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Monthly Archives: July 2022
DISCOVERY BEHAVIORAL HEALTH ACQUIRES ANEW ERA TMS & PSYCHIATRY WITH 12 LOCATIONS IN CALIFORNIA AND TEXAS – PR Newswire
Posted: July 19, 2022 at 2:27 am
A third of Americans believe it is harder to find a mental health care than it is to find a physical health care.
Discovery President & CEO John Peloquin states, "We are pleased to welcome the team at Anew into the Discovery family. This addition builds on our strategic mission to create a fully integrative care model, with multiple treatment models, both conventional and innovative, available through one access point. A 2022 Harris Poll report revealed that a third of Americans believe it is harder to find a mental health care provider than it is to find a physical health care provider[i]. We are removing those barriers by expanding outpatient and telehealth services in psychiatry and addiction medicine which includes TMS treatment. When people can access a wide range of behavioral health services based on their needs and preferences, they have a greater chance to live happier, more rewarding lives, and that's why we're here."
About Discovery Behavioral Health
Everyone deserves a happy, rewarding life. That's why Discovery Behavioral Health has made evidence-based, outcome driven healthcare accessible and affordable since inception. With a full continuum of care detoxification, medical residences, residential treatment centers, partial hospitalization, intensive outpatient, outpatient, psychiatric and addiction medicine, TMS, virtual and telehealth services, we can offer the right care at the right time for adults or teens struggling with mental health, substance use or eating disorders. We are a contracted provider with 100 payers and other managed care organizations. Our portfolio of more than 145 treatment centers includes service lines in successful operation since 1985. When treatment is complete, our patients become part of Discovery's growing family of alumni, connected through free aftercare programs, support groups, activities, and a caring community. Because when quality behavioral healthcare is within reach, so is happiness.
Press Contact:Greg PtacekCommunicationsDiscovery Behavioral Health, Inc.[emailprotected]323-841-8002 mobile
SOURCE Discovery Behavioral Health
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DISCOVERY BEHAVIORAL HEALTH ACQUIRES ANEW ERA TMS & PSYCHIATRY WITH 12 LOCATIONS IN CALIFORNIA AND TEXAS - PR Newswire
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Parker Seminars to Host NeuroCon 2022 Event on Parker University Campus July 29-30 – Yahoo Finance
Posted: July 19, 2022 at 2:27 am
Parker Seminars Hosts NeuroCon 2022
NeuroCon Keynote Speakers
Dallas, Texas, July 18, 2022 (GLOBE NEWSWIRE) -- From July 29-30, 2022, join Parker Seminars for an exciting in-person, two-day event designed specifically for healthcare professionals! Attendees will learn from and network with well-known worldwide leaders who specialize in disorders of the nervous system. Sessions are centered around a superior integrative approach to supporting research and application for treating neurological disorders.
Taking place on the Parker University campus in Dallas, Texas, attendees will hear from industry experts and speakers, earn CE hours, and network with each other and exhibitors.
Parker Seminars is excited to announce that its keynote speakers include Max Lugavere (New York TimesBest-Selling Author and host of the No.1 iTunes Health Podcast, The Genius Life),Kimberly Noble (Professor of Neuroscience and Education at Teachers College Columbia University),Tali Sharot (Neuroscientist and Professor of Cognitive Neuroscience at University College London and MIT), andOctavio Choi (Board-certified Forensic Neuropsychiatrist and Clinical Associate Professor in the Psychiatry Department at Stanford University School of Medicine).
NeuroCon 2022 will provide attendees with the expertise needed to equip themselves and their patients with the most relevant knowledge for maximizing the brains potential. To learn more or sign up, visitneurocon.parkerseminars.com.
About Parker University
Parker University, the fourth-fastest growing college in Texas and the fastest-growing college in Dallas, was founded in 1982 by Dr. James William Parker (formerly Parker College of Chiropractic). Today, Parker University has more than 1,800 students and more than 35 academic programs,including its famed chiropractic program, as well as masters degrees in neuroscience, clinical neuroscience, strength and human performance, and functional nutrition. Currently, Parker Universitys chiropractic cohort is the second largest of any campus in the world.Parker University has been recognized as a Great College to Work For, one of the 25 Fastest-Growing Colleges in the U.S.,and as a recipient of the 2021 FutureEdge 50 Awards.
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Parker Seminars to Host NeuroCon 2022 Event on Parker University Campus July 29-30 - Yahoo Finance
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Diagnosis and treatment of the alpha-Gal syndrome | JAA – Dove Medical Press
Posted: July 19, 2022 at 2:27 am
Introduction
Galactose--1,3-galactose (-Gal), an oligosaccharide that structurally resembles blood group B antigen, is present in both glycoproteins and glycolipids from non-catarrhine mammalian muscle cells and secretions.1,2 Old World monkeys, apes and humans evolved with the inability to synthesize -Gal epitopes and, therefore, produce natural anti--Gal antibodies to control pathogen infection.3 This carbohydrate epitope is the causal agent of the -Gal syndrome (AGS), a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in mammalian meat (eg pork, beef or lamb) or dairy products 3 to 6 hours post-consumption.47 Recently, an allergic cross reaction to flounder roe in patients suffering from AGS has been reported.8 The other clinical presentations of AGS comprise immediate hypersensitivity to -Gal-containing drugs, firstly discovered using the monoclonal antibody cetuximab in anticancer therapy.6,9 There is growing evidence of allergic reactions caused by the -Gal present in mammalian substances such as gelatin, glycerin, lactic acid and magnesium stearate used in the preparation process of several medications,9,10 such as gelatin-containing products (vaccines and volume colloids), mammalian serum-based antivenom and even various analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs).2,6,11,12 The IgE initial sensitization is caused by hard-bodied tick bites from different species according to geographic location and is attributed to -Gal-containing tick salivary glycoproteins, but also other tick salivary biomolecules without -Gal modifications such as prostaglandin E2 (PGE2).1317 The mechanisms behind tick -Gal induction of sensitization are still unknown, but besides the -Gal moiety, tick sialome components may play an important role in the chained immune reaction activation (Figure 1).18,19 Tick species such as Ixodes ricinus in Europe, Amblyomma americanum in North America, Haemaphysalis longicornis in Asia and Ixodes holocyclus in Australia are linked to AGS,20 currently considered an emergent life-threatening allergy in tick endemic areas worldwide.2123 However, not all individuals bitten by ticks or those that carry elevated specific IgE (sIgE) against -Gal develop AGS, in fact, the majority only produce sIgE against it.19 Symptomatic individuals typically show delayed pruritus, urticaria (acute or recurrent), angioedema, anaphylaxis, malaise or gut-related symptoms such as abdominal pain, vomits and diarrhea.22,24,25 Anaphylaxis has been triggered in up to 60% of AGS cases and can be fatal if it is not treated promptly.2628 Clinical features reported tend to be restricted to gastrointestinal complaints, hampering the suspicion of an allergic etiology.29 Nevertheless, clinical observations in AGS patients are widely variable, showing proof of individual sensitivity.5 Augmenting factors, also called cofactors, such as exercise and alcohol intake, have been reported to play an important role in modulation of this individual susceptibility between patients.30 The medical history is of importance in these cases and details like meat-associated delayed allergic reactions and tick bite-exposure represent crucial factors for uncovering AGS, which otherwise can be misdiagnosed as idiopathic anaphylaxis or chronic spontaneous angioedema.7,30,31 Risk factors for developing sIgE to -Gal are related to the probability of individual tick bite-exposure in certain environmental conditions, including practice of outdoor activities (eg, hunting or hiking), living in rural areas, pet-ownership, and certain jobs such as forest service employees.3235 The sIgE values tend to increase according to the number of tick bites per year and on how recent those bites are.34,36 Moreover, individuals that do not have type B or AB blood group may have a higher risk of developing AGS, as blood group B antigen, similar to -Gal, creates tolerance to this epitope.37
Figure 1 Alpha-Gal syndrome (AGS). (A) Sensitization after several tick bites. Tick saliva contains glycoproteins, glycolipids with -Gal epitopes and other unknown salivary biomolecules that could be involved in the pathology of AGS. The glycan -Gal is presented to T helper 2 (Th2) cells through antigen-presenting cells (APCs) as dendritic cells, macrophages or even B cells. Once T cells are activated, B cells are leading to produce IgE against -Gal (anti -Gal-IgE) in an enriched interleukin environment and potentiate IgE production in plasma cells. Free IgE are now available to interact and bind to IgE receptors present in basophils and mast cells. (B) Allergic Reaction. When AGS patients ingest mammalian meat containing -Gal bound to proteins or lipids, these molecules expressing the allergen epitope are absorbed and incorporated to lipid/protein macromolecules during digestion (chylomicrons, lipoproteins), which will be processed and transport through protein or lipid metabolism to systemic circulation and peripheral tissues. About 36 hours post-consumption, IgE-mediated and coated effectors will recognize the allergen, leading to degranulation of basophils and mast cells and promoting a systemic delayed allergic reaction. AGS can also comprise an immediate anaphylactic reaction, triggered using -Gal containing drugs, administered via parenteral due to therapeutic reasons.
On the other hand, immune response to -Gal has been studied for the control and prevention of diseases, exhibiting a protective role in human evolution catastrophic selection. The incidence of several infectious diseases caused by -Gal containing-pathogens such as malaria or tuberculosis might be positively correlated with the frequency of the specific blood type B, and then, with a reduced immune response to -Gal. However, this fact has been associated with a lower prevalence of food allergies related to anti--Gal IgE antibodies.38 In addition, it has been recently reported a positive correlation between anti--Gal IgM antibodies and the incidence of Plasmodium falciparum infection, decreasing its transmission.39 Despite the fact that uncontrolled levels of anti--Gal antibodies could compromise health in AGS patients, these findings suggest that anti--Gal antibodies (IgE or IgM) might protect against parasites containing -Gal on their surface. Interestingly, anti--Gal antibodies have also been studied not only in vector-borne diseases but also in emerging virus infections. Recently, it has been reported that anti--Gal antibody levels negatively correlate not only with SARS-CoV-2 infection but also with COVID-19 symptomatology severity.40
Over 10 years have passed since the discovery of AGS,41 but many questions remain unclear that still need to be elucidated, especially those related to the diagnostic and therapeutical approaches used for this syndrome. The aim of the present review article is to outline current diagnostic methods used for AGS and potentially future diagnostic tools, combined with the most recent forms of treatment/management of this syndrome. Furthermore, innovative topics such as current research methods and future treatment and preventive strategies are also discussed.
The AGS is an allergic disorder that challenges clinical diagnosis due to inapparent presentation and delayed reactions.19,42 Like any other allergic disease, diagnosis relies on a well-detailed medical history in order to reach an accurate evaluation and prognostic of individual signs and symptoms.25 Diagnostic techniques for this syndrome are not specific and/or represent a risk for the patients health, whereas more precise methods still show limitations to its use.43 As discussed here, it is important to address the diagnostic tests more commonly used and methods that could potentially be employed in the future (Figure 2) for the challenging and complex allergy that involves the pathology of AGS.
Figure 2 Conventional and next generation methods for the diagnosis of the alpha-Gal syndrome (AGS).
SPTs remains a useful diagnostic tool for several food allergies.44 Conversely, conducting this test for AGS diagnosis using conventional and commercially available mammalian meat extracts (beef, pork or lamb) lacks sensitivity, yielding low-reactive results (24 mm wheals), which may lead to misdiagnosis and incorrect patient management.45 Alternatively, cancer drug cetuximab can potentially be used as a sensitivity agent due to its high capacity to induce a strong skin reactivity in AGS patients, mainly caused by the larger amount of -Gal epitopes exposed to the surface.46,47 Robust reactions also occur when mammalian meat extract is used, although this is not a feasible option for daily practice.16 Meat-derived gelatin from porcine or bovine, sometimes forming colloids, has also been used in allergic reaction diagnostics. Furthermore, it is important to consider that, although rare, the use of high-sensitivity components in SPT could potentially trigger a fatal anaphylactic shock reaction.48,49 Less commonly, intradermal testing (IDT) can also be used as a standardized methodology to evaluate skin reactions. As described by the SPT method, 20 minutes after allergen intradermal injection (around 0.1 mg/mL), swelling, redness and wheals are observed in the area of injection.50 Nevertheless, IDT is more likely to induce systemic anaphylactic reactions when compared to SPT.44 Overall, the clinical utility of SPT remains doubtful as no food allergen fits flawlessly in this diagnostic technique, conveying on several limitations and therefore making it not fit for a primary approach diagnostic tool.
For the diagnosis of a food allergy (FA), OFC is the gold standard technique, offering further information regarding food tolerability and threshold of responsiveness.51 This method could be useful for discriminating AGS diagnosis from -Gal sensitization if it did not convey to a risk of fatal or near-fatal delayed anaphylactic reactions.7,52 Therefore, this challenge can only be performed in specialized allergic centers, requiring long patient observation periods.7,53 Besides risk, OFC is not established as a standardized procedure for AGS and exposure reaction presents a high variability between patients. In fact, some patients may require the presence of cofactors in order to react, while others only respond to a particular type of red meat.54 Nevertheless, this method, tested also in combination with cofactors, is essential in patients in which drugs-containing -Gal must be given for therapeutical reasons due to the clinically relevant information that it provides.55 Cofactors, such as acetylsalicylic acid (ASA) or alcohol, are well-known amplifiers of -Gal reactions.6 Due to the wide difference between symptomatology of AGS patients, sensitivity to -Gal can be truly variable.30 However, it has been observed that pork kidney intake, and no other product like muscle meat, even in the coadministration of cofactors, is a key element to raise AGS symptoms. This difference might be explained due to the higher number of -Gal epitopes present in pork or beef kidney in comparison to other meats/innards.56,57
Currently, serum anti-Gal IgE levels measured using an immune-enzymatic assay (bovine thyroglobulin-conjugated ImmunoCAP) is the confirmatory diagnostic method used for AGS diagnosis when medical history matches with this disease.5860 Nonetheless, it remains unclear the clinical relevance of positive testing for anti-Gal IgE using a cut-off value of 0.35 kU/L (where 1 kU/L = 1 IU/mL = 2.4 ng/mL).33,42,46,52,61 While Mabelane et al54 state that 5.5 kU/L is the cut-off point for clinically significant AGS, other studies reveal that there are no strict criteria regarding anti-Gal IgE levels as an allergic symptomatology predictor.25,62 One thing is clear, though, is that levels of specific IgE are not a useful biomarker for predicting the severity of allergic reactions, as AGS patients experiencing anaphylactic reactions may maintain IgE levels overtime or even in rare occasions with anti-Gal IgE negative results.25,63 Another issue with the anti-Gal IgE diagnostic assay is that it can lead to false-positive results in those individuals where Gal IgE sensitization may also be related to bee and wasp stings, parasitism, atopy or cat ownership, creating cases where these antibodies do not match the clinically pathognomonic history of AGS.25,42,62,64,65 For example, in a clinical study carried out in southern Germany, among 300 hunters with a 19.3% of IgE--Gal prevalence (58 individuals positive for cut-off value of 0.35 IU/mL), only 1.67% (5 individuals of the initial cohort) had allergic reactions to mammalian meat.33 Moreover, serum levels of IgE to Gal tend to drop when patients do not experience recurrent tick bites, but again, the rate of declination between individuals is widely variable, being therefore recommended to repeat testing every 8 to 12 months.25,45 Nevertheless, due to AGS non-related therapeutical reasons, sometimes the measurement of anti-Gal IgE levels may be needed to detect Gal sensitization and therefore prevent drug-induced anaphylaxis.60 In summary, anti-Gal IgE levels may be useful for AGS diagnosis, but clinical symptomatology and disease severity cannot be evaluated exclusively through this parameter, requiring complementation with other diagnostic techniques.
Over the years, research studies allowed to recognize distinct improved biomarkers that provide a more accurate diagnosis of food allergies.66 This led the way to the use of the in vitro functional assay BAT, a flow-cytometry-based technique that quantifies the expression of activation membrane markers, namely, CD63 and CD203c, in order to analyze basophil degranulation when triggered by a specific allergen.6668 In the research setting and specialized referral centers, BAT is being used as a diagnostic clarifier, allowing to distinguish between merely asymptomatic sensitized individuals and patients suffering from AGS.42,53,69 This newly emerging method offers good sensitivity and specificity, but presents several practical and logistical issues for implementation in clinical practice.43,70 First, blood must be processed within 24 hours after being collected in order to guarantee that basophil viability and reactivity are preserved.6,71 Second, questions regarding reproducibility and cost must be addressed before BAT implementation in practicing allergists.72 Unfortunately, methodology, concentration and markers are not standardized between laboratories in order to allow result comparison and test validation.73 Furthermore, standardization between systems and instruments required for accreditation (eg, EuroFlow Standard Operating Procedures) is missing, reducing BAT availability.74,75 This technique also lacks an established proficiency testing by regulatory entities. The current European Directive 98/79/EC on in vitro diagnostic medical devices76 will be replaced in 2022 by the new Regulation (EU) 2017/746 and introduce major changes in the sector, aiming for a smooth functioning of the internal market.77 In sum, efforts should be made to convey on transforming BAT into an on-hand tool for clinicians, due to the benefits it presents on risk allergy stratification, precise decision-making for -Gal sensitized patients who lack medical evidence and selection of the correct doses for OFC in AGS-suffering individuals.53,72
Another in vitro assay executed by flow cytometry is the MAT, a technique that measures CD63, a membrane activation marker that increases when mast cells (MCs) degranulate. This phenomenon occurs when MCs are triggered by allergen-sIgE antibodies.66,78 MAT presents high sensitivity and leads to a dose-dependent response to allergens,79 making it a potential and attractive complementary candidate for AGS diagnosis. Furthermore, MAT seems to overcome BATs major limitations. First, the use of MCs rather than basophils appears to be more suitable for allergy diagnosis due to the well-recognized effector function of MCs in comparison to the mere regulatory activity of basophils.80 Secondly, serum samples can be frozen prior to their use, as MAT does not require fresh viable cells, facilitating logistics and sample shipment if required.81 The MCs line can be activated directly through mas-related G protein-coupled receptor X2 (MGPRX2) with simultaneous analysis of positive and negative populations for this receptor. Herein, MC degranulation can be studied via upregulation of specific degranulation markers, such as CD63. Most common MRGPRX2-expressing cell lines used in combination with CD63 detection by flow cytometry are LAD-2 cells derived from human CD34+ cells.82,83 However, there is still a long way to go from standardization to validation to obtain a fully functional MAT assay, as currently this technique is particularly time-consuming and several key issues still persist regarding heterogeneity of MCs.70,84 Although MAT test is still under validation for clinical application, it represents a promising diagnostic approach, particularly as a confirmatory test when conventional methods generate ambiguous results.66,82
Another emerging diagnostic test in the FA field is the HR assay, a standardized test based on fluorescence intensity that measures the amount of histamine released by activated basophils.85 Although even further studies are required to support standard results, this technique could potentially be used for AGS diagnosis since basophil reactivity was found to be higher in these patients when compared to -Gal sensitized individuals.10 Indeed, this method displays similar high sensitivity and specificity values when compared to the BAT test,86 but further studies are required to support this result, especially involving AGS-suffering patients.
Collective characterization and quantitation of biomolecules known as omics technologies such as metabolomics, metagenomics, proteomics and transcriptomics could advance knowledge of the immune response in AGS and its molecular drivers, enabling the identification of biotargets for molecular diagnosis of this global impact disease.10,87 Not only the identification of host biomarkers and host-derived immune response mechanisms but also tick-derived biomolecules are important for the development of new diagnostic tools.52 Proteins present in tick sialome, especially highly conserved across tick species, could potentially serve as diagnostic antigens.47 A recent study by Villar et al88 identified by proteomics analysis of tick sialome and alphagalactome the 14-3-3 family chaperone that could possibly constitute a future diagnostic disease biomarker. The study identified that 14-3-3 family chaperone and other proteins were recognized by IgE in sera from AGS patients.88 Therefore, they proposed that these proteins may potentially be involved in the AGS and other disorders with the possibility of mediating protective immune mechanisms against tick infestations and pathogen infection.88 Nevertheless, there are also tick salivary gland proteins with non--Gal modifications that could probably be used to develop ELISA tests for antibody quantification as a complementary diagnostic method for AGS.47,52,89
Artificial intelligence (AI) and machine learning are considered to be powerful diagnostic assistance tools, which in the future could revolutionize the healthcare system providing an accurate and custom-based diagnosis.90 MBR algorithms aim to create a clinical diagnosis or decision-making model that utilize hybrid reasoning and data-driven AI in order to obtain high diagnostic yields by combining the integrative medicine concept.91 For puzzling and complex diseases, such as AGS, in which diagnostic tools lacking standardization and cofactors are also involved, the use of this integrative diagnostic technique could represent the best fitting method. The use of this methodology has been proposed by de la Fuente et al52 for improving AGS diagnosis, considering together clinical symptoms, risk factors and anti--Gal sIgE levels. They also proposed that the machine learning algorithm could be transformed into a code for a software creation with further implementation in clinical practice via mobile applications.52
Ticks are today the most accepted evidence for sensitization to -Gal, but other risk factors or co-factors are likely relevant.92 Daily diet counseling, tick bite avoidance or environmental education should be firstly considered in customizing an accurate treatment for the AGS.42,61 Subsequently, an expertise behind medical interventions is required for an adequate management of the disease over time.43 Although most cases are not emergency cases, invasive techniques are required for in shock patients treatment.6 Furthermore, established protocols, symptomatology, or information about the AGS characteristics are not available due to the wide natural history and variety of subjects all over the world. Herein we present some of the most common strategies and routinary methodology in AGS treatment/management when the disease is diagnosed.
The pillar of the non-medical approach is based on avoidance. The prevention of tick bites is relevant because continuous exposure to tick bites may maintain or increase anti--Gal IgE titers and lead to allergic responses to previously tolerated foods.92 Despite limited evidence, patients who successfully avoid tick bites on a long term (12 years) have a higher chance of recovering tolerance to meat products, allowing the reintroduction of red meat into diet.10,42,93 The most common strategy for tick-bite prevention and management includes the use of lighter colored protective clothes treated with insect repellents or insecticides such as permethrin.21 Furthermore, prompt embedded tick removal using specialized fine-tipped forceps should be performed in order to reduce the amount of secreted salivary allergens.24,92
Secondly, avoidance of mammalian meat, by-products of meat (innards), fat (gelatin and lards) and other -Gal-containing foods such as dairy products represent a crucial management strategy for AGS.10,92 To achieve this goal, dietary counseling is vital, and it can be combined with nutro clinical support to avoid nutritional deficiency, especially in highly sensitized individuals.6 Patients should receive a personalized dietary follow-up depending on which foods are allergy triggering and to routinely check for iron and vitamin B12 supplementation needs.21,61
Another major foundation for AGS management is education. Vulnerable patients should be taught on nutrition facts label reading, awareness of hidden exposures and be provided with a written plan on how to promptly operate in case of an allergic reaction.6,42,61 Clinicians must also inform patients of the risk of onset anaphylaxis not only due to cetuximab but also because of heparin, gelatin-containing vaccines and mammalian heart valves.94 The fact that numerous pharmaceutical products contain animal-derived excipients makes it harder to avoid all potentially immunogenic antigens.95 For this reason, it is recommended for AGS-suffering patients to wear warning bracelets about their condition so that physicians are aware and can prevent future life-threatening situations in emergency cases.61 In fact, due to the worldwide increase in individuals with high anti--Gal IgE titers and possibly undiagnosed AGS-patients, an allergy prescreening before administration of -Gal containing medication might be recommended.96
Due to the AGS delay and unexpected symptomatology, emergency treatment is of utmost importance to correctly manage allergic reactions and potentially life-threatening anaphylaxis.6 Furthermore, the high variability regarding severity and timing of the symptoms represents a challenge for the medical management of this disease.21 Intramuscular epinephrine administration represents the initial recommendation. For patients in shock, intravenous epinephrine should be applied alongside with fluid resuscitation and occasional vasopressors. In case of airway obstruction, intubation may be necessary.97 Afterwards, in order to properly reduce the risk of a multisystem allergic reaction, it is imperative to always carry an epinephrine auto-injector.21 For tick-bite local reactions, symptomatic treatment with oral antihistamines, corticosteroids and cold compresses should be enough to reduce non-serious symptoms such as pruritus, urticaria and angioedema.98 As AGS symptomatology and severity are reported to have high individual variability and rely mostly on symptomatic treatment, information collected mostly from case reports is presented in Table 1, together with their clinical management apart from the anaphylaxis acute treatment-response already discussed. A recent study described a clinical case with abnormal neuro-psychiatric behavior (abulia, aphasia, abnormal gait, and reduction of limb movement) related to AGS and a possible -Gal driven immune-related hypothalamic dysfunction that needs further investigation.99 Other symptomatology such as palpitations and tachycardia are self-limiting and therefore resolve spontaneously.100
Table 1 Drugs and Associated Pharmacological Class Used for -Gal Syndrome Medical Treatment
As described above, humans evolved as non-capable organisms to produce the glycan -Gal.114 Together with the fact that a wide variability exists between individuals suffering from this disease,5 AGS comprehension becomes a complex goal in which molecular and physiological mechanisms need to be elucidated. Several experimental model hosts are currently available for the study of AGS and the immune response to -Gal. Zebrafish (Danio rerio) model has been established and validated under laboratory conditions. This animal model was developed by Contreras et al,115 in which allergic hemorrhagic anaphylactic-type reactions together with behavior changes and mortality were observed in response to tick salivary compounds and mammalian meat consumption. The reactions were associated with tissue-specific toll-like-receptor-mediated responses in Th1 and Th2 helper cells. These data support the use of zebrafish as an animal model for the study of the AGS and bring a new perspective for future strategies in the control of infectious diseases as reported for tuberculosis using vaccination with -Gal.116
Murine models have been used for decades as validated experimental in vivo methodology for investigating both human and animal diseases due to the advantages that these models offer in terms of time, reproducibility and genetic characteristics.117,118 However, wild-type mice produce biologically active 1,3-galactosyltransferase (1,3GT) for the synthesis of -Gal and thus lack anti-Gal antibodies.119 Knocking out the 1,3GT gene results in the absence of -Gal epitopes, not only in murine models but also in pigs,120,121 thus becoming humanized experimental animal models.
The mice C57BL/6 line is one of the most common strains used in research.122 The humanized murine model of this strain for studying AGS (GTKO, AGKO or 1,3-GalT-KO), has been used for the study of tick-induced IgE response-model for -Gal reactions,123,124 but also for testing other immunological approaches as tick-borne allergies and Chagas disease investigation.125,126
Using these animal models, further research is needed to investigate AGS risk factors and epidemiology in order to propose an accurate treatment strategy for each patient.
Mammalian meat desensitization by oral immunotherapy (OIT) has been proposed as a promising treatment for AGS as it would improve patients welfare and safer management.127 It consists of daily intake of small and generally increasing amounts of allergen, in order to reduce the immune response and consequently produce own allergen desensitization.128 To date, there are only three successful case reports (two adults and one pediatric case) of AGS with oral desensitization to beef meat.127,129 Although this type of treatment leads to a sustained unresponsiveness,93 it requires an individual effort from the patient to consume daily 120 grams of cooked mammalian meat in order to maintain desensitization,129 which also becomes an obligation and can have an impact on the patients routine, commodity and mental wellbeing. Indeed, daily mammalian meat intake could compromise the patients to develop other metabolic and cardiometabolic diseases such as hypertension, diabetes and obesity.130,131 Additionally, allergen-specific immunotherapy (AIT) using natural and recombinant -Gal containing proteins from tick sialome is also being considered for AGS treatment.17 Nonetheless, this type of therapies comes with a risk of life-threatening anaphylactic adverse reactions and demand a thoughtful and balanced management of accurate dose efficacy versus side effect appearance.66,132
Given the potential risks associated with immunotherapy, the use of allergen non-specific treatments, such as anti-IgE therapeutic monoclonal antibodies (mAbs), has found application in the treatment of food allergy.133,134 In anti-IgE therapy, mAbs bind to free serum IgE and IgE-coated B cells, acting as a competitive substrate and reducing the availability and binding between these antibodies (natural IgE) and allergy mediators such as basophils and mast cells, which increases reaction threshold and consequently reduces the risk of mild and severe anaphylactic reactions (Figure 3).43,134 Combining anti-IgE therapy as a pre-treatment with immunotherapy techniques leads to a safer administration of OIT and allows to reach the maintenance dose more rapidly.128,133,135 The anti-IgE agent omalizumab has been sporadically used in specialized centers as monotherapy in AGS patients for successfully controlling continued reactivity, allowing the introduction of a small amount of mammalian meat in their diet.42 With such a positive preliminary outcome in these patients and promising data results in other FAs (peanut and cow milk), new clinical trials using biological therapies for AGS are needed, potentially representing a future effective treatment.42,43,133
Figure 3 Anti-IgE therapy. IgE-mediated reaction with release of histamine and other co-factors occurs due to interaction of allergen-specific IgE available with IgE receptor in mediator cells (basophils, eosinophils or mast cells), which are degranulated and increase the risk of life-threatening anaphylactic adverse reactions. The pharmacological and clinical aims of the use of anti-IgEs monoclonal antibodies (mAbs) as drugs is to downregulate and/or decrease IgE production by B cells. Anti-IgE antibodies bind to both IgE-expressing B cells and free serum IgE, markedly decreasing IgE levels available for binding to IgE receptor in allergic reaction-mediator cells and, consequently, gradually compromising mast cells and basophils sensitivity to allergens.
Management of FAs is becoming less generic and more target oriented.66 Consequently, there is still a need to improve our understanding of the immunological mechanisms behind tick bite sensitization and therefore identify new and more specific targets for the development of new treatment interventions for AGS.136
Prevention from developing AGS stands on avoiding the initial -Gal sensitization caused by tick bites, being particularly beneficial for at-risk population.21,35,36 Apart from the common strategies for tick-bite prevention mentioned above, the development of tick-antigen-based vaccines could not only protect against AGS but also against other tick-borne diseases.14
Therefore, to follow the vaccinomics approach, it is essential to identify tick bioactive molecules and consequent signaling pathways that mediate tick-host-pathogen interactions.137,138 For example, in a study by Mateos-Hernndez et al,47 tick sialome proteins, with or without -Gal modifications, that led to a protective immune response and were recognized by AGS patients but not control individuals could serve as potential target antigen candidates for vaccine development. The identification of the poorly understood molecular mechanisms behind the development of spontaneous acquired tick resistance (ATR) is also of key importance as it could help in the search for new vaccine formulations.139 Discovering which tick salivary antigens are natural targets of ATR will help to aim towards the inhibition of tick feeding, reproduction and further pathogen transmission.140
AGS is an atypical, underdiagnosed vector-borne allergy that presents clinical implications beyond expected due to the presence of -Gal in various animal-derived medical products, hindering the treatment of several other pathologies.141 Since the discovery of AGS, many advancements have been made in order to obtain a better knowledge in terms of disease epidemiology, medical approach and molecular mechanisms. Nevertheless, current diagnostic methods lack specificity or are too risky for routinary appliance, creating the need to overcome these limitations with more precise methods. Also, a uniformization-based approach of diagnostic guidelines could be beneficial, creating comparable data and offering an opportunity to improve clinical decision-making accuracy. Further diagnostic, treatment and preventive advances will only be possible if the molecular and immune mechanisms behind AGS are uncovered. Furthermore, it is of utmost importance to identify tick salivary molecules, with or without -Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. With climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide,22 which will pose new challenges for clinicians in the future.
Research on AGS was funded by Ministerio de Ciencia e Innovacin/Agencia Estatal de Investigacin MCIN/AEI/10.13039/501100011033, Spain and EU-FEDER (Grant BIOGAL PID2020-116761GB-I00). R. Vaz-Rodrigues was supported by a doctoral contract (2022/20675) from Universidad de Castilla-La Mancha (UCLM), Spain, co-financed by the European Social Fund (ESF). L. Mazuecos was supported by a post-doctoral grant (2021-POST-32002) from UCLM co-financed by ESF.
The authors declare that they have no conflicts of interest in this work.
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New Online Program: Master of Science in Integrative Nutrition – Classes Begin Fall 2022 – Benzinga – Benzinga
Posted: July 19, 2022 at 2:27 am
Bastyr University is proud to announce its first fully online degree program, the Master of Science in Integrative Nutrition.
KENMORE, Wash., July 14, 2022 /PRNewswire-PRWeb/ -- Bastyr University announces the launch of its Master of Science in Integrative Nutrition (MSIN), available online starting Fall 2022. The MSIN is an accelerated, two-year program that prepares its graduates to be integrative nutrition experts. The program allows students in the program to take one course at a time, making it ideal for adults working full-time.
Bastyr created the online MSIN program in response to demand from prospective students outside of the geographic radii of its Seattle and San Diego area campuses, as well as to address the need for integrative nutrition experts in our health system.
"Making innovative nutrition education accessible to more people, everywhere, is a step forward for Bastyr University and the people our graduates serve as they help others build healthier bodies, minds, and spirits," says Bastyr University President Devin Byrd, Ph.D."It's online, one course at a time format makes this ideal for working professionals everywhere."
Upon degree completion, graduates can continue their education at the doctoral level or move into the workplace in areas such as:
A key distinction of this program is its intersectionality of diet, lifestyle, environment, and culture. MSIN students learn about culinary medicine, dietary supplementation, disease prevention through nutrition, social justice and food systems, whole food nutrition, and gain research skills that foster a passion for lifelong learning.
Bastyr University is an accredited, nonprofit, private university offering doctoral,graduate,and undergraduate degrees, with a multidisciplinary curriculum in science-based natural health and medicine. Recognized globally for its rigorous curriculum and strong research, Bastyr University has campuses in Kenmore, Washington, and San Diego, California. Bastyr's facultyeducatefuture leaders in the natural health arts and sciences, with an emphasis on integrating mind, body,spirit,and nature.
For more information about the MSIN program, visit https://bastyr.edu/academics/nutrition/master-science-integrative-nutrition-online.
Media Contact
Nicole Francois, Bastyr University, 206.799.4414, nicole@marketwellnow.com
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Ananta Medicare Provides Preventative Health Solutions to the World – PR Newswire
Posted: July 19, 2022 at 2:23 am
The Global Manufacturer's High-Quality Supplements and Medications Are Designed to Help Support a Healthy Body
FORT LAUDERDALE, Fla., July 14, 2022 /PRNewswire/ -- Reactive medicine is important and essential. However, it is often focused on things like addressing critical dangers, providing damage control, and aiding in recovery. In contrast, often the best form of medicine and healthcare is reactive in nature.
It's a theme that the team at health and wellness manufacturer Ananta Medicare takes to heart. "Our goal isn't to temporarily address a medical issue," explains company president Pradeep Jain, "Our tagline is literally 'endless care about your health.' Most of our products are geared towards the prevention of medical conditions, not just now, but over the long term."
Ananta Medicare's company vision is to create a constant level of care that maintains health and improves the quality of human life across the board. It's this perpetual preventative mentality that has guided the manufacturer over the more than two decades of its existence so far.
Ananta Medicare already operates multiple manufacturing facilities in India. It also has offices in Europe, including the U.K. and Ukraine. This global reach, coupled with the company's devotion to high quality products, has enabled Ananta to lead the charge in shining a light on preventative health for consumers and medical professionals, alike.
"We have earned the confidence of patients and doctors from different countries around the world through our team's exemplary results," Jain explains, " Our success isn't accidental. It is the result of tireless work, devotion to our mission, and the high degree of professionalism our employees display on a daily basis."
The scale of production allows Ananta to focus on preventative health solutions across a broad product range that includes both food supplements and other herbal products. Some of these, such as Femimens and Femicycle, focus on women. Others, like Anantavati Kids, are for younger ages.
The Ananta team always strongly recommends consulting with a doctor before utilizing their products (or any health-related solution) to ensure that it meets the needs dictated by their particular symptoms. Even so, the ability to access clean, effective herbally-based remedies from a reputable manufacturer is a welcome relief for the many Ananta Medicare customers around the globe soon to include the United States.
About Ananta Medicare: Ananta Medicare Limited was founded in 1999 and consists of a group of companies that specialize in the manufacturing and marketing of high-quality products with natural components. These include generic medicines, food supplements, and cosmetics. The brand has plants in India each dedicated to specific manufacturing needs. It also has offices in the UK, India, and Ukraine. The vision of the company is and always has been to protect and preserve health and increase quality of life. Learn more at anantamedicare.com.
Media Contact:SourabhKumarBusiness Development ManagerAnanta Medicare Limited+91 9570620303[emailprotected]
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5 "Health Tips" That are Terrible for Over 50s Eat This Not That – Eat This, Not That
Posted: July 19, 2022 at 2:23 am
Preventative health care is important not just for prevention, but for the early diagnosis and treatment of age-related diseases. "While care for medical emergencies is critical, preventive care is also important to optimize health, especially among older adults," says Dr. Laurie Archbald-Pannone, associate professor of medicine and geriatrics, University of Virginia. "As a geriatrician and professor of medicine, I think one of the best things the US health care system could do now is focus on preventive care, particularly for older adults." Here are five health care tips older adults should ignore, according to experts. Read onand to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.
Using aspirin as a daily blood thinner is no longer standard medical recommendation, experts warn. "Most health professionals agree that long-term aspirin use to prevent a heart attack or stroke in healthy people is unnecessary," warns the FDA. "If you are using aspirin to lower these risks and have not talked with a health professional about it, you may be putting your health at risk. You should ONLY use daily aspirin therapy under the guidance of a health care provider."6254a4d1642c605c54bf1cab17d50f1e
Carbs are not created equalwhile ultra processed carbs and junk food should be avoided, people over 50 can benefit from eating healthy carbs, especially for exercise. "Carbohydrate remains the most important fuel during high-intensity exercise, and there are countless studies to prove it," says registered dietician Edwina Clark.
Researchers believe over 40% of older adults have chronic sleep issues, many of which are undiagnosed. Napping during the daytime can make it harder to sleep at night, experts say. "Limiting naps is one strategy to improve overall nighttime sleep," says Dr. Suzanne Bertisch, an Associate Physician and Clinical Director of Behavioral Sleep Medicine at Harvard-affiliated Brigham and Women's Hospital. "If you take a nap in the late afternoon or evening, it will likely be harder to fall asleep later If you need to nap during the day, it is important to assess why you may be sleepy enough to fall asleep during the day, especially if you nap regularly."
A healthy diet is crucial for healthy agingand no, supplements cannot undo the damage of an unhealthy lifestyle. "The thinking is that taking these pills can somehow improve your health or protect you from disease," says Dr. Pieter Cohen, associate professor at Harvard Medical School and general internist at Harvard-affiliated Cambridge Health Alliance. "While some people may need specific vitamins or supplements to help with deficiencies, for the average healthy person, following a diet with plenty of fruits and vegetables provides all the essential vitamins and minerals."
Healthy fats can help prevent heart disease and stroke, experts say. "After the no-fat eating craze of the '90s, some people still have a dietary fat phobia," says Harvard Health. "Fats do have more calories per gram compared with carbohydrates and protein, but unsaturated fats are important for cardiovascular health. They've been found to lower LDL and total cholesterol when substituted for saturated fats. Include healthy fats in your diet by choosing avocados, olive oil, nuts, nut butters, and seeds."
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‘Death Cap’ Mushrooms Pose Threat to Dogs – University of Wisconsin School of Veterinary Medicine – University of Wisconsin School of Veterinary…
Posted: July 19, 2022 at 2:23 am
While enjoying the warm weather of summer, pet parents should take precautions to protect their dogs from dangerous variations of mushrooms along paths, trails and yards.
Death cap mushrooms, in particular a member of the amanita genus of mushrooms are a poisonous species found in Wisconsin and, more broadly, in the U.S. Ingesting even a single mushroom can be fatal to an adult human. Because pets typically have smaller body weights, doses can be lethal in less quantity.
These large mushrooms, known scientifically as Amanita phalloides, have a broad, off-white cap. When mature, they measure several inches tall and across; immature death cap mushrooms have a rounded cap. They grow readily in moist and warm conditions and are often found in late summer and fall, particularly during heavy rainfall, growing under trees or in forests.
Death caps look fairly bland and have no reported distinctive taste, notes Megan Climans, a veterinary pathology resident with the University of WisconsinMadison School of Veterinary Medicine. For pets, unfortunately, that means there isnt much deterrent to eating them.
If ingested, toxins within death cap mushrooms damage the bodys cells. They target the liver and kidney specifically and can become deadly when the exposure leads to liver failure.
According to Climans, an animal will not typically experience noticeable signs in the first six to 24 hours after ingestion. However, a period of gastrointestinal upset follows, with the affected pet experiencing abdominal cramping and vomiting.
After the abdominal pain passes, patients can seem to fully recover, but damage to the liver and kidney is ongoing, and organ failure can result, Climans explains. This progression of signs and symptoms can vary depending on the size of the patient and the toxic dose consumed.
In Wisconsin, fatal cases of death cap poisoning have occurred in dogs. Organ transplants arent typically an accessible treatment option for dogs, so taking preventative steps remains vital.
Monitor your pets when they go outside, particularly if they tend to be indiscriminate eaters, Climans advises. Its very important to catch a case of mushroom poisoning as early as possible.
If you see your pet eating a wild mushroom, contact a veterinarian or poison control immediately, she adds. Save a sample of the mushroom that was eaten or others growing next to it if possible, for later identification.
If there is suspicion of intoxication, the UW School of Veterinary Medicine can diagnose mushroom poisoning through mushroom identification or laboratory urine tests. Several UW Veterinary Care hospital services are also currently partnering to potentially begin carrying a patient-side urine test to detect toxins.
Alisyn Amant
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Overcoming T Cell Therapy Barriers with Engineered Proteins – The Scientist
Posted: July 19, 2022 at 2:22 am
This webinar will be hosted live and available on-demand
Tuesday, September 13 20222:30 PM Eastern Time (11:30 AM PT)
The tumor microenvironment can severely diminish adoptive T cell therapy efficacy by expressing ligands that activate T cell inhibitory receptors and by downregulating costimulatory ligand expression. To address these issues, researchers developed fusion proteins (FPs) that combine the ectodomain of one receptor with a different intracellular costimulatory signaling domain. Using in vitro assays, including the Incucyte serial killing over-time (SKO) assay, they evaluated T cell engineering strategies in persistence and survival studies.
In this LabTools webinar brought to you by Sartorius, Shannon Oda will discuss how pairing different extracellular and intracellular domains in FPs confers different attributes to therapeutic T cells.
Topics to be covered
Shannon K. Oda, PhDPrincipal InvestigatorSeattle Childrens Research InstituteAssistant ProfessorDepartment of Pediatrics Division of Hematology/Oncology University of Washington School of Medicine
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Patients Waiting Months for ‘Last Chance’ CAR T-Cell Therapy – Medscape
Posted: July 19, 2022 at 2:22 am
Some patients with blood cancers for whom all other therapeutic options have been exhausted have one final chance of getting rid of their disease treatment with chimeric antigen-receptor (CAR) T cells.
Described as a "living drug," the treatment involves genetically engineering the patient's own blood cells and reinfusing them back into their system. These CAR T cells then hunt down and destroy cancer cells, and in some cases, they manage to totally eradicate the disease.
About half of patients with leukemia or lymphoma and about a third with myeloma who receive this treatment have a complete remission and achieve a functional "cure."
But not all patients who could benefit from this therapy are able to get it.
Some are spending months on waiting lists, often deteriorating while they wait. These patients have exhausted all other therapeutic options, and many are facing hospice and death.
The scope of this problem was illustrated by a recent survey of the centers that are certified to deliver this complex therapy.
The survey was led by Yi Lin, MD, PhD, associate professor of medicine at the Mayo Clinic, Rochester, Minnesota, and medical director for the cellular therapy program. It was published as an abstract at the recent annual meeting of the American Society of Clinical Oncology, although it was not presented at the meeting.
"We wanted to find out just how widespread this problem is," she said, adding, "There had been nothing in the literature thus far about it."
The team contacted 20 centers across the US and received responses from 17.
The results showed that the median time on the waiting list was 6 months and that only 25% of patients eventually received CAR T-cell therapy.
An additional 25% were able to enter a CAR-T clinical trial.
The remaining 50% of patients either were enrolled in a different type of trial, entered hospice, or died.
For patient selection, all centers reported using a committee of experienced physicians to ensure consistency. They employed different ethical principles for selection. Some centers sought to maximize the total benefit, such as selecting the patients most likely to achieve leukapheresis or a clinical response, while others based their decisions on the time patients spent on waiting list or gave priority to the patients who were the "worst off" with the most limited therapeutic options.
The shortages in CAR T-cell therapies primarily involve the products used for patients with multiple myeloma.
The problem has not, as yet, noticeably spilled over to lymphoma and leukemia treatments, which use a slightly different type of CAR T-cell therapy (it targets CD19, whereas the cell therapies used for myeloma target BCMA).
"We have backlog of myeloma patients who don't have access," said Nina Shah, MD, a hematologist and professor of medicine at the University of California, San Francisco. "We have only four slots for the two myeloma products but about 50 to 60 eligible patients."
Long waiting times for CAR T cells for myeloma have been an issue ever since the first of these products appeared on the market idecabtagene vicleucel (ide-cel; Abecma), developed by Bluebird Bio and Bristol-Myers Squibb (BMS). "As soon as it became available in March 2021, we had people waiting and limits on our access to it," Shah said.
A second CAR T-cell therapy for myeloma, ciltacabtagene autoleucel (cilta-cel, Carvykti), developed by Janssen and Legend Biotech, received approval in February 2022.
While that helped provide centers with a few more slots, it wasn't sufficient to cut the waiting times, and the demand for these myeloma therapies continues to outstrip the capacity to produce CAR-T products in a timely manner.
"For myeloma, the demand is very high, as most patients are not cured from any other existing myeloma therapies, and most patients will make it to fifth-line therapy where the two CAR T-cell products are approved right now," said Krina K. Patel, MD, medical director of the Department of Lymphoma/Myeloma in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, Houston.
"We likely have 10 eligible CAR-T myeloma patients each month at our center," she said, "but were getting two slots per month for the past 8 months, and now are getting four slots a month."
"Our clinic has also experienced the impact of the low number of manufacturing slots offered to each cancer center for some CAR T-cell products," said David Maloney, MD, PhD, medical director, Cellular Immunotherapy and Bezos Family Immunotherapy Clinic, Seattle Cancer Care Alliance, Washington.
He noted that, as with other cancer centers, for multiple myeloma, they are provided a specific number of manufacturing slots for each treatment. "Our providers discuss which patients are most appropriate for available slots for that month," said Maloney.
"Additionally, juggling patient schedules may be required to address the extended manufacturing time for some products. In some cases, clinical trials may be available in a more timely fashion for appropriate patients, and in some cases, switching to an alternative product is possible," he commented.
The cause of the current bottleneck for myeloma patients is complex. It stems from a shortage of raw materials and supply chain restraints, among other things.
While the biggest impact of shortages has been on patients with multiple myeloma, Patel pointed out that these constraints are also affecting patients with lymphoma at her institution, but to a lesser degree currently.
"This is multifactorial as to why, but most of the issues arise from manufacturing," Patel told Medscape Medical News. "Initially, the FDA limited how many slots each new product could have per month, then there was a viral vector shortage, and then the quality-control process the FDA requires takes longer than the manufacturing of the cells actually do," she explained.
On top of that, "we have about a 5% manufacturing fail rate so far," she added. Such failures occur when the cells taken from a patient cannot be converted into CAR T cells for therapy.
Matthew J. Frigault, MD, from the Center for Cellular Therapies, Mass General Cancer Center, Boston, explained that the growing excitement about the potential for cellular therapy and recent approvals for these products for use in earlier lines of treatment have increased demand for them.
There are also problems regarding supply. The manufacturing and delivery of CAR-T is complicated and takes time to scale up, Frigault pointed out. "Therefore, we are seeing limited access, more so for the BCMA-directed therapies [which are used for myeloma]."
The shortages and delays likely involve two main factors. "For the newer indications, there is a significant backlog of patients who have been waiting for these therapies and have not been able to access them in the clinical trial setting, and manufacturing is extremely complicated and not easily scaled up," he said.
"That being said, manufacturers are trying to increase the number of available manufacturing slots and decrease the time needed to manufacture cells," Frigault commented.
Delays in access to myeloma CAR T-cell therapy are also affecting patient care at the Fox Chase Cancer Center. "We have had about one slot every 2 months for Abecma," noted Henry Fung, MD, chair of the Department of Bone Marrow Transplant and Cellular Therapies. "For Carvykti, there are only 32 certified centers in US, and access is very limited."
Fung explained that they have had to offer alternative treatments to many of their patients. "There are rumors that there's shortage in obtaining raw materials, such as the virus used for transduction, although we have not encountered any problems in other CAR-T products used for lymphomas," he said.
Medscape Medical News reached out to the manufacturers of the CAR-T products. All have reported that they are doing what they feasibly can to ramp up production.
"The complexity of delivering CAR T-cell therapies is unlike any other traditional biologic or small-molecule medicine, using a patient's own cells to start a highly sophisticated and personalized manufacturing process," commented a spokesperson for BMS, which has two CAR T-cell products currently on the market.
"In this nascent field of cell therapy, we continue to evolve every day, addressing supply and manufacturing challenges head on by applying key learnings across our three state-of-the-art cell therapy facilities and two new facilities in progress.
"We have been encouraged by a steady increase in our manufacturing capacity, and we continue efforts to ramp up further to meet the demand for our cell therapies," the BMS spokesperson commented. "We have already seen improvements in the stabilization of vector supply and expect additional improvements in capacity in the second half of 2022."
Novartis said much the same thing. They have a "comprehensive, integrated global CAR-T manufacturing footprint that strengthens the flexibility, resilience, and sustainability of the Novartis manufacturing and supply chain. Together with an improved manufacturing process, we are confident in our ability to meet patient demand with timely delivery," said a Novartis spokesperson.
The spokesperson also pointed out that the company has continuously incorporated process improvements that have significantly increased manufacturing capacity and success rates for patients in need of CAR T cells.
"Data presented at American Society of Hematology annual meeting in 2021 showed the Novartis Morris Plains facility our flagship CAR-T manufacturing site had commercial manufacturing and shipping success rates of 96% and 99%, respectively, between January and August 2021," according to the spokesperson.
Legend and Janssen, the companies behind Carvykti, one of the two approved cell products for myeloma, which launched earlier this year, said that they have continued to activate certified treatment centers in a phased approach that will enable them to expand availability throughout 2022 and beyond.
"This phased approach was designed to ensure the highest level of predictability and reliability for the patient and the certified treatment centers," the spokesperson said. "We understand the urgency for patients in need of Carvyki and are committed to doing everything we can to accelerate our ability to deliver this important cell therapy in a reliable and timely manner."
With regard to the industry-wide supply shortage of lentivirus, Legend and Jassen say they have put in place multiple processes to address the shortage, "including enhancing our own internal manufacturing capabilities of this essential drug substance, to ensure sufficient and sustained supply."
The supply shortage that myeloma patients are experiencing is all the more poignant and distressing, given the immense potential of CAR T-cell therapy. While not everyone benefits, some patients for whom every other therapy failed and who were facing hospice have had dramatic results.
"Incredibly exciting with unbelievable potential" was how one expert described these new therapies when the first product was about to enter the marketplace. Since then, six CAR T-cell therapies have received regulatory approval for an ever-increasing range of hematologic malignancies.
But these CAR T-cell therapies have their own set of adverse events, which can be serious and even life-threatening. In addition, not all patients become cancer free, although long-term data are impressive.
A study that included one of the longest follow-ups to date was reported at the 2020 annual meeting of the American Society of Clinical Oncology. The researchers reported that remissions lasted over 9 years for patients with relapsed/refractory B-cell lymphoma or chronic lymphocytic leukemia who underwent treatment with Kite's axicaptagene cilleucel (Yescarta). This review included 43 patients and showed an overall remission rate of 76%. Complete remission was achieved for 54% of patients, and partial remission was achieved for 22%.
The results with CAR T-cell therapy in multiple myeloma are not quite as impressive, but even so, the clinical data that supported the approval of Abecma showed that a third of patients, who had previously received a median of six prior therapies, achieved a complete response.
At the time of the Abecma approval, the lead investigator of the study, Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, Massachusetts, commented: "The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients."
Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.
For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.
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New Mesenchymal Stromal Cell Therapy Shows Promise for People with Difficult-to-Treat Lupus – Lupus Foundation of America
Posted: July 19, 2022 at 2:22 am
Newly published results from a Phase I clinical trial suggest that mesenchymal stromal cells (MSCs, a type of cell derived from bone marrow and other bodily tissue) can be used as a safe and potentially effective therapy for the treatment of lupus.
In this Phase I study, six women with refractory lupus (lupus that is resistant to treatment) were treated with MSCs derived from umbilical cord tissue. Three of the participants were Caucasian, two were African American and one was Hispanic.
Overall, five of the six women achieved a clinically meaningful decrease in lupus disease activity scores compared to their baseline level of disease activity, as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). By week 24 post-treatment, SLEDAI scores decreased by an average of 5.4 points, from an average of 8.2 at baseline to 2.8 at the end of the trial period.
Additionally, researchers noted encouraging changes in other lupus biomarkers among the participants, and no serious side effects were observed. Based on these promising early results, researchers are moving forward with a Phase II trial, which will include a larger group of study participants and collect data over a longer time period to assess its effectiveness.
This study was funded by the Lupus Foundation of America in partnership with the National Institute of Allergy and Infectious Diseases. MSC therapy is an exciting new frontier in lupus research, and its especially promising for those living with refractory lupus. Learn more about these Phase I and Phase II trials, and the importance of MSC research.
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