, related question was, if we could understand who was not responding well to treatment, could we understand the genetics of these tumors to suggest new potential therapies beyond chemotherapy? The answer to both questions was ‘yes.’”

Dr Staudt and his colleagues analyzed tumor samples from 574 patients with DLBCL, performing exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to find recurrent aberrations.

The team also developed an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations.

In this way, they identified 4 genetic subtypes:

• MCD, which was named based on the co-occurrence of MYD88L265P and CD79B mutations
• BN2, whose name was based on the presence of BCL6 fusions and NOTCH2 mutations
• N1, named for NOTCH1 mutations
• EZB, named for EZH2 mutations and BCL2 translocations.

The researchers said aberrations in multiple genes distinguished each of these subtypes from other DLBCLs, and the subtypes differed phenotypically.

Patients with BN2 or EZB subtypes had much higher OS rates after receiving R-CHOP than patients with MCD or N1 subtypes. The predicted 5-year OS rates were 26% for MCD patients, 36% for N1 patients, 65% for BN2 patients, and 68% for EZB patients.

The researchers said they found evidence to suggest that MCD and BN2 DLBCLs rely on chronic active B-cell receptor signaling that is amenable to therapeutic inhibition.

The team also noted that some of the subtypes they identified can be found in both ABC and GCB DLBCLs. For example, a patient could have ABC DLBCL, which is associated with a lower OS rate after R-CHOP, but also have the BN2 genetic subtype that responds well to R-CHOP.

“This shows we’ve gone beyond where we were,” Dr Staudt said. “Before, even with our most advanced molecular diagnosis, we would have said all ABC tumors are the ‘bad’ type, and they need to be treated aggressively.”

“Now, we can implement this kind of classification and say that, even if a patient has the ‘bad’ ABC type, they have the ‘good’ genetic type, BN2. So there’s a much better chance of chemotherapy curing the disease.”

Data from this study will be shared through the National Cancer Institute’s Genomic Data Commons to make it available for future research.

Dr Staudt said he and his colleagues hope their new molecular classification will be used in clinical trials so that DLBCL treatment can move toward more targeted therapies.

“The goal is to find the right drug for the right person at the right time,” Dr Staudt said. “And we feel this genetic understanding of diffuse lymphoma is a step forward in precision therapy.”

Lab mouse

Preclinical results support clinical testing of an experimental agent in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to researchers.

The agent, ALRN-6924, was shown to combat AML and MDS by restoring activity of the tumor-suppressing protein p53.

ALRN-6924 exhibited antileukemic activity in AML cells and mouse models of the disease, as well as in a patient with MDS and excess leukemic blasts who received the drug on a compassionate-use basis.

These results, published in Science Translational Medicine, have led to a phase 1 trial of ALRN-6924 in patients with AML or MDS.

ALRN-6924 was developed by Aileron Therapeutics Inc., to target p53 by inhibiting 2 naturally occurring proteins, MDMX and MDM2. Overexpression of these proteins inactivates p53, allowing cancer cells to multiply unchecked.

In the current study, researchers set out to confirm ALRN-6924’s mechanism of action and determine the efficacy of the drug in AML/MDS. This work was supported, in part, by grants from Aileron Therapeutics Inc., and the National Institutes of Health.

The researchers did find that ALRN-6924 targets both MDMX and MDM2, blocking their interaction with p53 in AML cells.

The team said ALRN-6924 inhibited proliferation by inducing cell-cycle arrest and apoptosis in AML cell lines and AML patient cells, including leukemic stem cell-enriched populations.

“This is important because AML is driven by stem cells, and, if you don’t target stem cells, the disease will come back very quickly,” said study author Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York.

The researchers also found that ALRN-6924 greatly increased survival in a mouse model of AML. The median survival was 34 days in vehicle-treated control mice, 83 days in mice that received ALRN-6924 at 20 mg/kg twice a week, and 151 days in mice that received ALRN-6924 at 20 mg/kg three times a week.

“This is a very striking response,” Dr Steidl said. “Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40% of the treated mice, meaning they were disease-free more than 1 year after treatment, essentially a lifetime for a mouse.”

Finally, the researchers assessed the effects of ALRN-6924 in a patient who had high-risk MDS with excess leukemic blasts.

The team found the p53 protein “was rapidly induced” in CD34+ leukemic blasts but not in healthy lymphocytes. And ALRN-6924 reduced the number of malignant cells circulating in the blood.

“This test was not designed to assess the efficacy of the drug in humans,” Dr Steidl noted. “That has to be done in a proper clinical trial. Our goal was to determine whether it can hit the desired target in human cells in a clinical setting, which it did in this individual.”

ALRN-6924 is a stapled alpha-helical peptide, a class of drugs whose helical structure is stabilized using hydrocarbon “staples.” The stapling prevents the peptides from being degraded by enzymes before reaching their intended target. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

In the phase 1 trial (NCT02909972), researchers are testing ALRN-6924 in patients with relapsed/refractory AML or advanced MDS.

Lab mouse

Preclinical results support clinical testing of an experimental agent in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to researchers.

The agent, ALRN-6924, was shown to combat AML and MDS by restoring activity of the tumor-suppressing protein p53.

ALRN-6924 exhibited antileukemic activity in AML cells and mouse models of the disease, as well as in a patient with MDS and excess leukemic blasts who received the drug on a compassionate-use basis.

These results, published in Science Translational Medicine, have led to a phase 1 trial of ALRN-6924 in patients with AML or MDS.

ALRN-6924 was developed by Aileron Therapeutics Inc., to target p53 by inhibiting 2 naturally occurring proteins, MDMX and MDM2. Overexpression of these proteins inactivates p53, allowing cancer cells to multiply unchecked.

In the current study, researchers set out to confirm ALRN-6924’s mechanism of action and determine the efficacy of the drug in AML/MDS. This work was supported, in part, by grants from Aileron Therapeutics Inc., and the National Institutes of Health.

The researchers did find that ALRN-6924 targets both MDMX and MDM2, blocking their interaction with p53 in AML cells.

The team said ALRN-6924 inhibited proliferation by inducing cell-cycle arrest and apoptosis in AML cell lines and AML patient cells, including leukemic stem cell-enriched populations.

“This is important because AML is driven by stem cells, and, if you don’t target stem cells, the disease will come back very quickly,” said study author Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York.

The researchers also found that ALRN-6924 greatly increased survival in a mouse model of AML. The median survival was 34 days in vehicle-treated control mice, 83 days in mice that received ALRN-6924 at 20 mg/kg twice a week, and 151 days in mice that received ALRN-6924 at 20 mg/kg three times a week.

“This is a very striking response,” Dr Steidl said. “Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40% of the treated mice, meaning they were disease-free more than 1 year after treatment, essentially a lifetime for a mouse.”

Finally, the researchers assessed the effects of ALRN-6924 in a patient who had high-risk MDS with excess leukemic blasts.

The team found the p53 protein “was rapidly induced” in CD34+ leukemic blasts but not in healthy lymphocytes. And ALRN-6924 reduced the number of malignant cells circulating in the blood.

“This test was not designed to assess the efficacy of the drug in humans,” Dr Steidl noted. “That has to be done in a proper clinical trial. Our goal was to determine whether it can hit the desired target in human cells in a clinical setting, which it did in this individual.”

ALRN-6924 is a stapled alpha-helical peptide, a class of drugs whose helical structure is stabilized using hydrocarbon “staples.” The stapling prevents the peptides from being degraded by enzymes before reaching their intended target. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

In the phase 1 trial (NCT02909972), researchers are testing ALRN-6924 in patients with relapsed/refractory AML or advanced MDS.

Lab mouse

Preclinical results support clinical testing of an experimental agent in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to researchers.

The agent, ALRN-6924, was shown to combat AML and MDS by restoring activity of the tumor-suppressing protein p53.

ALRN-6924 exhibited antileukemic activity in AML cells and mouse models of the disease, as well as in a patient with MDS and excess leukemic blasts who received the drug on a compassionate-use basis.

These results, published in Science Translational Medicine, have led to a phase 1 trial of ALRN-6924 in patients with AML or MDS.

ALRN-6924 was developed by Aileron Therapeutics Inc., to target p53 by inhibiting 2 naturally occurring proteins, MDMX and MDM2. Overexpression of these proteins inactivates p53, allowing cancer cells to multiply unchecked.

In the current study, researchers set out to confirm ALRN-6924’s mechanism of action and determine the efficacy of the drug in AML/MDS. This work was supported, in part, by grants from Aileron Therapeutics Inc., and the National Institutes of Health.

The researchers did find that ALRN-6924 targets both MDMX and MDM2, blocking their interaction with p53 in AML cells.

The team said ALRN-6924 inhibited proliferation by inducing cell-cycle arrest and apoptosis in AML cell lines and AML patient cells, including leukemic stem cell-enriched populations.

“This is important because AML is driven by stem cells, and, if you don’t target stem cells, the disease will come back very quickly,” said study author Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York.

The researchers also found that ALRN-6924 greatly increased survival in a mouse model of AML. The median survival was 34 days in vehicle-treated control mice, 83 days in mice that received ALRN-6924 at 20 mg/kg twice a week, and 151 days in mice that received ALRN-6924 at 20 mg/kg three times a week.

“This is a very striking response,” Dr Steidl said. “Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40% of the treated mice, meaning they were disease-free more than 1 year after treatment, essentially a lifetime for a mouse.”

Finally, the researchers assessed the effects of ALRN-6924 in a patient who had high-risk MDS with excess leukemic blasts.

The team found the p53 protein “was rapidly induced” in CD34+ leukemic blasts but not in healthy lymphocytes. And ALRN-6924 reduced the number of malignant cells circulating in the blood.

“This test was not designed to assess the efficacy of the drug in humans,” Dr Steidl noted. “That has to be done in a proper clinical trial. Our goal was to determine whether it can hit the desired target in human cells in a clinical setting, which it did in this individual.”

ALRN-6924 is a stapled alpha-helical peptide, a class of drugs whose helical structure is stabilized using hydrocarbon “staples.” The stapling prevents the peptides from being degraded by enzymes before reaching their intended target. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

In the phase 1 trial (NCT02909972), researchers are testing ALRN-6924 in patients with relapsed/refractory AML or advanced MDS.

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

The FP made the diagnosis of nevus depigmentosus.

Nevus depigmentosus is usually present at birth or develops in early childhood. There is a decreased number of melanosomes within a normal number of melanocytes. The hypopigmented area typically has a serrated or jagged edge and has been compared to the appearance of a continent.

Nevus depigmentosus presents no danger or increased malignant potential. Excision, which is not an advisable option, is the only available treatment. Patients who want to camouflage the appearance of the hypopigmentation can use cover-up makeup.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M, Usatine R. Benign nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:945-952.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP made the diagnosis of nevus depigmentosus.

Nevus depigmentosus is usually present at birth or develops in early childhood. There is a decreased number of melanosomes within a normal number of melanocytes. The hypopigmented area typically has a serrated or jagged edge and has been compared to the appearance of a continent.

Nevus depigmentosus presents no danger or increased malignant potential. Excision, which is not an advisable option, is the only available treatment. Patients who want to camouflage the appearance of the hypopigmentation can use cover-up makeup.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M, Usatine R. Benign nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:945-952.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP made the diagnosis of nevus depigmentosus.

Nevus depigmentosus is usually present at birth or develops in early childhood. There is a decreased number of melanosomes within a normal number of melanocytes. The hypopigmented area typically has a serrated or jagged edge and has been compared to the appearance of a continent.

Nevus depigmentosus presents no danger or increased malignant potential. Excision, which is not an advisable option, is the only available treatment. Patients who want to camouflage the appearance of the hypopigmentation can use cover-up makeup.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M, Usatine R. Benign nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:945-952.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Rare but serious adverse events associated with alemtuzumab treatment of multiple sclerosis (MS) have recently been revealed by postmarketing surveillance, according to three new case reports and series in Neurology.

The complications include acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients.

copyright Zerbor/Thinkstock

The cardiac arrest incident occurred in a 24-year old woman with spinal-onset relapsing-remitting multiple sclerosis (RRMS) during alemtuzumab infusion. She had experienced two clinical relapses and a significant increase in cerebral and spinal MRI lesion load, despite previous treatment with natalizumab (Tysabri). The only striking thing about her medical history was allergic asthma.

On the third day of treatment, she developed severe asymptomatic sinus bradycardia (HR, 38 beats per minute), which resolved with treatment, and clinicians continued the regimen. The following morning, she experienced acute coronary syndrome, which later resolved.

The authors recommend that clinicians treating RRMS patients with alemtuzumab consider a baseline preinfusion ECG and monitoring heart rate at least hourly while infusion is being carried out.

The HLH cases occurred in a man and a woman with RRMS, both in their 20s. The woman was switched from natalizumab to alemtuzumab because of a high anti-JC virus antibody index. Both cases presented in the time frame typical of secondary autoimmunity. The female patient had an acalculous gallbladder with thickened walls and pericholecystic fluid and responded to intravenous antibiotics, but 3 weeks later she developed thrombocytopenia, coagulopathy, and anemia with abnormal liver enzymes. Treatment failed and she succumbed to the condition.

The man received alemtuzumab as first-line therapy for RRMS during the Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis (CAM-THY) clinical trial. He received boluses of either placebo or palifermin (Kepivance) before and after each alemtuzumab dose in order to reduce secondary autoimmunity. At 30 months after his initial cycle of alemtuzumab, he was admitted to the hospital with HLH and also developed acquired factor VIII hemophilia. He responded positively to 4 months of corticosteroid treatment combined with two doses of rituximab (Rituxan) and ultimately returned to work. However, he experienced a relapse of acquired hemophilia during later doses of corticosteroids and rituximab.

A search of the Food and Drug Administration Adverse Event Reporting System (FAERS) revealed eight cases of acute acalculous cholecystitis (AAC) – four assessed as possibly caused by alemtuzumab, and four assessed as probable – that occurred in patients with RRMS. Seven of the cases involved presentation during treatment or soon afterward, which suggests that acute cytokine release syndrome (ACRS) may be the cause. The cases did not share all of the manifestations of typical ACRS, but the researchers noted that coadministration of methylprednisolone in the RRMS dosing schedule may have masked some of the features.

Unlike typical AAC, these cases occurred primarily in females (six of eight) and were not associated with concurrent critical illnesses. Other risk factors were not consistently present. Historically, AAC is associated with treatment of older male patients in the ICU. Three of the patients underwent surgical treatment, and five received conservative treatment of antibiotics or an unspecified treatment. Seven patients recovered. The outcome in the eighth patient was not reported.

Despite these good outcomes, the authors of the report note that longer-term outcomes in this AAC population are not yet understood.

The findings led to the addition of AAC to the Warnings and Precautions section of the alemtuzumab label in October 2017.

None of the reports received funding. Some of the authors had financial ties to the pharmaceutical industry.

SOURCES: Croteau D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422. Saarela M et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005420. Ferraro D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005417.

Rare but serious adverse events associated with alemtuzumab treatment of multiple sclerosis (MS) have recently been revealed by postmarketing surveillance, according to three new case reports and series in Neurology.

The complications include acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients.

copyright Zerbor/Thinkstock

The cardiac arrest incident occurred in a 24-year old woman with spinal-onset relapsing-remitting multiple sclerosis (RRMS) during alemtuzumab infusion. She had experienced two clinical relapses and a significant increase in cerebral and spinal MRI lesion load, despite previous treatment with natalizumab (Tysabri). The only striking thing about her medical history was allergic asthma.

On the third day of treatment, she developed severe asymptomatic sinus bradycardia (HR, 38 beats per minute), which resolved with treatment, and clinicians continued the regimen. The following morning, she experienced acute coronary syndrome, which later resolved.

The authors recommend that clinicians treating RRMS patients with alemtuzumab consider a baseline preinfusion ECG and monitoring heart rate at least hourly while infusion is being carried out.

The HLH cases occurred in a man and a woman with RRMS, both in their 20s. The woman was switched from natalizumab to alemtuzumab because of a high anti-JC virus antibody index. Both cases presented in the time frame typical of secondary autoimmunity. The female patient had an acalculous gallbladder with thickened walls and pericholecystic fluid and responded to intravenous antibiotics, but 3 weeks later she developed thrombocytopenia, coagulopathy, and anemia with abnormal liver enzymes. Treatment failed and she succumbed to the condition.

The man received alemtuzumab as first-line therapy for RRMS during the Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis (CAM-THY) clinical trial. He received boluses of either placebo or palifermin (Kepivance) before and after each alemtuzumab dose in order to reduce secondary autoimmunity. At 30 months after his initial cycle of alemtuzumab, he was admitted to the hospital with HLH and also developed acquired factor VIII hemophilia. He responded positively to 4 months of corticosteroid treatment combined with two doses of rituximab (Rituxan) and ultimately returned to work. However, he experienced a relapse of acquired hemophilia during later doses of corticosteroids and rituximab.

A search of the Food and Drug Administration Adverse Event Reporting System (FAERS) revealed eight cases of acute acalculous cholecystitis (AAC) – four assessed as possibly caused by alemtuzumab, and four assessed as probable – that occurred in patients with RRMS. Seven of the cases involved presentation during treatment or soon afterward, which suggests that acute cytokine release syndrome (ACRS) may be the cause. The cases did not share all of the manifestations of typical ACRS, but the researchers noted that coadministration of methylprednisolone in the RRMS dosing schedule may have masked some of the features.

Unlike typical AAC, these cases occurred primarily in females (six of eight) and were not associated with concurrent critical illnesses. Other risk factors were not consistently present. Historically, AAC is associated with treatment of older male patients in the ICU. Three of the patients underwent surgical treatment, and five received conservative treatment of antibiotics or an unspecified treatment. Seven patients recovered. The outcome in the eighth patient was not reported.

Despite these good outcomes, the authors of the report note that longer-term outcomes in this AAC population are not yet understood.

The findings led to the addition of AAC to the Warnings and Precautions section of the alemtuzumab label in October 2017.

None of the reports received funding. Some of the authors had financial ties to the pharmaceutical industry.

SOURCES: Croteau D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422. Saarela M et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005420. Ferraro D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005417.

Rare but serious adverse events associated with alemtuzumab treatment of multiple sclerosis (MS) have recently been revealed by postmarketing surveillance, according to three new case reports and series in Neurology.

The complications include acute coronary syndrome in one patient, hemophagocytic lymphohistiocytosis (HLH) in two patients, and acute acalculous cholecystitis in eight patients.

copyright Zerbor/Thinkstock

The cardiac arrest incident occurred in a 24-year old woman with spinal-onset relapsing-remitting multiple sclerosis (RRMS) during alemtuzumab infusion. She had experienced two clinical relapses and a significant increase in cerebral and spinal MRI lesion load, despite previous treatment with natalizumab (Tysabri). The only striking thing about her medical history was allergic asthma.

On the third day of treatment, she developed severe asymptomatic sinus bradycardia (HR, 38 beats per minute), which resolved with treatment, and clinicians continued the regimen. The following morning, she experienced acute coronary syndrome, which later resolved.

The authors recommend that clinicians treating RRMS patients with alemtuzumab consider a baseline preinfusion ECG and monitoring heart rate at least hourly while infusion is being carried out.

The HLH cases occurred in a man and a woman with RRMS, both in their 20s. The woman was switched from natalizumab to alemtuzumab because of a high anti-JC virus antibody index. Both cases presented in the time frame typical of secondary autoimmunity. The female patient had an acalculous gallbladder with thickened walls and pericholecystic fluid and responded to intravenous antibiotics, but 3 weeks later she developed thrombocytopenia, coagulopathy, and anemia with abnormal liver enzymes. Treatment failed and she succumbed to the condition.

The man received alemtuzumab as first-line therapy for RRMS during the Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis (CAM-THY) clinical trial. He received boluses of either placebo or palifermin (Kepivance) before and after each alemtuzumab dose in order to reduce secondary autoimmunity. At 30 months after his initial cycle of alemtuzumab, he was admitted to the hospital with HLH and also developed acquired factor VIII hemophilia. He responded positively to 4 months of corticosteroid treatment combined with two doses of rituximab (Rituxan) and ultimately returned to work. However, he experienced a relapse of acquired hemophilia during later doses of corticosteroids and rituximab.

A search of the Food and Drug Administration Adverse Event Reporting System (FAERS) revealed eight cases of acute acalculous cholecystitis (AAC) – four assessed as possibly caused by alemtuzumab, and four assessed as probable – that occurred in patients with RRMS. Seven of the cases involved presentation during treatment or soon afterward, which suggests that acute cytokine release syndrome (ACRS) may be the cause. The cases did not share all of the manifestations of typical ACRS, but the researchers noted that coadministration of methylprednisolone in the RRMS dosing schedule may have masked some of the features.

Unlike typical AAC, these cases occurred primarily in females (six of eight) and were not associated with concurrent critical illnesses. Other risk factors were not consistently present. Historically, AAC is associated with treatment of older male patients in the ICU. Three of the patients underwent surgical treatment, and five received conservative treatment of antibiotics or an unspecified treatment. Seven patients recovered. The outcome in the eighth patient was not reported.

Despite these good outcomes, the authors of the report note that longer-term outcomes in this AAC population are not yet understood.

The findings led to the addition of AAC to the Warnings and Precautions section of the alemtuzumab label in October 2017.

None of the reports received funding. Some of the authors had financial ties to the pharmaceutical industry.

SOURCES: Croteau D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005422. Saarela M et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005420. Ferraro D et al. Neurology. 2018 Mar 30. doi: 10.1212/WNL.0000000000005417.

Giants In Chest Medicine

Professor Emeritus Elizabeth F. Juniper, MCSP, MSc

By Dr. P. M. O’Byrne
 

Original Research

A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome.

Evidence-Based Medicine

Screening for Lung Cancer: CHEST Guideline and Expert Panel Report.

By Dr. P. J. Mazzone, et al.



Treating Cough Due to Non-CF and CF Bronchiectasis With Nonpharmacological Airway Clearance: CHEST Expert Panel Report.

By Dr. A. T. Hill, et al.

Giants In Chest Medicine

Professor Emeritus Elizabeth F. Juniper, MCSP, MSc

By Dr. P. M. O’Byrne
 

Original Research

A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome.

Evidence-Based Medicine

Screening for Lung Cancer: CHEST Guideline and Expert Panel Report.

By Dr. P. J. Mazzone, et al.



Treating Cough Due to Non-CF and CF Bronchiectasis With Nonpharmacological Airway Clearance: CHEST Expert Panel Report.

By Dr. A. T. Hill, et al.

Giants In Chest Medicine

Professor Emeritus Elizabeth F. Juniper, MCSP, MSc

By Dr. P. M. O’Byrne
 

Original Research

A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome.

Evidence-Based Medicine

Screening for Lung Cancer: CHEST Guideline and Expert Panel Report.

By Dr. P. J. Mazzone, et al.



Treating Cough Due to Non-CF and CF Bronchiectasis With Nonpharmacological Airway Clearance: CHEST Expert Panel Report.

By Dr. A. T. Hill, et al.

The World Health Organization (WHO) has announced its annual SAVE LIVES: Clean Your Hands 2018 campaign (Saito, et al. J Hosp Infect. 2018;98[4]:321), designating May 5, 2018, as world hand hygiene day.

Health-care-associated infections are a major patient safety problem. Unfortunately, their spread is common in hospitals and ICUs around the globe. The vehicle for these infections, including multidrug-resistant organisms, is frequently the contaminated hands of health-care workers. Health-care-acquired infections, as any other infection, can lead to sepsis and death. Infections acquired in the ICU are especially deadly, with mortalities that can be as high as 80%. Proper hand hygiene, despite being simple and inexpensive, is the single most important means of reducing the prevalence of hospital-acquired infections and the spread of antimicrobial resistance.

We have known about the significance of hand washing since the early 19th century. More recent data show that hand washing can reduce the overall prevalence of hospital-acquired infections and the cross-transmission of multidrug-resistant organisms. It is estimated that we can prevent 15% to 30% of these infections with adequate hand washing alone.

Despite the clear benefit and the understanding of the importance of hand washing, compliance with this simple intervention is only about 50%. Health-care workers tend to overestimate these rates, self-reporting a compliance of 75%. Even the latter number represents a lot of missed opportunities, and we must do something about it.

A multifaceted approach that combines education with written material, reminders, and continued feedback on performance can have an important effect on hand washing compliance and rates of hospital-acquired infections.

Sepsis is the single most important cause of death in hospitals in the United States. The campaign (http://www.who.int/infection-prevention/campaigns/clean-hands/en/), sponsored by the World Health Organization, should serve as a reminder to all health-care workers about the importance of adequate hand washing and as an opportunity to improve our compliance moving forward.

Despite the progress made, there is still a lot of room for improvement. We can have an impact on the number of deaths from sepsis by preventing them to occur in the first place. Wash your hands and do it well, it does not cost us anything.

Remember: It is in our hands – prevent sepsis and save lives!

Shruti Gadre, MD

Steering Committee Member, Critical Care NetWork

Angel Coz, MD, FCCP

Chair, Critical Care NetWork

The World Health Organization (WHO) has announced its annual SAVE LIVES: Clean Your Hands 2018 campaign (Saito, et al. J Hosp Infect. 2018;98[4]:321), designating May 5, 2018, as world hand hygiene day.

Health-care-associated infections are a major patient safety problem. Unfortunately, their spread is common in hospitals and ICUs around the globe. The vehicle for these infections, including multidrug-resistant organisms, is frequently the contaminated hands of health-care workers. Health-care-acquired infections, as any other infection, can lead to sepsis and death. Infections acquired in the ICU are especially deadly, with mortalities that can be as high as 80%. Proper hand hygiene, despite being simple and inexpensive, is the single most important means of reducing the prevalence of hospital-acquired infections and the spread of antimicrobial resistance.

We have known about the significance of hand washing since the early 19th century. More recent data show that hand washing can reduce the overall prevalence of hospital-acquired infections and the cross-transmission of multidrug-resistant organisms. It is estimated that we can prevent 15% to 30% of these infections with adequate hand washing alone.

Despite the clear benefit and the understanding of the importance of hand washing, compliance with this simple intervention is only about 50%. Health-care workers tend to overestimate these rates, self-reporting a compliance of 75%. Even the latter number represents a lot of missed opportunities, and we must do something about it.

A multifaceted approach that combines education with written material, reminders, and continued feedback on performance can have an important effect on hand washing compliance and rates of hospital-acquired infections.

Sepsis is the single most important cause of death in hospitals in the United States. The campaign (http://www.who.int/infection-prevention/campaigns/clean-hands/en/), sponsored by the World Health Organization, should serve as a reminder to all health-care workers about the importance of adequate hand washing and as an opportunity to improve our compliance moving forward.

Despite the progress made, there is still a lot of room for improvement. We can have an impact on the number of deaths from sepsis by preventing them to occur in the first place. Wash your hands and do it well, it does not cost us anything.

Remember: It is in our hands – prevent sepsis and save lives!

Shruti Gadre, MD

Steering Committee Member, Critical Care NetWork

Angel Coz, MD, FCCP

Chair, Critical Care NetWork

The World Health Organization (WHO) has announced its annual SAVE LIVES: Clean Your Hands 2018 campaign (Saito, et al. J Hosp Infect. 2018;98[4]:321), designating May 5, 2018, as world hand hygiene day.

Health-care-associated infections are a major patient safety problem. Unfortunately, their spread is common in hospitals and ICUs around the globe. The vehicle for these infections, including multidrug-resistant organisms, is frequently the contaminated hands of health-care workers. Health-care-acquired infections, as any other infection, can lead to sepsis and death. Infections acquired in the ICU are especially deadly, with mortalities that can be as high as 80%. Proper hand hygiene, despite being simple and inexpensive, is the single most important means of reducing the prevalence of hospital-acquired infections and the spread of antimicrobial resistance.

We have known about the significance of hand washing since the early 19th century. More recent data show that hand washing can reduce the overall prevalence of hospital-acquired infections and the cross-transmission of multidrug-resistant organisms. It is estimated that we can prevent 15% to 30% of these infections with adequate hand washing alone.

Despite the clear benefit and the understanding of the importance of hand washing, compliance with this simple intervention is only about 50%. Health-care workers tend to overestimate these rates, self-reporting a compliance of 75%. Even the latter number represents a lot of missed opportunities, and we must do something about it.

A multifaceted approach that combines education with written material, reminders, and continued feedback on performance can have an important effect on hand washing compliance and rates of hospital-acquired infections.

Sepsis is the single most important cause of death in hospitals in the United States. The campaign (http://www.who.int/infection-prevention/campaigns/clean-hands/en/), sponsored by the World Health Organization, should serve as a reminder to all health-care workers about the importance of adequate hand washing and as an opportunity to improve our compliance moving forward.

Despite the progress made, there is still a lot of room for improvement. We can have an impact on the number of deaths from sepsis by preventing them to occur in the first place. Wash your hands and do it well, it does not cost us anything.

Remember: It is in our hands – prevent sepsis and save lives!

Shruti Gadre, MD

Steering Committee Member, Critical Care NetWork

Angel Coz, MD, FCCP

Chair, Critical Care NetWork