Day: July 1, 2024

Jul 01

Everything to Know About Septic Arthritis

Septic arthritis is a rare and severe arthritis that affects one or more of your joints. Bacteria generally cause it, but sometimes, it can develop after exposure to a virus or fungus. The infection will spread to the joints and cause inflammation. Septic arthritis is also called pyogenic arthritis or bacterial arthritis. It typically affects the large joints of the hips and knees but can affect other joints, such as the shoulder or ankle, as well. Symptoms include severe pain and swelling, limited joint range of motion, fever, and chills. Risk factors include prior joint surgery, a weakened immune system, diabetes, inflammatory arthritis, or an open wound. Septic arthritis is treated with antibiotics and can be a serious condition if left untreated. It can lead to progressive and irreversible joint damage or become a life-threatening medical emergency. This article will cover the causes and risk factors for septic arthritis, its effects on joints, symptoms, treatment, and more. prpicturesproduction / Getty Images What Causes Septic Arthritis? Septic arthritis is caused by bacteria, viruses, and fungi, with Staphylococcus aureus (staph) as the most common infectious cause. Staphylococcus aureus bacteria are linked to pneumonia, skin infections, sepsis, and bone and joint infections. Staph infections can become life-threatening if not adequately treated. Septic arthritis can develop when an infection, such as a skin infection, spreads into the bloodstream to a joint. This might be because of an open wound related to surgery or injury, which allows germs to enter the joint space. It typically affects one joint. However, it is possible to experience the condition in multiple joints depending on the bacterium that caused it. For example, Neisseria bacteria can lead to septic arthritis in multiple joints (polyarticular arthritis). With polyarticular septic arthritis, usually both knees are involved, but other joints can also be affected. Inflammation linked to septic arthritis occurs at the cartilage surface (the connective tissue that allows bones and joints to move over one another smoothly) or the synovium (joint lining). It can also invade the synovial fluid that lubricates the joints. The most common organisms that lead to pediatric septic arthritis are methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, group B Streptococcus, Klebsiella pneumoniae, and Gram-negative bacilli. Common pathogens for adult septic arthritis include Staphylococcus aureus, coagulase-negative Staphylococcus, Streptococcus, and Pseudomonas, and other Gram-negative bacteria. Who Is at Risk for Septic Arthritis? Septic arthritis frequently affects children, but adults get it too. Children are at a higher risk for infections that could lead to septic arthritis. Some risk factors in children and adults increase the risk for infections, including those that lead to septic arthritis. Risk factors include: Arthritis conditions, including osteoarthritis, gout, and autoimmune arthritis like rheumatoid arthritis (RA) and lupus: The medications you take to treat these conditions could also raise the risk for septic arthritis. For example, people with RA are treated with drugs that suppress the immune system and increase their risk for infection, including, disease-modifying antirheumatic drugs (DMARDs) and corticosteroids. Previous septic arthritis: If you have had septic arthritis in the past, you are more likely to get it a second time. Having a weakened immune system: People with diabetes and kidney or liver problems are at an increased risk for septic arthritis. The medications they take to treat these conditions can add to that risk. Having an artificial joint: Bacteria can enter the joint space during joint surgery, or an artificial joint can be infected after an infection from a nearby body area. Joint trauma: If you have an open wound or cut near a joint, germs from the skin can enter the joint space through the bloodstream. Skin problems: People with fragile skin might be at an increased risk for septic arthritis. This includes people with psoriasis, an autoimmune skin condition that causes overgrowth of skin cells. Injection drug use: This is a newer known risk factor often linked to non-medically administered injections that are not sterile and can introduce bacteria through the skin into the bloodstream. These bacteria might be more antibiotic-resistant or infectious, leading to disease complications and life-threatening medical situations. Two or more of the above risk factors put you at a greater risk for developing septic arthritis compared to one risk factor alone. What Joints Are More Likely to Have Septic Arthritis? In general, infections in native joints (joints you’re born with as opposed to prosthetic, or artificial, joints that are implanted) commonly occur in the knees, hips, shoulders, ankles, elbows, and wrists. However, the location may depend on the type of pathogen, underlying conditions, or exposure type. Additionally, children may experience septic arthritis in different joints than adults. Research shows that children are more likely to get septic arthritis in the hip or knee. Children can also experience elbow septic arthritis caused by a staph infection. Pathogens that cause septic arthritis in adults are typically linked to medical history, health status, orthopedic surgery, and injection drug misuse. Adults are more likely to get septic arthritis in the knee or the small joints of the interphalangeal joints (hinge joints) of the fingers. Septic arthritis causes excess fluid in and around the knee joint. “Knee joint effusion” is the medical term for this condition, and it is seen on ultrasound in 91% of people with septic arthritis. One 2021 Orthopedics report finds the joints most affected by septic arthritis caused by injection drug use include the knees, ankles, shoulders, elbows, wrists, and fingers. Additional research suggests septic arthritis linked to injection drugs may also affect the sacroiliac joints connecting the pelvis and lower spine, the facet joints in the lower spine, and the sternoclavicular joint connecting the collarbone to the breastbone. What Are the Symptoms of Septic Arthritis? The symptoms of septic arthritis will occur in the infected joints. You may also experience systemic (whole-body) symptoms. Symptoms of septic arthritis include: Severe pain and tenderness in the affected joint, especially with movement Visible swelling from increased fluid in the joint Warmth (the joint is warm to the touch) Stiffness of

Jul 01

Officials ID Death Due To Rare, Flesh-Eating Disease On LI As Man, 55

LONG ISLAND, NY — Officials confirmed Friday that the person who died of a rare, flesh-eating bacteria on Long Island was a 55-year-old-man. Suffolk County officials said the man lived in Brookhaven Town but did not give any additional information. Health officials this week warned of a rare flesh-eating bacterium known as Vibrio vulnificus, found naturally in warm coastal waters, that has killed at least eight people along the East Coast this summer. In addition to the Long Island death, two people died in Connecticut after becoming infected, health officials in both states said this week. Five people have died in Florida so far this year, according to state health officials. Vibrio infections are commonly associated with eating raw or undercooked oysters and other seafood, but also occur when people with open wounds or cuts come in contact with seawater or brackish water where the bacteria are present, according to the U.S. Centers for Disease Control and Prevention. New York State Health Commissioner Dr. James McDonald said: “We are reminding providers to be on the lookout for cases of vibriosis, which is not often the first diagnosis that comes to mind. We are also suggesting to New Yorkers that if you have wounds, you should avoid swimming in warm seawater. And, if you have a compromised immune system, you should also avoid handling or eating raw seafood that could also carry the bacteria.” Three people in all were hospitalized in Connecticut after becoming infected. Two of the three Vibrio vulnificus infections reported in that state were wound infections not associated with seafood. The third infection was a Connecticut resident who consumed raw oysters at an out-of-state establishment. “The bacteria is extraordinarily dangerous,” New York Gov. Kathy Hochul said after the Long Island resident died as a result of the infection. Hochul said that vibriosis can cause skin breakdown and ulcers. Hochul urged New Yorkers to learn how to avoid exposure and to take appropriate precautions, as the New York State Department of Health reminded providers to consider vibriosis when diagnosing wound infections or sepsis of unknown origins. “While rare, the vibrio bacteria has unfortunately made it to this region and can be extraordinarily dangerous,” Hochul said. “As we investigate further, it is critical that all New Yorkers stay vigilant and take responsible precautions to keep themselves and their loved ones safe, including protecting open wounds from seawater and for those with compromised immune systems, avoiding raw or undercooked shellfish which may carry the bacteria.” Vibriosis is caused by several species of bacteria, including the Vibrio vulnificus bacteria, which occurs naturally in saltwater coastal environments and can be found in higher concentrations from May to October when the weather is warmer, Hochul added. Infection with vibriosis can cause a range of symptoms when ingested, including diarrhea, stomach cramps, vomiting, fever and chills. Exposure can also result in ear infections and cause sepsis and life-threatening wound infections. The death in Suffolk County is still being investigated to determine if the bacteria was encountered in New York waters or elsewhere, Hochul said. “While we continue to investigate the source of this rare infection, it is important for residents to remain aware and vigilant on precautions that can be taken,” Suffolk County Executive Steve Bellone said. While anyone can get vibriosis, those with liver disease, cancer or a weakened immune system or people taking medicine to decrease stomach acid levels may be more likely to get an infection or develop complications when infected, Hochul said. To help prevent vibriosis, people with a wound, such as a cut or scrape, a recent piercing or tattoo, should avoid exposing skin to warm seawater in coastal environments or cover the wound with a waterproof bandage. In addition, those with compromised immune systems should avoid eating raw or undercooked shellfish, such as oysters, which can carry the bacteria. Wear gloves when handling raw shellfish and thoroughly wash your hands with soap and water when finished. People infected by the Vibrio vulnificus bacteria often require intensive care or limb amputations, and about one in five die, often within a day or two of becoming ill, according to the CDC. People at greatest risk for illness from the infection are those with weakened immune systems and the elderly. Some Vibrio vulnificus infections lead to necrotizing fasciitis, a severe infection in which the flesh around an open wound dies, inspiring the “flesh-eating bacteria” moniker. The necrotizing fasciitis can be caused by more than one type of bacteria, according to the CDC. Besides occurring naturally in warm coastal waters, Vibrio vulnificus infections have also been associated with hurricanes, storm surges and coastal flooding.

Jul 01

Dr Islam on the Current and Expanding Role of Pirtobrutinib in MCL

Prioty Islam, MD, MSc, attending physician, medical oncologist, Leukemia, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, discusses how the approval of the noncovalent BTK inhibitor pirtobrutinib (Jaypirca) has transformed the treatment of patients with mantle cell lymphoma (MCL), and where this agent fits in to the current treatment armamentarium. Pirtobrutinib received FDA approval in January, 2023, for the treatment of patients with relapsed/refractory MCL who have been previously exposed to at least 2 prior lines of systemic therapy, including a BTK inhibitor. This approval was supported by data from the phase 1/2 BRUIN trial (NCT03740529), in which a subset of patients with MCL achieved a high overall response rate (ORR) with the agent. Historically, patients with relapsed/refractory MCL experienced poor prognosis and did not respond well to chemoimmunotherapy regimens, Islam begins. However, the introduction of single-agent, oral targeted BTK inhibitors, such as pirtobrutinib, to the treatment armamentarium has improved the durability of patient responses to treatment, Islam states, as well as patients’ quality of life. Accordingly, this drug class has significantly affected the treatment of relapsed/refractory MCL, she says. Much like its activity in chronic lymphocytic leukemia, pirtobrutinib has been shown to successfully restore BTK inhibitor dependency in patients with MCL, as well as induce responses in those who previously progressed on a different BTK inhibitor, Islam continues. Although there is interest in moving pirtobrutinib into earlier lines of therapy in MCL, efforts to accomplish this remain both a challenge and a subject of debate due to a lack of data on patient responses after progression on pirtobrutinib, Islam cautions. The ongoing, randomized phase 3 BRUIN-MCL-321 trial (NCT04662255) is investigating pirtobrutinib vs investigator’s choice of BTK inhibitor in patients with pretreated, BTK inhibitor–naïve MCL. Findings from the trial are hoped to illuminate the feasibility of utilizing pirtobrutinib in the frontline, as the current FDA indication for this agent is after progression on or intolerance to a prior covalent BTK inhibitor, Islam says. Disclosures: Dr Islam reports consulting roles with AbbVie, AstraZeneca, BeiGene, DAVA Oncology, and LOXO Oncology; as well as speaking roles with Targeted Oncology and The Video Journal of Hematologic Oncology (VJHemOnc).

Jul 01

Evolving Drug Classes Expand Treatment Options Across Hematologic Malignancies

Raajit K. Rampal, MD, PhD Individualized myelofibrosis treatment begins with correctly identifying a patient’s disease subtype and considering their symptoms, from which accurate decisions regarding the use of JAK inhibitors vs radiation vs hypomethylating agents (HMAs) can lead to spleen and symptom burden reductions, according to Raajit K. Rampal, MD, PhD. During an OncLive® State of the Science Summit™ on hematologic malignancies, Rampal and colleagues highlighted the role of JAK inhibitors in myelofibrosis; considerations for CAR T-cell therapy in follicular lymphoma (FL); efficacy and safety findings with asciminib (Scemblix) in chronic myeloid leukemia (CML); the future of BTK inhibitors in mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL); unmet needs in diffuse large B-cell lymphoma (DLBCL); and research on the horizon in lower-risk myelodysplastic syndrome (MDS). Rampal, who chaired the event, is the director of the Myeloproliferative Neoplasms Program and an associate attending physician at Memorial Sloan Kettering Cancer Center in New York, New York. Rampal was joined by his colleagues: Alexander P. Boardman, MD, assistant attending physician, Memorial Sloan Kettering Cancer Center Michael J. Mauro, MD, leader, Myeloproliferative Neoplasm Program, Leukemia Service, Memorial Sloan Kettering Cancer Center Prioty Islam, MD, MSc, assistant attending physician, Memorial Sloan Kettering Cancer Center Jennifer K. Lue, MD, clinical director, Lymphoma Service, Memorial Sloan Kettering Cancer Center Jan Philipp Bewersdorf, MD, hematology/oncology fellow, Memorial Sloan Kettering Cancer Center Below, Rampal, Boardman, Mauro, Islam, Lue, and Bewersdorf summarize the main messages from their presentations. Current and Emerging Treatments in Myelofibrosis Rampal: [Myelofibrosis] treatment depends on the issue. This is 1 of the major principles in treating [patients with] myelofibrosis. It’s not a monolithic entity. This disease has different manifestations, and we need to treat the manifestation that is causing the patient the major issue. [When] some patients [present with myelofibrosis], anemia is the major [symptom] they’re [experiencing], not spleen [issues]––nothing else, just anemia. For those patients, a JAK inhibitor may not necessarily be the right choice, but [treatments such as] erythropoiesis-stimulating agents [ESAs], danazol, corticosteroids, or even immunomodulatory agents may be an appropriate first-line choice. However, for patients with symptomatic splenomegaly or constitutional symptoms, JAK inhibitors have made their mark. Compared with [treatments such as] hydroxyurea, JAK inhibitors have superior efficacy, reducing both spleen size and symptom burden. We have 3 FDA-approved [JAK inhibitors] currently. For other manifestations of this disease, there are other [treatments] we can use. For patients with extramedullary hematopoiesis in the lungs or bones, radiation is appropriate. For patients who are early in their disease, sometimes pegylated interferon can be useful; some data support that. When patients progress to accelerated or blast-phase disease, HMAs are the backbone of therapy, usually in combination with other agents. CAR T-Cell Therapy in FL Boardman: CAR T-cell therapy is clearly active in relapsed/refractory FL, with high response rates, and is effective in patients with high-risk disease. Current data suggest that these remissions are durable but given [that FL is] an indolent lymphoma, we need more time to [confirm these data]. Adverse effects [AEs] [including] cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome are common and must be considered when weighing treatment options for patients, especially those who may be frailer. Lastly, the optimal timing of CAR T-cell therapy vs bispecific antibodies and other targeted agents will require further study. Current and Novel TKIs in CML Mauro: We might think of ponatinib [Iclusig] being favored [over asciminib] in patients with primary resistance [and] high transcript levels. For patients with compound mutations and pan cytopenias, neither drug may be successful. These can be challenges. Patients with a mixture of intolerance and resistance who have perhaps more preserved response or at least more residual response from prior therapy exposure may have a better AE experience and better long-term outcomes with asciminib, at least speculatively. The T315I [mutation] is up for grabs. [Either ponatinib or asciminib may effectively target this mutation] because [both drugs seem to have activity there], and we don’t have concerns about the differences in dosing [between] asciminib [and ponatinib]. Looking into the future, other drugs are under further study. Olverembatinib, which is approved In China, is the drug that is closest to ponatinib and is in trials in the United States [US] now. [Regarding] other agents, we have some trials at Memorial Sloan Kettering Cancer Center. The [phase 1] ELVN-001 trial [NCT05304377] is open, [investigating an] ATP-competitive inhibitor that’s probably [similar to] ponatinib in its activity but may be much safer. Some other second-line allosteric inhibitors, such as TERN-701, [will also be investigated in clinical trials]. [The evolution of TKIs in CML is] a good story. A growing number of patients with CML are surviving CML, so survivorship is another effort and project at Memorial Sloan Kettering Cancer Center. The number of patients living with CML in the US will probably be 10 times what it used to be by the middle of the century. Asciminib will be a big help, [because] it offers better safety [than other TKIs]. We’ll see how other trials look. BTK Inhibitors in CLL and MCL Islam: BTK inhibition with small-molecule–targeted drugs has transformed the way we treat [patients with] B-cell malignancies over the past decade, ever since the advent of ibrutinib [Imbruvica] in the early 2010s. Newer-generation BTK inhibitors continue to improve safety and efficacy and are now even trying to overcome the resistance mechanisms we’ve seen with covalent BTK inhibitors. These drugs are being studied as monotherapies and have promising efficacy as single agents. [They] are also being combined with already-approved and emerging therapies. This has been a paradigm shift in both CLL and MCL, away from combination chemoimmunotherapy and more intensive therapies like autologous stem cell transplantation, potentially. There’s much to come, and many exciting data will be published in the next couple of years. Updates in DLBCL Management Lue: POLA-R-CHP [rituximab (Rituxan), cyclophosphamide, doxorubicin, polatuzumab vedotin-piiq (Polivy), and prednisone], has become the standard of care [(SOC) for patients with DLBCL with an] International Prognostic Index [score of] 2 and activated B-cell biology. We

Jul 01

Severe COVID-19 may lead to long-term innate immune system changes

Media Advisory Friday, August 18, 2023 NIH-funded research links alterations to inflammatory protein, underscores vaccine importance. What Severe COVID-19 may cause long-lasting alterations to the innate immune system, the first line of defense against pathogens, according to a small study funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. These changes may help explain why the disease can damage so many different organs and why some people with long COVID have high levels of inflammation throughout the body. The findings were published online today in the journal Cell. Researchers led by Steven Z. Josefowicz, Ph.D., of Weill Cornell Medicine in New York City examined immune cells and molecules in blood samples from 38 people recovering from severe COVID-19 and other severe illnesses, as well as from 19 healthy people. Notably, the researchers established a new technique for collecting, concentrating and characterizing very rare blood-forming stem cells that circulate in the blood, eliminating the need to extract such cells from bone marrow. In these rare stem cells—the parents of immune-system cells—taken from people recovering from COVID-19, the scientists identified changes in the instructions for which genes got turned on or off. These changes were passed down to daughter cells, leading them to boost production of immune cells called monocytes. In the monocytes from people recovering from severe COVID-19, the changes in gene expression led the cells to pump out greater amounts of molecules called inflammatory cytokines than monocytes from people who were healthy or had non-COVID-19 illnesses. The researchers observed these changes as much as a year after the participants came down with COVID-19. Due to the small number of study participants, the scientists could not establish a direct association between the cellular and molecular changes and health outcomes. The investigators suspected that an inflammatory cytokine called IL-6 might play role in establishing the changes in gene-expression instructions. They tested their hypothesis both in mice with COVID-19-like disease and in people with COVID-19. In these experiments, some of the subjects received antibodies at the early stage of illness that prevented IL-6 from binding to cells. During recovery, these mice and people had lower levels of altered stem cell gene-expression instructions, monocyte production and inflammatory cytokine production than subjects that didn’t receive the antibody. In addition, the lungs and brains of mice that received the antibodies had fewer monocyte-derived cells and less organ damage. These findings suggest that SARS-CoV-2 can cause changes in gene expression that ultimately boost the production of inflammatory cytokines, and one type of those cytokines perpetuates the process by inducing these changes in stem cells even after the illness is over. Additionally, the findings suggest that early-acting IL-6 is likely a major driver of long-term inflammation in people with severe COVID-19. These findings shed light on the pathogenesis of SARS-CoV-2 infection and may provide new leads for therapies. The results also underscore the importance of staying up to date with recommended COVID-19 vaccines, which are proven to protect against serious illness, hospitalization and death. Article JG Cheong et al. Epigenetic memory of coronavirus infection in innate immune cells and progenitors. Cell DOI: 10.1016/j.cell.2023.07.019 (2023). Who Joy Liu, M.D., a program officer in the NIAID Division of Allergy, Immunology and Transplantation, is available to discuss this research. NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov. NIH…Turning Discovery Into Health® ###

Jul 01

White Plains Hospital and Montefiore Bring Pediatric Specialty Care to White Plains

With a new office dedicated to specialty conditions in children, White Plains Hospital and Montefiore commit to expanding pediatric care in Westchester. Advanced pediatric care in Westchester became more convenient with the opening of the new Montefiore Pediatric Specialty practice. Pediatric cardiologists, pediatric gastroenterologists, pediatric surgeons, a pediatric rheumatologist and a pediatric nephrologist from the renowned Children’s Hospital at Montefiore (CHAM) are now seeing patients at 33 Davis Avenue in White Plains. Unlike general pediatricians, pediatric subspecialists are the only physicians uniquely qualified to diagnose, treat, and manage infants, children and adolescents with specialized complex, chronic conditions. They also focus on the developmental and emotional needs of children and adolescents, which can be different from those of adults. “Having access to advanced pediatric care, closer to home, is so important for families,” says Frances Bordoni, Executive Vice President for Ambulatory and Physician Services and Business Development at White Plains Hospital. “Montefiore has some of the best pediatric specialists in the country. To bring these services to Westchester eliminates barriers and heightens peace of mind for families who no longer have to scramble to get their children the care they need.” Through its partnership with Montefiore Einstein and CHAM, which has long been recognized as one of the nation’s best pediatric hospitals by U.S. News & World Report, White Plains Hospital enhances its pediatric specialty care in several critical areas with the addition of nationally recognized specialists who are leaders in their respective fields and actively engaged in clinical research to advance their respective specialties. CHAM’s Pediatric Heart Center is a world leader in advanced cardiovascular care for patients of all ages, from newborns to adults with congenital heart diseases. Pediatric cardiologist Dr. Daphne Hsu is one of the nation’s leading experts in children’s heart failure and heart transplantation. In addition to caring for pediatric and adult patients with congenital heart disease, Dr. Hsu conducts ongoing clinical research and is a nationally recognized pediatric cardiologic thought leader. For children with gastrointestinal conditions, liver disease, or nutritional concerns, CHAM offers one of the leading pediatric gastrointestinal (GI) programs in the nation, led by Dr. John F. Thompson. Dr. Thompson specializes in short bowel syndrome, Crohn’s disease, ulcerative colitis, celiac disease, eosinophilic esophagitis, feeding disorder, and chronic abdominal pain. Dr. Thompson is also the director of the Intestinal Rehabilitation Program at CHAM. His research focuses on ways to improve the lives and outcomes of children who have intestinal failure and short bowel syndrome. In addition, pediatric gastroenterologist Dr. Gitit Tomer leads CHAM’s Inflammatory bowel disease (IBD) program, which is dedicated to providing excellent care and improving the health and quality of life of patients with inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). IBD are chronic relapsing inflammatory gastrointestinal diseases causing severe diarrhea abdominal pain and weight loss that can lead to life-threatening complications. CHAM also offers nationally-recognized care for pediatric patients with kidney conditions. Dr. Frederick Kaskel, an internationally recognized expert in pediatric nephrology, who specializes in the treatment of kidney disorders in infants, children and adolescents and in end-stage kidney replacement therapy and transplantation, is Chief Emeritus of its Division of Pediatric Nephrology. The Ira Greifer Children’s Kidney Center includes New York state’s first dedicated pediatric dialysis facility. “We are delighted to enhance access to our team of pediatric subspecialists, many of whom have raised their own children in Westchester. No matter the symptom, condition or question, our team is ready to care for children and families in need of sophisticated specialty care at the Davis Avenue location,” said Michael D. Cabana, MD, MPH, Physician-in-Chief, The Children’s Hospital at Montefiore and The Michael I. Cohen, MD, University Chair, Department of Pediatrics, Albert Einstein College of Medicine. To make an appointment at the Montefiore Pediatric Specialty office, call 914-849-KIDS (5437). The providers seeing patients at 33 Davis Avenue include: Pediatric Cardiologist Daphne Hsu, MD Pediatric Gastroenterologists Inessa Normatov, MDJohn Thompson, MDGitit Tomer, MD Pediatric Nephrologist Frederick J. Kaskel, MD Pediatric Rheumatologist Tamar Rubinstein, MD Pediatric Surgeons Steven H. Borenstein, MDAlexandre N. Darani, MDDominique M. Jan, MD

Jul 01

Second-Line Axi-Cel Elicits Complete Metabolic Responses in Transplant-Ineligible LBCL

Francois Lemonnier, MD, PhD Second-line treatment with axicabtagene ciloleucel (axi-cel; Yescarta) led to an investigator-assessed, 3-month complete metabolic response (CMR) rate of 71.0% (95% CI, 58.05%-81.80%) in patients with large B-cell lymphoma who were ineligible for autologous stem cell transplant (ASCT), according to data from the final analysis of the phase 2 ALYCANTE trial (NCT04531046). Findings presented at the 2023 EHA Congress showed that evaluable patients (n = 62) experienced a 3-month objective response rate (ORR) of 75.8%, including a partial response (PR) rate of 4.8%, per investigator assessment. No patients had stable disease (SD), 11.3% of patients had progressive disease, and 12.9% of patients were not evaluated. Notably, 59.7% of patients remained in CMR at 6 months. Per investigator assessment of best response, the ORR was 90.3%, including a CMR rate of 79.0%, a PR rate of 11.3%, and SD and progressive disease rates of 4.8% each. “The study met its primary end point with a CMR [rate] of 71% at 3 months vs a 12% expected [CMR rate] with historical controls,” presenting study author Francois Lemonnier, MD, PhD, of the Lymphoid Malignancies Unit at Henri-Mondor University Hospital in Créteil, France, said. The single-arm, open-label, multicenter trial conducted at 20 centers in France enrolled patients with aggressive B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), and grade 3B follicular lymphoma, who were relapsed or refractory within 12 months of first-line chemoimmunotherapy. Patients needed to be ineligible for ASCT per physician assessment and at least 1 of the following: At least 65 years of age At least 18 years of age with a Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score of at least 3 At least 18 years of age and underwent prior ASCT as first-line consolidation Other key inclusion criteria included an ECOG performance status of 0 to 2, adequate vascular access for leukapheresis, an absolute neutrophil count of at least 1 G/L, a platelet count of at least 75 G/L, an absolute lymphocyte count of at least 0.1 G/L, creatinine clearance of at least 40 mL/min, serum alanine transaminase/aspartate transaminase of no more than 2.5 times the upper limit of normal (ULN), a total bilirubin of no more than 26 µmol/L (unless a patient had Gilbert’s syndrome), a left ventricular ejection fraction of at least 45%, and a baseline oxygen saturation of at least 92% on room air. Following leukapheresis, bridging therapy with 1 or 2 cycles of R-GEMOX or corticosteroids was optional. After patients underwent lymphodepleting chemotherapy with 30 mg/m2 of fludarabine per day plus 500 mg/m2 of cyclophosphamide per day for 3 days, they received a single infusion of axi-cel. Patients underwent a PET scan and circulating tumor DNA (ctDNA) analysis on day 14 and at months 1, 3, 6, 9, and 12. Patients were enrolled between April 26, 2021, and June 15, 2022, and the data cutoff for the final analysis was January 19, 2023. The median follow-up was 12 months (range, 2.1-17.9). Investigator-assessed 3-month CMR rate was the primary end point. Secondary end points included 3-month CMR rate per independent review committee (IRC) assessment, event-free survival (EFS), duration of response, progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life. The median age for patients treated with axi-cel was 70 years (range, 49-81), and 53.2% of patients were at least 70 years of age. Additionally, 75.8% of patients were male, 3.2% of patients underwent prior ASCT, and 32.3% of patients had a HCT-CI score of at least 3. The majority of patients had an ECOG performance status of 0 or 1 (98.4%), an International Prognostic Index score of 2 or higher (88.8%), Ann Arbor stage III or IV disease (74.2%), and were refractory to their first line of therapy (54.8%). Furthermore, 11.3% of patients had lactate dehydrogenase of at least the ULN at baseline, and 19.4% had a C-reactive protein serum level of more than 30 mg/L at infusion. Regarding histology, 83.9% of patients had DLBCL, 9.7% had HGBCL with MYC and BCL2 rearrangements with or without BCL6 rearrangements, 1.6% had follicular lymphoma with possible transformation to DLBCL not otherwise specified, 1.6% had grade 3B follicular lymphoma, and 3.2% had grade 1, 2, or 3A follicular lymphoma. Additionally, 83.9% of patients underwent bridging therapy. Among these patients, 98.1% received R-GEMOX, and 17.3% were given corticosteroids. The best response to bridging therapy included CMR (7.7%), partial metabolic response (26.9%), no response/stable disease (26.9%), progressive metabolic disease (36.5%), and not evaluated (1.9%). The median time between inclusion and axi-cel infusion was 41.5 days (min, 21; max, 71). A total of 69 patients underwent leukapheresis, and 7 patients were not infused with axi-cel due to death (n = 1), cutaneous nocardiosis (n = 1), complete remission prior to the infusion of CAR T-cell therapy (n = 1), absence of documented relapsed on biopsy prior to axi-cel infusion (n = 1), withdrawal of consent (n = 1), progressive disease (n = 1), and receipt of an investigational medical product and second-line chemotherapy for progression (n = 1). Five patients infused with axi-cel died prior to month 3 due to adverse effects (AEs; n = 3) and lymphoma (n = 2). At data cutoff, 50 patients were still alive, and 7 more deaths were reported due to AEs (n = 3), lymphoma (n = 3), and unknown (n = 1). Additional data showed that per IRC assessment, the 3-month ORR was 69.4%, including CMR, PR, SD, and progressive disease rates of 66.1%, 3.2%, 1.6%, and 14.5%, respectively. Notably, 14.5% of patients were not evaluated for 3-month response. Regarding best response, the IRC ORR was 91.9%, including CMR, PR, SD, and progressive disease rates of 82.3%, 9.7%, 1.6%, and 6.5%. Lemonnier noted that 3-month CMR rates were similar across evaluated subgroups. At day 14 following axi-cel infusion, 61.1% of evaluable patients (n = 33/54) had a negative PET-CT, and 48.1% (n = 25/52) had undetectable ctDNA. The median EFS was 12.3 months, and the 12-month EFS rate was 51.2% (95% CI, 38.3%-62.8%).

Jul 01

AbbVie explores the emotional side of rare chronic cancer in ongoing CLL video series

When fam­i­ly doc­tor Bri­an Koff­man found some bumps on the back of his neck, he ran some tests on him­self. Every­thing checked out ex­cept his white blood cell count, which was ex­treme­ly high. With­in a week, he was di­ag­nosed with chron­ic lym­pho­cyt­ic leukemia (CLL), but even as a physi­cian him­self, he still had a lot to learn about the rare blood can­cer. That’s one of the rea­sons why he and his wife found­ed the CLL So­ci­ety, and why he’s work­ing with Ab­b­Vie to make sure new and ex­ist­ing pa­tients can ac­cess in­for­ma­tion, treat­ment op­tions and qual­i­ty care. Unlock this article instantly by becoming a free subscriber. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

Jul 01

US FDA staff raise no concerns about Otsuka, Medtronic blood pressure devices

Aug 18 (Reuters) – The U.S. Food and Drug Administration (FDA) staff reviewers said on Friday they found no safety and effectiveness issues with devices made by Otsuka Holdings (4578.T) and rival Medtronic Plc (MDT.N) for use in a blood pressure treatment surgery. The FDA staff’s assessment comes ahead of meetings of two independent expert panels next week, where they will make recommendations on whether or not to approve the devices for treatment. The surgery, known as renal denervation, is allowed in Europe and other parts of the world, but is not yet approved in the U.S., after initial studies of older devices used in the procedure failed key trials. The staff reviewers said the available safety data for the device made by ReCor, a unit of Otsuka Holdings, did not raise concerns, while pointing that there was limited long-term data. There was no specific comment on Medtronic’s device. ReCor’s device, a balloon-like structure inside a catheter, is inserted through a small cut into the kidney’s arteries and sends ultrasound energy to burn nerves that are believed to control blood pressure. On the other hand, Medtronic’s device is a spiral shaped catheter and generator combination that uses targeted radiofrequency energy to destroy select nerves. The devices are meant for patients whose hypertension, or high blood pressure, cannot be controlled with drugs. These devices have successfully met the main goal of reducing blood pressure as their makers re-designed their trials and reconstituted their patient groups after earlier tests failed. Details on the patient group were not available. Needham analysts expect the devices might see limited sales for the first few years as the companies take time to build a market. According to Medtronic, the market size could reach $500 million by 2026 and $2 billion to $3 billion by 2030. The FDA advisers will meet on Tuesday to discuss ReCor’s device and convene the day after to deliberate on rival Medtronic’s equipment. Reporting by Sriparna Roy in Bengaluru Editing by Vinay Dwivedi Our Standards: The Thomson Reuters Trust Principles. Acquire Licensing Rights, opens new tab

Jul 01

Mouth rinse might spot early heart disease risk, study says

Aug. 18 (UPI) — Scientists from Canada said they have found a link between high white blood cells in the saliva of healthy adults and an early cardiovascular disease warning sign. The research, led by Trevor King of Mount Royal University, was published Friday in the peer-reviewed health journal Frontiers in Oral Health. Advertisement The foundation of the study is that gum inflammation can lead to periodontitis, which is linked with cardiovascular disease, according to researchers. King and his team used a simple oral rinse to see if levels of white blood cells, an indicator of gum inflammation, in the saliva of healthy adults, could be linked to warning signs for cardiovascular disease. The scientists discovered that high levels correlated with compromised flow-mediated dilation were an early indicator of poor arterial health. “Even in young healthy adults, low levels of oral inflammatory load may have an impact on cardiovascular health, one of the leading causes of death in North America,” King said. Advertisement Researchers believe that periodontitis, a common infection of the gums, has previously been linked to the development of cardiovascular disease. Scientists believe that inflammatory factors may get into the bloodstream through the gums and damage the vascular system. The scientists concentrated on examining healthy young people to determine whether lower levels of oral inflammation can be relevant to cardiovascular health. “We are starting to see more relationships between oral health and risk of cardiovascular disease,” said Ker-Yung Hong, first author of the study, now studying dentistry at the University of Western Ontario. “If we are seeing that oral health may have an impact on the risk of developing cardiovascular disease even in young healthy individuals, this holistic approach can be implemented earlier on.” The researchers used what is called pulse-wave velocity to measure the stiffness of the arteries. Stiff and poorly functioning arteries raise patients’ risk of cardiovascular disease. The scientists recruited 28 non-smokers between ages 18 and 30 with no comorbidities or medications that could affect cardiovascular risk. They were asked to fast for six hours, except for drinking water, before visiting the lab. The volunteers then rinsed their mouths with water before rinsing their mouths with saline which was collected for analysis. The volunteers then laid down for 10 minutes for an electrocardiogram. Then they were tested for blood pressure, flow-mediated dilation and pulse-wave velocity. Advertisement “The mouth rinse test could be used at your annual checkup at the family doctor or the dentist,” said Michael Glogauer, from the dental faculty of the University of Toronto and a co-author of the study. “It is easy to implement as an oral inflammation measuring tool in any clinic.”