Single-Dose CRISPR Gene Editing Reduces Hereditary Angioedema Attacks by 87%
A single infusion of investigational CRISPR-based lonvoguran ziclumeran reduced monthly hereditary angioedema attacks by 87% compared with placebo in the phase 3 HAELO trial. Although the findings point to the potential of gene editing as a treatment strategy for this rare genetic disorder, longer follow-up is needed to establish durability and assess uncommon or delayed safety risks.
KEY FINDINGS: A single infusion of investigational CRISPR-based lonvo-z substantially reduced HAE attack frequency compared with placebo in the phase 3 HAELO trial. The findings support further development of in vivo gene editing as a potential long-term treatment strategy for HAE. However, the trial was relatively small and follow-up remains limited for assessing the durability of gene editing and uncommon or delayed adverse effects. Longer-term monitoring and additional evidence will be important to establish the treatment's sustained efficacy and safety. Lonvo-z remains investigational; these results should not be interpreted as establishing it as an approved replacement for currently available HAE therapies.
BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of swelling that can affect the skin, gastrointestinal tract, and upper airway. Laryngeal attacks can be life-threatening. Current management relies on preventive and on-demand therapies, often requiring repeated administration. In vivo gene editing offers a potential alternative by targeting the underlying pathway responsible for attacks. The phase 3 HAELO trial evaluated lonvoguran ziclumeran (lonvo-z), an investigational CRISPR-based treatment administered as a single intravenous infusion.
DETAILS: In this randomized, double-blind, placebo-controlled phase 3 trial, 80 patients aged 16 years or older with HAE associated with C1 inhibitor deficiency were assigned in a 2:1 ratio to receive a single 50-mg intravenous infusion of lonvo-z (52 patients) or placebo (28 patients). The primary endpoint was the rate of investigator-confirmed HAE attacks per month from week 5 through week 28 after infusion. Follow-up data were available through February 10, 2026, with a median follow-up duration of 7.5 months (range, 4.9-12.8 months).
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The least-squares mean monthly HAE attack rate from weeks 5 through 28 was 0.26 (95% confidence interval [CI], 0.15-0.45) in the lonvo-z group, compared with 2.10 (95% CI, 1.55-2.86) in the placebo group. This represented an 87% relative reduction in monthly attacks (95% CI, 78%-93%; P < .001).
Adverse events occurring during or after infusion through week 28 were reported in 92% of patients receiving lonvo-z and 86% receiving placebo. Events reported more frequently with lonvo-z included infusion-related reactions, headache, fatigue, back pain, and upper respiratory tract infection. No serious adverse events or adverse events of grade 3 or higher were reported in the lonvo-z group during the reported period.
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Source: Cohn, D. M., Gurugama, P., Longhurst, H. J., et al. Lonvoguran Ziclumeran — In Vivo CRISPR Gene Editing in Hereditary Angioedema. New England Journal of Medicines. 2026; 395: 1471-1482. Published: October, 2026. DOI: 10.1056/NEJMoa2600931.
Incidence of Pre-eclampsia in Triplet Pregnancies With and Without Embryo Reduction
The authors estimated that PE-associated delivery occurred, on average, 14.5 weeks earlier in non-reduced triplets, 12.7 weeks earlier in triplets reduced to twins, and 6.5 weeks earlier in triplets reduced to singletons than in comparable singleton pregnancies. These findings may inform risk assessment and counseling in pregnancies initially diagnosed as triplets.
KEY FINDINGS: Triplet pregnancies managed without embryo reduction were associated with substantially higher risks of early PE than singleton and twin pregnancies. Reduction from triplets to twins was associated with a lower risk of PE before 34 weeks than in non-reduced triplets, although risk remained elevated relative to twin pregnancies. Following reduction to a singleton, PE risk was comparable to that observed in singleton pregnancies, but the reduced sample size of 96 pregnancies warrants caution when interpreting this finding. The authors estimated that PE-associated delivery occurred, on average, 14.5 weeks earlier in non-reduced triplets, 12.7 weeks earlier in triplets reduced to twins, and 6.5 weeks earlier in triplets reduced to singletons than in comparable singleton pregnancies. These findings may inform risk assessment and counseling in pregnancies initially diagnosed as triplets.
BACKGROUND: Pre-eclampsia (PE) is an important cause of maternal and perinatal morbidity and mortality. Although multiple pregnancies are associated with greater PE risk than singleton pregnancies, evidence regarding the incidence and timing of PE in triplet pregnancies, particularly following embryo reduction, has been limited. This study examined PE risk in triplet pregnancies managed expectantly or reduced to twins or singletons, using twin and singleton pregnancies as comparators.
DETAILS: This retrospective multicenter study included 1,020 triplet pregnancies with three live, phenotypically normal fetuses at the 11-13-week ultrasound examination and delivery at a gestational age of ≥24 weeks. Of these, 456 pregnancies were managed expectantly, 468 underwent embryo reduction to twins, and 96 were reduced to singletons. Outcomes were compared with previously collected data from 1,169 twin pregnancies and 61,174 singleton pregnancies. The primary assessments included PE incidence associated with delivery before 37, 34, and 32 weeks of gestation and the relative risk compared with singleton and twin pregnancies.
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The incidence of PE associated with delivery before 37 weeks was 9.9% in non-reduced triplet pregnancies, 9.8% following reduction to twins, 2.1% following reduction to singletons, 7.0% in twin pregnancies, and 0.8% in singleton pregnancies. Before 34 weeks, the respective incidences were 7.2%, 4.1%, 0%, 0.9%, and 0.4%. Before 32 weeks, PE incidence was 3.1% in non-reduced triplets, 1.5% in triplets reduced to twins, 0% in triplets reduced to singletons, 0.6% in twins, and 0.2% in singletons. Compared with singleton pregnancies, non-reduced triplet pregnancies had relative risks of 12.3 (95% CI, 9.1-16.3) for PE associated with delivery before 37 weeks and 20.6 (95% CI, 14.4-29.2) before 34 weeks. For triplet pregnancies reduced to twins, the corresponding relative risks were 12.2 (95% CI, 9.1-16.2) and 11.6 (95% CI, 7.3-18.2). Compared with twin pregnancies, non-reduced triplets had relative risks of 1.4 (95% CI, 1.0-2.0) before 37 weeks and 7.7 (95% CI, 4.0-14.9) before 34 weeks. Triplet pregnancies reduced to twins had corresponding relative risks of 1.4 (95% CI, 1.0-2.0) and 4.3 (95% CI, 2.1-8.9).
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Source: Yerlikaya-Schatten, G., Wright, A., Kristensen, S., et al. Incidence of pre-eclampsia in triplet pregnancies with and without embryo reduction. Ultrasound in Obstetrics & Gynecology. 2026; 68(4): 504-509. Published: September, 2026. DOI: 10.1002/uog.70341.
Measles Cases Surge in the United States: 4,410 Confirmed Cases Reported in 2026
The CDC reported 4,410 confirmed measles cases in the United States as of October 15, 2026 - nearly twice the total for all of 2025. With 96% of cases associated with outbreaks and kindergarten MMR coverage down to 92.4%, the resurgence highlights the consequences of gaps in community immunity. Early recognition, appropriate infection-control precautions, and maintaining vaccination coverage remain critical to preventing further spread.
Summary
PUBLIC HEALTH ALERT
Updated October 17, 2026 | Source: US Centers for Disease Control and Prevention (CDC)
[Posted 19/Oct/2026]
AUDIENCE: Infectious Disease, Internal Medicine
Key Surveillance Findings: According to the CDC, 4,410 confirmed measles cases were reported in the United States during 2026 as of October 15. Cases were reported across 47 jurisdictions, with 18 cases involving international visitors. The CDC recorded 42 new outbreaks during the year, and 96% of confirmed cases (4,228 of 4,410) were associated with outbreaks. This total includes cases linked to outbreaks that began in both 2025 and 2026.
The contrast with earlier years is marked. The United States reported 285 cases in 2024 and 2,289 in 2025. The current 2026 total reflects a significant increase in transmission and underscores the vulnerability of communities with inadequate immunization coverage.
Backround: The United States is experiencing a substantial resurgence of measles, with 4,410 confirmed cases reported as of October 15, 2026. The total has already exceeded the 2,289 cases recorded throughout 2025 by approximately 93%, highlighting the ongoing challenge of controlling a highly contagious, vaccine-preventable infection.
Declining Vaccination Coverage Raises Concern: Measles was declared eliminated in the United States in 2000, meaning sustained endemic transmission had been interrupted. However, imported infections can trigger outbreaks when the virus reaches susceptible populations.
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National measles, mumps, and rubella (MMR) vaccination coverage among kindergarteners declined from 95.2% during the 2019-2020 school year to 92.4% in 2025-2026. The CDC estimates that approximately 280,000 kindergarteners were at risk during the 2025-2026 school year. Because measles spreads exceptionally efficiently, clusters of unvaccinated individuals can sustain transmission even in areas where overall vaccination coverage appears relatively high.
Two doses of MMR vaccine are approximately 97% effective against measles, compared with 93% effectiveness after one dose. Maintaining high coverage and identifying susceptible individuals remain central to preventing further spread.
Clinical and Public Health Implications
Clinicians should remain alert to possible measles in patients with compatible symptoms, particularly when there is a history of travel, known exposure, or residence in an affected community. Measles can cause serious complications, especially in infants and young children. Suspected cases require prompt infection-control precautions and coordination with public health authorities; patients should not be directed into routine waiting areas where others may be exposed.
Healthcare professionals should review patients’ immunization histories, recommend vaccination in accordance with current guidance, and reinforce the importance of protection before international travel. Public health teams should continue surveillance, contact tracing, and targeted vaccination efforts in communities with low coverage.
Key Takeaway
The rise to more than 4,400 confirmed cases in 2026 demonstrates that measles elimination does not eliminate the risk of renewed outbreaks. Sustained vaccination coverage, rapid recognition of suspected cases, and coordinated public health action are essential to limit transmission and protect vulnerable populations.
Data note: CDC surveillance figures are provisional and include confirmed cases reported by jurisdictions as of noon on Thursday, October 15, 2026. Counts may change as additional cases are confirmed. An outbreak is defined by the CDC as three or more related cases.
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Source: US Centers for Disease Control and Prevention. Measles Cases and Outbreaks. Updated October 16, 2026. CDC.
Enhanced Recovery Protocols May Improve Outcomes After Pediatric Gastrointestinal Surgery When Adherence Is High
In the ENRICH-US trial of 597 children and adolescents undergoing gastrointestinal surgery, implementing an enhanced recovery protocol did not significantly reduce overall hospital length of stay. However, patients who received at least 13 protocol elements had stays that were 1.14 days shorter and lower odds of postoperative complications. The findings underscore the importance of consistent protocol adherence when translating enhanced recovery strategies into better surgical outcomes.
KEY FINDINGS: The ENRICH-US trial did not demonstrate a significant overall reduction in length of stay from introducing a multifaceted implementation strategy. However, patients receiving a greater number of protocol elements experienced shorter hospital stays and fewer complications. These findings emphasize that the clinical benefit of enhanced recovery pathways may depend on consistent delivery of their components, not simply on adopting a protocol. Hospitals implementing pediatric ERPs should therefore monitor adherence alongside clinical outcomes and address organizational barriers that limit reliable implementation.
BACKGROUND: Enhanced recovery protocols (ERPs) combine evidence-based perioperative practices to support recovery, reduce opioid exposure, and minimize complications after surgery. Although these protocols are well established in adult surgical care, their implementation in pediatric populations has been slower. The ENRICH-US trial evaluated whether a structured implementation strategy could improve adherence to a pediatric gastrointestinal surgery ERP and enhance clinical outcomes.
DETAILS: This prospective, stepped-wedge cluster-randomized implementation-effectiveness trial included 597 patients aged 10-18 years undergoing elective gastrointestinal surgery at 18 US sites between September 2019 and June 2024. The protocol included 21 perioperative elements, supported by a structured implementation toolkit, multidisciplinary learning sessions, adherence feedback, and implementation reports. Outcomes were assessed during baseline usual care, implementation, and sustainability phases. The primary clinical outcome was postoperative hospital length of stay (LOS). Secondary outcomes included time to resumption of a regular diet, inpatient opioid use, postoperative complications, opioid prescriptions at discharge, 30-day readmission, and patient-reported health-related quality of life.
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Inflammatory bowel disease was the most common surgical indication, accounting for 433 patients (72.5%). Across the three study phases, the implementation strategy did not significantly reduce overall hospital LOS or produce significant differences in most secondary outcomes. However, patients resumed a regular diet sooner and had lower opioid use during hospitalization as the protocol progressed. A patient-level analysis demonstrated the importance of adherence. Patients who received at least 13 ERP elements had a median hospital stay that was 1.14 days shorter (95% CI, -2.01 to -0.27) and lower odds of postoperative complications (adjusted odds ratio, 0.48; 95% CI, 0.28-0.82) than patients with lower adherence. The median number of protocol elements delivered increased from 11 during baseline to 14 during both implementation and sustainability phases (P < .001).
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Source: Raval, M. V., Tian, Y., Schäfer, W., et al. Implementation and Effectiveness of an Enhanced Recovery Protocol for Children Undergoing Surgery: The ENRICH-US Stepped-Wedge Cluster-Randomized Trial. JAMA Surgery. 2026; 161(7): 670-680. Published: October, 2026. DOI: 10.1001/jamasurg.2026.1382.
Diversified Segmental Defocus Optimization Lenses May Improve Myopia Control in Children
A multicenter study of 1,541 children found that DSDO lenses were associated with less axial elongation than DIMS lenses in children with myopia and less eye growth than no optical correction in children without myopia. Benefits appeared greater among younger children and those with low myopia. Although the observational design limits conclusions about causality, the findings support further research into individualized optical strategies for myopia control.
KEY FINDINGS: DSDO lenses were associated with modestly lower axial elongation than DIMS lenses in children with myopia, with greater differences in younger children and those with low myopia. In children without myopia, DSDO lens use was associated with less axial growth than no optical correction. Because lens selection reflected routine clinical decisions and parental preference rather than random allocation, residual confounding remains possible. The findings support further evaluation of individualized optical strategies for myopia control and prevention but do not establish that DSDO lenses are superior for every child.
BACKGROUND: Myopia in childhood is associated with progressive elongation of the eye, which can increase the risk of future ocular complications. Optical interventions designed to slow axial elongation are an important component of myopia management. Diversified segmental defocus optimization (DSDO) lenses are designed to influence peripheral retinal defocus, potentially limiting eye growth. However, evidence from routine clinical practice comparing these lenses with established defocus incorporated multiple segments (DIMS) lenses, particularly in children without myopia, remains important.
DETAILS: A prospective, multicenter clinical practice study conducted across eight Aier Eye Hospital Group centers in China evaluated 1,541 children and adolescents aged 6–16 years. The myopic cohort included 654 participants wearing DSDO lenses and 661 wearing DIMS lenses. The nonmyopic cohort included 85 participants wearing DSDO lenses and 141 untreated controls. Axial length was measured at baseline, six months, and 12 months. Propensity score matching was used to balance baseline characteristics, including age, sex, spherical equivalent, and axial length, between comparison groups.
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Among children with myopia, mean axial elongation was lower with DSDO lenses than with DIMS lenses at six months (0.07 ± 0.12 mm versus 0.09 ± 0.10 mm; P = 0.026) and at 12 months (0.17 ± 0.18 mm versus 0.19 ± 0.16 mm; P = 0.019). Subgroup analyses indicated greater benefit among children aged 10 years or younger (P = 0.022) and those with low myopia (P = 0.001). Among nonmyopic participants, axial growth at 12 months was 0.18 ± 0.14 mm with DSDO lenses, compared with 0.29 ± 0.14 mm in untreated controls (P = 0.01). The difference was also significant among children with emmetropic or low hyperopic refractive error (P = 0.004). The greatest apparent effect in the nonmyopic cohort occurred during the first six months.
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Source: Wen, L., Yang, Y., He, Y., et al. Efficacy of Diversified Segmental Defocus Optimization Lenses on Axial Length Growth in Children and Adolescents with or without Myopia: Evidence from a Multicenter Clinical Practice. Ophthalmology. 2026; 133(10): 1197-1206. Published: October, 2026. DOI: 10.1016/j.ophtha.2026.04.015.
Defibrotide Prophylaxis and Transplant Outcomes After Inotuzumab in Pediatric B-ALL
A retrospective study of 92 children and young adults with B-ALL found that defibrotide prophylaxis following inotuzumab treatment was associated with an SOS incidence comparable to that in patients without prior inotuzumab exposure (15% vs 12%). Prophylaxis was generally well tolerated, with no significant difference in nonrelapse mortality between transplant groups. The findings support further prospective evaluation of defibrotide for preventing transplant-associated SOS in high-risk patients.
KEY FINDINGS: In this retrospective cohort of pediatric and young adult patients with relapsed or refractory B-ALL, defibrotide prophylaxis following InO exposure was associated with an SOS incidence comparable to that observed in patients without prior InO treatment. The findings also showed no significant difference in nonrelapse mortality between the two transplant groups.
The results suggest that defibrotide prophylaxis may help mitigate transplant-associated SOS risk following InO treatment, potentially supporting the use of InO in selected patients requiring HSCT. However, the small number of patients who received InO without prophylaxis, retrospective design, and potential treatment-selection bias prevent conclusions about a causal preventive effect. Prospective studies with standardized pediatric SOS diagnostic criteria are needed.
BACKGROUND: Inotuzumab ozogamicin (InO), an anti-CD22 antibody-drug conjugate, is used in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, its use before hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of sinusoidal obstruction syndrome (SOS), a potentially life-threatening hepatic complication of transplantation.
Although defibrotide is established in the treatment of transplant-associated SOS, its preventive role remains less clearly defined. This study evaluated transplant outcomes following InO reinduction and examined the institutional use of defibrotide prophylaxis during HSCT.
DETAILS: This single-center retrospective study included children, adolescents, and young adults with B-ALL who underwent HSCT at Dana-Farber/Boston Children's Cancer and Blood Disorders Center between January 1, 2016, and October 1, 2024. Patients were categorized according to whether they received InO during reinduction before transplantation. The analysis evaluated SOS incidence, nonrelapse mortality (NRM), relapse-free survival (RFS), overall survival (OS), and transplant-related outcomes. Defibrotide prophylaxis was administered to selected patients considered at increased risk of SOS, particularly those with previous InO exposure.
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Among 92 patients undergoing HSCT, 32 had received InO before transplantation and 60 had received non-InO reinduction regimens. The median age at HSCT was 14 years. Of the patients receiving InO, 81% achieved complete remission with this treatment, and 81% received InO as their final therapy before HSCT. Overall, 34 patients (37%) received defibrotide prophylaxis. Among InO-treated patients, 26 of 32 (81%) received prophylaxis. SOS developed in 7 of 32 patients (22%) in the InO group compared with 7 of 60 (12%) in the non-InO group (P=0.19).
Among InO-treated patients receiving defibrotide prophylaxis, SOS occurred in 4 of 26 (15%), compared with 3 of 6 (50%) who did not receive prophylaxis. The SOS incidence among InO-treated patients receiving prophylaxis was comparable to that in the non-InO cohort (15% vs 12%; P=0.61). Nonrelapse mortality did not differ significantly between the InO and non-InO groups (P=0.54). At 100 days after HSCT, NRM was 0% in the InO group and 3% in the non-InO group. Three-year overall survival was 68% and 87%, respectively (P=0.14), while 3-year relapse-free survival was 54% and 75% (P=0.07).
Defibrotide prophylaxis was generally well tolerated. Two of the 34 patients receiving prophylaxis discontinued treatment because of adverse reactions involving bleeding symptoms.
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Source: Paolino, J. D., Hebert, K., Yang, J., et al. Allogeneic HSCT outcomes and impact of defibrotide prophylaxis on SOS after inotuzumab in pediatric B-ALL. Blood Advances. 2026; 10(19):6395-6406. Published: August 22, 2026. DOI: 10.1182/bloodadvances.2026020336.
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