3D elastography displays better performance in differentiating benign and malignant breast lesions

Ultrasound imaging is an alternative option for breast cancer detection, especially for women with dense breasts. However, using hand-held transducers makes screening dependent on the operator and time-consuming, leading to increased costs. Automated breast volume scanners (ABVSs) were introduced to address this issue. ABVSs use a large linear transducer to acquire ultrasound data and reconstruct 3-D images of the breast, which can be visualized in multiple planes.

In their recent study, Gijs A.G.M. Hendriks and colleagues concluded that three-dimensional strain imaging was successfully implemented on a clinically used ABVS to obtain, visualize and analyze in vivo strain images in three dimensions. Results showed significantly increased maximal principal strain ratios in malignant lesions compared to benign lesions.

This study was published in Ultrasound in Medicine and Biology.

Studies show that adding 2-D quasi-static elastography to B-mode ultrasound improves malignant lesion detection specificity. Malignant lesions are typically stiffer than benign lesions. However, this method has user dependency issues, making it unsuitable for breast screening. To overcome this, researchers implemented quasi-static elastography in an ABVS, a 3-D ultrasound system that is operator-independent and useful for screening women with dense breasts. The present study aimed to determine if 3-D quasi-static elastography in a clinically used ABVS can differentiate between benign and malignant breast lesions.

Volumetric breast ultrasound radiofrequency data sets from 82 patients were collected before and after automated transducer lifting for breast examinations. Lesions were marked, and strain was calculated using a custom algorithm. Two strain ratios were calculated for each lesion based on axial and maximal principal strain.

The study results are:

  • Forty-four lesions were detected, including 9 carcinomas, 23 cysts and 12 other benign lesions.
  • There was a significant difference between malignant and benign using maximal principal strain ratios.
  • The axial strain ratio did not reveal a significant difference between benign and malignant lesions.

Concluding further, they said that our study results revealed that maximal principal strain ratios are increased in malignant lesions compared to benign lesions.

This research is supported by Siemens Healthineers and the Dutch Technology Foundation, which is partly funded by the Ministry of Economic Affairs, they acknowledged.

Reference:

Hendriks GAGM, et al. Automated 3-D Ultrasound Elastography of the Breast: An In Vivo Validation Study. Ultrasound Med Biol. 2023 Dec 15:S0301-5629(23)00367-8. doi: 10.1016/j.ultrasmedbio.2023.11.006. Epub ahead of print. PMID: 38103946.

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Cholesterol-lowering therapy could help prevent and treat serrated-type colorectal tumours

USA: A recent preclinical study from researchers at Weill Cornell Medicine points to the possibility of using cholesterol-lowering drugs to prevent or treat hard-to-detect colorectal pre-cancerous lesions known as serrated polyps, and the aggressive tumours that develop from them. 

According to the study, published in Nature Communications, such tumors depend heavily on the ramped-up production of cholesterol. 

In the study, the researchers analyzed mice that develop serrated polyps and tumours, detailing the chain of molecular events in these tissues that leads to increased cholesterol production.

They confirmed their findings in analyses of human serrated polyps and tumours, and showed in mouse models that replicate the human cancer that blocking cholesterol production prevented the progression of these types of intestinal tumors.

“Serrated-type polyps and tumors currently are not treated differently from other colorectal neoplasias, but as our work shows, they have this specific metabolic vulnerability that can be targeted,” said study co-senior author Dr. Jorge Moscat, a Homer T. Hirst III Professor of Oncology in Pathology, Vice-Chair for Cell and Cancer Pathobiology in the Department of Pathology and Laboratory Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

The other co-senior author is Dr. Maria Diaz-Meco, also a Homer T. Hirst III Professor of Oncology in Pathology and a member of the Meyer Cancer Center at Weill Cornell Medicine. The study’s first author is Dr. Yu Muta, a postdoctoral associate in the Moscat/Diaz-Meco laboratories.

Cholesterol is generally considered a pro-growth molecule, being a building block for cell membranes and having other growth-supporting functions. Prior studies have linked high blood cholesterol levels to various cancers, including colorectal cancers. However, it hasn’t been clear that lowering cholesterol, for example with common statin drugs, can prevent colorectal cancers.

“Trials of statins to prevent colorectal cancer have had conflicting results,” Dr. Diaz-Meco said. “Our findings suggest that this is because targeting cholesterol has a preventive but selective effect only against polyps and tumors of this serrated type.”

Serrated polyps are so-called because of their sawtooth appearance under a microscope. They are flatter than ordinary colorectal polyps and can often be missed during colonoscopies. Yet the tumors into which they develop, which account for roughly 15 to 30 percent of colorectal cancers, contain many “metaplastic” cells that are particularly invasive and resistant to treatments.

Several years ago, the Moscat/Diaz-Meco team linked serrated polyps and tumors to low levels of two enzymes known as aPKCs. They showed that mice engineered to lack these aPKC enzymes in their gut linings reliably form serrated polyps and then aggressive tumors.

In the new study, the scientists found that in serrated-type tumors in these mice, and even in intestinal tissue poised to develop these types of cancerous lesions, cholesterol synthesis was strikingly upregulated, suggesting that cholesterol may be an early driver of tumor development.

The researchers revealed how the absence of aPKC enzymes, especially in metaplastic tumor cells, unleashes the activation of a transcription factor called SREBP2, which switches on cholesterol production. Tests on colorectal polyp and tumor samples from human patients dovetailed with the mouse findings. They found, for example, that only serrated-type tumors had low aPKC levels concomitant with the accumulation of SREBP2, a driver and a marker of upregulated cholesterol biosynthesis in the serrated cancer cells.

Lastly, the researchers tested a combination of two cholesterol synthesis-blocking drugs, including the widely used atorvastatin. The treatment, delivered when the low-aPKC mice were still quite young, significantly lowered the rate at which both serrated polyps and tumors later formed—and the serrated-type tumors that did form were less aggressive than those normally arising in the untreated mice.

The results indicate that targeting cholesterol could be a viable strategy for treating and preventing serrated-type colorectal tumors. The Moscat and Diaz-Meco labs are now hoping to set up an initial clinical trial of a cholesterol-lowering intervention in patients from whom serrated colorectal polyps have been removed.

“Currently when these polyps are detected early with colonoscopy, they are removed and patients have to hope that they don’t come back,” Dr. Moscat said. “In the future, we hope to have a more active method to prevent this very aggressive form of cancer before it is fully developed and more difficult to treat.”

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Pitolisant effectively reduces daytime sleepiness among patients of sleep apnea

A recent study published in the CHEST Journal unveiled promising long-term effects of Pitolisant in curbing excessive daytime sleepiness. Even in patients adhering to the standard continuous positive airway pressure (CPAP) therapy, daytime drowsiness can persist, posing a significant challenge to effective obstructive sleep apnea (OSA) management.

Initial outcomes of two 12-week randomized controlled trials (HAROSA 1 and HAROSA 2) demonstrated the efficacy of Pitolisant in reducing daytime sleepiness, with one trial focusing on CPAP-compliant patients and the other on those resistant or intolerant to CPAP. 

The subsequent open-label cohort study provided a resounding affirmative. Adults who participated in the initial trials underwent both Pitolisant and placebo arms and were offered Pitolisant for an additional 40 weeks (from week 13 onwards). The primary measure of success was the change in the Epworth Sleepiness Score (ESS) over the course of 52 weeks.

The results found the pooled mean difference in ESS from baseline to one year was -8.0 [-8.3, -7.5], indicating a significant reduction in daytime sleepiness. Importantly, this effect was consistent across patients using CPAP and those who were not.

In addition to its efficacy, the safety profile of Pitolisant over the year-long study was encouraging. The overall occurrence of treatment-emergent adverse events (TEAE) was 35.1%, with only 2.0% deemed serious. Special interest TEAE, including cardiovascular parameters, did not raise significant concerns.

This study suggests that Pitolisant not only tackles daytime sleepiness but does so sustainably over an extended period. Further exploration and validation are anticipated to solidify the role of Pitolisant in enhancing the quality of life for those navigating the challenges of OSA.

Source:

Pépin, J.-L., Attali, V., Caussé, C., Verbraecken, J., Hedner, J., Lecomte, I., Tamisier, R., Lévy, P., Lehert, P., & Dauvilliers, Y. (2023). Long-term efficacy and safety of pitolisant for residual sleepiness due to Obstructive Sleep Apnea. In CHEST. Elsevier BV. https://doi.org/10.1016/j.chest.2023.11.017

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Higher BMI associated with higher prevalence of thin-cap fibroatheroma in Younger T2D Patients with CAD

Japan: Masahiro Katamine et and colleagues, in a recent study, said that higher BMI is linked to a higher prevalence of TCFA in younger type 2 diabetes (T2D) patients with a history of coronary artery disease (CAD), especially those who have HbA1c ≥7.0%.

This study was published in Nutrition Metabolism and Cardiovascular Diseases.

The relationship between BMI and coronary plaque characteristics in younger T2D patients with CAD is yet to be explored.

One hundred thirty-eight younger T2D patients (<65 yrs) with CAD underwent OCT (optical coherence tomography) imaging of the culprit lesion. Patients were divided into higher BMI (n=68) and lower BMI (n=70) groups according to the median BMI (25.9 kg/m2.

Key findings from this investigation are:

  • The high BMI group had a higher prevalence of thin-cap fibroatheroma (TCFA) (35.3 vs. 17.1%) than the lower BMI group.
  • The prevalence of TCFA was higher in patients with higher BMI compared to lower BMI among patients with haemoglobin A1c (HbA1c) ≥7.0% with an odds ratio of 5.40, although a significant difference was not observed among patients with HbA1c <7.0% with OR 0.89.

Researchers from Kitasato University School of Medicine concluding further said, “Our study highlighted that Higher BMI in younger diabetes patients with coronary artery disease is linked to vulnerable coronary plaques. In patients with HbA1c ≥7.0%, higher BMI is associated with a higher prevalence of thin-cap fibroatheromas. However, in patients with HbA1c <7.0%, higher BMI is not associated with a higher prevalence of thin-cap fibroatheromas.”

Reference:

Katamine, M. et al. Body mass index and characteristics of coronary plaque in younger patients with type 2 diabetes. Nutrition Metabolism and Cardiovascular Diseases. https://doi.org/10.1016/j.numecd.2023.12.009

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Tirzepatide may reduce CVD Risk in Non-Diabetic Overweight Patients

The outcomes from the SURMOUNT-1 phase 3 trial found tirzepatide to effectively manage the long-term risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with obesity or overweight but with no diabetes. The findings were published in the Journal of Diabetes, Obesity and Metabolism.

The study assessed the efficacy and safety of tirzepatide in adults with a body mass index (BMI) of ≥30 or ≥27 kg/m² and at least one weight-related complication, excluding diabetes. Participants were randomly assigned to receive tirzepatide at varying doses (5/10/15 mg) or a placebo. Over 72 weeks, cardiometabolic variables were scrutinized and 10-year ASCVD risk scores were calculated using the American College of Cardiology/American Heart Association risk engine.

The tirzepatide-treated groups exhibited reductions in cardiometabolic variables throughout the study duration. In the 2461 participants without a history of ASCVD, the baseline median risk score, ranging from 1.5% to 1.6%, showed no significant differences. The relative change in ASCVD risk from baseline to week 72 was remarkably greater for the tirzepatide cohort (-23.5% to -16.4%) compared to the placebo group (12.7%; P < 0.001). This trend was found true for participants with intermediate-to-high baseline risk by showing a significantly greater relative change (P < 0.05) and underlining the potential impact of tirzepatide in this subgroup.

Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD in individuals with obesity or overweight but without diabetes. These findings deepen our understanding of the potential of tirzepatide and also helps in addressing cardiovascular risks in a population facing the challenges of excess weight.

Reference:

Hankosky, E. R., Wang, H., Neff, L. M., Kan, H., Wang, F., Ahmad, N. N., Griffin, R., Stefanski, A., & Garvey, W. T. (2023). Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT‐1 post hoc analysis. In Diabetes, Obesity and Metabolism (Vol. 26, Issue 1, pp. 319–328). Wiley. https://doi.org/10.1111/dom.15318

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Weight loss with anti-obesity medications improve survival in people with knee or hip osteoarthritis: Study

China: A population-based study revealed that the slow-to-moderate, but not fast, rate of weight loss induced by antiobesity medications is linked with lower all-cause mortality in patients with obesity or overweight and knee or hip osteoarthritis (OA). The findings were published online in Arthritis & Rheumatology on December 6, 2023.

“For people overweight or with obesity who also have knee or hip osteoarthritis, a slow-to-moderate-but not fast-rate of weight loss caused by anti-obesity medications may lower their risk of premature death,” the researchers wrote.

The current guidelines recommend weight loss for overweight/obese patients with knee or hip osteoarthritis; however, there is a lack of data on the relation of weight loss to death among patients with OA. Chao Zeng, Central South University, Changsha, China, and colleagues aimed to examine the relation of the rate of weight loss induced by antiobesity medications over one year to all-cause mortality among patients with overweight or obesity and knee or hip OA.

For this purpose, the researchers identified people with obesity or overweight and hip or knee OA using the IQVIA Medical Research Database. They emulated analyses of a hypothetical target trial to evaluate the effect of slow-to-moderate (2%–10%) or fast (≥10%) weight loss induced by the initiation of antiobesity medications within one year on all-cause mortality and secondary outcomes over a follow-up of five years. 

Among 6,524 participants with knee or hip osteoarthritis who were taking orlistat, sibutramine, or rimonabant, the 5-year death rate was 5.3%, 4.0%, and 5.4% for the “weight gain/stable”, “slow-to-moderate weight loss,” and “fast weight loss” groups, respectively. Compared with the “weight gain/stable” group,” the risk of death was 28% lower for the “slow-to-moderate weight loss” group and only 1% lower for the “fast weight loss” arm.

“A slow-to-moderate rate of weight loss induced by anti-obesity medications may lower the risk of death in overweight/obese people with knee/hip osteoarthritis”, said first author Jie Wei, PhD, of Xiangya Hospital, Central South University, in China.

Reference:

Jie Wei, David Hunter, Nancy E. Lane, Jing Wu, Chao Zeng, Guanghua Lei, Yuqing Zhang, Weight Loss Induced by Antiobesity Medications and All-Cause Mortality Among Patients With Knee or Hip Osteoarthritis,https://doi.org/10.1002/art.42754.

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More than 4 hours of daily smartphone use associated with health risks for adolescents

In a new study of more than 50,000 Korean adolescents, those who used a smartphone for more than 4 hours per day had higher rates of adverse mental health and substance use. Jin-Hwa Moon and Jong Ho Cha of Hanyang University Medical Center, Korea, and colleagues present these findings in the open-access journal PLOS ONE on December 6, 2023.

Prior research has shown that smartphone use among adolescents has increased in recent years, and that this usage may be associated with higher risk of adverse health-such as psychiatric disorders, sleep issues, eye-related problems, and musculoskeletal disorders. However, growing evidence suggests that at least some daily internet usage may be associated with better physical and mental health for adolescents.

To deepen understanding of the relationship between adolescents’ use of smartphones and health, Moon, Cha and colleagues analyzed data on more than 50,000 adolescent participants in the ongoing Korea Youth Risk Behavior Web-based Survey collected in 2017 and in 2020. The data included the approximate number of daily hours each participant spent on a smartphone as well as various health measures. The statistical analysis employed propensity score matching to help account for other factors that could be linked to health outcomes, such as age, sex, and socioeconomic status.

The researchers found that in 2020, the percentage of adolescents in the study who used a smartphone more than 2 hours per day was 85.7 percent-up from 64.3 percent in 2017. Adolescents who used a smartphone for more than 4 hours per day had higher rates of stress, thoughts of suicide, and substance use than those with usage below 4 hours per day. However, adolescents that used a smartphone 1-2 hours per day encountered fewer problems than adolescents who did not use a smartphone at all.

The authors note that this study does not confirm a causal relationship between smartphone use and adverse health outcomes. Nonetheless, the findings could help inform usage guidelines for adolescents-especially if daily usage continues to rise.

The authors add: “This research shows the impact of using smart devices for more than 4 hours a day on adolescent health.”

Reference:

Jong Ho Cha,Young-Jin Choi,Soorack Ryu,Jin-Hwa Moon, Association between smartphone usage and health outcomes of adolescents: A propensity analysis using the Korea youth risk behavior survey, https://doi.org/10.1371/journal.pone.0294553. 

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Study finds no Direct Association Between Cholesterol Intake and Chronic Kidney Disease Risk

A recent investigation exploring the link between cholesterol intake and the risk of chronic kidney disease (CKD) has yielded intriguing insights, suggesting a nuanced relationship between dietary cholesterol and CKD risk. This study was published in the journal of Nutrition Metabolism and Cardiovascular Diseases by Haekyung Lee and colleagues.

The study, utilizing data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2019-2021 and the Korean Genome and Epidemiology Study (KoGES), aimed to examine the potential association between cholesterol intake and CKD risk. Cholesterol intake was assessed through a 24-hour recall food frequency questionnaire, and participants were categorized based on their cholesterol intake levels.

Results from the KNHANES revealed a modest association between higher cholesterol intake and increased serum levels of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol. However, despite this link between cholesterol intake and altered serum cholesterol levels, the study did not find a significant association between cholesterol intake and the prevalence of CKD in the KNHANES dataset, regardless of participants having a history of hypercholesterolemia.

In the KoGES dataset, which included a median follow-up of 11.4 years, researchers found that cholesterol intake was not significantly associated with the incidence of CKD. This held true for individuals both with and without hypercholesterolemia. Egg consumption, often a source of dietary cholesterol, also showed no significant association with the risk of incident CKD.

The study’s findings challenge the conventional notion of a direct correlation between cholesterol intake and CKD risk. Despite observing an association between cholesterol intake and altered serum cholesterol levels, researchers did not find a direct link between dietary cholesterol and the prevalence or incidence of CKD. These results suggest that solely reducing cholesterol intake may not suffice in preventing CKD development.

The study’s outcomes signal the need for a more comprehensive understanding of the multifaceted factors contributing to CKD risk. While dyslipidemia remains a known risk factor for CKD, this study suggests that focusing solely on dietary cholesterol intake might not effectively mitigate CKD risk. Further research is warranted to explore additional dietary, lifestyle, and physiological factors contributing to CKD development.

Reference:

Lee, H., Park, J., Kwon, S. H., Jeon, J. S., Noh, H., & Kim, H. Dietary cholesterol intake is not associated with the development of chronic kidney disease: results from two Korean cohort studies. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD,2023. https://doi.org/10.1016/j.numecd.2023.12.011

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Modify Phase IV CT protocol: CDSCO Panel Tells Alkem on Amoxicillin, Clavulanate Oral Suspension

New Delhi: The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the drug major Alkem Pharmaceutical to modify the Phase IV clinical trial protocol of the fixed-dose combination (FDC) drug Amoxicillin plus Clavulanate Potassium oral suspension in accordance with the Inclusion criteria, dose of the Potassium Clavulanate, sites of study.

This came after the firm presented the Phase IV clinical trial protocol before the committee, in light of the condition mentioned in permission in Form CT-23 dated 10.09.2021.

In line with the inclusion criteria, the expert panel suggested that inclusion criteria should be changed for Community-acquired bacterial pneumonia to include microbiology confirmatory tests.

Furthermore, the committee stated that participants should be enrolled in thousands, and North Indian sites should be included to represent pan-Indian representation.

In addition, the committee noted that the dose of Potassium Clavulanate should be corrected.

Amoxicillin/clavulanic acid is a combination of penicillin-type antibiotics used to treat a wide variety of bacterial infections. It works by stopping the growth of bacteria. This antibiotic treats only bacterial infections.
Amoxicillin belongs to the group of medicines known as penicillin antibiotics. Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin-binding proteins. Penicillin-binding proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin-binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action.
It is used to treat bacterial infections, such as chest infections (including pneumonia) and dental abscesses. It can also be used together with other antibiotics and medicines to treat stomach ulcers. It’s often prescribed for children, to treat ear infections and chest infections.
Clavulanate potassium (the potassium salt of clavulanic acid) is a β-lactamase inhibitor that is added to amoxicillin to prevent inactivation by bacterial enzymes. β-Lactamase inhibitors (clavulanate, sulbactam, tazobactam) irreversibly bind to β-lactamase.
At the recent SEC meeting for Antimicrobial and Antiviral held on 29th November 2023, the expert panel reviewed the Phase IV clinical trial protocol of FDC Amoxicillin plus Clavulanate Potassium Oral Suspension.
After detailed deliberation, the committee recommended the following modification in the Phase IV clinical trial Protocol:
1. As it is presented as a phase IV clinical study, participants should be enrolled in thousands.
2. Inclusion criteria should be changed for Community-acquired bacterial pneumonia to include microbiology confirmatory tests.
3. Dose of the Potassium Clavulanate should be corrected.
4. North Indian sites should be included to represent pan-Indian representation.

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Submit Justification and Rational: CDSCO Panel tells Pfizer on protocol amendment proposal for Palbociclib

New Delhi: In response to the proposal presented by the drug major Pfizer for the protocol amendment, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has recommended the firm to submit the justification and rationale for the proposed amendment of the anti-cancer drug Palbociclib.

This came after the firm presented Protocol Amendment 7.0 dated 31 May 2023, Protocol no. A5481092.
Palbociclib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells.
Palbociclib is an oral medicine that is used to treat specific types of breast cancer in adults. It is used in combination with other cancer treatments, either aromatase inhibitor or fulvestrant depending on clinical factors.
At the recent SEC meeting for Oncology and Hematology held on the 29th and 30th of November 2023, the expert panel reviewed the proposal presented by the drug major Pfizer for the protocol Amendment of the anti-cancer drug (Palbociclib).
After detailed deliberation, the committee recommended that the justification and rationale for the proposed amendment need to be submitted for further review by the committee.

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