A novel whole blood assay was unable to predict clinical severity in patients with type 1 von Willebrand disease (VWD).

The whole blood ristocetin-induced platelet agglutination (WB-RIPA) assay has shown potential for use as a diagnostic test for patients with type 1 VWD. However, the ability of the assay to predict clinical severity of the disease is unknown.

Yuto Nakajima, MD, of the Nara (Japan) Medical University and his colleagues studied the diagnostic and clinical capabilities of the assay in 55 patients with type 1 VWD and 20 healthy controls. The results of the study were published in Haemophilia.

The team examined relationships between WB-RIPA levels, VWF-associated measurements, and bleeding scores using whole blood samples. Bleeding severity was assessed using scores from a standardized assessment tool.

After analysis, the team found that assay values were significantly lower in patients with type 1 VWD versus healthy controls (P less than .0001), which validated the detection abilities of the test.

However, correlations between WB-RIPA levels and specific VWF-associated measurements were found to be weak. Similar results were reported with assay levels and bleeding scores. There were no significant differences seen in WB-RIPA between patients with a bleeding score of 4 or greater (abnormal bleeding tendency) and less than 4 (no abnormal bleeding tendency).

“Our study indicated that the WB-RIPA assay would not be useful for assessing and predicting the clinical severity in type 1 VWD,” they wrote.

The authors acknowledged that a key limitation was that the definition of type 1 VWD used in the study was not based on the most current classification.

The study was supported by grant funding from the Ministry of Education, Culture, Sports, Science and Technology (Japan). The authors reported having no conflicts of interest.

SOURCE: Nakajima Y et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13725.

A novel whole blood assay was unable to predict clinical severity in patients with type 1 von Willebrand disease (VWD).

The whole blood ristocetin-induced platelet agglutination (WB-RIPA) assay has shown potential for use as a diagnostic test for patients with type 1 VWD. However, the ability of the assay to predict clinical severity of the disease is unknown.

Yuto Nakajima, MD, of the Nara (Japan) Medical University and his colleagues studied the diagnostic and clinical capabilities of the assay in 55 patients with type 1 VWD and 20 healthy controls. The results of the study were published in Haemophilia.

The team examined relationships between WB-RIPA levels, VWF-associated measurements, and bleeding scores using whole blood samples. Bleeding severity was assessed using scores from a standardized assessment tool.

After analysis, the team found that assay values were significantly lower in patients with type 1 VWD versus healthy controls (P less than .0001), which validated the detection abilities of the test.

However, correlations between WB-RIPA levels and specific VWF-associated measurements were found to be weak. Similar results were reported with assay levels and bleeding scores. There were no significant differences seen in WB-RIPA between patients with a bleeding score of 4 or greater (abnormal bleeding tendency) and less than 4 (no abnormal bleeding tendency).

“Our study indicated that the WB-RIPA assay would not be useful for assessing and predicting the clinical severity in type 1 VWD,” they wrote.

The authors acknowledged that a key limitation was that the definition of type 1 VWD used in the study was not based on the most current classification.

The study was supported by grant funding from the Ministry of Education, Culture, Sports, Science and Technology (Japan). The authors reported having no conflicts of interest.

SOURCE: Nakajima Y et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13725.

A novel whole blood assay was unable to predict clinical severity in patients with type 1 von Willebrand disease (VWD).

The whole blood ristocetin-induced platelet agglutination (WB-RIPA) assay has shown potential for use as a diagnostic test for patients with type 1 VWD. However, the ability of the assay to predict clinical severity of the disease is unknown.

Yuto Nakajima, MD, of the Nara (Japan) Medical University and his colleagues studied the diagnostic and clinical capabilities of the assay in 55 patients with type 1 VWD and 20 healthy controls. The results of the study were published in Haemophilia.

The team examined relationships between WB-RIPA levels, VWF-associated measurements, and bleeding scores using whole blood samples. Bleeding severity was assessed using scores from a standardized assessment tool.

After analysis, the team found that assay values were significantly lower in patients with type 1 VWD versus healthy controls (P less than .0001), which validated the detection abilities of the test.

However, correlations between WB-RIPA levels and specific VWF-associated measurements were found to be weak. Similar results were reported with assay levels and bleeding scores. There were no significant differences seen in WB-RIPA between patients with a bleeding score of 4 or greater (abnormal bleeding tendency) and less than 4 (no abnormal bleeding tendency).

“Our study indicated that the WB-RIPA assay would not be useful for assessing and predicting the clinical severity in type 1 VWD,” they wrote.

The authors acknowledged that a key limitation was that the definition of type 1 VWD used in the study was not based on the most current classification.

The study was supported by grant funding from the Ministry of Education, Culture, Sports, Science and Technology (Japan). The authors reported having no conflicts of interest.

SOURCE: Nakajima Y et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13725.

The Food and Drug Administration has approved testosterone undecanoate (Jatenzo), an oral capsule for the treatment of male hypogonadism caused by certain conditions, such as genetic disorders or tumors that have damaged the pituitary gland.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is based on results from a 4-month clinical trial involving 166 men with hypogonadism. Patients received 237 mg testosterone undecanoate twice a day initially, a dosage that was adjusted downward or upward to a maximum of 396 mg twice a day, based on testosterone levels. At the end of the trial, 87% of men had achieved testosterone levels within the normal range.

The label for testosterone undecanoate contains a warning that the drug can cause an increase in blood pressure, raising the risk of heart attack, stroke, and cardiovascular death. Other common adverse events associated with testosterone undecanoate include headache, an increase in hematocrit, a decrease in HDL cholesterol, and nausea.

“[The] oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who, until now, have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive, and urologic products at the FDA’s Center for Drug Evaluation and Research, in the press release.

Testosterone undecanoate is not approved to treat age-related hypogonadism, even in cases in which men have symptoms caused by low testosterone. The drug’s benefits do not outweigh its risks in those cases, the agency noted.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved testosterone undecanoate (Jatenzo), an oral capsule for the treatment of male hypogonadism caused by certain conditions, such as genetic disorders or tumors that have damaged the pituitary gland.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is based on results from a 4-month clinical trial involving 166 men with hypogonadism. Patients received 237 mg testosterone undecanoate twice a day initially, a dosage that was adjusted downward or upward to a maximum of 396 mg twice a day, based on testosterone levels. At the end of the trial, 87% of men had achieved testosterone levels within the normal range.

The label for testosterone undecanoate contains a warning that the drug can cause an increase in blood pressure, raising the risk of heart attack, stroke, and cardiovascular death. Other common adverse events associated with testosterone undecanoate include headache, an increase in hematocrit, a decrease in HDL cholesterol, and nausea.

“[The] oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who, until now, have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive, and urologic products at the FDA’s Center for Drug Evaluation and Research, in the press release.

Testosterone undecanoate is not approved to treat age-related hypogonadism, even in cases in which men have symptoms caused by low testosterone. The drug’s benefits do not outweigh its risks in those cases, the agency noted.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved testosterone undecanoate (Jatenzo), an oral capsule for the treatment of male hypogonadism caused by certain conditions, such as genetic disorders or tumors that have damaged the pituitary gland.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The approval is based on results from a 4-month clinical trial involving 166 men with hypogonadism. Patients received 237 mg testosterone undecanoate twice a day initially, a dosage that was adjusted downward or upward to a maximum of 396 mg twice a day, based on testosterone levels. At the end of the trial, 87% of men had achieved testosterone levels within the normal range.

The label for testosterone undecanoate contains a warning that the drug can cause an increase in blood pressure, raising the risk of heart attack, stroke, and cardiovascular death. Other common adverse events associated with testosterone undecanoate include headache, an increase in hematocrit, a decrease in HDL cholesterol, and nausea.

“[The] oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who, until now, have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, MD, MMSc, director of the division of bone, reproductive, and urologic products at the FDA’s Center for Drug Evaluation and Research, in the press release.

Testosterone undecanoate is not approved to treat age-related hypogonadism, even in cases in which men have symptoms caused by low testosterone. The drug’s benefits do not outweigh its risks in those cases, the agency noted.

Find the full press release on the FDA website.

[email protected]

In patients with multiple sclerosis (MS), the risk of acute myocardial infarction (AMI) is elevated but may not be accounted for by traditional vascular risk factors, a new study found. Researchers conducted a retrospective matched cohort study using population-based administrative data in 2 Canadian provinces. Incident MS cases were identified and for each case, up to 5 controls without MS were matched on age, sex, and region. The incidence of AMI between cohorts was compared using incidence rate ratios (IRRs). Among the findings:

• 14,565 persons with MS and 72,825 matched controls were identified.
• The crude incidence of AMI per 100,000 population was 146.2 in the MS population vs 128.8 in the matched population.
• After age standardization, the incidence of AMI was higher in the MS population vs the matched population (IRR 1.18).
• After adjustment, the hazard of AMI was 60% higher in the MS population vs the matched population (hazard ratio 1.63).

Marrie RA, Garland A, Schaffer SA. Traditional risk factors may not explain increased incidence of myocardial infarction in MS. [Published online ahead of print March 6, 2019]. Neurology. doi:10.1212/WNL.0000000000007251.

In patients with multiple sclerosis (MS), the risk of acute myocardial infarction (AMI) is elevated but may not be accounted for by traditional vascular risk factors, a new study found. Researchers conducted a retrospective matched cohort study using population-based administrative data in 2 Canadian provinces. Incident MS cases were identified and for each case, up to 5 controls without MS were matched on age, sex, and region. The incidence of AMI between cohorts was compared using incidence rate ratios (IRRs). Among the findings:

• 14,565 persons with MS and 72,825 matched controls were identified.
• The crude incidence of AMI per 100,000 population was 146.2 in the MS population vs 128.8 in the matched population.
• After age standardization, the incidence of AMI was higher in the MS population vs the matched population (IRR 1.18).
• After adjustment, the hazard of AMI was 60% higher in the MS population vs the matched population (hazard ratio 1.63).

Marrie RA, Garland A, Schaffer SA. Traditional risk factors may not explain increased incidence of myocardial infarction in MS. [Published online ahead of print March 6, 2019]. Neurology. doi:10.1212/WNL.0000000000007251.

In patients with multiple sclerosis (MS), the risk of acute myocardial infarction (AMI) is elevated but may not be accounted for by traditional vascular risk factors, a new study found. Researchers conducted a retrospective matched cohort study using population-based administrative data in 2 Canadian provinces. Incident MS cases were identified and for each case, up to 5 controls without MS were matched on age, sex, and region. The incidence of AMI between cohorts was compared using incidence rate ratios (IRRs). Among the findings:

• 14,565 persons with MS and 72,825 matched controls were identified.
• The crude incidence of AMI per 100,000 population was 146.2 in the MS population vs 128.8 in the matched population.
• After age standardization, the incidence of AMI was higher in the MS population vs the matched population (IRR 1.18).
• After adjustment, the hazard of AMI was 60% higher in the MS population vs the matched population (hazard ratio 1.63).

Marrie RA, Garland A, Schaffer SA. Traditional risk factors may not explain increased incidence of myocardial infarction in MS. [Published online ahead of print March 6, 2019]. Neurology. doi:10.1212/WNL.0000000000007251.

In a recent survey, patients with multiple sclerosis (MS) displayed a wide range of risk tolerance (RT) to MS therapies. People with MS from the North American Research Committee on Multiple Sclerosis Registry’s online cohort and the National Multiple Sclerosis Society were invited to complete a questionnaire on tolerance to real-world risks associated with a hypothetical therapy. Multiple risk levels were presented, including skin rash, infection, kidney injury, thyroid injury, liver injury, and progressive multifocal leukoencephalopathy (PML). Researchers found:

• Both PML and kidney injury had the lowest RT; thyroid and infection risk had the highest tolerance.
• Men, younger individuals, and those with greater disability reported a higher tolerance to all risk scenarios.
• Participants currently taking an MS therapy reported higher tolerance vs those not taking any therapy.

Fox RJ, Cosenza C, Cripps L, et al. A survey of risk tolerance to multiple sclerosis therapies. [Published online ahead of print March 13, 2019]. Neurology. doi:10.1212/WNL.0000000000007245.

In a recent survey, patients with multiple sclerosis (MS) displayed a wide range of risk tolerance (RT) to MS therapies. People with MS from the North American Research Committee on Multiple Sclerosis Registry’s online cohort and the National Multiple Sclerosis Society were invited to complete a questionnaire on tolerance to real-world risks associated with a hypothetical therapy. Multiple risk levels were presented, including skin rash, infection, kidney injury, thyroid injury, liver injury, and progressive multifocal leukoencephalopathy (PML). Researchers found:

• Both PML and kidney injury had the lowest RT; thyroid and infection risk had the highest tolerance.
• Men, younger individuals, and those with greater disability reported a higher tolerance to all risk scenarios.
• Participants currently taking an MS therapy reported higher tolerance vs those not taking any therapy.

Fox RJ, Cosenza C, Cripps L, et al. A survey of risk tolerance to multiple sclerosis therapies. [Published online ahead of print March 13, 2019]. Neurology. doi:10.1212/WNL.0000000000007245.

In a recent survey, patients with multiple sclerosis (MS) displayed a wide range of risk tolerance (RT) to MS therapies. People with MS from the North American Research Committee on Multiple Sclerosis Registry’s online cohort and the National Multiple Sclerosis Society were invited to complete a questionnaire on tolerance to real-world risks associated with a hypothetical therapy. Multiple risk levels were presented, including skin rash, infection, kidney injury, thyroid injury, liver injury, and progressive multifocal leukoencephalopathy (PML). Researchers found:

• Both PML and kidney injury had the lowest RT; thyroid and infection risk had the highest tolerance.
• Men, younger individuals, and those with greater disability reported a higher tolerance to all risk scenarios.
• Participants currently taking an MS therapy reported higher tolerance vs those not taking any therapy.

Fox RJ, Cosenza C, Cripps L, et al. A survey of risk tolerance to multiple sclerosis therapies. [Published online ahead of print March 13, 2019]. Neurology. doi:10.1212/WNL.0000000000007245.

In an age and gender-based US national retrospective analysis, overall 30-day readmission in multiple sclerosis (MS) was ∼10%, with higher readmission rates observed in older patients. The retrospective observational cohort study included patients hospitalized with primary discharge diagnosis of MS using 2013 Nationwide Readmission Database (NRD). Age (<40 vs >40 years) and gender-based analyses were performed using multivariable logistic regression adjusting co-variables to identify the patient/system-specific factors associated with 30-day readmission. Researchers found:

• 30-day readmission rate in MS was 10.2% in the cohort.
• Higher 30-day readmission was observed in patients aged >40 years due to burden of comorbidities.
• Readmission causes were MS exacerbations, sepsis, and respiratory complications.
• Readmission was associated with higher cost of care and longer length of stay compared to index admissions.

Patel S, SirDeshpande P, Desai R, et al. Thirty-day readmissions in multiple sclerosis: An age and gender-based US national retrospective analysis. [Published online ahead of print March 20, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.03.012.

In an age and gender-based US national retrospective analysis, overall 30-day readmission in multiple sclerosis (MS) was ∼10%, with higher readmission rates observed in older patients. The retrospective observational cohort study included patients hospitalized with primary discharge diagnosis of MS using 2013 Nationwide Readmission Database (NRD). Age (<40 vs >40 years) and gender-based analyses were performed using multivariable logistic regression adjusting co-variables to identify the patient/system-specific factors associated with 30-day readmission. Researchers found:

• 30-day readmission rate in MS was 10.2% in the cohort.
• Higher 30-day readmission was observed in patients aged >40 years due to burden of comorbidities.
• Readmission causes were MS exacerbations, sepsis, and respiratory complications.
• Readmission was associated with higher cost of care and longer length of stay compared to index admissions.

Patel S, SirDeshpande P, Desai R, et al. Thirty-day readmissions in multiple sclerosis: An age and gender-based US national retrospective analysis. [Published online ahead of print March 20, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.03.012.

In an age and gender-based US national retrospective analysis, overall 30-day readmission in multiple sclerosis (MS) was ∼10%, with higher readmission rates observed in older patients. The retrospective observational cohort study included patients hospitalized with primary discharge diagnosis of MS using 2013 Nationwide Readmission Database (NRD). Age (<40 vs >40 years) and gender-based analyses were performed using multivariable logistic regression adjusting co-variables to identify the patient/system-specific factors associated with 30-day readmission. Researchers found:

• 30-day readmission rate in MS was 10.2% in the cohort.
• Higher 30-day readmission was observed in patients aged >40 years due to burden of comorbidities.
• Readmission causes were MS exacerbations, sepsis, and respiratory complications.
• Readmission was associated with higher cost of care and longer length of stay compared to index admissions.

Patel S, SirDeshpande P, Desai R, et al. Thirty-day readmissions in multiple sclerosis: An age and gender-based US national retrospective analysis. [Published online ahead of print March 20, 2019]. Mult Scler Relat Disord. doi:10.1016/j.msard.2019.03.012.

It’s the pits

Physical therapists sometimes use therapeutic ball pits to provide stimulation to pediatric patients with sensory impairments. However, anyone who’s ever been to a fast food joint or a Chuck E. Cheeses in the last 30 years knows that ball pits are not as innocent as they seem – instead of being simply a joyous sunken hole of fun, they are a prime breeding ground for all sorts of bacteria. And adhesive bandages. Why are there always bandages??

andresr/gettyimages

Researchers recently took a deep, disgusting dive into the underworld of clinical ball pits, which do not seem to be regulated by any governing body. There are no clinical guidelines from the Ball Pit Association of America on how or when to clean these cesspools of spheres. In fact, there’s no Ball Pit Association of America at all! Shocking.

Unsurprisingly (for any parent or person older than 14), the ball pits sampled were teeming with human and zoonotic-associated microorganisms. Researchers found that “bacterial colonization was found to be as high as thousands of cells per ball” (gag), exposing children to a lot of opportunity for infections. In case the diapers and bandages swimming in the McDonald’s ball pit didn’t turn you off them, this certainly should.
 

Zom-bacteria are coming

Special edition: Zombie Bacteria vs. The World. Recent research reveals that one type of bacteria, Bacillus subtilis, enters an oligotrophic state when nutrient starved, in which they are not fully dormant but verrrrrry slowly continue to grow and divide. Much like zombies verrrrry slowly continue to walk and eat flesh.

inhauscreative/gettyimages

This research fundamentally changes the way we look at bacteria’s ability to survive. Previously, all bacteria were thought to go into a state of complete dormancy within a protective endospore. It appears that the zombie-like bacteria can awaken more easily from their oligotrophic state than bacteria using an endospore, which may shed light on how bacteria can escape antibiotic treatments. As if superbugs weren’t enough to deal with already.
 

An OTC beer keeps the doctor away

There’s plenty of evidence that a beer or two every now and again is good for your health. But the owner of the Seery Athlone Brewing Company in Addison, Ill., may have taken things too far.

While the reason of its closure just a few months after its grand opening in December 2018 is technically still a mystery, we feel fairly safe in speculating that it had something to do with the fact that brewery owner James Stephen was making his beer at the same location as his main business – a pharmaceutical company engaging in testing of over-the-counter drugs.

In fact, the Food and Drug Administration sent Mr. Stephen a letter in August 2018 warning him that, among numerous other transgressions, fermenting beer literally 10 feet away from where drugs were being tested is a health hazard, for both the beer and the drugs. The FDA ordered the brewery shut down, but the intrepid Mr. Stephen soldiered on, to obviously limited success.

Our advice to Mr. Stephen? Go all in with the pharmaceutical theme. Who wouldn’t want to drink an ibuprofen IPA, ranitidine red ale, loratadine lambic, pseudoephedrine porter, or diphenhydramine doppelbock? You’ll make millions!
 

A seat in the oval office

No, not that seat, and not the Oval Office. This is LOTME, after all, not Politico. The “seat” we’re talking about is a cardiovascular monitoring system, and “oval office” is just a euphemism for a toilet.

A. Sue Weisler/Rochester Institute of Technology

Here’s the deal: A company called Heart Health Intelligence (See? Intelligence is involved, so clearly we’re not talking about politics) has developed a toilet seat equipped “with an integrated electrocardiogram, ballistocardiogram , and photoplethysmogram … capable of clinical-grade measurements of systolic and diastolic blood pressure, stroke volume, and peripheral blood oxygenation.” Wait, ballistocardiogram? That sounds like something from that show House; it sounds too cool to pass up: “Chase, you idiot, why didn’t you do that ballistocardiogram I ordered?”

The idea is to prevent expensive readmissions by keeping track of patients with heart failure after they leave the hospital in a way that fits into their daily routine and ensures adherence.

It would cost about $200,000 to provide 150 heart failure patients with the toilet seats when they left the hospital, the company estimated, but the penalties from the Centers for Medicare & Medicaid Services for readmitting 150 patients come to $500,000 a year. Thus saving money by flushing it down the toilet.

So it looks like we were talking about politics after all. An intelligent toilet seat is like the Oval Office because, in both cases, the buck stops here.

It’s the pits

Physical therapists sometimes use therapeutic ball pits to provide stimulation to pediatric patients with sensory impairments. However, anyone who’s ever been to a fast food joint or a Chuck E. Cheeses in the last 30 years knows that ball pits are not as innocent as they seem – instead of being simply a joyous sunken hole of fun, they are a prime breeding ground for all sorts of bacteria. And adhesive bandages. Why are there always bandages??

andresr/gettyimages

Researchers recently took a deep, disgusting dive into the underworld of clinical ball pits, which do not seem to be regulated by any governing body. There are no clinical guidelines from the Ball Pit Association of America on how or when to clean these cesspools of spheres. In fact, there’s no Ball Pit Association of America at all! Shocking.

Unsurprisingly (for any parent or person older than 14), the ball pits sampled were teeming with human and zoonotic-associated microorganisms. Researchers found that “bacterial colonization was found to be as high as thousands of cells per ball” (gag), exposing children to a lot of opportunity for infections. In case the diapers and bandages swimming in the McDonald’s ball pit didn’t turn you off them, this certainly should.
 

Zom-bacteria are coming

Special edition: Zombie Bacteria vs. The World. Recent research reveals that one type of bacteria, Bacillus subtilis, enters an oligotrophic state when nutrient starved, in which they are not fully dormant but verrrrrry slowly continue to grow and divide. Much like zombies verrrrry slowly continue to walk and eat flesh.

inhauscreative/gettyimages

This research fundamentally changes the way we look at bacteria’s ability to survive. Previously, all bacteria were thought to go into a state of complete dormancy within a protective endospore. It appears that the zombie-like bacteria can awaken more easily from their oligotrophic state than bacteria using an endospore, which may shed light on how bacteria can escape antibiotic treatments. As if superbugs weren’t enough to deal with already.
 

An OTC beer keeps the doctor away

There’s plenty of evidence that a beer or two every now and again is good for your health. But the owner of the Seery Athlone Brewing Company in Addison, Ill., may have taken things too far.

While the reason of its closure just a few months after its grand opening in December 2018 is technically still a mystery, we feel fairly safe in speculating that it had something to do with the fact that brewery owner James Stephen was making his beer at the same location as his main business – a pharmaceutical company engaging in testing of over-the-counter drugs.

In fact, the Food and Drug Administration sent Mr. Stephen a letter in August 2018 warning him that, among numerous other transgressions, fermenting beer literally 10 feet away from where drugs were being tested is a health hazard, for both the beer and the drugs. The FDA ordered the brewery shut down, but the intrepid Mr. Stephen soldiered on, to obviously limited success.

Our advice to Mr. Stephen? Go all in with the pharmaceutical theme. Who wouldn’t want to drink an ibuprofen IPA, ranitidine red ale, loratadine lambic, pseudoephedrine porter, or diphenhydramine doppelbock? You’ll make millions!
 

A seat in the oval office

No, not that seat, and not the Oval Office. This is LOTME, after all, not Politico. The “seat” we’re talking about is a cardiovascular monitoring system, and “oval office” is just a euphemism for a toilet.

A. Sue Weisler/Rochester Institute of Technology

Here’s the deal: A company called Heart Health Intelligence (See? Intelligence is involved, so clearly we’re not talking about politics) has developed a toilet seat equipped “with an integrated electrocardiogram, ballistocardiogram , and photoplethysmogram … capable of clinical-grade measurements of systolic and diastolic blood pressure, stroke volume, and peripheral blood oxygenation.” Wait, ballistocardiogram? That sounds like something from that show House; it sounds too cool to pass up: “Chase, you idiot, why didn’t you do that ballistocardiogram I ordered?”

The idea is to prevent expensive readmissions by keeping track of patients with heart failure after they leave the hospital in a way that fits into their daily routine and ensures adherence.

It would cost about $200,000 to provide 150 heart failure patients with the toilet seats when they left the hospital, the company estimated, but the penalties from the Centers for Medicare & Medicaid Services for readmitting 150 patients come to $500,000 a year. Thus saving money by flushing it down the toilet.

So it looks like we were talking about politics after all. An intelligent toilet seat is like the Oval Office because, in both cases, the buck stops here.

It’s the pits

Physical therapists sometimes use therapeutic ball pits to provide stimulation to pediatric patients with sensory impairments. However, anyone who’s ever been to a fast food joint or a Chuck E. Cheeses in the last 30 years knows that ball pits are not as innocent as they seem – instead of being simply a joyous sunken hole of fun, they are a prime breeding ground for all sorts of bacteria. And adhesive bandages. Why are there always bandages??

andresr/gettyimages

Researchers recently took a deep, disgusting dive into the underworld of clinical ball pits, which do not seem to be regulated by any governing body. There are no clinical guidelines from the Ball Pit Association of America on how or when to clean these cesspools of spheres. In fact, there’s no Ball Pit Association of America at all! Shocking.

Unsurprisingly (for any parent or person older than 14), the ball pits sampled were teeming with human and zoonotic-associated microorganisms. Researchers found that “bacterial colonization was found to be as high as thousands of cells per ball” (gag), exposing children to a lot of opportunity for infections. In case the diapers and bandages swimming in the McDonald’s ball pit didn’t turn you off them, this certainly should.
 

Zom-bacteria are coming

Special edition: Zombie Bacteria vs. The World. Recent research reveals that one type of bacteria, Bacillus subtilis, enters an oligotrophic state when nutrient starved, in which they are not fully dormant but verrrrrry slowly continue to grow and divide. Much like zombies verrrrry slowly continue to walk and eat flesh.

inhauscreative/gettyimages

This research fundamentally changes the way we look at bacteria’s ability to survive. Previously, all bacteria were thought to go into a state of complete dormancy within a protective endospore. It appears that the zombie-like bacteria can awaken more easily from their oligotrophic state than bacteria using an endospore, which may shed light on how bacteria can escape antibiotic treatments. As if superbugs weren’t enough to deal with already.
 

An OTC beer keeps the doctor away

There’s plenty of evidence that a beer or two every now and again is good for your health. But the owner of the Seery Athlone Brewing Company in Addison, Ill., may have taken things too far.

While the reason of its closure just a few months after its grand opening in December 2018 is technically still a mystery, we feel fairly safe in speculating that it had something to do with the fact that brewery owner James Stephen was making his beer at the same location as his main business – a pharmaceutical company engaging in testing of over-the-counter drugs.

In fact, the Food and Drug Administration sent Mr. Stephen a letter in August 2018 warning him that, among numerous other transgressions, fermenting beer literally 10 feet away from where drugs were being tested is a health hazard, for both the beer and the drugs. The FDA ordered the brewery shut down, but the intrepid Mr. Stephen soldiered on, to obviously limited success.

Our advice to Mr. Stephen? Go all in with the pharmaceutical theme. Who wouldn’t want to drink an ibuprofen IPA, ranitidine red ale, loratadine lambic, pseudoephedrine porter, or diphenhydramine doppelbock? You’ll make millions!
 

A seat in the oval office

No, not that seat, and not the Oval Office. This is LOTME, after all, not Politico. The “seat” we’re talking about is a cardiovascular monitoring system, and “oval office” is just a euphemism for a toilet.

A. Sue Weisler/Rochester Institute of Technology

Here’s the deal: A company called Heart Health Intelligence (See? Intelligence is involved, so clearly we’re not talking about politics) has developed a toilet seat equipped “with an integrated electrocardiogram, ballistocardiogram , and photoplethysmogram … capable of clinical-grade measurements of systolic and diastolic blood pressure, stroke volume, and peripheral blood oxygenation.” Wait, ballistocardiogram? That sounds like something from that show House; it sounds too cool to pass up: “Chase, you idiot, why didn’t you do that ballistocardiogram I ordered?”

The idea is to prevent expensive readmissions by keeping track of patients with heart failure after they leave the hospital in a way that fits into their daily routine and ensures adherence.

It would cost about $200,000 to provide 150 heart failure patients with the toilet seats when they left the hospital, the company estimated, but the penalties from the Centers for Medicare & Medicaid Services for readmitting 150 patients come to $500,000 a year. Thus saving money by flushing it down the toilet.

So it looks like we were talking about politics after all. An intelligent toilet seat is like the Oval Office because, in both cases, the buck stops here.

Switching from the sucrose‐formulated recombinant factor VIII replacement therapy rFVIII‐FS (Kogenate) to the rFVIII product BAY 81‐8973 (Kovaltry) resulted in a longer half-life and improved bleeding rates in patients with hemophilia A, according to a recent report.

Juan Eduardo Megías‐Vericat, PharmD, of the Hospital Universitari i Politècnic La Fe, Valencia, Spain, and his colleagues conducted a comparative, cross‐sectional, pharmacokinetic analysis of switching from rFVIII‐FS to BAY 81‐8973 in patients with hemophilia A. The results of the analysis were reported in a letter to the editor published in Haemophilia.

“All the patients of this cohort were switched in a short period of time, while maintaining the same dose and frequency of infusions,” the researchers wrote.

The study included 14 patients who had moderate (n = 3) or severe (n = 11) hemophilia A and received pharmacokinetic-guided prophylaxis with rFVIII. The median weekly doses were 60.6 IU/kg and 61.6 IU/kg for rFVIII‐FS and BAY 81‐8973, respectively.

After analysis, the researchers found that the half-life of BAY 81‐8973 was significantly longer than rFVIII‐FS (median half-life, 16.9 hours vs. 15.4 hours; P = .001), with a median improvement of 3.0 hours (range, 1.5-4.0 hours). No significant differences were seen in any other pharmacokinetic factors.

With respect to bleeding, significant reductions were seen in annualized joint bleeding rate (P = .021), annualized bleeding rate (P = .038), and the number of spontaneous bleeds (P = .028) after the switch to BAY 81-8973.

The researchers acknowledged that the external validity of the study was a key limitation. As a result, Dr. Megías‐Vericat and his colleagues recommended that the findings be interpreted with discretion.

“The results of this study should be validated with an independent and larger cohort of patients, analyzing also the differences between adult and pediatric patients,” they concluded.

The study was partially funded by an unrestricted grant from Bayer. The authors reported having no conflicts of interest.

SOURCE: Megías-Vericat JE et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13733.

Switching from the sucrose‐formulated recombinant factor VIII replacement therapy rFVIII‐FS (Kogenate) to the rFVIII product BAY 81‐8973 (Kovaltry) resulted in a longer half-life and improved bleeding rates in patients with hemophilia A, according to a recent report.

Juan Eduardo Megías‐Vericat, PharmD, of the Hospital Universitari i Politècnic La Fe, Valencia, Spain, and his colleagues conducted a comparative, cross‐sectional, pharmacokinetic analysis of switching from rFVIII‐FS to BAY 81‐8973 in patients with hemophilia A. The results of the analysis were reported in a letter to the editor published in Haemophilia.

“All the patients of this cohort were switched in a short period of time, while maintaining the same dose and frequency of infusions,” the researchers wrote.

The study included 14 patients who had moderate (n = 3) or severe (n = 11) hemophilia A and received pharmacokinetic-guided prophylaxis with rFVIII. The median weekly doses were 60.6 IU/kg and 61.6 IU/kg for rFVIII‐FS and BAY 81‐8973, respectively.

After analysis, the researchers found that the half-life of BAY 81‐8973 was significantly longer than rFVIII‐FS (median half-life, 16.9 hours vs. 15.4 hours; P = .001), with a median improvement of 3.0 hours (range, 1.5-4.0 hours). No significant differences were seen in any other pharmacokinetic factors.

With respect to bleeding, significant reductions were seen in annualized joint bleeding rate (P = .021), annualized bleeding rate (P = .038), and the number of spontaneous bleeds (P = .028) after the switch to BAY 81-8973.

The researchers acknowledged that the external validity of the study was a key limitation. As a result, Dr. Megías‐Vericat and his colleagues recommended that the findings be interpreted with discretion.

“The results of this study should be validated with an independent and larger cohort of patients, analyzing also the differences between adult and pediatric patients,” they concluded.

The study was partially funded by an unrestricted grant from Bayer. The authors reported having no conflicts of interest.

SOURCE: Megías-Vericat JE et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13733.

Switching from the sucrose‐formulated recombinant factor VIII replacement therapy rFVIII‐FS (Kogenate) to the rFVIII product BAY 81‐8973 (Kovaltry) resulted in a longer half-life and improved bleeding rates in patients with hemophilia A, according to a recent report.

Juan Eduardo Megías‐Vericat, PharmD, of the Hospital Universitari i Politècnic La Fe, Valencia, Spain, and his colleagues conducted a comparative, cross‐sectional, pharmacokinetic analysis of switching from rFVIII‐FS to BAY 81‐8973 in patients with hemophilia A. The results of the analysis were reported in a letter to the editor published in Haemophilia.

“All the patients of this cohort were switched in a short period of time, while maintaining the same dose and frequency of infusions,” the researchers wrote.

The study included 14 patients who had moderate (n = 3) or severe (n = 11) hemophilia A and received pharmacokinetic-guided prophylaxis with rFVIII. The median weekly doses were 60.6 IU/kg and 61.6 IU/kg for rFVIII‐FS and BAY 81‐8973, respectively.

After analysis, the researchers found that the half-life of BAY 81‐8973 was significantly longer than rFVIII‐FS (median half-life, 16.9 hours vs. 15.4 hours; P = .001), with a median improvement of 3.0 hours (range, 1.5-4.0 hours). No significant differences were seen in any other pharmacokinetic factors.

With respect to bleeding, significant reductions were seen in annualized joint bleeding rate (P = .021), annualized bleeding rate (P = .038), and the number of spontaneous bleeds (P = .028) after the switch to BAY 81-8973.

The researchers acknowledged that the external validity of the study was a key limitation. As a result, Dr. Megías‐Vericat and his colleagues recommended that the findings be interpreted with discretion.

“The results of this study should be validated with an independent and larger cohort of patients, analyzing also the differences between adult and pediatric patients,” they concluded.

The study was partially funded by an unrestricted grant from Bayer. The authors reported having no conflicts of interest.

SOURCE: Megías-Vericat JE et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13733.

A common phrase you see on inspirational posters is “sing like nobody’s listening, dance like nobody’s watching.”

milindri/Thinkstock

In medicine, it should be “speak as if everyone is recording, behave as if everyone is filming.”

In this day and age, you’d think that would be obvious. Every few hours there’s a viral video of someone getting upset, then losing their temper and saying something most of us would regret. A few years ago it would be a private matter, but today things are rapidly spread over Facebook and Twitter. Even if it’s entirely false, that doesn’t matter. It’s easy for anyone with a smartphone and apps to edit the clip to make it entirely different from what really happened. People go with their first reaction. By the time the facts come out, they’ve moved on and don’t care about the truth.

Occasionally, I get a request to record what I’m saying. In most cases I decline, and never allow myself to be filmed. I do this because anything can be altered, and unless I go to the effort to record it myself, I have no way to prove who’s telling the truth. So it’s easier just to not do it at all.

Unfortunately, this is often taken as “proof” of me trying to hide something. I’m certainly not. Being open and honest with patients is always something I focus on. But the truth of what happened in a 30- to 60-minute visit can be misconstrued in an edited, and possibly altered, sound bite of 5-10 seconds. People who want to do such things have their own motives and aren’t interested in reason or honesty.

Doctors, like everyone else, are susceptible to human emotions and reactions, but a big part of the job is keeping them controlled and hidden when working with patients. It’s the best way to make reasoned decisions and work with someone who’s frightened, angry, or irrational.

If you find yourself losing the battle to stay in control, sometimes it’s good to remember that your words and actions could be being recorded and posted on Facebook in an hour, whether you permitted it or not. Because you don’t want to learn the hard way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A common phrase you see on inspirational posters is “sing like nobody’s listening, dance like nobody’s watching.”

milindri/Thinkstock

In medicine, it should be “speak as if everyone is recording, behave as if everyone is filming.”

In this day and age, you’d think that would be obvious. Every few hours there’s a viral video of someone getting upset, then losing their temper and saying something most of us would regret. A few years ago it would be a private matter, but today things are rapidly spread over Facebook and Twitter. Even if it’s entirely false, that doesn’t matter. It’s easy for anyone with a smartphone and apps to edit the clip to make it entirely different from what really happened. People go with their first reaction. By the time the facts come out, they’ve moved on and don’t care about the truth.

Occasionally, I get a request to record what I’m saying. In most cases I decline, and never allow myself to be filmed. I do this because anything can be altered, and unless I go to the effort to record it myself, I have no way to prove who’s telling the truth. So it’s easier just to not do it at all.

Unfortunately, this is often taken as “proof” of me trying to hide something. I’m certainly not. Being open and honest with patients is always something I focus on. But the truth of what happened in a 30- to 60-minute visit can be misconstrued in an edited, and possibly altered, sound bite of 5-10 seconds. People who want to do such things have their own motives and aren’t interested in reason or honesty.

Doctors, like everyone else, are susceptible to human emotions and reactions, but a big part of the job is keeping them controlled and hidden when working with patients. It’s the best way to make reasoned decisions and work with someone who’s frightened, angry, or irrational.

If you find yourself losing the battle to stay in control, sometimes it’s good to remember that your words and actions could be being recorded and posted on Facebook in an hour, whether you permitted it or not. Because you don’t want to learn the hard way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A common phrase you see on inspirational posters is “sing like nobody’s listening, dance like nobody’s watching.”

milindri/Thinkstock

In medicine, it should be “speak as if everyone is recording, behave as if everyone is filming.”

In this day and age, you’d think that would be obvious. Every few hours there’s a viral video of someone getting upset, then losing their temper and saying something most of us would regret. A few years ago it would be a private matter, but today things are rapidly spread over Facebook and Twitter. Even if it’s entirely false, that doesn’t matter. It’s easy for anyone with a smartphone and apps to edit the clip to make it entirely different from what really happened. People go with their first reaction. By the time the facts come out, they’ve moved on and don’t care about the truth.

Occasionally, I get a request to record what I’m saying. In most cases I decline, and never allow myself to be filmed. I do this because anything can be altered, and unless I go to the effort to record it myself, I have no way to prove who’s telling the truth. So it’s easier just to not do it at all.

Unfortunately, this is often taken as “proof” of me trying to hide something. I’m certainly not. Being open and honest with patients is always something I focus on. But the truth of what happened in a 30- to 60-minute visit can be misconstrued in an edited, and possibly altered, sound bite of 5-10 seconds. People who want to do such things have their own motives and aren’t interested in reason or honesty.

Doctors, like everyone else, are susceptible to human emotions and reactions, but a big part of the job is keeping them controlled and hidden when working with patients. It’s the best way to make reasoned decisions and work with someone who’s frightened, angry, or irrational.

If you find yourself losing the battle to stay in control, sometimes it’s good to remember that your words and actions could be being recorded and posted on Facebook in an hour, whether you permitted it or not. Because you don’t want to learn the hard way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

MIAMI – Hyperglycemia increases intestinal permeability, which facilitates enteric infections and systemic inflammation, reported Christoph Thaiss, PhD.

The findings upend the old idea that intestinal barrier dysfunction leads to diabetes, Dr. Thaiss said during a plenary session at the annual Gut Microbiota for Health World Summit. Multiple mouse models link hyperglycemia to intestinal barrier dysfunction, and hemoglobin A_1C (HbA_1c) levels in humans “highly correlate with the influx of microbial molecules into the intestinal epithelium.”

Researchers often struggle to decide if apparent causes are really confounders or even downstream results (reverse causation). In the metabolic syndrome, patients are known to have increased intestinal permeability – so-called leaky gut – and microbes crossing the gastrointestinal epithelium have been found to cause both gut mucosal infections and chronic systemic inflammation. But because these mechanisms were poorly understood, some experts posited that intestinal barrier dysfunction induced pancreatic beta cell inflammation, insulin resistance, and diabetes.

To take a deeper dive, Dr. Thaiss and his associates at the University of Pennsylvania, Philadelphia started with a mouse model of morbid obesity. The mice had multiple systemic sites with microbial pattern recognition ligands, signifying microbial influx from the gut. They also had genetic signatures indicating a marked disruption of junctions between epithelial cells, compared with healthy controls.

The obese mice also were much more susceptible to enteric infections with Citrobacter rodentium (a Salmonella analog), but obesity itself did not drive this risk, Dr. Thaiss explained. In fact, two different murine models of nonobese type 1 diabetes mellitus showed “leaky” intestinal epithelial adherence junctions, heightened susceptibility to C. rodentium infection, and showed systemic pathogen spread. Ribosomal DNA sequencing showed that these hyperglycemic (diabetic) mice had shifts in their gut microbiomes; however, translocating the altered microbiota to normal mice did not make them more susceptible to enteric infections or systemic inflammation.

Based on these findings, the researchers hypothesized that hyperglycemia itself drove susceptibility to enteric infections. They confirmed this by administering insulin to the mice with type 1 diabetes, which restored intestinal epithelial adherence junctions and stopped the systemic spread of pathogens. In vitro, exposing intestinal epithelial cells to glucose-induced barrier dysfunctions that increased over time and with higher glucose concentrations. RNA sequencing demonstrated that hyperglycemia markedly changed expression of genes that encode proteins that regulate intestinal barrier function. Moreover, hyperglycemic mice lacking the bidirectional glucose transporter GLUT2 showed no intestinal barrier dysfunction and were not susceptible to C. rodentium infection and systemic spread.

Finally, the investigators studied more than 30 clinical measures and microbial products in the systemic circulation of 27 healthy human volunteers. “Of all the variables we measured, HbA_1c showed the strongest correlation with the influx of microbial molecules,” said Dr. Thaiss. Serum HbA_1c correlated highly (P = .008) with levels of toll-like receptor 4, an indicator of systemic pathogens, but not with body mass index (P = .76).

The findings in humans confirm those in mice and indicate that hyperglycemia is a direct cause of intestinal barrier dysfunction and susceptibility to enteric infection, Dr. Thaiss said, adding that the systemic influx of microbial products might explain the wide range of otherwise unrelated inflammatory conditions seen in patients with metabolic syndrome. Future studies of therapies for enteric infection and systemic inflammation might focus on glucose as a modifier of intestinal barrier function.

These findings, reported at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, were also published in Science.

The work was supported by a Boehringer Ingelheim Funds PhD fellowship, the Leona M. and Harry B. Helmsley Charitable Trust, the Adelis Foundation, the Gurwin Family Fund for Scientific Research, the Crown Endowment Fund for Immunological Research, and others. Dr. Thaiss and his coinvestigators reported having no conflicts of interest.

SOURCE: Thaiss CA et al. Science. 2018;359(6382):1376-83.




 

MIAMI – Hyperglycemia increases intestinal permeability, which facilitates enteric infections and systemic inflammation, reported Christoph Thaiss, PhD.

The findings upend the old idea that intestinal barrier dysfunction leads to diabetes, Dr. Thaiss said during a plenary session at the annual Gut Microbiota for Health World Summit. Multiple mouse models link hyperglycemia to intestinal barrier dysfunction, and hemoglobin A_1C (HbA_1c) levels in humans “highly correlate with the influx of microbial molecules into the intestinal epithelium.”

Researchers often struggle to decide if apparent causes are really confounders or even downstream results (reverse causation). In the metabolic syndrome, patients are known to have increased intestinal permeability – so-called leaky gut – and microbes crossing the gastrointestinal epithelium have been found to cause both gut mucosal infections and chronic systemic inflammation. But because these mechanisms were poorly understood, some experts posited that intestinal barrier dysfunction induced pancreatic beta cell inflammation, insulin resistance, and diabetes.

To take a deeper dive, Dr. Thaiss and his associates at the University of Pennsylvania, Philadelphia started with a mouse model of morbid obesity. The mice had multiple systemic sites with microbial pattern recognition ligands, signifying microbial influx from the gut. They also had genetic signatures indicating a marked disruption of junctions between epithelial cells, compared with healthy controls.

The obese mice also were much more susceptible to enteric infections with Citrobacter rodentium (a Salmonella analog), but obesity itself did not drive this risk, Dr. Thaiss explained. In fact, two different murine models of nonobese type 1 diabetes mellitus showed “leaky” intestinal epithelial adherence junctions, heightened susceptibility to C. rodentium infection, and showed systemic pathogen spread. Ribosomal DNA sequencing showed that these hyperglycemic (diabetic) mice had shifts in their gut microbiomes; however, translocating the altered microbiota to normal mice did not make them more susceptible to enteric infections or systemic inflammation.

Based on these findings, the researchers hypothesized that hyperglycemia itself drove susceptibility to enteric infections. They confirmed this by administering insulin to the mice with type 1 diabetes, which restored intestinal epithelial adherence junctions and stopped the systemic spread of pathogens. In vitro, exposing intestinal epithelial cells to glucose-induced barrier dysfunctions that increased over time and with higher glucose concentrations. RNA sequencing demonstrated that hyperglycemia markedly changed expression of genes that encode proteins that regulate intestinal barrier function. Moreover, hyperglycemic mice lacking the bidirectional glucose transporter GLUT2 showed no intestinal barrier dysfunction and were not susceptible to C. rodentium infection and systemic spread.

Finally, the investigators studied more than 30 clinical measures and microbial products in the systemic circulation of 27 healthy human volunteers. “Of all the variables we measured, HbA_1c showed the strongest correlation with the influx of microbial molecules,” said Dr. Thaiss. Serum HbA_1c correlated highly (P = .008) with levels of toll-like receptor 4, an indicator of systemic pathogens, but not with body mass index (P = .76).

The findings in humans confirm those in mice and indicate that hyperglycemia is a direct cause of intestinal barrier dysfunction and susceptibility to enteric infection, Dr. Thaiss said, adding that the systemic influx of microbial products might explain the wide range of otherwise unrelated inflammatory conditions seen in patients with metabolic syndrome. Future studies of therapies for enteric infection and systemic inflammation might focus on glucose as a modifier of intestinal barrier function.

These findings, reported at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, were also published in Science.

The work was supported by a Boehringer Ingelheim Funds PhD fellowship, the Leona M. and Harry B. Helmsley Charitable Trust, the Adelis Foundation, the Gurwin Family Fund for Scientific Research, the Crown Endowment Fund for Immunological Research, and others. Dr. Thaiss and his coinvestigators reported having no conflicts of interest.

SOURCE: Thaiss CA et al. Science. 2018;359(6382):1376-83.




 

MIAMI – Hyperglycemia increases intestinal permeability, which facilitates enteric infections and systemic inflammation, reported Christoph Thaiss, PhD.

The findings upend the old idea that intestinal barrier dysfunction leads to diabetes, Dr. Thaiss said during a plenary session at the annual Gut Microbiota for Health World Summit. Multiple mouse models link hyperglycemia to intestinal barrier dysfunction, and hemoglobin A_1C (HbA_1c) levels in humans “highly correlate with the influx of microbial molecules into the intestinal epithelium.”

Researchers often struggle to decide if apparent causes are really confounders or even downstream results (reverse causation). In the metabolic syndrome, patients are known to have increased intestinal permeability – so-called leaky gut – and microbes crossing the gastrointestinal epithelium have been found to cause both gut mucosal infections and chronic systemic inflammation. But because these mechanisms were poorly understood, some experts posited that intestinal barrier dysfunction induced pancreatic beta cell inflammation, insulin resistance, and diabetes.

To take a deeper dive, Dr. Thaiss and his associates at the University of Pennsylvania, Philadelphia started with a mouse model of morbid obesity. The mice had multiple systemic sites with microbial pattern recognition ligands, signifying microbial influx from the gut. They also had genetic signatures indicating a marked disruption of junctions between epithelial cells, compared with healthy controls.

The obese mice also were much more susceptible to enteric infections with Citrobacter rodentium (a Salmonella analog), but obesity itself did not drive this risk, Dr. Thaiss explained. In fact, two different murine models of nonobese type 1 diabetes mellitus showed “leaky” intestinal epithelial adherence junctions, heightened susceptibility to C. rodentium infection, and showed systemic pathogen spread. Ribosomal DNA sequencing showed that these hyperglycemic (diabetic) mice had shifts in their gut microbiomes; however, translocating the altered microbiota to normal mice did not make them more susceptible to enteric infections or systemic inflammation.

Based on these findings, the researchers hypothesized that hyperglycemia itself drove susceptibility to enteric infections. They confirmed this by administering insulin to the mice with type 1 diabetes, which restored intestinal epithelial adherence junctions and stopped the systemic spread of pathogens. In vitro, exposing intestinal epithelial cells to glucose-induced barrier dysfunctions that increased over time and with higher glucose concentrations. RNA sequencing demonstrated that hyperglycemia markedly changed expression of genes that encode proteins that regulate intestinal barrier function. Moreover, hyperglycemic mice lacking the bidirectional glucose transporter GLUT2 showed no intestinal barrier dysfunction and were not susceptible to C. rodentium infection and systemic spread.

Finally, the investigators studied more than 30 clinical measures and microbial products in the systemic circulation of 27 healthy human volunteers. “Of all the variables we measured, HbA_1c showed the strongest correlation with the influx of microbial molecules,” said Dr. Thaiss. Serum HbA_1c correlated highly (P = .008) with levels of toll-like receptor 4, an indicator of systemic pathogens, but not with body mass index (P = .76).

The findings in humans confirm those in mice and indicate that hyperglycemia is a direct cause of intestinal barrier dysfunction and susceptibility to enteric infection, Dr. Thaiss said, adding that the systemic influx of microbial products might explain the wide range of otherwise unrelated inflammatory conditions seen in patients with metabolic syndrome. Future studies of therapies for enteric infection and systemic inflammation might focus on glucose as a modifier of intestinal barrier function.

These findings, reported at the meeting sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility, were also published in Science.

The work was supported by a Boehringer Ingelheim Funds PhD fellowship, the Leona M. and Harry B. Helmsley Charitable Trust, the Adelis Foundation, the Gurwin Family Fund for Scientific Research, the Crown Endowment Fund for Immunological Research, and others. Dr. Thaiss and his coinvestigators reported having no conflicts of interest.

SOURCE: Thaiss CA et al. Science. 2018;359(6382):1376-83.




 

References

1.    Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A report of The American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 Nov 8. doi: 10.1016/j.jacc.2018.11.003. [Epub ahead of print].
2.    Alenghat FJ, Davis AM. Management of blood cholesterol. JAMA. 2019;321:800-801.
3.    Fanaroff AC, Califf RM, Windecker S, et al. Levels of evidence supporting American College of Cardiology/American Heart Association and European Society of Cardiology Guidelines, 2008-2018. JAMA. 2019;321:1069-1080. [ ]
4.    US Preventive Services Task Force. Cardiovascular disease: risk assessment with nontraditional risk factors. July 2018. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cardiovascular-disease-screening-using-nontraditional-risk-assessment. Accessed March 26, 2019.
5.    American Academy of Family Practitioners. Clinical Practice Guideline: Cholesterol. February 2019. https://www.aafp.org/patient-care/clinical-recommendations/all/cholesterol.html. Accessed March 26, 2019.

References

1.    Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A report of The American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 Nov 8. doi: 10.1016/j.jacc.2018.11.003. [Epub ahead of print].
2.    Alenghat FJ, Davis AM. Management of blood cholesterol. JAMA. 2019;321:800-801.
3.    Fanaroff AC, Califf RM, Windecker S, et al. Levels of evidence supporting American College of Cardiology/American Heart Association and European Society of Cardiology Guidelines, 2008-2018. JAMA. 2019;321:1069-1080. [ ]
4.    US Preventive Services Task Force. Cardiovascular disease: risk assessment with nontraditional risk factors. July 2018. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cardiovascular-disease-screening-using-nontraditional-risk-assessment. Accessed March 26, 2019.
5.    American Academy of Family Practitioners. Clinical Practice Guideline: Cholesterol. February 2019. https://www.aafp.org/patient-care/clinical-recommendations/all/cholesterol.html. Accessed March 26, 2019.

References

1.    Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A report of The American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 Nov 8. doi: 10.1016/j.jacc.2018.11.003. [Epub ahead of print].
2.    Alenghat FJ, Davis AM. Management of blood cholesterol. JAMA. 2019;321:800-801.
3.    Fanaroff AC, Califf RM, Windecker S, et al. Levels of evidence supporting American College of Cardiology/American Heart Association and European Society of Cardiology Guidelines, 2008-2018. JAMA. 2019;321:1069-1080. [ ]
4.    US Preventive Services Task Force. Cardiovascular disease: risk assessment with nontraditional risk factors. July 2018. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/cardiovascular-disease-screening-using-nontraditional-risk-assessment. Accessed March 26, 2019.
5.    American Academy of Family Practitioners. Clinical Practice Guideline: Cholesterol. February 2019. https://www.aafp.org/patient-care/clinical-recommendations/all/cholesterol.html. Accessed March 26, 2019.