Rare case of Giant Cell Tumor as Cause of Loose Bodies in Knee Joint– A Report

Ravi Mittal et al reported the case of an unusual cause of loose body in the knee joint of a 35-year-old male who reported for follow-up 3 years after the surgical management of giant cell tumor (GCT) of the distal femur. The case report has been published in ‘Journal of Orthopaedic Case Reports.’

Loose bodies in the knee joint are relatively common, and when freely mobile (unstable), they are prone to get entrapped between the articular surfaces causing intermittent joint locking, limitation of motion, pain, intra-articular effusion, and erosion of articular cartilage. The common causes of loose bodies in the knee joint taking into account the disease frequency include transchondral fractures, synovial chondromatosis, osteochondritis dissecans, and meniscal injury. Osteoarthritis is a common cause of loose bodies in the old age.

Although GCT commonly involves the subchondral bone intra-articular extension of GCT remains exceptional, even in cases with pathologic fracture, extended curettage and void filling with bone graft or acrylic cement is the standard treatment and is associated with a local recurrence rate of 10–20%.

The patient had symptoms of loose bodies in the joint without any complaint specific to the operative site. Imaging revealed loose bodies within the joint which were removed arthroscopically. Histopathology showed the loose bodies as GCT. The patient had relief of symptoms after removal and the patient has no evidence of recurrence at the primary site or in the knee joint.

The authors concluded – “GCTs should be considered a cause of loose bodies in the joint when there is a neighbouring bone affected by GCT and all such loose bodies removed should undergo histopathological examination.”

The authors opined – “Loose bodies in the knee joint are relatively common. Neoplastic growths from synovium have been reported to have presentations mimicking loose bodies or meniscus tears and even neoplastic growths of the neighbouring bones should be included in the differentials and all such loose bodies should undergo histopathology.”

Further reading:

Giant Cell Tumor as a Rare Cause of Loose Bodies in the Knee Joint – A

Case Report

Ravi Mittal et al

Journal of Orthopaedic Case Reports 2024 September:14(9): Page 70-73

DOI: https://doi.org/10.13107/jocr.2024.v14.i09.4734

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Omega-3 PUFA supplementation fails to improve symptoms of Adolescent Depression: Study

Researchers have found that while omega-3 polyunsaturated fatty acid (PUFA) supplementation might just modestly be associated with smaller effects on self-reported depression symptoms in adolescents, the evidence is very uncertain. A recent study was conducted by Susan C. and colleagues published in Cochrane Database Systematic Reviews.

Adolescent depression has become an increasingly alarming public health issue, with a rise of more than 25% during the COVID-19 pandemic. The problem is compounded by the unavailability of accessible mental health services. Omega-3 PUFA, with its established anti-inflammatory effects and modulatory action on neurotransmission, has been advocated for adults experiencing depression; however, its efficacy and safety in younger populations to treat depression remain less explored and thus warranted this comprehensive synthesis of existing evidence.

This review enrolled five RCTs in patients aged 19 or younger diagnosed with depression and had 228 participants. Comparators utilized were placebo, wait-list controls, no treatment, or standard care. Trials ranged from 10–16 weeks, and the median was 12 weeks. Followed were self-reported depression symptoms, clinical remission of depression, attrition rates, adverse effects, and compliance. GRADE methodology was utilized to assess the degree of certainty in the evidence.

The key findings of the study were as follows:

Impact on Depression Symptoms:

  • Omega-3 PUFA supplementation may reduce self-reported symptoms, but the evidence is very uncertain (SMD: -0.34, 95% CI: -0.85 to 0.17; 185 participants).

Depression Remission:

  • No significant difference in remission rates was observed between omega-3 PUFA and placebo (50% vs. 48%, OR: 1.11, 95% CI: 0.45 to 2.75; 127 participants).

Attrition and Compliance:

  • Attrition rates were comparable in both arms (18% vs. 19%; OR: 0.94, 95% CI: 0.46 to 1.90; 228 participants).

Side Effects:

  • No side effects serious in nature were observed. Mild ones included muscle cramps (13/27 in omega-3 group and 6/29 in the placebo group), increased frequency of defecation (1/29 in the omega-3 group), and sporadic cases of rash in skin and abnormal behavior in the placebo arm.

This systematic review highlights the uncertain efficacy of omega-3 PUFA supplementation in reducing symptoms of depression or reaching remission among children and adolescents. Although the intervention seems safe, it confers no significant benefits compared with placebo. Future rigorous studies are needed to draw conclusive findings and give clinicians working with adolescent depression some concrete direction.

Reference:

Campisi SC, Zasowski C, Shah S, Bradley-Ridout G, Szatmari P, Korczak D. Omega‐3 fatty acid supplementation for depression in children and adolescents. Cochrane Database Syst Rev. 2021 Jun 7;2021(6):CD014803. doi: 10.1002/14651858.CD014803. PMCID: PMC8183339.

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FDA Approves First Acellular Tissue Engineered Vessel to Treat Vascular Trauma in Extremities

The U.S. Food and Drug Administration approved Symvess, the first acellular tissue engineered vessel indicated for use in adults as a vascular conduit for extremity arterial injury when urgent revascularization (restoration of blood flow) is needed to avoid imminent limb loss, and autologous vein graft is not feasible.

Vascular trauma occurs when a blood vessel is injured such as a rupture of an artery in the extremities, which can lead to serious, life-threatening complications such as hemorrhage or blood clotting. When damage to an artery in the extremity occurs, urgent surgical repair is needed to restore normal blood flow. The current standard of care for patients with extremity vascular injuries can include procedures such as autologous vein grafting (surgical repair using the patient’s own blood vessels) or implantation of a synthetic graft. These treatments are not suitable or available for every patient.

“Today’s approval provides an important additional treatment option for individuals with vascular trauma, produced using advanced tissue engineering technology,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “The FDA remains committed to facilitating the development of innovative products that offer potentially life-saving benefits for patients with severe injuries.”

Symvess is a sterile, acellular tissue engineered vessel composed of human extracellular matrix (ECM) proteins typically found in human blood vessels. It is manufactured using a tissue engineering process utilizing human vascular smooth muscle cells derived from human aortic tissue. Symvess is a one-time, single-use product surgically implanted to replace a patient’s damaged blood vessel after a traumatic injury to the extremity.

“Currently available treatment options are limited for vascular trauma, which can lead to severe and potentially life-threatening complications,” said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. “Today’s decision to approve a new therapeutic product based on novel medical technology represents important progress in addressing a significant unmet medical need.”

The safety and effectiveness of Symvess was assessed based on data from a prospective, single arm, multicenter study in patients with life- or limb-threatening vascular trauma. A total of 54 patients received Symvess to repair an arterial vessel in the extremity. Efficacy was evaluated based on primary patency (blood flow present without any intervention) and secondary patency (at least one intervention required to maintain blood flow) 30 days after implantation. Of the 54 patients evaluated, 36 (67%) retained primary patency and 39 (72%) retained secondary patency at day 30. Five patients (9%) underwent amputation of the treated limb within the first 30 days and eight (15%) patients underwent amputation of the treated limb by end of study (month 36).

The most common adverse reactions of Symvess are thrombosis (blood clot in Symvess), fever, pain, anastomotic stenosis (abnormal narrowing where the Symvess was sewn to the patient’s blood vessel). The serious risks of Symvess include graft rupture, anastomotic failure and thrombosis. Because Symvess uses cells from a human donor and reagents of human and bovine (cow) origin, transmission of infectious diseases or infectious agents can occur. The cells used in the manufacture of Symvess are derived from a donor who meets the donor eligibility requirements in place to prevent transmissible infectious diseases.

The application received Priority Review, Regenerative Medicine Advanced Therapy (RMAT) designation and is designated as a Priority Product by the U.S. Department of Defense (DoD). Public Law 115-92 authorized DoD to request, and the FDA to provide, assistance to expedite development and the FDA’s review of products to diagnose, treat or prevent serious or life-threatening diseases or conditions facing American military personnel.

The FDA granted approval of Symvess to Humacyte Global, Inc.

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Improving Physical Activity Could Add Over 5 Years to Life Expectancy: BMJ

A recent study published in the British Journal of Sports Medicine highlighted the life-prolonging benefits of increased physical activity (PA), revealing how much healthier Americans could become if they embraced more movement. This research was conducted using data from the 2019 US population and mortality statistics from 2017 which illuminates a clear association between low physical activity and reduced life expectancy.

The study analyzed adults aged 40 and above and found that boosting physical activity to match the levels of the most active 25% of the population could extend life expectancy by an average of 5.3 years. This study employed device-measured PA data from the 2003 to 2006 National Health and Nutritional Examination Survey (NHANES), combined with a predictive risk model. They used a life-table approach to simulate mortality outcomes for the population, based on varying levels of physical activity.

The findings suggest that if all Americans over 40 were as physically active as the top quartile of the population, the average life expectancy could rise by over 5 years. This figure is supported by a 95% uncertainty range of 3.7 to 6.8 years, showcasing a robust benefit from higher activity levels. Among the individuals in the lowest quartile of physical activity, even small increases in PA could yield significant benefits. For instance, walking for just one additional hour per day could add roughly 6.3 hours of life expectancy (with an uncertainty interval ranging from 5.4 to 7.1 hours).

These results demonstrated that individuals who are the least active stand to gain the most from incremental increases in physical activity. Also, the research emphasized that these findings highlight the need for increased investment in promoting physical activity at both individual and community levels. Designing environments that encourage walking, cycling, and other forms of exercise could significantly contribute to public health and longevity.

This research builds to the growing evidence of the role of physical activity in reducing disease burden and mortality risk. By quantifying life expectancy gains with clear, device-measured data, it provides actionable insights for public health initiatives. As a society, tackling sedentary behavior could become as crucial as combating smoking or unhealthy diets. Overall, this study not only illustrates the benefits of being active but also provides a strong case for making physical activity a central component of public health strategies.

Source:

Veerman, L., Tarp, J., Wijaya, R., Wanjau, M. N., Möller, H., Haigh, F., Lucas, P., & Milat, A. (2024). Physical activity and life expectancy: a life-table analysis. In British Journal of Sports Medicine (p. bjsports-2024-108125). BMJ. https://doi.org/10.1136/bjsports-2024-108125

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Tirzepatide taken for weight loss may lead to Colonic Ischemia: Case report

A recent case published in the
journal ACG CASE REPORTS JOURNAL found a possible risk of colonic ischemia
caused by the usage of tirzepatide for weight loss. Tirzepatide is a glucagon-like
peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)
receptor agonist drug commonly prescribed for weight loss and Type 2 diabetes. Even
though it is well tolerated, it can cause mild gastrointestinal side effects
where the blood supply to the colon is reduced, leading to conditions like
Colon ischemia.

Also Read: New pancreatic cancer treatment proves effective in shrinking, clearing tumors, unravels research

The presented case was a 62-year-old
woman who presented with acute onset abdominal pain and bloody stools. She had
a history of obesity, venous thromboembolism, and heart failure with preserved ejection
fraction. Previous screening for colorectal cancer showed benign polyps and
diverticulosis. Medical history included once-a-week injections of tirzepatide 2.5mg
subcutaneously along with apixaban 5mg twice daily, spironolactone 25 mg once daily,
furosemide 20mg once daily, atorvastatin 20mg once daily, fluoxetine 30 mg once
daily, lisinopril 2.5 mg once daily, and atenolol 37.5 mg once daily. Tirzepatide
was started just 4 weeks before, after which she developed constipation.

The patient presented with lower
abdominal cramping pain, an urge to defecate, and bloody stools lasting one
day. The medical evaluation included imaging tests like the computed tomography
scan showing the colon. A colonoscopy showed ischemia signs like denudation,
sloughing, and crypt withering from the mid-sigmoid colon through the distal
transverse colon. A tissue biopsy confirmed colonic ischemia. The patient was
admitted to the hospital and treated with intravenous fluids, bowel rest,
broad-spectrum antibiotics, and analgesics. Apixaban, furosemide,
spironolactone, and tirzepatide were paused for the moment. The patient was
discharged on day 3 of hospitalization due to rapid and spontaneous resolution of
symptoms.

The above case is an eye-opener
on the occurrence of colonic ischemia caused by occlusive ischemia secondary to
tripeptide-induced constipation. This could be due to the volume depletion and
subsequent hypo perfusion caused by increased stool burden and reduced cardiac
output at the baseline. Previous literature has shown similar occurrences of
colonic ischemia due to tirzepatide. Although the exact cause and association
cannot be established, it can be suggested that constipation and volume depletion
could be some of the significant factors contributing to colonic ischemia.

Also Read: Meta-Analysis Highlights Gestational Diabetes as Novel Risk Factor for Maternal GBS Transmission

This case highlights the
potential risk of colonic ischemia in individuals taking tirzepatide. Hence,
careful evaluation of the patient should be done before prescribing this
medication. Prior counselling, evaluation of drug history, maintaining
hydration, and proactively monitoring the symptoms can reduce the risk of
colonic ischemia.

Further reading: Bayless D, Singh J, Park BU,
Sweetser S. Tirzepatide-Associated Colonic Ischemia. ACG Case Rep J.
2024;11(11):e01551. Published 2024 Nov 6. doi:10.14309/crj.0000000000001551

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Researchers develop clinically validated, wearable ultrasound patch for continuous blood pressure monitoring

A team of researchers at the University of California San Diego has developed a new and improved wearable ultrasound patch for continuous and noninvasive blood pressure monitoring. Their work marks a major milestone, as the device is the first wearable ultrasound blood pressure sensor to undergo rigorous and comprehensive clinical validation on over 100 patients.

The technology, published on Nov. 20 in Nature Biomedical Engineering, has the potential to improve the quality of cardiovascular health monitoring in the clinic and at home.

“Traditional blood pressure measurements with a cuff, which are limited to providing one-time blood pressure values, can miss critical patterns. Our wearable patch offers a continuous stream of blood pressure waveform data, allowing it to reveal detailed trends in blood pressure fluctuations,” said study co-first author Sai Zhou, who recently graduated with his Ph.D. in materials science and engineering from the UC San Diego Jacobs School of Engineering.

The patch is a soft and stretchy device, about the size of a postage stamp, that adheres to the skin. When worn on the forearm, it offers precise, real-time readings of blood pressure deep within the body. The patch is made of a silicone elastomer that houses an array of small piezoelectric transducers sandwiched between stretchable copper electrodes. The transducers transmit and receive ultrasound waves that track changes in the diameter of blood vessels, which are then converted into blood pressure values.

Technological improvements to wearable ultrasound

The wearable ultrasound patch builds upon an earlier prototype that was pioneered by the lab of Sheng Xu, a professor in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at UC San Diego. Researchers re-engineered the patch with two key improvements to enhance its performance for continuous blood pressure monitoring. First, they packed the piezoelectric transducers closer together, enabling them to provide wider coverage so they could better target smaller arteries such as the brachial and radial arteries, which are more clinically relevant. Second, they added a backing layer to dampen redundant vibrations from the transducers, resulting in improved signal clarity and tracking accuracy of arterial walls.

In tests, the device produced comparable results to a blood pressure cuff and another clinical device called an arterial line, which is a sensor inserted into an artery to continuously monitor blood pressure. While the arterial line is the gold standard for blood pressure measurement in intensive care units and operating rooms, it is highly invasive, limits patient mobility, and can cause pain or discomfort. The patch provides a simpler and more reliable alternative, as shown in validation tests conducted on patients undergoing arterial line procedures in cardiac catheterization laboratories and intensive care units.

Comprehensive clinical validation

Researchers conducted extensive tests to validate the patch’s safety and accuracy. A total of 117 subjects participated in studies that evaluated blood pressure across a wide range of activities and settings. In one set of tests, seven participants wore the patch during daily activities such as cycling, raising an arm or leg, performing mental arithmetic, meditating, eating meals and consuming energy drinks. In a larger cohort of 85 subjects, the patch was tested during changes in posture, such as transitioning from sitting to standing. Results from the patch closely matched those from blood pressure cuffs in all tests.

The patch’s ability to continuously monitor blood pressure was evaluated in 21 patients in a cardiac catheterization laboratory and four patients who were admitted to the intensive care unit after surgery. Measurements from the patch agreed closely with results from the arterial line, showcasing its potential as a noninvasive alternative.

“A big advance of this work is how thoroughly we validated this technology, thanks to the work of our medical collaborators,” said Xu. “Blood pressure can be all over the place depending on factors like white coat syndrome, masked hypertension, daily activities or use of medication, which makes it tricky to get an accurate diagnosis or manage treatment. That’s why it was so important for us to test this device in a wide variety of real-world and clinical settings. Many studies on wearable devices skip these steps during development, but we made sure to cover it all.”

Next steps

The research team is preparing for large-scale clinical trials and plans to integrate machine learning to further improve the device’s capabilities. Efforts are also underway to validate a wireless, battery-powered version for long-term use and seamless integration with existing hospital systems.

Reference:

Sai Zhou, Geonho Park, Katherine Longardner, Muyang Lin, Baiyan Qi, Xinyi Yang, Xiaoxiang Gao, Hao Huang, Xiangjun Chen, Yizhou Bian, Hongjie Hu, Ray S. Wu, Wentong Yue, Mohan Li, Chengchangfeng Lu, Ruotao Wang, Siyu Qin, Esra Tasali, Theodore Karrison, Isac Thomas, Benjamin Smarr, Erik B. Kistler, Belal Al Khiami, Irene Litvan, Sheng Xu. Clinical validation of a wearable ultrasound sensor of blood pressure. Nature Biomedical Engineering, 2024; DOI: 10.1038/s41551-024-01279-3

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Schizophrenia and MDD causally linked to increased constipation risk, discovers study

Schizophrenia and MDD causally linked to increased constipation risk, discovers study published in the Clinical and Experimental Gastroenterology.

Psychiatric disorders have been associated with Constipation in observational studies, although their causal relationships remain uncertain. We used Mendelian randomization analysis to infer causality between Schizophrenia and Major Depressive Disorder with Constipation. The exposure of interest was Psychiatric disorders, including Schizophrenia (SCZ) and Major Depressive Disorder (MDD). Summary statistics for psychiatric disorders were recruited from the PGC, SCZ (30,490 cases and 312,009 controls), MDD (170,756 cases and 329,443 controls), whereas Constipation summary genetic data were obtained from a FinnGen involving 17,246 cases and 201,546 controls. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between SCZ and MDD with Constipation. Results: LDSC indicated that Constipation was genetically correlated with Psychiatric disorders (r g range: |0.04-0.05). The Mendelian randomization analysis indicated that there was significant evidence that genetically determined SCZ (OR = 1.05, 95% CI = 1.02-1.07, P<0.01) and MDD (OR = 1.21, 95% CI = 1.10-1.33, P<0.01) were statistically significantly causally associated with the risk of Constipation. SCZ effects remained within the range of practical equivalence (ROPE). The Mendelian randomization analysis suggested that SCZ and MDD increase the risk of Constipation. However, the association between SCZ and constipation, predominantly within the ROPE range, suggested only limited clinical implications.

Reference:

Liu J, Huang Y, Fu X, Wei J, Wei P. Associations of Schizophrenia and Major Depressive Disorder with Constipation: A Mendelian Randomization Study. Clin Exp Gastroenterol. 2024 Nov 26;17:349-357. doi: 10.2147/CEG.S485504. PMID: 39618883; PMCID: PMC11608058.

Keywords:

Schizophrenia, MDD, causally, linked, increased, constipation, risk, discovers, study, Liu J, Huang Y, Fu X, Wei J, Wei P, Clinical and Experimental Gastroenterology, MDD; Mendelian randomization; SCZ; Schizophrenia; constipation; major depressive disorder.

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Exposure to interparental physical violence in early life associated with incidence of CVD in adulthood: JAMA

Researchers have established a strong correlation between witnessing physical violence during childhood and high risks for cardiovascular disease at adulthood. A population-based cohort of more than 10,000 participants elucidates this association as partly mediated through depressive symptoms that occur during later life. This study was recently published in JAMA Network Open conducted by Cancan C. and colleagues.

Childhood exposure to adversity, including witnessing violence between parents, has been linked to several adult health outcomes; however, the specific association of childhood witness to interparental violence with increased risk for cardiovascular disease and its underlying mechanisms has been poorly understood. Therefore, this study was established to assess the association of witness to interparental physical violence during childhood to later heart disease and stroke and to consider whether mediation occurs through depressive symptoms at an adult stage.

Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which enrolled participants aged 45 years or older. Participants were followed up for nine years, thus providing robust evidence of the long-term impact of early-life exposures on adult health outcomes. A cohort study based on CHARLS data from 2011 to 2020, with a follow-up period of nine years. 10,424 adults aged 45 years or older; mean age: 58.1 ± 9.0 years; 51.2% female. Early-life exposure to interparental physical violence assessed using a validated early-life exposure questionnaire. Self-reported and physician-diagnosed heart disease (including myocardial infarction, angina, coronary heart disease, and heart failure) and stroke.

Key findings

Exposure Prevalence:

  • Reported childhood exposure to interparental physical violence in 872 participants (8.4%)

Cardiovascular Risks:

  • Overall CVD risk: Hazard ratio (HR) 1.36 (95% CI: 1.20–1.55).

  • Risk of heart disease: HR 1.36 (95% CI: 1.17–1.57).

  • Risk of stroke: HR 1.28 (95% CI: 1.03–1.61).

Depressive Symptoms:

  • 25.4% of exposed participants (2371 of 9335) reported depressive symptoms, as compared with non-exposed individuals.

  • Depressive symptoms mediated 11.0% of the association between interparental violence and CVD (HR 1.26; 95% CI: 1.09–1.45).

Experiences of interparental physical violence in childhood significantly increase the risk for adult-onset cardiovascular disease. These findings underscore an urgent need for comprehensive approaches aimed at addressing the social determinants of interparental violence and promoting mental health to reduce the long-term health consequences of childhood adversity.

Reference:

Cui C, Liu L, Li H, et al. Childhood Exposure to Interparental Physical Violence and Adult Cardiovascular Disease. JAMA Netw Open. 2024;7(12):e2451806. doi:10.1001/jamanetworkopen.2024.51806

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Asthma comorbidity of Primary ciliary dyskinesia among Children: JAMA

A recent study published in the
journal JAMA Network Open found that children with primary ciliary dyskinesia
can develop asthma.

Primary ciliary dyskinesia (PCD) is
a condition that affects the structure and function of motile cilia. It occurs
due to a genetic mutation. Literature shows that Asthma can be a comorbidity
for PCD due to the antigen stasis that develops on the airway surface. However,
there is an ambiguity in considering asthma a routine comorbidity for PCD in
children. Hence, researchers conducted a study to assess whether asthma should
be routinely considered a comorbidity among children with PCD.

Also Read: Combination therapy with Montelukast Sodium effective for managing Cough Variant Asthma in children, finds study

A case-control study was carried
out by collecting data from 2 large electronic health record (EHR)–based
databases: the Indiana Network for Patient Care Research (INPCR) cohort of 20
million EHRs and, in a validation cohort, TriNetX, which includes 112 million
EHRs.

Due to the lack of a specific
ICD-10 code for PCD, identifying PCD became a challenge for the authors. Hence,
researchers analyzed cases of co-occurring bronchiectasis (ICD-10 J47) and
situs inversus totalis (ICD-10 Q89.3) that are unlikely to occur without PCD.
The analysis assessed whether individuals with B-SIT also had asthma (ICD-10
J45). Cases and controls were matched by age, sex, ethnicity, and race (1:3
ratio in INPCR, 1:1 in TriNetX). Conditional logistic regression was performed,
adjusting for the matching strategy. A conditional exact test was done to
compare the proportion of asthma between cases and controls for INPCR.

Findings:

  • Out of 266 participants, including 124 B-SIT
    patients and 142 controls, participants were matched for age, sex, ethnicity,
    and race.
  • In the INPCR study, 9 children had B-SIT, and 27
    were in the control group.
  • All 9 B-SIT patients had asthma compared with
    only 1 among the controls (P < .001).
  • In TriNetX, which included 115 with B-SIT and
    same-matched controls, 84 had asthma, and 31 did not.
  • In the controls, 12 had asthma, and 103 did not.
  • The adjusted odds ratio for asthma patients with
    B-SIT was 22.3.
Also Read: Advances in the Diagnosis and Treatment of Primary Ciliary Dyskinesia: A Review

Thus, the study concluded that most
children with likely PCD (B-SIT) had asthma, highlighting the relationship
between PCD and asthma. The researchers underscore the importance of routinely
evaluating asthma as a potential comorbidity in PCD. Further research should be
done to clarify the immunopathogenesis and validation and should consider whether
asthmatic children exhibit PCD.

Further reading: Zein J, Owora
A, Kim HJ, Marozkina N, Gaston B. Asthma Among Children With
Primary Ciliary Dyskinesia. JAMA Netw Open. 2024;7(12):e2449795.
doi:10.1001/jamanetworkopen.2024.49795.

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FDA approves Alyftrek once-daily oral combination for cystic fibrosis

The US Food and Drug Administration has approved Alyftrek, a once-daily oral combination of vanzacaftor, tezacaftor, and deutivacaftor, for the treatment of cystic fibrosis (CF) in adults and children aged 6 and older, Vertex Pharmaceuticals announced on Friday.

“ALYFTREK is our fifth CFTR modulator to secure FDA approval and represents another significant milestone in our journey to serially innovate and to improve the lives of people living with cystic fibrosis,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “Our north star for more than 20 years has been to address the underlying cause of cystic fibrosis, treat more people with this disease, and bring more people to normal levels of CFTR function-ALYFTREK, with once-daily dosing, efficacy in 31 additional mutations, and lower sweat chloride levels than TRIKAFTA, is another step in achieving this goal.”

This approval is based on the most comprehensive Phase 3 pivotal program ever conducted in CF, including more than 1,000 patients across more than 20 countries and more than 200 sites. These data were previously released at the conclusion of the studies and presented at the North American Cystic Fibrosis Conference in September of this year. The Phase 3 studies in people with CF ages 12 years and older met their primary endpoint (non-inferiority on absolute change from baseline in ppFEV1 compared to TRIKAFTA) and all key secondary endpoints (including absolute change from baseline in sweat chloride [SwCl] compared to TRIKAFTA). In the Phase 3 study of children with CF ages 6-11 years, ALYFTREK demonstrated safety, the primary endpoint. Secondary endpoints, such as absolute change from baseline in ppFEV1 and absolute change from baseline in SwCl, were presented, supporting the benefit of ALYFTREK in this age group. ALYFTREK was generally well tolerated across all studies.

“In Phase 3 clinical trials, across a broad range of genotypes, once-daily ALYFTREK demonstrated non-inferiority to TRIKAFTA in ppFEV1 response and statistically significant improvement in SwCl, a welcomed advancement for the treatment of CF,” said Claire L. Keating, M.D., Co-Director of the Gunnar Esiason Adult Cystic Fibrosis and Lung Program at Columbia University and investigator in the ALYFTREK clinical trial program. “ALYFTREK has the potential to improve the care of patients with CF.”

ALYFTREK is the first, once-daily CFTR modulator. In a recent survey, approximately 75% of physicians reported that more convenient dosing is a very high unmet need for people with CF. Specifically, people with CF will have the added benefit from a once-daily dosing regimen, given the need to take CFTR modulators with fat-containing food. ALYFTREK also offers a potentially transformative option for approximately 150 people with CF in the U.S. with one of 31 mutations who are now eligible for a CFTR modulator for the first time.

ALYFTREK was also submitted to global health authorities and is under regulatory review in the European Union, the United Kingdom, Canada, Switzerland, Australia and New Zealand.

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 92,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes-one from each parent-to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving.

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