A Histological Study in a Porcine Model.

[Posted 26/Aug/2025]

AUDIENCE: General Surgery, Dermatology, Family Medicine

KEY FINDINGS: MRF predominantly promotes the synthesis of Collagen I and Collagen III, increasing the Collagen I/III ratio, and regulates the expression of MMP-1, MMP-3, MMP-9, TGF-ß, and EGF. These factors collectively drive fibroblast activation, migration, and ECM remodeling. These changes are indicative of the potential for MRF to support skin regeneration and rejuvenation. Preliminary findings suggest that ADSCs may contribute to these regenerative processes.

BACKGROUND: Microneedle radiofrequency (MRF) is a promising skin rejuvenation treatment. However, the mechanisms underlying its effects on extracellular matrix (ECM) remodeling remain unclear. This study aimed to investigate the immediate histological effects of MRF under varying settings, its short-term impact on collagen and elastin synthesis, and the roles of fibroblasts and adipose-derived stem cells (ADSCs).

DETAILS: Porcine abdominal skin was treated with an MRF device containing 49 insulated microneedles using varying energy parameters (8-12 W; 100-300 ms). Immediate histological responses to treatment were evaluated through hematoxylin and eosin (H&E) staining. Short-term changes in collagen and elastin synthesis at Days 7 and 28 posttreatment were assessed via picrosirius red and Victoria blue staining. Additionally, expression and distribution of ECM remodeling-related proteins (MMPs, TGF-ß, EGF, Ki67) and ADSCs were analyzed by multiplex immunohistochemistry (mIHC) and western blot analysis. H&E staining revealed thermal coagulation zones in the dermis immediately after MRF treatment, with zone size increasing with higher power and longer pulse durations (p < 0.05). By Day 28, Collagen I and III densities and organization significantly improved, with the Collagen I/III ratio rising to 7.05 ± 1.21 in the treatment area (p < 0.01) and 3.90 ± 0.37 in the surrounding dermis (p < 0.001). Elastic fibers also showed increased density. mIHC staining demonstrated significant upregulation of MMP-1, MMP-3, and MMP-13 expression in treated and surrounding dermal regions by Day 7 (p < 0.01); however, by Day 28, MMP-1, MMP-9, and MMP-13 expression significantly decreased (p < 0.05), whereas MMP-3 remained elevated. Furthermore, expression levels of TGF-ß, EGF, and Ki67 significantly increased by Day 28 (p < 0.05). mIHC analysis of the fibroblast marker FSP-1 coexpression, along with Western blot analysis of Collagen I, Collagen III, MMP-1, MMP-3, TGF-ß, and EGF, revealed similar trends. Notably, significant expression of ADSC markers was detected at Day 7 posttreatment (p < 0.01).

Copyright © John Wiley & Sons, Inc or related companies. All rights reserved.

Source: Yidan, X., Yi, Z., Hao, W., et al. (2025). Microneedle Radiofrequency Induces Extracellular Matrix Remodeling Through Fibroblast Activation: A Histological Study in a Porcine Model. Lasers Surg. Med.. 2025; 57(6): 528-543. Published: August, 2025. DOI: 10.1002/lsm.70033.

A Randomised, Open-Label, Multicentre, Phase 3 Trial

[Posted 28/Aug/2025]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: With the limitation of a smaller sample size than planned due to the trial's early interruption, these results, to authors' knowledge, showed for the first-time high rates of MRD negativity with weekly carfilzomib added to lenalidomide-dexamethasone in patients with transplantation-ineligible newly diagnosed multiple myeloma. In the carfilzomib-lenalidomide-dexamethasone group, higher MRD negativity rates were associated with a progression-free survival advantage over lenalidomide-dexamethasone. Toxicities were predictable and generally manageable.

BACKGROUND: Before the introduction of daratumumab-lenalidomide-dexamethasone as a first-line treatment for patients with newly diagnosed transplant-ineligible multiple myeloma, lenalidomide-dexamethasone was a standard of care. Authors aimed to explore whether addition of the second-generation proteasome inhibitor carfilzomib to lenalidomide-dexamethasone improved the rates of measurable residual disease (MRD) negativity and progression-free survival.

DETAILS: EMN20 is a randomised, open-label, multicentre, phase 3 trial comparing weekly carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed transplant-ineligible multiple myeloma, conducted in 27 centres in Italy. Key inclusion criteria included fit or intermediate-fit status according to the International Myeloma Working Group (IMWG) frailty score, measurable disease according to IMWG criteria, and Eastern Cooperative Oncology Group performance status lower than 3. Patients randomly assigned to the carfilzomib-lenalidomide-dexamethasone group received 28-day carfilzomib-lenalidomide-dexamethasone cycles (carfilzomib 20 mg/m² intravenously on day 1 for cycle 1, followed by 56 mg/m² intravenously on days 8 and 15 for cycle 1, then 56 mg/m² intravenously on days 1, 8, and 15 for cycles 2-12, and 56 mg/m² intravenously on days 1 and 15 from cycle 13 until 5 years after randomisation; lenalidomide 25 mg orally on days 1-21 until disease progression or intolerance; dexamethasone 40 mg orally on days 1, 8, 15, and 22 until disease progression or intolerance). Patients assigned to the lenalidomide-dexamethasone group received 28-day cycles with lenalidomide-dexamethasone (same dosing and schedule used in the carfilzomib-lenalidomide-dexamethasone group). Primary endpoints were MRD negativity by next-generation sequencing (sensitivity 10-5) after 2 years of treatment and progression-free survival; and were assessed in the intention-to-treat (ITT) population (all patients who were eligible to receive treatment and who were randomly assigned to one of the treatment groups). On Nov 23, 2021, after enrolling 30% of planned patients (101/340), the trial was prematurely stopped due to the introduction of daratumumab-lenalidomide-dexamethasone as a first-line treatment in Italy, which caused the lenalidomide-dexamethasone control group to no longer be considered a standard treatment. This trial is registered with ClinicalTrials.gov, NCT04096066, and study recruitment is complete. Between Nov 14, 2019, and Nov 23, 2021, 82 of 101 enrolled patients were assessed for eligibility and were randomised to receive carfilzomib-lenalidomide-dexamethasone (n=42) or lenalidomide-dexamethasone (n=40). In the ITT population, 35 (43%) of 82 patients were female and 47 (57%) were male. At data cutoff (March 29, 2024), the median follow-up was 35.2 months (IQR 30.3-38.7). The 2-year MRD negativity rates were 25 (60% 95% CI 43-74) of 42 patients with carfilzomib-lenalidomide-dexamethasone versus 0 (0%; 0-9) of 40 patients with lenalidomide-dexamethasone (p<0.0001). Median progression-free survival was not reached (not reached-not reached) with carfilzomib-lenalidomide-dexamethasone versus 20.9 months (15.7-not reached) with lenalidomide-dexamethasone (hazard ratio 0.24 [95% CI 0.11-0.56], p=0.00084). One patient was excluded from the safety analysis because they died before starting treatment. The most frequent grade 3 or worse adverse events were neutropenia (nine [22%] of 41 patients), thrombocytopenia (four [10%]), diarrhoea (four [10%]), cardiac events (three [7%]), infections (three [7%]), and arterial hypertension (two [5%]) with carfilzomib-lenalidomide-dexamethasone, and neutropenia (six [15%] of 40) and skin rash (four [10%]) with lenalidomide-dexamethasone. The most common serious adverse event was SARS-CoV-2-related pneumonia in both the carfilzomib-lenalidomide-dexamethasone group (two [5%] of 41 patients) and lenalidomide-dexamethasone group (three [7%] of 40 patients). Treatment-emergent adverse events leading to death were observed in two patients in the carfilzomib-lenalidomide-dexamethasone (two SARS-CoV-2 infections) and four patients in the lenalidomide-dexamethasone group (one acute myocardial infraction, one heart failure, one septic shock, and one SARS-CoV-2 infection).

Copyright © Elsevier Ltd. All rights reserved.

Source: Bringhen, S., Cani, L., Antonioli, E., et al. (2024). Carfilzomib-Lenalidomide-Dexamethasone Versus Lenalidomide-Dexamethasone in Patients With Newly Diagnosed Myeloma Ineligible for Autologous Stem-Cell Transplantation (EMN20): A Randomised, Open-Label, Multicentre, Phase 3 Trial. The Lancet Haematology. 2025; 12(8): e621-e634. Published: August, 2025. DOI: 10.1016/S2352-3026(25)00162-0.

[Posted 28/Aug/2025]

AUDIENCE: Neurology, Pediatric, Neurosurgery

KEY FINDINGS: Infants up to 6 weeks of age with genetically diagnosed SMA who were treated with risdiplam before the development of clinical signs or symptoms appeared to have better functional and survival outcomes at 12 and 24 months than untreated infants in natural history studies. Larger, controlled studies with longer follow-up are needed to further understand the relative efficacy and safety of presymptomatic treatment of SMA with risdiplam.

BACKGROUND: Risdiplam, an oral pre–messenger RNA splicing modifier, is an efficacious treatment for persons with symptomatic spinal muscular atrophy (SMA). The safety and efficacy of risdiplam in presymptomatic disease are unclear.

DETAILS: Authors conducted an open-label study of daily oral risdiplam (with the dose adjusted to 0.2 mg per kilogram of body weight) in infants 1 day (birth) to 42 days of age with genetically diagnosed SMA but without strongly suggestive clinical signs or symptoms. The primary outcome, assessed in infants with two SMN2 copies and a baseline ulnar compound muscle action potential (CMAP) amplitude of at least 1.5 mV, was the ability to sit without support at month 12. Natural history studies have shown that the majority of infants with two SMN2 copies who are untreated would have a severe SMA phenotype (type 1), would never sit independently, would receive permanent ventilation and feeding support, or would die by 13 months of age. Secondary outcomes that were assessed over a period of 24 months included survival, ventilatory support, motor milestones, the development of clinically manifested SMA, feeding, and growth. A total of 26 infants with two, three, or four or more copies of SMN2 were enrolled. After 12 months of treatment, 21 infants (81%) could sit unsupported for 30 seconds, 14 (54%) could stand alone, and 11 (42%) could walk alone. A total of 4 of 5 infants (80%; 95% confidence interval, 28 to 100) with two SMN2 copies and a baseline ulnar CMAP amplitude of at least 1.5 mV were able to sit without support for at least 5 seconds. Three infants were withdrawn from the study by a parent or caregiver after the month 12 visit. Of 23 infants who completed 24 months of treatment, all were alive without the use of permanent ventilation or feeding support. Over a period of 24 months, nine treatment-related adverse events were reported in 7 infants; none of these events were serious.

Copyright © Massachusetts Medical Society. All rights reserved.

Source: Finkel, R. S., Servais, L., Vlodavets, D., et al. (2024). Risdiplam in Presymptomatic Spinal Muscular Atrophy. N Engl J Med. 2025; 393(7): 671-682. Published: August 13, 2025. DOI: 10.1056/NEJMoa2410120.

[Posted 22/Aug/2025]

AUDIENCE: All Healthcare Professionals

KEY FINDINGS:

BACKGROUND: Recurrent Respiratory Papillomatosis (RRP) is a rare and chronic condition caused by human papillomavirus (HPV) types 6 and 11. The disease leads to the formation of benign tumors in the respiratory tract, most often in the larynx, which can cause significant symptoms like voice changes and difficulty breathing. Historically, the primary treatment for RRP has been repeated surgical removal of the tumors, as there have been no approved medical therapies to address the underlying cause.

DETAILS: The U.S. Food and Drug Administration (FDA) has approved Papzimeos (zopapogene imadenovec-drba), a groundbreaking immunotherapy, for the treatment of adult patients with RRP. This therapy is a non-replicating adenoviral vector that works by stimulating a targeted immune response against the HPV-infected cells. It is administered via a subcutaneous injection and represents the first non-surgical therapeutic option for this rare disease, offering a new approach beyond traditional surgical management.

The approval of Papzimeos was based on data from a single-arm, open-label trial. The study demonstrated that 51.4% of patients who received the treatment achieved a complete response, defined as not needing any further surgical intervention for 12 months following the treatment. The clinical benefits were shown to be durable for most patients over a two-year period and correlated with the development of specific T-cells targeting HPV 6 and 11. The therapy had a favorable safety profile with no serious treatment-related adverse events.

Key information:

• First-of-its-kind Approval: Papzimeos is the first approved medical therapy for RRP.
• Novel Mechanism: It is an immunotherapy that targets the root cause of the disease, HPV-infected cells.
• Approval Pathway: The product received Orphan Drug and Breakthrough Therapy designations and was approved under Priority Review, reflecting the significant unmet medical need for RRP patients.

Source: FDA Approves First Immunotherapy for Recurrent Respiratory Papillomatosis. FDA. 2025; Published: August 14, 2025.

[Posted 17/May/2025]

AUDIENCE: General Surgery, Family Medicine

KEY FINDINGS: Sinus laser therapy (SiLaT) demonstrated superior early outcomes, including faster recovery, reduced pain, and fewer complications with earlier resumption of daily activities compared to the lay-open technique. However, recurrence rates remain similar, necessitating long-term studies to evaluate its effectiveness as a first-line treatment. These findings support the use of SiLaT as a day-case surgical procedure, for treating simple PS disease, particularly in young active patients seeking rapid recovery with minimal morbidity.

BACKGROUND: Pilonidal sinus (PS) predominantly impacts adolescent and young adult males. This condition may be asymptomatically or escalate to painful acute abscesses and recurrent discharge. Purpose of this study is to evaluate the early postoperative outcomes of laser therapy compared to the lay-open technique in the treatment of chronic pilonidal sinus disease.

DETAILS: Prospective randomized comparative study including 40 patients, divided into two equal groups: (a) The SiLaT group: PS treated with diode laser therapy (SiLaT) and (b) the lay-open group: PS treated with lay-open (sinotomy). Postoperative outcomes such as operative time, hospital stay, pain scores, healing time, complications, and recurrence rates were analyzed. Operative time was significantly shorter in the SiLaT group (18.4 ± 2.1 min vs. 26.2 ± 3.7 min, p = 0.022). Hospital stay was shorter in the SiLaT group (6.60 ± 1.47 h vs. 15.10 ± 5.52 h, p < 0.001). Pain scores were lower in the SiLaT group (2.30 ± 0.92 vs. 4.80 ± 1.01, p < 0.001). Wound healing was significantly faster in the SiLaT group (10.1 ± 2.7 days vs. 34.1 ± 15.1 days, p < 0.0001). Recurrence rates (p = 0.998) and surgical site infection (p = 1.00) were comparable among both groups.

Copyright © John Wiley & Sons, Inc or related companies. All rights reserved.

Source: Deen, M. S. E., Hassan, Y. M., Sorour, M. A., et al. A Comparitive Study Between Early Outcomes of Laser and Lay-Open Technique in Management of Simple Pilonidal Sinus. Lasers Surg. Med.. 2025; 57(4): 321-328. Published: April, 2025. DOI: 10.1002/lsm.70008.

[Posted 17/Oct/2024]

AUDIENCE: Emergency Medicine

KEY FINDINGS:

BACKGROUND: Over several days in late September 2024, Hurricane Helene caused extensive damage to the southeastern United States. The storm affected the Baxter International's North Cove facility in North Carolina, the largest manufacturer of peritoneal dialysis and intravenous solutions in the United States, halting production.

DETAILS: CDC is issuing this Health Alert Network (HAN) Health Advisory to inform healthcare providers, pharmacists, healthcare facility administrators, and state, tribal, local, and territorial health departments of a supply disruption of peritoneal dialysis (PD) and intravenous (IV) solutions from the Baxter International's North Cove facility in North Carolina, due to Hurricane Helene.

The supply disruption may impact patient care and require adjustments to the clinical management of patients. Healthcare providers, pharmacists, healthcare facility administrators, and state, tribal, local, and territorial health departments, regardless of supply chain disruptions, should immediately assess their supply and develop plans and mitigation strategies to reduce the impact on patient care.

This Health Advisory summarizes recommendations from the Food and Drug Administration (FDA); the Administration for Strategic Preparedness and Response Technical Resources, Assistance Center, and Information Exchange (ASPR TRACIE) ; the American Society of Health-System Pharmacists (ASHP); the American Society of Nephrology (ASN); and the American Society of Pediatric Nephrology (ASPN) among others, to address supply disruptions of PD and IV solutions.

Facilities can implement strategies early to conserve their fluid supplies and avoid waste to reduce the impact on services. Strategies must ensure patient safety, timely and effective safety notifications, and education of healthcare personnel and patients. Emergency medical and outpatient services must be included in these strategies.

Additional supply disruption may occur in the aftermath of Hurricane Milton.

Recommendations

Healthcare Providers, Pharmacists, and Healthcare Facility Administrators in Healthcare Facilities

• Assess inventory, supply, and conserve available IV solutions.
• Determine the type of IV solutions your pharmacy or facility uses, including expiration dates, and whether this supply disruption will impact your facility.
• Monitor current and future supplies of IV solutions at your facility.
• Report any potential shortages or interruptions to the Food and Drug Administration (FDA) at DrugShortages@fda.hhs.gov.
• Implement a facility-specific action plan to optimize the use of IV solutions using evidence-based fluid management protocols.
• Evaluate all protocols, including the clinical need to continue IV fluid replacement at every shift change, bag change, and during the transition of care unless clinically necessary.
• Ensure that advisory committees with appropriate authorities are established to determine complex issues in supply disruptions and allocation of limited resources and patient triage as needed.
• Use oral formulations when IV options are not available and when appropriate and safe.
• Identify safe and effective alternative IV options (e.g., working with a nearby facility or licensed manufacturer who is not affected by the supply disruption).
• Review standing orders, including drug records and order sets.
• Ensure thorough documentation of the situation, including consumption of IV solutions.
• See FDA's Temporary Policies for Compounding Certain Parenteral Drug Products, for compounders to help fill the gaps from the impact of Hurricane Helene on Baxter International's North Cove facility.
• Ensure multidisciplinary team involvement to determine and develop conservation and stewardship strategies using IV solutions in specific patient populations.
• Include providers from various expertise (including key outpatient settings such as emergency departments, hematology/oncology, ambulatory surgery centers, wound care centers, infusion centers, home healthcare, etc.), pharmacists, nurses, infection control, informatics, patient safety, supply chain leadership, and emergency preparedness.
• Provide education and training to healthcare providers regarding any changes in protocols.
• Communicate changes in current practice, disruption, new shortages, and action plan adjustments to hospital leadership and frontline staff.
• Communicate with patients to assess supplies and provide a mechanism to notify their providers of insufficient supplies.

Providers and Administrators in Dialysis Facilities

• Assess and monitor inventory of available PD solutions.
• Review current practices to identify changes that extend the PD solution supply safely.
• Monitor current and future supplies of PD solutions.
• Report any interruptions to the FDA at DrugShortages@fda.hhs.gov.

• Implement an action plan for emergency PD treatment protocols
• Assess emergency PD protocols.
• Ensure optimal PD catheter function and flow of all patients to maximize ultrafiltration and solute exchange (malposition, etc.).
• Optimize prescriptions; overall approaches should prioritize bag-sparing rather than solution-sparing.
• For example, consider changing dwell times rather than adding a PD solution bag if a prescription change is needed for a patient.
• Monitor patients closely after prescription adjustments, including phone check-ins.
• Communicate with patients receiving peritoneal dialysis at home and their care providers.
• Assess supplies and provide a mechanism to notify their provider of insufficient supplies.
• Provide education and training to patients and their care providers regarding any changes in PD bags or associated products (e.g., adaptors, tubing, etc.) used for their treatments.
• Consider options for individual patients, keeping safety in mind.
• Continuous ambulatory PD (CAPD) may be a good option for some patients.
• Transitioning to hemodialysis (HD) should be avoided as much as possible. However, if adjustment of PD prescription has been explored and exhausted, a temporary transition to HD may be necessary if the available supply is insufficient to provide adequate PD.
• Reinforce patient safety principles when not using usual products and procedures to prevent patient injury and medical errors.

State, Tribal, Local, and Territorial Health Departments

• Maintain situational awareness of the severity of the supply disruption and implement strategies.
• Where possible, facilitate communication across health systems within the jurisdictions related to acute supply needs.

Source: CDC Issues Health Alert In Light of Disruptions in Availability of PD and IV Solutions from Baxter International Facility in North Carolina. CDC. 2024; Published: October, 2024.