Citations

Objective To develop evidence-based clinical practice guidelines for non-invasive neuromodulation devices in acute and preventive migraine treatment. Methods A systematic review was conducted across six databases from 1946 to April 2025. Randomized controlled trials evaluating Food and Drug Administration-cleared or Conformité Européenne (CE)-marked non-invasive neuromodulation devices were included. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and recommendations were developed through consensus following GRADE Evidence-to-Decision frameworks. The working group comprised 15 senior members and six junior members. Results From 1536 initial records, 15 studies met the inclusion criteria and were finally used to develop evidence-based recommendations. Evidence quality ranged from very low to moderate. Weak recommendations were issued for SAVI Dual, Cefaly, Relivion, and Nerivio in the treatment of acute migraine attacks, and for gammaCore Sapphire, Cefaly, and Nerivio in the preventive migraine treatment. Other cleared devices received no recommendations or have no eligible studies for the GRADE assessment. The primary limitations across studies included imprecision due to small sample sizes and various methodological concerns. Additionally, expert consensus recommendations were developed for devices and clinical scenarios not adequately covered by randomized controlled trials, including potential applications in pediatric populations, vestibular migraine, chronic migraine, menstrual migraine, and medication overuse headache. Conclusion Non-invasive neuromodulation devices offer promising alternatives to drug treatment for migraine management. These devices are safe and generally well tolerated and devoid of drug interactions. While current evidence quality varies, ongoing research and technological advancements show encouraging potential. Future studies should adhere to International Headache Society guidelines for neuromodulation device trials, address proper sham controls and blinding assessment, and account for patient adherence challenges in device use. Expanded insurance coverage would enhance cost-effectiveness and device accessibility. These guidelines provide a framework for clinical decision-making while highlighting areas requiring further research.

Abstract The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood. Here, we report a new regulatory link between HELLS and single-strand break (SSB) repair in cellular responses to DNA alkylation damage. We found that loss of HELLS impairs SSB repair and selectively sensitizes cells to DNA alkylating agents and PARP inhibitors (PARPi). Our data reveal non-epistatic interactions between HELLS and PARP1 and suggest that HELLS functionally compensates for PARP1 deficiency in promoting cell survival in response to DNA alkylation damage. Furthermore, we found that HELLS is co-expressed with PARP1 in cancer cells, and its loss is synthetic lethal with homologous recombination deficiency (HRD). This work unveils new functions of HELLS in modulating SSB repair and responses to clinically relevant DNA alkylation damage, thus offering new insights into the potential therapeutic value of targeting HELLS in cancer.

Targeting C1 domains is a promising strategy for modulating the activity of signaling proteins driving tumor growth and progression. While most small molecules developed to date have focused on typical C1 domains, the development of regulators targeting atypical C1 domains remains under‐explored. Herein, we describe the design and synthesis of novel cationic diacylglycerol DAG‐lactones to efficiently interact with the negatively charged residues present in the atypical C1 domain of Vav1, a guanine nucleotide exchange factor playing a critical role in tumor development, including pancreatic cancer. We evaluated the therapeutic potential of this new family of compounds using models from this dismal condition where Vav1 is aberrantly expressed. Treatment of cultured pancreatic tumor cells with sn‐1 cationic DAG‐lactones inhibited proliferation of Vav1‐expressing cells while Vav1‐negative cells showed no response. Additionally, we demonstrated that these compounds inhibited growth of patient‐derived organoids models of pancreatic cancer. These findings underscore the translational value of these cationic DAG‐lactones for pancreatic cancer patients expressing Vav1 and serve as foundation for future approaches targeting atypical C1 domain‐containing signaling proteins.

Background: Massive weight loss after bariatric surgery (BS) often results in excess skin, leading to physical discomfort and impaired quality of life (QoL). Body contouring surgery (BCS) addresses these issues by restoring body image, improving function, and enhancing overall QoL, but its added value on patient-reported outcome measures (PROMs) remains underexplored. Methods: A systematic search of PubMed, Scopus, Embase, Web of Science, and Cochrane databases was conducted from inception to March of 2025. Studies comparing PROMs between patients undergoing BS alone and those undergoing BS + BCS were included. Retrieved studies were assessed using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. Outcomes were pooled using random effects models. Results: Fifteen non-randomized studies involving 7339 patients were included (BS, 4339 [59.1%]; BS + BCS, 3000 [40.9%]). Patients undergoing BS + BCS had a significantly greater percentage of total weight loss (mean difference [MD], 4.40% [95% CI, 1.69, 7.10]; P < 0.01). BODY-Q improvements favored the BS + BCS group in body image, physical, psychological, sexual, and social function (MD, 16.07 [95% CI, 12.14, 20.0]; P < 0.01). Among patients receiving only BS, those desiring BCS reported lower body satisfaction (MD, −0.40 [95% CI, −0.70, −0.10]; P < 0.01) and lower appraisal of excess skin scores (standardized MD, −1.09 [95% CI, −1.83, −0.36]; P = 0.02) than those without desire for BCS. Conclusions: BCS after BS yields substantial improvements in overall QoL. These findings highlight the importance of BCS as a fundamental element of comprehensive postbariatric care that significantly enhances long-term patient satisfaction and drives durable multidimensional recovery.

In the phase III placebo-controlled DeFi trial (ClinicalTrials.gov identifier: NCT03785964 ) primary analysis, nirogacestat showed significant improvement versus placebo in progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PRO) in adult patients with progressing desmoid tumors (DT; median [range] exposure: 20.6 [0.3-33.6] months). Here, long-term nirogacestat efficacy and safety were evaluated in patients randomly assigned to nirogacestat and followed through the final data cutoff date of December 19, 2024. End points included PFS and ORR per RECIST v1.1, PRO, and safety. The median (range) duration of exposure was 33.6 (0.3-61.8) months. Median PFS was not reached. The ORR with up to 4 years of nirogacestat treatment was 45.7% (32 of 70), with three additional partial and three additional complete responses since the primary analysis. Further target tumor size reduction occurred in most patients. Benefits in PROs were sustained while on treatment. Frequently reported treatment-emergent adverse events (TEAEs) decreased in incidence and severity over time. Since the primary analysis, four patients discontinued nirogacestat because of TEAEs between years 2 and 4. In conclusion, long-term continuous nirogacestat treatment was associated with further tumor size reductions, durable objective responses, sustained PRO benefits, and a manageable safety profile consistent with the primary analysis.

Abstract Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the proliferation of immature lymphoid cells. Despite advances in chemotherapy, a significant proportion of patients continue to have poor outcomes. Immunotherapy has emerged as a transformative approach in the treatment of ALL, offering new hope for these patients. This advances viewpoint article provides a comprehensive overview of the role of immunotherapy in ALL, focusing on the mechanisms of action, the timing of its use, the patient populations most likely to benefit, and drug resistance. We discussed the major immunotherapeutic modalities, including monoclonal antibodies, bispecific T-cell engagers, and chimeric antigen receptor T-cell therapy. We review key clinical trials that have shaped the current landscape of immunotherapy in B-cell precursor (BCP)–ALL, along with future directions in this rapidly evolving field and discussed our perspective on how best to exploit the use of immunotherapy for patients with newly diagnosed adult BCP-ALL.