Tisotumab Vedotin Shows Superior Efficacy in Recurrent Cervical Cancer Treatment, reveals research

Researchers in a recent study have found that tisotumab vedotin, a novel therapy, significantly enhances survival outcomes in patients with recurrent or metastatic cervical cancer who have progressed after initial treatments. This study was published in The New England Journal Of Medicine. Ignace Vergote and colleagues conducted a phase 3, multinational trial to assess the efficacy of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. The study aimed to compare its effectiveness against standard chemotherapy options, offering new hope for patients facing limited treatment alternatives.

The trial enrolled 502 patients who were randomly assigned to receive either tisotumab vedotin monotherapy or a choice of chemotherapy agents (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary endpoint was overall survival, with secondary endpoints including progression-free survival and objective response rate.

The study’s findings were as follows:

  • Patients treated with tisotumab vedotin had a median overall survival of 11.5 months, compared to 9.5 months in the chemotherapy group—a 30% reduction in the risk of death (HR 0.70, 95% CI 0.54-0.89, P=0.004).

  • Progression-free survival was also significantly longer with tisotumab vedotin (4.2 months vs. 2.9 months, HR 0.67, 95% CI 0.54-0.82, P<0.001).

  • The confirmed objective response rate was 17.8% with tisotumab vedotin versus 5.2% with chemotherapy (OR 4.0, 95% CI 2.1-7.6, P<0.001).

  • Adverse events were common in both groups, occurring in over 98% of patients, with grade 3 or greater events reported in 52.0% of the tisotumab vedotin group and 62.3% of the chemotherapy group.

  • Approximately 14.8% of patients discontinued tisotumab vedotin due to treatment-related toxic effects.

In conclusion, the study highlights the superior efficacy of tisotumab vedotin over standard chemotherapy in treating recurrent cervical cancer. The findings underscore its potential as a valuable treatment option in later lines of therapy, offering improved survival outcomes and a higher objective response rate.

Reference:

Vergote, I., González-Martín, A., Fujiwara, K., Kalbacher, E., Bagaméri, A., Ghamande, S., Lee, J.-Y., Banerjee, S., Maluf, F. C., Lorusso, D., Yonemori, K., Van Nieuwenhuysen, E., Manso, L., Woelber, L., Westermann, A., Covens, A., Hasegawa, K., Kim, B.-G., Raimondo, M., … Slomovitz, B. M. (2024). Tisotumab vedotin as second- or third-line therapy for recurrent cervical cancer. The New England Journal of Medicine, 391(1), 44–55. https://doi.org/10.1056/nejmoa2313811

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FDA approves first oral dissolvable contraceptive pill

The US Food and Drug Administration has approved a mouth dissolving hormonal birth control pill for people who have trouble swallowing.

The approval is  based  on positive results from a study involving 743 women ages 18 to 45 who received the tablets for up to 6 28-day cycles. At the end of the 6 cycles, 5 of the 583 women had on-treatment pregnancies within 3,565 treatment cycles.

Contraceptive pills are hormonal treatment commonly used to prevent pregnancy. Further they have other beneficial applications in managing endometriosis, polycystic ovary syndrome, menstrual symptoms, irregular menstrual cycles, and premenstrual dysphoric disorder (PMDD). Many of these conditions can be debilitating with significant quality of life implications for affected individuals. Hormonal contraceptives may have either 1 or a combination of estrogen and progestin and are available as oral medications, patches, injections, and intrauterine devices.

The FDA  has approved Femlyv (norethindrone acetate and ethinyl estradiol), the first orally disintegrating tablet approved for the prevention of pregnancy. Earlier Norethindrone acetate and ethinyl estradiol main ingredients in Femlyv, had been approved in U.S. for the prevention of pregnancy as a swallowable tablet since 1968.

“Femlyv is the first FDA approved dissolvable birth control pill, designed for individuals who have trouble swallowing their medication,” said Janet Maynard, M.D., M.H.S., director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research. “There are many variables that might cause someone to have difficulty swallowing. This drug provides another treatment option and expands access to this form of contraception for individuals who may have experienced those challenges.”

The most common adverse reactions to Femlyv are headache, vaginal candidiasis, nausea, menstrual cramps, breast tenderness, bacterial vaginitis, abnormal cervical smear, acne, mood swings, and weight gain. See full prescribing information for additional information on the safety and effectiveness of Femlyv.

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Frozen shoulder could be early indicator of Parkinson’s disease: Study

A recent study published in the Clinical Epidemiology journal suggests that frozen shoulder characterized by stiffness and pain in the shoulder joint, may be an early preclinical symptom of Parkinson’s disease (PD). This study examined the risk of developing PD after a frozen shoulder diagnosis and assessed whether this condition could be a manifestation of parkinsonism that precedes the clinical recognition of PD.

The study utilized data from the Danish population-based medical registries by focusing on individuals over 40 years, who were diagnosed with frozen shoulder for the first time between 1995 and 2016. The study selected a cohort from the general population matched by age and sex for comparison. To address the potential detection bias and verify the specificity of the frozen shoulder diagnosis, a sensitivity analysis was performed using a similar patients group diagnosed with back pain.

The study included a total of 37,041 individuals with frozen shoulder with 3,70,410 general population comparators and 1,11,101 individuals to compare for back pain. The primary outcome measured was the incidence of PD. Over a follow-up period of up to 22 years, the cumulative incidence of PD was 1.51% in the frozen shoulder cohort when compared to 1.03% in the general population cohort and 1.32% in the back pain cohort.

When comparing the group with frozen shoulder to the general population, the adjusted hazard ratios (HRs) revealed a significantly increased risk of PD. Within the first year of follow-up, the HR was 1.94 which indicated nearly double the risk of PD development for the individuals with frozen shoulder. Over the entire follow-up period of 22 years, the HR remained elevated close to 1.45. This indicates that individuals with frozen shoulder have a 45% higher risk of PD development when compared to the general population.

The frozen shoulder cohort was compared to the back pain cohort and found the adjusted HRs were 0.89 at 0 to1 years and 1.01 over the entire follow-up period. These findings suggest no significant difference in risk of PD between the frozen shoulder and back pain cohorts which highlighted the importance of the general population as a more suitable group for comparison.

The study found that patients with frozen shoulder have an elevated risk of developing PD when compared to the general population, although the absolute risks remained relatively low. The findings suggest that frozen shoulder could sometimes represent an early manifestation of PD. These findings unveil the potential of using frozen shoulder as a screening tool for early PD detection. Clinicians could implement earlier monitoring and intervention strategies by identifying individuals at higher risk, this could potentially improve the patient outcomes and quality of life.

Source:

Gadgaard, N., Veres, K., Henderson, V., & Pedersen, A. (2024). Frozen Shoulder and the Risk of Parkinson’s Disease: A Danish Registry-Based Cohort Study. In Clinical Epidemiology: Vol. Volume 16 (pp. 447–459). Informa UK Limited. https://doi.org/10.2147/clep.s463571

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Ultrasound and mammography scores over AI for Early Breast Cancer Detection in Dense Breasts, Study suggests

South Korea: Using a combination of mammography and supplemental ultrasound (US) provides superior outcomes compared to relying solely on artificial intelligence (AI)-enhanced mammography assessment for screening women with dense breasts, according to a recent study.

The study, published in the Radiology Journal, found that although AI enhanced the specificity of mammography interpretation, the combination of mammography and supplemental ultrasound identified more early breast cancers that were node-negative and not detectable by AI-enhanced mammography alone.

AI aids radiologists in interpreting screening mammography but cannot completely overcome its inherent low sensitivity in women with dense breasts,” the researchers wrote.

The effectiveness of AI compared to supplemental ultrasound for screening women with dense breasts remains uncertain. Previous studies indicate that AI systems can assist radiologists in interpreting images. However, some research suggests that AI, like human readers with mammography interpretation, may face challenges in detecting malignant lesions in dense breast tissue.

Against the above background, Jung Min Chang, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea, and colleagues aimed to compare the performance of mammography alone, mammography with AI, and mammography plus supplemental US for screening women with dense breasts, and to examine the characteristics of the detected cancers.

The study enrolled 5,707 asymptomatic women with an average age of 52.4 years, all aged 40 and above. Between January 2017 and December 2018, these women underwent mammography along with supplemental whole-breast handheld ultrasound at a primary healthcare center.

During the study, five breast radiologists performed sequential readings for mammography alone, and mammography assisted by an AI system. Additionally, a dedicated breast radiologist reviewed the mammography marks either independently or with AI assistance to verify lesion identification.

The reference standard consisted of histologic examination and 1-year follow-up data. The study compared the cancer detection rate (CDR) per 1000 screening examinations, as well as sensitivity, specificity, and abnormal interpretation rate (AIR), across mammography alone, mammography with AI, and mammography plus the US.

The researchers reported the following findings:

  • Among 5707 asymptomatic women (mean age, 52.4 years ± 7.9), 33 had cancer (median lesion size, 0.7 cm).
  • Mammography with AI had higher specificity (95.3%) and lower AIR (5.0%) than mammography alone (94.3% and 6.0%, respectively).
  • Mammography plus US had a higher CDR (5.6 versus 3.5 per 1000 examinations) and sensitivity (97.0% versus 60.6%) but lower specificity (77.6% versus 95.3%) and higher AIR (22.9% vs 5.0%) than mammography with AI.
  • Supplemental US alone helped detect 12 cancers, mostly stage 0 and I (92%, 11 of 12).

“Supplemental screening ultrasound revealed additional early breast cancers that were node-negative and not detected by mammography and artificial intelligence in women with dense breasts, albeit with an increase in false-positive findings,” the researchers concluded.

Reference:

https://doi.org/10.1148/radiol.233391

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Modified Mini Open-TLIF as effective as MIS-TLIF for lumbar degenerative disease: study

Shengwen Li et al conducted a study to compare the clinical and radiological outcomes of modified mini-open transforaminal lumbar interbody fusion (mMO-TLIF) via posterior midline incision for “targeted limited dissection” versus minimal invasive transforaminal lumbar interbody fusion (MIS-TLIF) via Wiltse approach in lumbar degenerative diseases.

The study has been published in ‘Indian journal of orthopedics.’

A total of 60 consecutive patients in single centre were enrolled, including 30 patients who were treated with mMO-TLIF via posterior midline incision and 30 treated with MIS-TLIF through the Wiltse approach. Perioperative parameters were recorded. The questionnaires of Oswestry Disability Index (ODI) and Visual Analogue Score (VAS) were conducted before the operation and after the operation (3 days, 1 week, and 2 years). CT and MRI radiological outcomes were evaluated before the operation and at a 2-year follow-up.

Key findings of the study were:

• There were no significant differences in the general data, gender, age, and BMI between the two groups.

• All patients were successfully operated without intraoperative complications.

• There were significant differences between the two groups in the operation time (p<0.001) and intraoperative bleeding (p<0.05).

• There was no difference in ODI and VAS scores between groups pre- and post-operatively, but they were both significantly improved compared to those before the operation (p<0.01).

• At a 2-year follow-up, the paraspinal muscle atrophy and fat infiltration were increased comparing to pre-operation, but the difference was also not statistically significant (p>0.05).

• In addition, both the two groups’ fusion rates were more than 90% at a 2-year follow-up, however, no difference was detected between the two groups.

The authors concluded that – ‘The mMO-TLIF via the posterior midline incision for “targeted limited dissection” and MIS-TLIF via the Wiltse approach achieve similar clinical and radiological satisfaction for lumbar degenerative disease. The mMO-TLIF is beneficial to tissue exposure, operation time, and intraoperative bleeding.’

Further reading:

Comparison of mMO TLIF via Midline Incision Versus MIS TLIF via Wiltse Approach in Lumbar Degenerative Disease

Shengwen Li et al

Indian Journal of Orthopaedics

https://doi.org/10.1007/s43465-024-01150-2

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Rheumatoid Arthritis genes associated with reduced risk of colorectal cancer development, suggests study

A recent study published in the Journal of Cellular and Molecular Medicine highlighted the complex relationship between rheumatoid arthritis (RA) and cancer. Despite the ongoing debate about whether RA increases the risk of malignancy, this research suggests that RA might actually reduce the risk of certain malignancy like colorectal cancer.

The study utilized Mendelian randomization (MR) analysis to investigate the potential causal relationship between RA and various cancers. The research employed a multi-faceted investigation to explore the overall relationship between RA and cancer (referred to as “pan-cancer” analysis). The results found a negative correlation between RA and pan-cancer (p = 0.008) which suggests the role of RA which might actually lower the overall risk of cancer development. An intermediate MR analysis was set out to understand how immune-mediated inflammation influences cancer risk. The autoimmune traits were identified as the main mediating variable which indicated the heightened activity of immune system in RA patients and its protective role against cancer development.

Further validation from a large-scale meta-analysis compared the standardized incidence rate (SIR) of malignancy in RA patients against the general population. This analysis confirmed that RA patients had a reduced likelihood of developing colorectal cancer with an SIR of 0.69 (95% CI 0.53–0.85). This meant that RA patients were 31% less likely to develop colorectal cancer when compared to the general population.

The study performed a detailed pan-cancer analysis of genes associated with RA which were identified through the MR analysis. This was to uncover the genetic mechanisms behind the observed protective effect, where one gene stood out. IL6R showed the highest correlation with immune cells in colorectal cancer. High expression of RA-related genes, the IL6R, was negatively correlated with colon adenocarcinoma.

IL6R is known for its role in the immune response regulation where this study suggests that IL6R and other RA-related genes might enhance the ability of immune system to target and destroy cancer cells in the colon. This study provides strong evidence that RA is associated with a reduced risk of colorectal cancer and the protective effect is primarily driven by immune-mediated inflammation where IL6R plays a crucial role. These findings open new opportunities for understanding the underlying interplay between autoimmune diseases and cancer which could lead to novel therapeutic strategies.

Source:

Li, Q., Zhou, L., Xia, D., & Wang, J. (2024). Rheumatoid arthritis reduces the risk of colorectal cancer through immune inflammation mediation. In Journal of Cellular and Molecular Medicine (Vol. 28, Issue 13). Wiley. https://doi.org/10.1111/jcmm.18515

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Increasing cardiac ketones may help heart failure in mouse study

Increasing ketone supply to the heart in mice with heart failure with preserved ejection fraction (HFpEF) allowed their hearts to utilize more ketones and produce more energy, according to preliminary research presented today at the American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2024. The meeting is in Chicago, July 22–25, 2024, and offers the latest research on innovations and discovery in cardiovascular science.

Heart failure with preserved ejection fraction, a common type of heart failure, occurs when there are signs and symptoms of heart failure with a high left ventricle filling pressure despite normal or a near-normal left ventricle ejection fraction of 50% or higher. Heart failure with reduced ejection fraction is when the heart’s pumping power is 40% or less. A normal ejection fraction reading is between 50 to 70%. Heart failure with reduced ejection fraction (HFrEF) is well-studied and has established management plans and therapeutic strategies; in contrast, there is no current evidence-based treatment for HFpEF.

Healthy hearts require a high rate of adenosine triphosphate (ATP) production (provides the energy to drive and support the heart) to maintain their continuous pumping action. This energy comes from a balanced use of glucose and fats to support the heart’s contractile function.

“Ketones are a special energy resource,” said study author Qiuyu (Violet) Sun, B.Sc., a Ph.D. candidate at the University of Alberta in Canada. “Humans normally rely on carbohydrates and fat for energy. However, when blood glucose levels fall, such as after prolonged fasting or strenuous exercise, it poses a risk to our brain, which depends on glucose and cannot utilize fats for energy. To address this, our body has a built-in mechanism to produce this special energy substrate called ketones.”

“This process is known as ketogenesis and involves breaking down fats from fat storage. The liver then converts these fats into ketone bodies, which enter the bloodstream to fuel the brain,” Sun explained. “Ketones can convert the chemical energy in the form of ATP to improve the heart’s pumping ability in a continuous fashion.”

According to the researchers, relying on fatty acids to produce ATP could be problematic. Fatty acids are a less efficient fuel source compared to glucose because fats require more oxygen to produce the same amount of ATP as glucose.

In this study, researchers assessed mice hearts’ metabolism and found that hearts with HFpEF reconstructed their metabolic profiles. Specifically, the researchers found in HFpEF hearts, ketone use was impaired, as well was also an impaired glucose oxidation rate coupled with an increase in fatty acid oxidation. These two changes balance each other, leading to overall preserved energy production.

When HFpEF hearts were given more ketones, this resulted in an increase in overall ATP production coming from ketones and glucose oxidation to ATP from 15% to 28% with preserved pumping ability. So, increasing ketone supply to the heart in HFpEF mice led to higher ATP production.

“This is crucial because this increase in ketone use by the heart did not cause any interference with glucose or fat use. In other words, ketones were not competing with glucose or fats as the energy source. As such, elevated ketone oxidation does not further aggravate the disrupted metabolic profile of the heart in HFpEF,” Sun said.

According to the American Heart Association’s 2024 Heart Disease and Stroke Statistics, an estimated 56.2 million people were living with heart failure across 204 countries globally in 2019. However, this estimate likely underrepresents the true rate of heart failure because of data and diagnostic gaps in low-resource regions and countries.

“The prevalence of heart failure with preserved ejection fraction is rising, driven by an aging population and increasing obesity rates. Unfortunately, there is still a lack of clinically effective treatment for this condition,” Sun said. “We hope our study can help us better understand this condition. Identifying key proteins involved in cardiac energy metabolism could potentially lead to identification of druggable targets for future development of medications to treat HFpEF.”

Sun said the next steps are to investigate the precise role of ketone use by the heart in HFpEF and to assess whether increasing the ketone supply to the heart could potentially optimize heart energy production and lead to improved cardiac function.

The AHA/ACC/HFSA 2022 joint guideline for the management of heart failure calls for increased focus on preventing heart failure in people who are showing early signs of “pre-heart failure,” and updated treatment strategies for people with symptomatic heart failure to include SGLT-2 inhibitor (SGLT2i) medicines. SGLT-2 inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with Type 2 diabetes.

Study background:

  • In a lab setting, two groups of mice were used. The first experimental group of mice received a 60% high-fat diet and L-NAME (an inhibitor of nitric oxide synthesis) every day for 6 weeks to induce HFpEF. The second control group (HFpEF was not induced) were fed a low-fat diet and regular drinking water.
  • The mouse hearts were removed and treated with two different levels of β-hydroxybutyrate and studied for how quickly the hearts used the major energy sources, such as glucose, fatty acids and ketones.

Study limitations were that it focused on the metabolic phenotype of HFpEF. However, there are different subgroups of HFpEF that possess varied clinical presentation, such as the fibrotic type or the diastolic dysfunction phenotypes of HFpEF. Both subgroups of HFpEF are of equal importance and should be investigated further. Additionally, because mice have different physiology and metabolic profiles than humans, future research should better characterize cardiac energy metabolism in HFpEF using experimental models that more closely align and translate to humans.

Reference:

Increasing cardiac ketones may help heart failure in mouse study, American Heart Association, Meeting: American Heart Association’s Basic Cardiovascular Sciences Scientific Sessions 2024.

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Conflicting health advice from agencies drives confusion, study finds, but doctors remain most trusted

Distrust of health experts and credulity towards misinformation can kill. For example, during the COVID-19 crisis, high-profile health experts received death threats while misinformation went viral on social media. And already long before the pandemic, easily preventable but potentially serious diseases had been making a comeback around the world due to vaccine hesitancy—often powered by conspiracy theories.

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Unplanned pregnancies among active service women likely curb US military readiness, research suggests

Unplanned pregnancies among active service women may be curbing overall US military readiness for action and compromising its Women, Peace and Security objectives, suggests research published online in the journal BMJ Military Health.

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Southeastern states have highest unintentional gun death rates, study finds

There’s more than a 10-fold difference in the rates of unintentional gun deaths across US states, with such incidents claiming more than 12,000 lives between 2001 and 2021, finds research published online in the journal Injury Prevention.

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