Background: Locally advanced rectal cancer (LARC) represents a pivotal stage of rectal cancer where it is possible to completely cure the cancer before its systemic spread, thus often requiring an aggressive multimodal therapy. Recent trials suggest that programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors combined with neoadjuvant chemoradiotherapy (CRT) may improve treatment outcomes. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors when integrated into neoadjuvant CRT regimens for LARC patients. Methods: A systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Library was conducted up to October 11, 2024. Randomized controlled trials (RCTs) comparing neoadjuvant CRT with or without PD-1/PD-L1 inhibitors were included. The primary outcomes assessed were pathological complete response (pCR), clinical complete response (cCR), and serious adverse events (SAEs). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses were performed to explore variations in radiotherapy strategies, types of PD-1/PD-L1 inhibitors used, and mismatch repair (MMR) status. Results: Six RCTs (861 patients) met the inclusion criteria. PD-1 inhibitors significantly improved pCR rates (OR = 2.10, 95% CI: 1.32–3.32, p = 0.001), particularly with short-course radiotherapy (SCRT) and agents like Camrelizumab and Tislelizumab. However, PD-1 inhibitors did not significantly enhance cCR (OR = 1.54, 95% CI: 0.51–4.63, p = 0.44) or increase SAEs (OR = 1.08, 95% CI: 0.73–1.60). Subgroup analysis based on MMR status revealed a significantly higher pCR rate in the proficient MMR (pMMR) subgroup compared to the deficient MMR (dMMR) subgroup, although the result for dMMR was non-significant due to limited sample size and the absence of reported events. Conclusions: The addition of PD-1 inhibitors to neoadjuvant CRT significantly improves pCR rates in LARC without increasing toxicity. These findings support their potential role in standard treatment protocols, warranting further phase III trials. Registration number: CRD42024619949.

Status epilepticus is one of the most commonly occuring emergencies among children across the world. Time is crucial in the treatment of SE, with increasing risk of long term adverse events and sequelae with delay in treatment or action of drugs. This systematic review and meta-analysis aims to compare levetiracetam, a drug known for its comparatively safer profile, with other routinely used drugs in pediatric SE like phenytoin, fosphenytoin and valproate. A comprehensive literature search was conducted across four databases from 1996 till November 2024. All original studies evaluating the efficacy of levetiracetam vis-a-vis other anti-seizure medications in pediatric children in an emergency setting were included in the study. Data analysis was conducted using RevMan software, using a random-effects model. A total of fourteen studies, comprising a patient population of 2,473, were included for further quantitative analysis. No differences were noted between the drugs when comparing seizure termination and recurrence at 24 h. Levetiracetam notably reduced the time to cessation of seizures when compared to phenytoin or fosphenytoin (MD=-3.97, 5% CI [-6.18, -1.76], p = 0.0004) and length of ICU stay over phenytoin (MD = 0.77, 95% CI [0.54, 1.00], p < 0.00001). A lower risk of adverse events was noted on use of levetiracetam over fosphenytoin (RR = 0.62, 95% CI [0.40, 0.96], p = 0.03); however risk of agitation was the least on use of phenytoin (RR = 3.90, 95% CI [1.42, 10.73], p = 0.008). Non significant differences in mortality rates were observed. The study concludes better immediate effects of levetiracetam such as faster cessation of seizures. Levetiracetam was also suggested to stabilize patients faster, as implied by the lesser ICU stay and lower risk of adverse events. Further studies are needed to evaluate the efficacy of levetiracetam over other anti-seizure medications.

e16284 Background: Hepatocellular carcinoma (HCC) is associated with frequent recurrences and relapse. Camrelizumab (CAM), an anti-PD-1 immune checkpoint inhibitor, is known to convert “cold” tumors to “hot”, allowing immune system activation. In this systematic review and network meta-analysis, we aim to compare CAM monotherapy with its combinations with other agents like Lenvatinib (LEN), Sorafenib (SOR), Rivoceranib (RIV), other tyrosine kinase inhibitors (TKI), hepatic arterial infusion chemotherapy (HAIC), and trans arterial chemoembolization (TACE). Methods: Literature search was conducted across 5 databases to identify original studies evaluating the use of CAM as a mono- or combination therapy in patients diagnosed with HCC. Data was quantified as either odds ratio (OR) or hazard ratio (HR). Data analysis was conducted in netmeta employing a common-effects model, with the common comparator being CAM. Results: A total of 25 studies comprising a population of 5,062 patients were included for quantitative analysis. Among all treatment arms, CAM+LEN was associated with the highest overall survival (HR: 1.46 [1.25, 1.7], p < 0.0001) and progression-free survival (HR: 1.63 [1.41, 1.89], p < 0.0001), followed by CAM+RIV+HAIC, and CAM+TKI. The highest disease control rate was achieved with the use of CAM+TACE (OR: 56.47 [3.03, 1053.1], p = 0.007), followed by CAM+TACE+LEN, and TACE+LEN. Similar trends were observed for objective response rates as well. However, monotherapy with TACE was associated with the highest mortality (OR: 557.4 [24.48, 12691.11], p < 0.0001), followed by TACE+LEN and CAM+TACE. While assessing individual adverse events, incidence of nausea was highest with TACE based chemotherapies, including CAM+TACE, CAM+TACE+LEN, CAM+TACE+TKI; however, significantly lower odds of developing diarrhea was observed on use of CAM +LEN (OR: 0.23 [0.07, 0.72], p = 0.03). Patients treated with CAM+TACE+TKI had the highest incidence of diarrhea (OR: 1.43 [0.47, 4.35), p = 0.03). Incidence of anemia significantly decreased over CAM monotherapy on use of CAM+RIV (OR: 0.09 [0.02, 0.4], p = 0.001), followed by CAM+RIV+HAIC (OR: 0.14 [0.03, 0.63], p = 0.01) and CAM+SOR. Conclusions: LEN-based combinations offered the highest survival benefits, suggesting a synergistic action in reducing tumor burden. While TACE based regimens offered the highest immediate response and control rate, these therapies were associated with a significantly higher risk of chemotherapy-associated adverse events. Combination therapies with LEN or RIV significantly reduced the risk of adverse events, implying a safer profile. Further studies are needed to assess the superiority of each combination therapies over a longer follow-up period.

Purpose of Review: Pediatric Emergency Medicine (PEM) in high-resource settings continues to benefit from technological advancements, standardized protocols, and advanced training. However, PEM in low-resource settings—despite facing infrastructure limitations, funding gaps, and high disease burdens—offers innovative, adaptable, and culturally grounded care. This review explores how insights from low-resource pediatric emergency care can inform and enrich practices in high-resource settings. Recent Findings: Emerging literature highlights the value of frugal innovations and culturally contextualized care in low-resource PEM. Examples such as bubble CPAP, task-shifting models, and mobile health (mHealth) interventions have demonstrated scalable, cost-effective impact. Collaborative programs like Rwanda’s Human Resources for Health (HRH) initiative and the Global Initiative for Children’s Surgery (GICS) emphasize sustainable capacity-building and bidirectional learning. High-resource institutions increasingly recognize the need for integrating global health training, emphasizing equity, ethical engagement, and adaptability in complex care environments. Summary: Low-resource PEM settings foster clinical ingenuity, resilience, and a strong emphasis on local leadership. Integrating lessons from these contexts can enhance global equity, encourage innovation, and improve cultural competence among trainees. Global health must be framed as a core component of PEM training to bridge healthcare disparities and support sustainable, ethical partnerships across diverse settings