A Novel Unconventional T Cell Population Enriched In Crohn's Disease
Identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population.
KEY FINDINGS: Identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies.
BACKGROUND: One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls.
DETAILS: Bulk TCR repertoire profiling of both the TCR alpha and beta chains was performed using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. It was further characterised specific T cell clonotypes via single-cell RNAseq. Identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn's disease (CD) and particularly expanded in the CD8+ T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs.
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Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.
Source: Rosati, E., Rios Martini G., Pogorelyy, M. V., et al. (2022). A Novel Unconventional T Cell Population Enriched In Crohn's Disease. Gut. 2022; 71(11): 2194-2204. Published: November, 2022. DOI: XXXXXXXX.
Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda
Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine.
Summary
A randomised, open-label, phase 4 clinical trial
[Posted 22/Jan/2026]]
AUDIENCE: Infectious Disease, Family Medicine
KEY FINDINGS: Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine.
BACKGROUND: Anti-malarial artemisinin-based combination therapies (ACTs) might be losing efficacy in east Africa, with the spread of artemisinin partial resistance and reduced partner drug activity. Our trial aimed to measure the efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine in three sites in Uganda.
DETAILS: This randomised, open-label, phase 4 clinical trial was carried out at three sites in the Agago, Arua, and Busia districts of Uganda. Children aged 6 months to 10 years with uncomplicated Plasmodium falciparum malaria were randomly assigned to receive either artemether-lumefantrine (20 mg artemether; 120 mg lumefantrine; twice a day for 3 days) in all sites or dihydroartemisinin-piperaquine (40 mg dihydroartemisinin and 320 mg piperaquine, once a day for 3 days) in Agago, artesunate-amodiaquine (25 mg artesunate and 67.5 mg amodiaquine for children <9 kg or 50 mg artesunate and 135 mg amodiaquine for children >=9 kg, once a day for 3 days) in Busia; and artesunate-pyronaridine (60 mg artesunate and 180 mg pyronaridine for children >15 kg or 20 mg artesunate and 60 mg pyronaridine for children <15 kg, once a day for 3 days) in Arua, with follow-up to 42 days. Participants were not blinded to group assignments; however, investigators and those assessing outcome were masked. The primary outcome was parasitaemia, assessed by microscopy, either uncorrected or PCR-corrected to distinguish recrudescence from new infection. All participants who received the treatment per protocol and were not lost to follow-up were included in the primary outcome. All participants who were randomly allocated to treatment groups were included in the safety analyses. This study is registered with the Pan African Clinical Trials Registry, number PACTR202301796134887, and is complete. Between Nov 7, 2022, and March 24, 2023, 808 participants (437 [54%] female) were enrolled and assigned to treatment groups; 15 (2%) were lost to follow-up and 793 (98%) completed follow-up. The uncorrected adequate clinical and parasitological response for artemether-lumefantrine was 87 (51.8%; 95% CI 44.0-59.5) of 168 participants in Arua, 88 (51.8%; 44.0-59.4) of 170 and Busia, and 131 (79.4%; 72.3-85.1) of 165 in Agago. This response for artemether-lumefantrine was lower than that of the other ACTs at all sites: 97 (98.0%; 92.2-99.6) of 99 for dihydroartemisinin-piperaquine in Agago, 95 (99.0%; 93.5-99.9) of 96 for artesunate-amodiaquine in Busia, and 73 (73.7%; 63.8-81.8) of 99 for artesunate-pyronaridine in Arua. PCR-corrected 28-day efficacies were 88 (81.5%; 72.6-88.1) of 108 for artemether-lumefantrine and 95 (100%; 95.2-100.0) of 95 for artesunate-amodiaquine in Busia; 131 (97.0%; 92.1-99.0) of 135 for artemether-lumefantrine and 97 (100%; 95.3-100.0) of 97 for dihydroartemisinin-piperaquine in Agago; and 87 (82.1%; 73.2-88.6) of 106 for artemether-lumefantrine and 73 (92.4%; 83.6-96.9) of 79 for artesunate-pyronaridine in Arua. All regimens were well tolerated. The most common adverse events were upper respiratory tract infection, diarrhoea, and anaemia. None of the reported adverse events were attributed to the study drugs. There were two serious adverse events, both cases of severe malaria in Arua, one in each of the treatment groups. Parasite clearance half-lives were prolonged with parasites carrying the PfK13 Cys469Tyr (median 4.2 h; IQR 3.4-4.9) and Ala675Val (4.9 h; 3.4-5.7) mutations compared with wild-type parasites (2.8 h; 2.3-3.6; p<0.0001).
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Copyright © Elsevier Ltd. All rights reserved.
Source: Kamya, M. R., Nankabirwa, J. I., Ebong, C., et al. Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda: a randomised, open-label, phase 4 clinical trial. The Lancet Infectious Diseases. 2026; 26(1): 67-68. Published: January, 2026. DOI: 10.1016/S1473-3099(25)00407-4.
Medical Policy Brief: Shift in Universal Hepatitis B Vaccine Recommendation
The ACIP voted 8-3 to end the universal HepB birth dose recommendation. Vaccination at birth is recommended only for infants of mothers who are positive for HepB or have unknown status. Mothers who test negative are advised to consult their healthcare provider to decide the timing of their child's vaccination. A change in the recommendation, if approved by the CDC Director, could affect state policies and private insurance coverage of the vaccine.
KEY FINDINGS:
- Vote Margin: The ACIP voted 8-3 to end the universal HepB birth dose recommendation.
- New Guidance: Vaccination at birth is recommended only for infants of mothers who are positive for HepB or have unknown status.
- Negative Mothers: Mothers who test negative are advised to consult their healthcare provider to decide the timing of their child's vaccination.
- Policy Impact: A change in the recommendation, if approved by the CDC Director, could affect state policies and private insurance coverage of the vaccine.
BACKGROUND: The Hepatitis B (HepB) vaccine has historically been universally recommended for all infants at birth by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP). This policy ensures protection against perinatal transmission and helps reduce the overall disease burden.
DETAILS: The CDC's Advisory Committee on Immunization Practices (ACIP) recently held a vote to reconsider the universal recommendation for the HepB vaccine at birth. The panel voted by a margin of 8-3 to cease the blanket recommendation that all infants receive the vaccine at birth. The new guidance maintains the recommendation only for infants whose mothers test positive for the infection or have unknown status. Mothers who test negative for Hepatitis B would be advised to "talk with their healthcare provider and decide themselves when to vaccinate their child." The discussion involved controversy, including a newly appointed ACIP member without medical training who reportedly argued against the universal birth dose, claiming vaccines had "never tested (the vaccines) appropriately." Dr. Cody Meissner, the sole continuing ACIP member, criticized the proposed change, stating "no rational science [had] been presented" to justify it. The ACIP voted in favor of changing the recommendations. These recommendations must now go to the CDC director for approval. While states ultimately set their own immunization policies, they generally rely on CDC guidelines. A change in ACIP recommendations can also influence insurance coverage, as most private insurers are required to cover recommended vaccines.
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Efficacy and Safety of Time-Restricted Eating in Metabolic Dysfunction-Associated Steatotic Liver Disease
This 16-week RCT compared TRE, CR, and standard of care in patients with MASLD. It effectively reduced steatosis, with similar benefits on weight loss, body composition, and metabolic parameters as CR. TRE is a practical dietary strategy for MASLD and warrants further long-term study. TRE's effectiveness in MASLD remains unclear despite its potential metabolic benefits.
KEY FINDINGS: TRE effectively reduces hepatic steatosis in MASLD, with comparable benefits on weight loss, body composition, and metabolic parameters as CR. This approach may serve as a practical dietary strategy for MASLD management.
BACKGROUND: Time-restricted eating (TRE) may improve weight loss, insulin resistance, and body composition, which are key factors in the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, evidence on the efficacy of TRE in patients with MASLD is limited. This study aimed to evaluate the potential benefits of TRE in patients with overweight or obesity and MASLD.
DETAILS: In this 16-week randomized controlled trial, patients with overweight or obesity and MASLD were randomized into three groups in a 1:1:1 ratio: standard of care (SOC), calorie restriction (CR), and TRE. The primary endpoint was an improvement in hepatic steatosis, measured using MRI-proton density fat fraction. Changes in liver fibrosis, body composition, lipid profiles, glucose homeostasis, and sleep quality were also analyzed. Among the 337 participants randomized, 333 were included in the full analysis set (113 in SOC, 110 in CR, and 110 in TRE). After the 16-week intervention, hepatic steatosis significantly decreased in the TRE group (-25.8%) compared to the SOC group (0.7%, p <0.001), with no significant difference between TRE and CR (-24.7%, p >0.999). The TRE group also showed greater reductions in body weight, waist circumference, and body fat mass compared to the SOC group, while changes were comparable between TRE and CR. Liver stiffness, glucose homeostasis, and sleep quality were similar between the TRE and CR groups. No serious adverse events were reported.
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Copyright © Elsevier Inc. All rights reserved.
Source: Oh, J. H., Yoon, E. L., Park, H., et al. Efficacy and Safety of Time-Restricted Eating in Metabolic Dysfunction-Associated Steatotic Liver Disease. Journal of Hepatology. 2025; 83(6): 1256-1265. Published: December, 2025. DOI: 10.1016/j.jhep.2025.06.005.
PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer.
In the phase II Pancreatic Adenocarcinoma Signature Stratification for Treatment-01 (PASS-01) trial population, PFS was similar between GnP and mFFX; however, OS and safety trends favored GnP. The second-line setting appears inadequate to offer precision choices, given the short survival observed.
KEY FINDINGS: In the phase II Pancreatic Adenocarcinoma Signature Stratification for Treatment-01 (PASS-01) trial population, PFS was similar between GnP and mFFX; however, OS and safety trends favored GnP. The second-line setting appears inadequate to offer precision choices, given the short survival observed.
BACKGROUND: Goal of this study is to assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX [mFFX]) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers.
DETAILS: Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in BRCA1/2 or PALB2. The primary end point was progression-free survival (PFS) between arms with 0.3 significance. The per-protocol (PP) population included patients who received one dose of chemotherapy. Pretreatment biopsies underwent whole-genome/transcriptome sequencing and patient-derived organoid (PDO) development, providing correlate recommendations at a molecular tumor board and outcomes assessed according to RNA signatures (basal-like v classical). Of 160 patients randomly assigned (80 mFFX, 80 GnP), 140 patients were in the PP population (71 mFFX, 69 GnP), with median follow-up of 8.3 months. The median PFS was 4.0 months for mFFX versus 5.3 months for GnP (hazard ratio [HR], 1.37 [95% CI, 0.97 to 1.92]; P = .069) in intention-to-treat. Median overall survival (OS) was 8.5 months with mFFX and 9.7 months with GnP (HR, 1.57 [95% CI, 1.08 to 2.28]; P = .017). Genomic data were generated in 94%, transcriptomes in 74%, and PDOs in 50%. The median PFS for those with basal-like was 3.0 (mFFX) and 5.5 (GnP) months (P = .17), and classical PDAC was 6.3 (mFFX) versus 5.4 (GnP) months (P = .36). The median OS in basal-like was 7.5 (mFFX) and 8.9 (GnP) months (P = .75) versus in classical OS was 9.7 (mFFX) and 13.9 (GnP) months (P = .047). Overall, 75 (54%) of patients received second-line treatment, 33/75 (44%) correlate-guided. The median time on second-line treatment was only 2.1 months with a median OS of 5.4 months for a correlate-guided choice versus 4.4 months on a standard chemotherapy approach (P = .45).
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Copyright © American Society of Clinical Oncology. All rights reserved.
Source: Knox, J. J., O'Kane, G., King, D., et al. PASS-01: Randomized Phase II Trial of Modified FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel and Molecular Correlatives for Previously Untreated Metastatic Pancreatic Cancer. Journal of Clinical Oncology. 2025; 43(31):3325. Published: November, 2025. DOI: 10.1200/JCO-25-004.
UNC Researchers Discover Method to Combat Antibiotic Treatment Failure
In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.
KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.
BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.
DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.
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The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.
In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.
Copyright © UNC School of Medicine. All rights reserved.
Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.
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