King Chulalongkorn Memorial Hospital

c-Jun N-terminal kinase (JNK) is a key member of the mitogen-activated protein kinase (MAPK) family, playing a vital role in the innate immune response of crustaceans by regulating the expression of antimicrobial peptide (AMP) genes. This research aimed to isolate and characterize a JNK gene from Macrobrachium rosenbergii designated as MrJNK. The full-length cDNA of MrJNK consisted of 1455 bp with an open reading frame (ORF) of 1266 bp encoding 421 amino acids containing a conserved serine/threonine protein kinase catalytic (S_TKc) domain. The phylogenetic tree of JNK proteins indicated that MrJNK and JNK from M. nipponense (MnJNK) were closely related, and were classified within the same clade as other JNK proteins from various crustacean species. The expression analysis by real-time RT-PCR showed that MrJNK was expressed in all examined tissues demonstrating the highest expression in the hemocyte. Following an immune challenge with Aeromonas hydrophila, the transcriptional levels of MrJNK were significantly upregulated in gill, hepatopancreas, hemocyte, muscle, and intestine. The functional role of MrJNK was investigated using RNA interference (RNAi) assay. Knockdown of MrJNK by dsRNA resulted to significant downregulation of anti-lipopolysaccharide factor 5 (ALF5), crustin (Crs), mannose-binding lectin (MBL), lysozyme (Lyz), and prophenoloxidase (proPO) transcripts. In addition, the cumulative mortality rate in MrJNK-silenced M. rosenbergii was significantly increased after A. hydrophila injection. Moreover, the expression levels of two antimicrobial peptides (AMPs) and three immune-related genes were significantly inhibited after silencing MrJNK by dsRNA and A. hydrophila injection in prawns. These results indicate that MrJNK is required for normal transcription of these immune-related genes and is involved in the innate immune response of M. rosenbergii at the transcriptional level.

Postoperative wound complications — including surgical site infection (SSI), cerebrospinal fluid (CSF) leakage, and wound dehiscence — remain a significant challenge following surgery for spinal dysraphism, particularly in neonates and infants. Closed incisional negative pressure wound therapy (ciNPWT) has demonstrated benefit in several surgical subspecialties; however, evidence regarding its routine use in pediatric spinal dysraphism surgery is limited. A retrospective review was conducted of all pediatric patients (age < 18 years) who underwent surgery for spinal dysraphism and received ciNPWT as part of postoperative wound management at King Chulalongkorn Memorial Hospital between June 2020 and March 2024. Primary outcomes included postoperative wound complications (SSI, CSF leakage, wound dehiscence, and wound necrosis) within 30 days of surgery. The number of postoperative dressing changes was recorded as a secondary outcome and surrogate marker of wound care burden. A total of 28 patients were included: 8 with open spinal dysraphism (myelomeningocele, myeloschisis, or hemimyelomeningocele) and 20 with closed spinal dysraphism or related conditions (including 2 pygopagus conjoined twins). The median number of dressing changes was 3 (range 3–5) for open dysraphism and 2 (range 1–2) for closed dysraphism. Primary wound closure was achieved in all cases. No postoperative wound complications — including SSI, CSF leakage, wound dehiscence, or wound necrosis — were observed during the follow-up period. Closed incisional negative pressure wound therapy appears to be a safe and effective adjunct for postoperative wound management in pediatric spinal dysraphism surgery, demonstrating favorable wound outcomes across both open and closed dysraphism types, including complex high-risk cases.

Background: The estimated incidence of acute kidney injury requiring continuous renal replacement therapy (CRRT) in patients necessitating extracorporeal membrane oxygenation (ECMO) is approximately 50%. Currently, two well-known techniques—integration and separation—are utilized for combining CRRT and ECMO circuits. The efficacy of these two techniques is still unknown. Therefore, this study aimed to compare the circuit lifespan of CRRT between the integration and separation techniques. Methods: A multicentered randomized controlled study with an unblinded design will be conducted to determine circuit lifespan differences between integration and separation techniques. Hypothesis: We hypothesize that the integration technique will yield a longer circuit lifespan for CRRT compared to the separation technique. Trial registration: NCT05036616

Pathogenic variants in KCNT1, a gene encoding a sodium-activated potassium channel, are classically associated with severe early-onset epileptic encephalopathies. Emerging evidence indicates that some individuals with KCNT1-related disorders also develop systemic-to-pulmonary vascular anomalies, often initially misidentified as major aortopulmonary collateral arteries (MAPCAs) due to radiographic similarities with congenital heart disease. Unlike true MAPCAs, these vessels arise in the absence of structural cardiac defects and appear to result from abnormal angiogenesis driven by dysregulated KCNT1-mediated signaling. Misclassification may lead to inappropriate interventions or management strategies. Here, a multidisciplinary expert working group reviewed published cases, institutional experience, and imaging findings to develop an expert opinion for nomenclature, diagnosis, and management of these vascular anomalies. We recommend adopting the term systemic-pulmonary collaterals (SPCs) to accurately describe these angiogenic vessels. Risk-based screening, judicious catheter-based embolization when physiologically indicated, and careful avoidance of standard pulmonary vasodilators are emphasized. This statement aims to improve clinical recognition, precision in terminology, and safe management of vascular complications in patients with KCNT1-related disorders.

PURPOSE:To evaluate the safety and immunogenicity of intramuscularly delivered personalized neoantigen synthetic long peptide (SLP) vaccines in patients with advanced solid tumors. PATIENTS AND METHODS:In this phase I trial, 12 patients with advanced melanoma (n = 9) or renal cell carcinoma (n = 3) who lacked access to further reimbursed standard therapies at enrollment received intramuscular neoantigen SLP vaccines with Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC). Each vaccine contained about 20 predicted neoantigen peptides. Adverse events were monitored throughout vaccination and follow-up. Immune profiling was performed at baseline and predefined postvaccination time points. RESULTS:Intramuscular neoantigen vaccination was well tolerated, with only grade 1 to 2 local pain or fever and no immune-mediated toxicities. All participants developed de novo T-cell responses, which were detectable as early as 1 week after vaccination in most patients. On average, 53% of peptides per patient were immunogenic, inducing both CD8+ and CD4+ neoantigen-specific responses. Patients previously treated with immune checkpoint inhibitors (ICI) had higher baseline immunity but achieved comparable postvaccination responses to ICI-naïve patients. IFNγ-dominant CD8+ and TNFα-dominant CD4+ responses were observed, along with increased effector memory differentiation. Two patients with higher CD8+ terminal effector memory RA (TEMRA) proportions were the longest survivors. Tumor biopsies revealed enhanced CD8+ infiltration, and epitope spreading occurred in two evaluable cases. An analysis of 239 peptides showed greater immunogenicity for dual MHC I/II-binding, cysteine-containing, in-frame insertions or deletions-derived or low variant allele frequency-derived mutations, whereas proline substitutions reduced responses. CONCLUSIONS:Intramuscular neoantigen SLP vaccination with poly-ICLC is safe and induces rapid, mutation-specific T-cell immunity with robust CD8+ effector responses. These findings support intramuscular administration as a promising strategy for peptide-based cancer vaccines.