Insulin resistance linked with increased cardiovascular risk not kidney risk in diabetes patients: Study

A recent study published in the Journal of Diabetes Care investigated the association between insulin resistance, cardiorenal risk and the effectiveness of finerenone to the management of type 2 diabetes.

This FIDELITY study involved a total of 13,026 patients with type 2 diabetes and examined whether insulin resistance, measured by estimated glucose disposal rate (eGDR), influence the risk of cardiovascular and kidney complications. Furthermore, if the risk affected the effectiveness of finerenone when compared to a placebo was examined.

The results showed that patients with lower eGDR had a significantly higher incidence of cardiovascular events compared to those with higher eGDR, irrespective of treatment that indicates insulin resistance. The incidence rate of cardiovascular events per 100 patient-years for finerenone was 5.18 and for placebo was 6.34 in the lower eGDR group, versus 3.47 for finerenone and 3.76 for placebo in the higher eGDR group.

There was no significant association found between eGDR and kidney outcomes. Also, the study revealed that the efficacy of finerenone in reducing cardiovascular and kidney complications was consistent across patients with different levels of insulin resistance.

The findings underscore the importance of considering insulin resistance as a significant risk factor for cardiovascular events in patients with type 2 diabetes. While insulin resistance was not associated with kidney outcomes in this study, it remains as a crucial factor in assessing overall cardiorenal risk.

The outcomes provide valuable insights into the complex interplay between insulin resistance, cardiovascular risk and medication efficacy in individuals with type 2 diabetes. Understanding these relationships can improve more targeted treatment strategies for patients with this chronic condition.

Source:

Ebert, T., Anker, S. D., Ruilope, L. M., Fioretto, P., Fonseca, V., Umpierrez, G. E., Birkenfeld, A. L., Lawatscheck, R., Scott, C., Rohwedder, K., & Rossing, P. (2023). Outcomes With Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Baseline Insulin Resistance. In Diabetes Care. American Diabetes Association. https://doi.org/10.2337/dc23-1420

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Blood glucose fluctuation linked to in-hospital mortality in acute MI patients, reveals study

China: A recent study published in PLOS One has uncovered a significant association between blood glucose fluctuation and in-hospital mortality among patients experiencing acute myocardial infarction (AMI). The findings of this study provide important insights into managing blood glucose levels in AMI patients, with potential implications for improving outcomes and reducing mortality rates.

The study found a correlation between glycemic variability and in-hospital mortality, particularly among AMI patients with normal blood glucose levels at admission. The findings suggest that early intervention should be implemented to normalize high blood glucose levels at admission to AMI.

Acute myocardial infarction is a fatal disease caused by acute and persistent ischemia and hypoxia of coronary arteries, leading to high morbidity and mortality rates. It is crucial to explore simple biomarkers for assessing the risk of in-hospital mortality in patients with AMI. Therefore, Nan Liang, Department of Cardiology, Xinjiang Armed Police Corps Hospital, Urumqi City, Xinjiang Province, P. R. China, and colleagues aimed to assess the relationship between glycemic variability, glucose fluctuation trajectory, and the risk of in-hospital mortality in acute myocardial infarction patients.

For this purpose, the researchers conducted a retrospective cohort study that included AMI patients from the eICU Collaborative Research Database. In-hospital mortality of AMI patients was the primary endpoint. The three main study variables were blood glucose levels at admission, glycemic variability, and glucose fluctuation trajectory.

Admission blood glucose levels were stratified into normal, intermediate, and high. Glycemic variability was assessed using the coefficient of variation (CV) and divided into four groups based on quartiles: quartile 1: CV≤10; quartile 2: 1030.

In AMI patients, the relationship between blood glucose levels at admission, glycemic variability, glucose fluctuation trajectory, and in-hospital mortality was evaluated using univariate and multivariate Cox regression models. The study included 2590 participants.

The researchers reported the following findings:

  • There was a positive relationship between high blood glucose levels at admission and in-hospital mortality [hazard ratio (HR) = 1.42].
  • The fourth quartile (CV>30) of CV was associated with increased in-hospital mortality (HR = 2.06).
  • The findings indicated that only AMI individuals in the fourth quartile of glycemic variability exhibited an elevated in-hospital mortality among those with normal blood glucose levels at admission (HR = 2.33).
  • Elevated blood glucose level was a risk factor for in-hospital mortality in AMI patients.

In conclusion, the study conducted using data from the eICU collaborative research database highlights the importance of blood glucose fluctuation as a predictor of in-hospital mortality among patients with acute myocardial infarction. The findings underscore the need for careful glycemic management in this population and suggest potential avenues for improving outcomes through targeted interventions.

Reference:

Chen, J., Huang, W., & Liang, N. (2024). Blood glucose fluctuation and in-hospital mortality among patients with acute myocardial infarction: EICU collaborative research database. PLOS ONE, 19(4), e0300323. https://doi.org/10.1371/journal.pone.0300323

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Lower dose of mpox vaccine safe and generates six-week antibody response equivalent to standard regimen

A dose-sparing intradermal mpox vaccination regimen was safe and generated an antibody response equivalent to that induced by the standard regimen at six weeks (two weeks after the second dose), according to findings presented today at the European Society of Clinical Microbiology and Infectious Diseases Global Congress in Barcelona. The results suggest that antibody responses contributed to the effectiveness of dose-sparing mpox vaccine regimens used during the 2022 U.S. outbreak.

The mpox virus has been present in west, central and east Africa for decades, with the first human case identified in 1970. In May 2022, a global mpox outbreak caused by the clade IIb strain of the virus provided the first epidemiologic evidence of community mpox transmission outside of historically affected countries. The Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN, sold as JYNNEOS) vaccine was made available to help contain the outbreak in the United States. The National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID) sponsored a study of dose-sparing strategies to extend the limited vaccine supply.

The mid-stage study enrolled 225 adults aged 18 to 50 years in the United States who had not previously been vaccinated against mpox or smallpox. Participants were randomized to receive either the standard Food and Drug Administration-approved MVA-BN regimen, a regimen containing one-fifth of the standard dose, or one with one-tenth of the standard dose. The standard dose was injected under the skin (subcutaneously), while the dose-sparing regimens were injected between layers of the skin (intradermally). Participants in all study arms received two injections 28 days apart and were monitored for safety and immune response.

Two weeks after the second dose (study day 43), participants who received one-fifth of the standard dose had antibody levels equivalent to those of participants receiving the standard MVA-BN regimen, based on predefined criteria. By day 57, participants who received one-fifth of the standard dose had lower antibody levels than those in the standard regimen arm; the clinical significance of this difference is unknown. Participants who received one-tenth of the standard dose had inferior antibody levels at all measurements. The most reported adverse events were mild, local injection-site reactions. Adverse events were similar across all arms of the trial, and no serious adverse events related to the vaccine were reported.

The authors note that because there are no defined correlates of protection against mpox-immune processes confirmed to prevent disease-these findings cannot predict the efficacy of dose-sparing regimens with certainty. Real-world data from the Centers for Disease Control and Prevention and others have shown similar vaccine effectiveness for the dose-sparing regimen given intradermally and the standard regimen given subcutaneously. A study of the standard MVA-BN regimen in adolescents is ongoing and will report findings later this year.

Reference:

Frey et al. Safety and Immunogenicity of Fractional Doses of Modified Vaccinia Ankara-Bavarian Nordic. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global Congress in Barcelona, Spain. Saturday, April 27, 2024.

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PET/CT technique revolutionizes spinal bone metastases detection in pheochromocytoma and paraganglioma: Study

USA: Gallium-68 (Ga-68) DOTATATE PET/CT should be the modality of choice in pheochromocytoma/paraganglioma (PPGL)–-related spinal bone metastases due to its superior detection rate, a recent study published in European Radiology has shown.

The groundbreaking study has unveiled the diagnostic prowess of advanced imaging modalities in detecting spinal bone metastases associated with pheochromocytoma and paraganglioma. The research represents a significant leap forward in the early identification and management of metastatic disease in these rare neuroendocrine tumors.

“Ga-68 DOTATATE PET/CT appears to be the best approach for detecting spinal bone metastases in patients with certain neuroendocrine tumors,” the researchers stated. Bone metastases destroy and weaken skeletal tissue and predispose cancer patients to acute and chronic skeletal-related events (SREs).

In a study of patients with pheochromocytomas and paragangliomas, the group found the approach was superior to F-18 FDG-PET/CT, MRI of the spine, whole-body MRI, and whole-body CT. The finding is significant regarding efforts to prevent severe complications in these patients.

Bone metastases are frequently observed in patients with solid tumors; observed in up to 71% of metastatic PPGL patients. SREs such as spinal cord compression, bone pain, and fractures not only affect mortality and morbidity rates in these individuals but also increase medical costs. However, there is limited data from head-to-head comparisons among imaging techniques for detecting bone metastases in these patients.

To fill this knowledge gap, Karel Pacak, National Institutes of Health, Bethesda, MD, USA, and colleagues aimed to compare the diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body MRI and CT for detecting PPGL–related spinal bone metastases.

PPGL participants with spinal bone metastases prospectively underwent [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, contrast-enhanced MRI of the neck and thoracic-abdominopelvic regions (MRIWB), MRI of the cervical-thoracolumbar spine (MRIspine), and contrast-enhanced CT of the neck and thoracic-abdominopelvic regions (CTWB) between 2014 and 2020. They calculated per-lesion and per-patient detection rates.

Counting of spinal bone metastases was limited to a maximum of one lesion per vertebrae. A composite of all anatomic and functional imaging served as an imaging comparator. Detection rates between the scans were compared using the McNemar test.

The following were the key findings of the study:

· Forty-three consecutive participants (mean age, 41.7 ± 15.7 years; females, 22) with MRIspine were included who also underwent [68Ga]DOTATATE PET/CT (n = 43), [18F]FDG PET/CT (n = 43), MRIWB (n = 24), and CTWB (n = 33).

· Forty-one of 43 participants were positive for spinal bone metastases, with 382 lesions on the imaging comparator.

· [68Ga]DOTATATE PET/CT demonstrated a per-lesion detection rate of 98.7%, which was superior compared to MRIspine (80.6%), [18F]FDG (72.0%), MRIWB (55.3%), and CTWB (44.8%).

· The per-patient detection rate of [68Ga]DOTATATE PET/CT was 100%, which was higher compared to [18F]FDG PET/CT (90.2%), MRIspine (97.6%), MRIWB (95.7%), and CTWB (81.8%).

In conclusion, [68Ga]DOTATATE PET/CT demonstrated superiority in spinal bone metastase detection compared to [18F]FDG PET/CT, MRIspine, CTWB, and MRIWB indicating that it should be the imaging modality of choice when looking for metastatic spine disease associated with PPGL.

It is more sensitive than the other modalities and is also useful in the detection of primaries, soft tissue metastases, and the treatment planning and response assessment of targeted radionuclide therapy in patients with bone-only metastatic PPGL in whom response evaluation using anatomic imaging is challenging.

“Future studies may include diffusion-weighted and post-contrast images in the MRIspine protocol and determine its performance against [68Ga]DOTATATE PET/CT,” the researchers wrote.

Reference:

Jha, A., Patel, M., Ling, A. et al. Diagnostic performance of [68Ga]DOTATATE PET/CT, [18F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma. Eur Radiol (2024). https://doi.org/10.1007/s00330-024-10652-4

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Higher body mass index linked to slower rates of glaucoma progression: Study

A recent study from Duke University suggest that higher body mass index (BMI) may help slow the progression of glaucoma which is a leading cause of blindness. The key findings were published in the British Journal of Ophthalmology.

The study analyzed data from a total of 2,839 eyes of 1,584 glaucoma patients and provided new insights into how lifestyle factors may influence the rate of retinal nerve fibre layer (RNFL) loss in these individuals. Over a mean follow-up period of 4.7 years, the patients underwent approximately 5.1 spectral-domain optical coherency tomography (SD-OCT) tests and this study looked into the effects of BMI and personal histories of tobacco and alcohol use on glaucoma progression. The results show that while tobacco and alcohol consumption did not significantly impact the progression of the disease, a higher BMI was associated with a markedly slower rate of RNFL loss.

This study found that for each additional unit of BMI, the rate of RNFL thinning lowered by 0.014 micrometers per year where this statistically significant finding suggests a protective effect of higher body weight against glaucoma progression. Also, underweight subjects experienced significantly faster rates of structural loss that highlights potential risks associated with low BMI in glaucoma management.

The lack of significant association between tobacco and alcohol use and the rate of RNFL change was somewhat unexpected, given the well-documented impacts of these factors on other chronic diseases. This observation suggests that the pathways which link these habits to glaucoma progression may differ from those affecting other health conditions. This study opens a new avenue in our understanding of glaucoma management and careful practice that encourage weight gain as a protective strategy should be maintained until further research is conducted.

Glaucoma affects millions worldwide and is often associated with an irreversible loss of vision due to damage to the optic nerve. Current treatment strategies focus primarily on lowering intraocular pressure and this research suggests that managing body weight could also be a consideration in the comprehensive care of glaucoma patients. As these findings add a significance to the mystery of glaucoma progression and further studies will be imperative to understand the mechanisms by which BMI may protect against RNFL loss and to explore potential interactions with other risk factors.

Source:

Youssif, A. A., Onyekaba, N.-A., Naithani, R., Abdelazeem, K., Fathalla, A. M., Abdel‐Rhaman, M. S., Jammal, A. A., & Medeiros, F. A. (2024). Social history and glaucoma progression: the effect of body mass index, tobacco and alcohol consumption on the rates of structural change in patients with glaucoma. In British Journal of Ophthalmology (p. bjo-2023-323186). BMJ. https://doi.org/10.1136/bjo-2023-323186

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Active military service may heighten women’s risk of having low birthweight babies, reveals study

Active military service may heighten a woman’s risk of having a low birthweight baby, suggests a review of the available scientific evidence published online in the journal BMJ Military Health.

The findings highlight the need for more research specifically focused on women in the armed forces, and their reproductive health in particular, conclude the study authors.

Worldwide, increasing numbers of women are on active service in their country’s armed forces. The UK Armed Forces, for example, has set a target of 30% female representation by 2030. And more and more countries are deploying women in combat units, and in other challenging environments, such as submarines, note the study authors.

Mounting evidence suggests that stress experienced during pregnancy is associated with birth complications, such as preterm delivery and low birthweight. And a military career and lifestyle expose service personnel to a wide range of physical, mental, and environmental stressors that could potentially influence pregnancy outcomes.

The study authors therefore wanted to explore the potential impact of active military service on the risks of preterm labour and birth, low birthweight, and stillbirth.

They scoured research databases for relevant studies, and included 21 that met all the eligibility criteria in their analysis. The studies, which involved 650,628 women serving in the US military, were all published between 1979 and 2023.

Ten of the studies included a comparison group-usually the wives of active service personnel. By way of a proxy for those that didn’t include a comparator, the study authors drew on national data from the US National Vital Statistics for any given year.

Analysis of the study results indicated no heightened risk of preterm birth among pregnant active service women. But there were significant methodological differences; most studies had a moderate to high risk of bias; and several included only small sample sizes, caution the study authors.

There was no observed association between branch of military service and increased risk of preterm birth, although again this should be interpreted cautiously as 5 studies included mixed service samples and the study design varied considerably, say the study authors.

There was no clear evidence for an increased risk of stillbirth among women on active military service, either.

But nearly two thirds (62.5%) of the studies concluded that women on active service may be at heightened risk of having a low birthweight baby, including one study with the lowest risk of bias. And 4 of the 5 studies that included a comparison group also indicated an increased risk of low birthweight.

Seven of the 8 studies reporting on low birthweight were carried out in single-service settings. Both of those from the US Air Force suggested a higher prevalence of low birthweight babies born to active duty military personnel.

But some 53% and 38% of the studies reporting on preterm birth and low birthweight, respectively, didn’t have a matched comparison group and relied on a proxy drawn from national statistical data.

This introduces a risk of systematic error as the baseline characteristics of the two groups are inherently different, caution the study authors.

Women on active military service will also be medically screened before any tours of duty and will have fewer co existing conditions, while national data will include high risk and multiple pregnancies, they explain.

Only observational studies were included in the review, and the data collection methods and/or adjustment for influential factors varied, acknowledge the study authors. Only 8 studies reported on smoking status despite a high prevalence of smoking in the military and the fact that smoking is associated with several health issues before and during pregnancy.

The data also focused exclusively on the US military, which although unsurprising given that it is one of the largest in the world, this does limit the generalisability of the findings to armed forces personnel elsewhere, highlight the study authors.

Nevertheless, they conclude: This review highlights a need for more female-specific research in armed forces, beyond the US military setting, to inform military maternity pathways and policies in ways that safeguard mothers and their babies while enhancing military readiness.”

Reference:

Morris KAL, McKee MEffect of active-duty military service on neonatal birth outcomes: a systematic reviewBMJ Mil Health Published Online First: 22 April 2024. doi: 10.1136/military-2023-002634.

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Injection and energy-based treatments tied to highest response rates among patients with striae: Study

Canada: In dermatology, the quest for effective treatments for striae, commonly known as stretch marks, has been a perennial pursuit. A systematic review published in the latest edition of Dermatologic Surgery has shed light on the diverse treatment modalities and their outcomes, offering valuable insights for patients and practitioners.

The review found varied treatment options for striae, likely indicating a lack of effective treatments due to the diversity in striae subtypes. The researchers stressed that improved outcomes in striae management may be achieved with additional research on factors predicting treatment response.

For patients grappling with the physical and psychological impact of striae, the review offers a beacon of hope by providing a comprehensive overview of available treatment options and their respective efficacy profiles. “Understanding that viable treatment options available can empower patients to take proactive steps towards addressing their concerns,” the researchers wrote.

Striae are fine lines on the body following rapid skin stretching (i.e., following puberty, pregnancy, weight change). Ilya Mukovozov, Toronto Dermatology Centre, North York, Ontario, Canada, and colleagues aimed to assess the current literature on treatment outcomes associated with striae.

For this purpose, the researchers performed a systematic search on Embase, MEDLINE, and PubMed with no publication date or language restrictions. It included all articles with original data and treatment outcomes.

The researchers reported the following findings:

· One hundred fifty-one studies on the treatment of striae met inclusion criteria (83% female, mean age at diagnosis = 30.2), and 4,806 treatment outcomes of striae were described.

· Energy-based devices were the most reported modality (56%), followed by topicals (19%) and combinations (12%).

· The highest rates of complete response were injection-based devices for striae distensae (7%), CO2 lasers for striae alba (4%), and platelet-rich plasma injections for striae rubra (31%).

The findings revealed numerous treatment options for striae, and no treatment is consistently effective for each subtype.

“Future studies should aim to measure the degree of treatment response by subtype and patient characteristics,” the researchers wrote.

In conclusion, the systematic review serves as a seminal contribution to the field of dermatology, offering a roadmap for navigating the complex landscape of striae treatment. By synthesizing existing evidence and delineating key areas for future research, it paves the way for advancements that promise to alleviate the burden of striae for individuals worldwide.

Reference:

Zhu, Catherine Keying*; Mija, Lorena Alexandra†; Koulmi, Kaouthar BSc*; Barankin, Benjamin MD, FRCPC, FAAD‡; Mukovozov, Ilya MD, PhD, FRCPC, DABD, FAAD‡. A Systematic Review on Treatment Outcomes of Striae. Dermatologic Surgery ():10.1097/DSS.0000000000004151, March 7, 2024. | DOI: 10.1097/DSS.0000000000004151

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Highest dexmedetomidine dose best for AFONI in patients undergoing oromaxillofacial surgeries: Study

Recently published study aimed to evaluate the efficacy of different doses of dexmedetomidine (DEX) for awake fibreoptic nasotracheal intubation (AFONI) in patients undergoing oromaxillofacial and oral malignancy surgeries. This randomised, double‑blind study included 90 patients aged 18–60 years and with American Society of Anesthesiologists physical status I/II. The patients were divided into three groups receiving different doses of DEX: 0.5 µg/kg DEX, 1 µg/kg DEX, and 1.5 µg/kg DEX. The primary outcome measure was the airway obstruction score, and secondary outcome measures included intubation scores, 5‑point fibreoptic intubation comfort score, and sedation assessment using the Ramsay sedation score (RSS).

The study found that the airway obstruction score, vocal movement, coughing, limb movement, and fibreoptic intubation comfort score did not differ significantly between the three DEX groups. However, the mean RSS was significantly greater in the Group receiving the highest dose of DEX (1.5 µg/kg DEX) compared to the other two groups. The study concluded that all three doses of DEX, when combined with topical spray and airway block, provided comparable airway obstruction scores and favorable conditions for AFONI.

The study revealed that 1.5 µg/kg DEX provided superior intubation conditions compared to lower doses, although not statistically significant. It was found that high doses of DEX resulted in favorable intubation conditions but increased the chances of airway obstruction and desaturation. Additionally, high doses of DEX led to a significant decrease in heart rate, systolic and diastolic blood pressure, and respiratory rate compared to lower doses.

In conclusion, the study demonstrated that graded doses of DEX provided comparable airway obstruction and intubation scores but had differing effects on sedation, hemodynamic variables, and the risk of airway obstruction. The authors suggested that further large-scale trials are necessary to evaluate the role of DEX as a single agent for conscious sedation in patients with anticipated difficult airways.

Key Points –

– The study evaluated the efficacy of different doses of dexmedetomidine (DEX) for awake fibreoptic nasotracheal intubation (AFONI) in patients undergoing oromaxillofacial and oral malignancy surgeries.

– Three groups of patients received different doses of DEX (0.5 µg/kg DEX, 1 µg/kg DEX, and 1.5 µg/kg DEX), and the primary outcome measure was the airway obstruction score, with secondary measures including intubation scores, fibreoptic intubation comfort score, and sedation assessment using the Ramsay sedation score (RSS).

– The study found that all three doses of DEX provided comparable airway obstruction scores and favorable conditions for AFONI, but the highest dose of DEX (1.5 µg/kg) resulted in superior intubation conditions, higher sedation levels, decreased hemodynamic variables, and increased risk of airway obstruction and desaturation.

Reference –

Arora, Sanya; Govardhane, Balasaheb T.; Srinivasan, Vanchula; Karandikar, Gayatri. Evaluation of different doses of dexmedetomidine for awake fibreoptic nasotracheal intubation in patients undergoing oromaxillofacial and oral malignancy surgeries: A randomised, double-blind study. Indian Journal of Anaesthesia 68(5):p 447-453, May 2024. | DOI: 10.4103/ija.ija_1004_23.

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FDA approves immunotherapy drug combo for non-muscle invasive bladder cancer

The U.S. Food and Drug Administration (FDA) has approved the immunotherapy-boosting drug N-803, which is marketed under the brand name Anktiva, to be used in combination with the immunotherapy Bacillus Calmette-Guerin (BCG) for the treatment of patients with BCG-unresponsive non–muscle-invasive bladder cancer.

The decision was based on results of the QUILT 3.032 clinical trial, which was led by Dr. Karim Chamie, associate professor urology at the David Geffen School of Medicine at UCLA and a researcher at the UCLA Health Jonsson Comprehensive Cancer Center.

Findings from the phase 2/3 trial were presented at the 2022 American Society of Clinical Oncology annual meeting and published in NEJM Evidence. Chamie, who was the principal investigator for the trial, reported that this combination treatment resulted in longer overall survival and was more effective and safer than other treatments available for BCG-unresponsive non–muscle-invasive bladder cancer.

“The FDA approval of N-803 heralds a new era in the management of BCG-unresponsive non–muscle-invasive bladder cancer,” said Chamie. “By leveraging the body’s immune system to mount a targeted attack against cancer cells, N-803 offers a compelling alternative for patients who have exhausted conventional treatment options. What makes this really remarkable, is its ability to spare patients from invasive procedures, like a cystectomy, significantly enhancing the quality of life for patients.”

Roughly, 80% of new bladder cancer diagnoses are non-muscle invasive bladder cancer, which is found in the tissue that lines the inner surface of the bladder and hasn’t spread into the bladder wall. Patients with this type of cancer usually undergo surgery to remove the tumor followed by treatment with a bacteria-based immunotherapy called BCG, which is placed directly into the bladder. The treatment triggers an inflammatory response in the bladder that helps prevent cancer recurrence.

However, even with this treatment, the cancer can come back and many patients don’t respond well to further BCG treatment, leaving limited treatment options. For some patients, they may require surgery to remove the bladder entirely, facing significant risks like bleeding, kidney issues and infections, especially for older patients.

The QUILT 3.032 study evaluated the addition of the investigational drug N-803 to the treatment regimen to see if it can help boost the effectiveness of BCG.

Developed by ImmunityBio, N-803 is a protein the helps activate the body’s immune cells to fight cancer by promoting the proliferation and activation of natural killer cells and CD8+ T cells, which are crucial components of the body’s immune response against cancer cells.

Investigators enrolled 171 patients (81% male with a median age of 72) with non–muscle-invasive bladder cancer who didn’t respond well to BCG treatment from clinical locations across the country. The UCLA Health team enrolled 28 patients, making UCLA the top enrolling center.

The participants were then divided into two cohorts: one with carcinoma in situ and the other with papillary disease.

For the carcinoma in situ cohort, 71% of patients had a complete response ranging over 47 months, meaning they no longer had evidence of the disease or had any symptoms of the cancer. The response lasted for a median duration of 26.6 months. At 24 months, a cystectomy, surgical removal of the bladder, was avoided in over 90% of patients. All of the participants the study (100%) were still alive after a two-year follow-up.

For the papillary cohort, 57% remained disease-free after 12 months, and 48% after 24 months. Additionally, 94% of the patients in this group also avoided cystectomy.

“The treatment was particularly effective for carcinoma in situ patients, with a high complete response rate and long-lasting response,” Chamie said. “Even for papillary disease, the treatment showed good results in keeping the cancer from coming back and avoiding the need for cystectomy. Overall, the treatment was safer and more effective than other options available for BCG-unresponsive non–muscle-invasive bladder cancer.”

Reference:

Authors: Karim Chamie, Sam S. Chang, Eugene Kramolowsky, Mark L. Gonzalgo, Piyush Kumar Agarwal, Jeffrey C. Bassett, Marc Bjurlin, and Patrick Soon-Shiong, IL-15 Superagonist NAI in BCG-Unresponsive Non–Muscle-Invasive Bladder Cancer, NEJM Evidence, DOI: 10.1056/EVIDoa2200167.

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FDA approves over the counter naloxone hydrochloride spray for opioid overdose

The US Food and Drug Administration (FDA) has approved over-the-counter naloxone hydrochloride nasal spray for emergency treatment of opioid overdose.

Amneal’s Naloxone HCI Nasal Spray, manufactured in the U.S., is a generic equivalent to OTC NARCAN® HCI Nasal Spray, a medication that is widely used to help treat drug overdose from opioids, including heroin, fentanyl and prescription opioid medications.

“With today’s launch, Amneal is proud to help address this public health emergency by providing naloxone nasal spray at an affordable price and without a prescription. Our business is deeply rooted in a commitment to helping others. By enhancing access to naloxone nasal spray, we hope to get this affordable emergency treatment into the hands of even more people who could potentially save countless families and communities from further heartache and loss,” said Chirag and Chintu Patel, Co-Chief Executive Officers.

More than two-thirds of all drug overdose fatalities in 2022 involved illicit, synthetic opioids like fentanyl, which is the culprit in more deaths under age 50 than any other cause, including heart disease, cancer, homicide, suicide, and other accidents. According to the Centers for Disease Control and Prevention, in about 46% of overdose deaths, another person is present and has the potential to intervene.

Amneal Naloxone HCI Nasal Spray is now available. According to IQVIA®, U.S. annual commercial sales for NARCAN® Naloxone HCl Nasal Spray 4mg for the 12 months ended February 2024 were $266 million. In addition, there are significant volumes of the product acquired directly by U.S. states and municipalities. NARCAN® is a registered trademark of Emergent Operations Ireland Limited.

About Naloxone Nasal Spray

Naloxone Hydrochloride (Naloxone HCI) Nasal Spray is designed to rapidly reverse the effects of a life-threatening opioid emergency by binding to opioid receptors and reversing or blocking the effects of opioids. It can restore normal breathing within two to three minutes in a person whose breath has slowed, or even stopped, as a result of an overdose from opioids-including heroin, fentanyl and prescription opioid medications. Naloxone HCI Nasal Spray contains the same active ingredient and dose as NARCAN® Naloxone HCI Nasal Spray, 4 mg. It is easy to carry and can be safely used even if opioids are not present.

When using this product some people may experience symptoms when they wake up, such as shaking, sweating, nausea, or feeling angry. This is to be expected.

About the Opioid Crisis

The opioid epidemic was declared a national public health emergency in 2017 and has continually been renewed by the U.S. Secretary of Health and Human Services.4,5 Ending the epidemic is a top strategic priority of the U.S. government and Congress.6 Since 2000, about one million people in the U.S. have died of drug overdoses, the majority of which were due to opioids. Drivers of this crisis include the misuse of prescription pain medication and the unwitting use of drugs laced with fentanyl-which is 50 times more potent than heroin and 100 times more potent than morphine. In 2022, roughly twice as many people died in the U.S. from opioid-related overdoses than from motor vehicle crashes.

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