Odontoid fractures in the pediatric population: a systematic review and management algorithm.

Purpose: The management of odontoid fractures in adult patients has been widely described. However, there is sparse literature about this injury in the pediatric population. This study aimed to review published literature regarding the management and outcomes of pediatric odontoid fractures to develop a stepwise treatment algorithm. Methods: A literature review was conducted using PRISMA guidelines on PubMed to identify studies between 1960 and 2023 that reported on the management and outcomes of odontoid fracture in pediatric patients. Studies were included if they were published in English and if their sample included at least four patients aged 0-18, minimum follow-up of 6 weeks, and outcomes for each patient clearly differentiated. Results: In total, 15 studies including 125 pediatric patients with odontoid fractures were included. Treatment options varied from non-operative management with immobilization in rigid collars, halo vests, cervicothoracic orthosis, or soft collars to surgical management with fixation and/or arthrodesis. There were 73 patients initially treated nonoperatively, 47 initially treated surgically, 2 who healed with observation alone, and 3 who died acutely of concomitant injuries. The nonunion rate for nonoperative management was 5.5%. Surgery was successful, demonstrating bony union at final follow-up, in 94.6% of cases treated via a posterior approach and 85.7% of cases treated with an anterior approach. Conclusions: Odontoid fractures must be considered in pediatric patients with cervical spine trauma. This is the largest literature review of pediatric odontoid fractures. Various management strategies exist and can be considered. The proposed algorithm offers an evidence-based framework for the management of pediatric odontoid fractures.

Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada.

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.

A MAUDE database analysis on the new generation of active bone conduction hearing implants.

Objective: To analyze medical device reports (MDR) submitted to the Food and Drug Administration's (FDA) Manufacturer and User Device Facility Experience (MAUDE) database to identify adverse events (AEs) in patients implanted with novel active bone conduction hearing implants (BCIs). Methods: We conducted a search of the FDA MAUDE database on the newest generation of BCIs. Data were collected concerning device malfunctions, patient injuries, factors triggering these incidents, and the subsequent actions taken. Results: In total, 93 (16.7%) device malfunctions and 465 (83.3%) patient injuries with 358 subsequent interventions were identified, resulting in 558 AEs. Although the absolute AE number per device cannot be identified, the following trends were detected: Among the 494 AEs associated with OSI200, 55 (11.1%) reported device malfunctions and 454 (88.9%) cited patient injuries. Out of the 64 AEs linked to BCI602, 28 (59.4%) were associated with malfunctions, whereas 26 (40.6%) involved patient injuries. The most frequently reported particular AEs for the OSI200 were infection (n = 171, 34.6%), extrusion of the device (n = 107, 21.7%), and pain (n = 51, 10.3%). Conversely, no device output (n = 20, 31.3%) and loss of osseointegration (n = 7, 10.9%) were the most reported AEs for the BCI602. Various AEs led to 214 explanations and 77 revision surgeries. Sixty-seven AEs reported conservative treatment. Conclusion: The current study provides an overview of the most commonly reported complications with new active BCIs. Although providing an overview, given the limitations of the FDA MAUDE database, our results have to be interpreted with caution. Level of Evidence: 4.

Functional preoperative assessment of coronal knee laxity better predicts postoperative patient outcomes than intraoperative surgeon-defined laxity in total knee arthroplasty.

PURPOSE: Intraoperative laxity assessments in total knee arthroplasty (TKA) are subjective, with few studies comparing against standardised preoperative and postoperative assessments. This study compares coronal knee laxity in TKA patients awake and anaesthetised, preprosthesis and postprosthesis implantation, evaluating relationships to patient-reported outcome measures. METHODS: A retrospective analysis of 49 TKA joints included preoperative and postoperative computed tomography scans, stress radiographs and knee injury and osteoarthritis outcome score (KOOS) questionnaire results preoperatively and 12 months postoperatively. The imaging was used to assess functional laxity (FL) in awake patients, whereas computer navigation measured intraoperative surgical laxity (SL) preimplantation and postimplantation, with patients anaesthetised. Varus and valgus stress states and their difference, joint laxity, were measured. RESULTS: SL was greater than FL in both preimplantation [8.1° (interquartile range, IQR 2.0°) and 3.8° (IQR 2.9°), respectively] and postimplantation [3.5° (IQR 2.3°) and 2.5° (IQR 2.7°), respectively]. Preimplantation, SL was more likely than FL to categorise knees as correctable to ±3° of the mechanical axis. Preoperative FL correlated with KOOS Symptoms (r = 0.33, p = .02) and quality of life (QOL) (r = 0.38, p = .01), whereas reducing medial laxity with TKA enhanced postoperative QOL outcomes (p = .02). CONCLUSIONS: Functional coronal knee laxity assessment of awake patients is generally lower than intraoperative surgical assessments of anaesthetised patients. Preoperative SL may result in overcorrection of coronal TKA alignment, whereas preoperative FL better predicts postoperative patient outcomes and reflects the patients' native and tolerable knee laxity. Preoperative FL assessment can be used to guide surgical planning. LEVEL OF EVIDENCE: Level II.

Universal coverage for oral health care in 27 low-income countries: a scoping review.

BACKGROUND: Low-income countries bear a growing and disproportionate burden of oral diseases. With the World Health Organization targeting universal oral health coverage by 2030, assessing the state of oral health coverage in these resource-limited nations becomes crucial. This research seeks to examine the political and resource commitments to oral health, along with the utilization rate of oral health services, across 27 low-income countries. METHODS: We investigated five aspects of oral health coverage in low-income countries, including the integration of oral health in national health policies, covered oral health services, utilization rates, expenditures, and the number of oral health professionals. A comprehensive search was conducted across seven bibliographic databases, three grey literature databases, and national governments' and international organizations' websites up to May 2023, with no linguistic restrictions. Countries were categorized into "full integration", "partial integration", or "no integration" based on the presence of dedicated oral health policies and the frequency of oral health mentions. Covered oral health services, utilization rates, expenditure trends, and the density of oral health professionals were analyzed using evidence from reviews and data from World Health Organization databases. RESULTS: A total of 4242 peer-reviewed and 3345 grey literature texts were screened, yielding 12 and 84 files respectively to be included in the final review. Nine countries belong to "full integration" and thirteen countries belong to "partial integration", while five countries belong to "no integration". Twelve countries collectively covered 26 types of oral health care services, with tooth extraction being the most prevalent service. Preventive and public health-based oral health interventions were scarce. Utilization rates remained low, with the primary motivation for seeking care being dental pain relief. Expenditures on oral health were minimal, predominantly relying on domestic private sources. On average, the 27 low-income countries had 0.51 dentists per 10,000 population, contrasting with 2.83 and 7.62 in middle-income and high-income countries. CONCLUSIONS: Oral health care received little political and resource commitment toward achieving universal health coverage in low-income countries. Urgent action is needed to mobilize financial and human resources, and integrate preventive and public health-based interventions.

The clinical utility of multidisciplinary team meetings for patients with complex benign upper gastrointestinal conditions.

Patients with benign upper gastrointestinal (UGI) conditions such as achalasia, gastroparesis and refractory gastroesophageal reflux disease often suffer from debilitating symptoms. These conditions can be complex and challenging to diagnose and treat, making them well suited for discussion within a multidisciplinary meeting (MDM). There is, however, a paucity of data describing the value of a benign UGI MDM. The aim of this study was to assess the impact of our unit's benign UGI MDM service and its outcomes. This was a retrospective analysis of prospectively collected data for all consecutive patients reviewed in the monthly benign UGI MDM between July 2021 and February 2024. The primary outcome was the incidence that MDM review changed clinical treatment. Secondary outcomes included change in diagnosis, additional investigations and referrals to subspecialists. A total of 104 patients met inclusion criteria. A total of 73 (70.2%) patients had a change in their overall management following MDM review; 25 (24.0%), 31 (29.8%) and 48 (46.2%) patients had changes in pharmacological, endoscopic and surgical interventions respectively. Most changes in pharmacological and endoscopic intervention involved treatment escalation, whereas most changes in surgical intervention involved treatment de-escalation. A total of 84 (80.8%) patients had a documented diagnosis post-MDM with 44 (42.3%) having a change in their pre-MDM diagnosis. 50 (48.1%) patients had additional investigation/s requested and 49 (47.1%) had additional referral pathway/s recommended. Over two thirds of patients had at least one aspect of their management plan changed following MDM review. These changes occurred across pharmacological, endoscopic, and surgical interventions.

Factors Associated With Persisting Olfactory Dysfunction After COVID-19.

BACKGROUND: Fortunately, the majority of COVID-19 patients recover from olfactory dysfunction (OD) within the first couple of weeks. However, from approximately 5% up to 20% continue to suffer from OD even more than 1 year after the onset. Nonetheless, factors associated with long-lasting OD are hardly known. The aim of this study was to identify favourable and disadvantageous markers of persisting OD in COVID-19 patients. METHODOLOGY: Sixty-six patients (46 female; mean age: 39.9 years) that suffer from OD longer than 6 months due to laboratory-confirmed SARS-CoV-2 infection have participated in this longitudinal study. Participants completed comprehensive psychophysical chemosensory tests (i.e., Sniffin' Sticks = TDI) and questionnaires twice at our department-on average 219 ± 80 (T-1) and 489 ± 89 (T-2) days after the onset of symptoms, respectively. Olfactory recovery rates were associated with demographic factors and questionnaires using linear regression analysis. RESULTS: Patients below 40 years of age improved better (TDI: 4.1 ± 4.3 vs. 0.7 ± 5.8; p = 0.008) and achieved statistically significant higher scores (TDI: 31.5 ± 4.0 vs. 27.3 ± 6.7; p = 0.033) regarding psychophysical chemosensory tests. Furthermore, linear regression analysis revealed that parosmia was associated with worse orthonasal smell function (T-1: ß = -0.346, p = 0.004; T-2: ß = -0.384, p = 0.001), especially concerning identification subtest (T-1: ß = -0.395, p = 0.001; T-2: ß = -0.398, p < 0.001). Moreover, increasing parosmia between T-1and T-2 led to worse orthonasal olfactory function (ß = -0.294, p = 0.016). CONCLUSIONS: Older age and parosmia seem to be unfavourable factors of persisting OD in COVID-19 patients.

Integrated structural model of the palladin-actin complex using XL-MS, docking, NMR, and SAXS.

Palladin is an actin binding protein that accelerates actin polymerization and is linked to metastasis of several types of cancer. Previously, three lysine residues in an immunoglobulin-like domain of palladin have been identified as essential for actin binding. However, it is still unknown where palladin binds to F-actin. Evidence that palladin binds to the sides of actin filaments to facilitate branching is supported by our previous study showing that palladin was able to compensate for Arp2/3 in the formation of Listeria actin comet tails. Here, we used chemical crosslinking to covalently link palladin and F-actin residues based on spatial proximity. Samples were then enzymatically digested, separated by liquid chromatography, and analyzed by tandem mass spectrometry. Peptides containing the crosslinks and specific residues involved were then identified for input to HADDOCK docking server to model the most likely binding conformation. Small angle X-ray scattering was used to provide further insight into palladin flexibility and the binding interface, and NMR spectra identified potential interactions between palladin's Ig domains. Our final structural model of the F-actin:palladin complex revealed how palladin interacts with and stabilizes F-actin at the interface between two actin monomers. Three actin residues that were identified in this study also appear commonly in the actin binding interface with other proteins such as myotilin, myosin, and tropomodulin. An accurate structural representation of the complex between palladin and actin extends our understanding of palladin's role in promoting cancer metastasis through regulation of actin dynamics. Significance: In this study we have combined various advanced structural biology techniques to provide the first comprehensive model of the palladin-actin complex. Considering palladin's role in cancer cell metastasis, this structure could be useful in screening and developing chemotherapeutic agents that target this interaction and prevent cancer cell metastasis.

How to repair a para-conduit hernia post minimally invasive oesophagectomy: the left hiatoplasty approach.

Repair of a paraconduit hernia post oesophagectomy can be challenging. We present a safe and effective method of left hiatoplasty which is feasible in the majority of cases, achieving primary no-mesh repair while protecting the gastric conduit. Operative photos and videos describe the technique and key considerations.

DNAJB1-PRKACA fusion drives fibrolamellar liver cancer through impaired SIK signaling and CRTC2/p300-mediated transcriptional reprogramming.

Fibrolamellar carcinoma (FLC) is a liver cancer of adolescents and young adults characterized by fusions of the genes encoding the protein kinase A catalytic subunit, PRKACA, and heat shock protein, DNAJB1. The chimeric DNAJB1-PRKACA protein has increased kinase activity and is essential for FLC xenograft growth. Here, we explore the critical oncogenic pathways controlled by DNAJB1-PRKACA using patient-derived FLC models, engineered systems, and patient samples. We show that a core function of DNAJB1-PRKACA is the phosphorylation and inactivation of Salt-inducible kinases (SIKs). This leads to deregulation of the CRTC2 transcriptional co-activator and p300 acetyltransferase, resulting in transcriptional reprogramming and increased global histone acetylation, driving malignant growth. Our studies establish a central oncogenic mechanism of DNAJB1-PRKACA and suggest the potential of targeting CRTC2/p300 in FLC. Notably, these findings link this rare cancer's signature fusion oncoprotein to more common cancer gene alterations involving STK11 and GNAS, which also function via SIK suppression.

Amphiphilic shuttle peptide delivers base editor ribonucleoprotein to correct the CFTR R553X mutation in well-differentiated airway epithelial cells.

Base editing could correct nonsense mutations that cause cystic fibrosis (CF), but clinical development is limited by the lack of delivery methods that efficiently breach the barriers presented by airway epithelia. Here, we present a novel amphiphilic shuttle peptide based on the previously reported S10 peptide that substantially improved base editor ribonucleoprotein (RNP) delivery. Studies of the S10 secondary structure revealed that the alpha-helix formed by the endosomal leakage domain (ELD), but not the cell penetrating peptide (CPP), was functionally important for delivery. By isolating and extending the ELD, we created a novel shuttle peptide, termed S237. While S237 achieved lower delivery of green fluorescent protein, it outperformed S10 at Cas9 RNP delivery to cultured human airway epithelial cells and to pig airway epithelia in vivo, possibly due to its lower net charge. In well-differentiated primary human airway epithelial cell cultures, S237 achieved a 4.6-fold increase in base editor RNP delivery, correcting up to 9.4% of the cystic fibrosis transmembrane conductance regulator (CFTR) R553X allele and restoring CFTR channel function close to non-CF levels. These findings deepen the understanding of peptide-mediated delivery and offer a translational approach for base editor RNP delivery for CF airway disease.

Robotic-Assisted Total Knee Arthroplasty Results in Shorter Navigation Working Time With Similar Clinical Outcomes Compared to Computer-Navigated Total Knee Arthroplasty.

BACKGROUND: Early clinical data is important in the appraisal of newly introduced robotic-assisted surgery (RAS) systems in total knee arthroplasty (TKA). However, there are few studies to date comparing one-year clinical outcomes between RAS and computer-assisted navigation (CAS), the forerunner in reducing alignment outliers. The aim of this study was to determine if there was a difference between these two groups in early clinical outcomes, including functional outcome and patient-reported outcome measures (PROMs). METHODS: A total of 158 propensity score-matched patients who underwent primary TKA with either CAS or RAS were retrospectively analyzed. Perioperative outcomes (navigation time, length of stay, complications, readmissions, transfusions, and technical failure), as well as functional outcome measures (range of motion, sit to stand test, timed up and go test, single leg stance test, calf raises, and step count), and patient-reported outcome measures (Oxford Knee Score, Knee Injury and Osteoarthritis Outcome Score, 12-item Short Form Survey, Forgotten Joint Score-12, and satisfaction) were compared between those who underwent CAS and those who underwent RAS. RESULTS: Navigation time was shorter in the RAS group compared to the CAS group (mean difference, 15.4 minutes; P < 0.001). There were two complications reported in the CAS group (1 patellar clunk, 1 periprosthetic joint infection), but none in the RAS group. There were no other readmissions, transfusions, or technical failures in either group. Postoperatively, there were no clinical differences in function between groups. Clinically meaningful improvement in PROMs was observed in both groups, with no differences. CONCLUSION: The use of RAS resulted in shorter navigation time compared to CAS in TKA. No other differences were observed in early clinical outcomes between patients who underwent RAS and CAS.

Low-dose clonidine infusion to improve sleep in postoperative patients in the high-dependency unit. A randomised placebo-controlled single-centre trial.

PURPOSE: Dexmedetomidine increases sleep and reduces delirium in postoperative patients, but it is expensive and requires a monitored environment. Clonidine, another α 2-agonist, is cheaper and is used safely for other purposes in wards. We assessed whether clonidine would improve sleep in postoperative high-dependency unit (HDU) patients. METHODS: The Clonidine at Low dosage postoperatively to Nocturnally Enhance Sleep (CLONES) study was a double-blind, placebo-controlled, parallel-group pilot effectiveness randomised trial involving adult elective surgery HDU patients in a single academic hospital. Patients received clonidine 0.3 µg/kg/h or saline placebo on the night of surgery. The primary outcome was total sleep time measured using a consumer actigraphy/photoplethysmography device. RESULTS: Of the 83 randomised patients, three had no data available, leaving 80 (39 clonidine, 41 placebo) in the intention-to-treat analysis, modified for missing data. Median patient ages of the groups were similar (61 and 59 years), as were other baseline characteristics. Clonidine patients had a mean of 100.8 (95% confidence interval [CI] 38.2-163.4) minutes (p = 0.002) longer total sleep time (mean 497.2 vs. 396.4 min) and reported better sleep overall. Delirium was only observed in one patient prior to study drug infusion, and none at the end of the study. Safety outcomes were not different. Four clonidine patients had their medication ceased due to bradycardia and hypotension that required no additional treatment. CONCLUSION: Among postoperative elective surgical patients admitted to HDU, low-dose non-titrated clonidine, compared to placebo, was associated with longer and subjectively better-quality sleep.

Public interest and seasonal peaks for wisdom teeth related web inquiries - A google trends analysis.

Objective: The study aimed to analyze the public interest in wisdom teeth-related search terms as well as regional and seasonal trends based on information from the Google search engine. METHODS: With the help of the online search query tool, Google Trends, the public interest in the primary search term "wisdom teeth" for the timeframe between January 1st, 2004 and September 31st, 2021 was analyzed. To do so, a country-specific search was conducted in English-speaking countries (the USA, the UK, Canada, and Australia) in the northern and southern hemispheres. The extracted time series was examined for reliability, and a Cosinor analysis evaluated the statistical significance of seasonal interest peaks. RESULTS: The reliability of averaged time series data on the search term "wisdom teeth" was excellent in all examined countries. In all countries analyzed, "wisdom teeth removal" was one of the most common related search terms. Significant interest peaks for wisdom teeth-related search terms were found in Canada and the USA during summer (p < .001). In Canada and the USA, significant seasonal patterns with the highest interest during the summer months, could be displayed. CONCLUSION: This phenomenon could be caused by increased wisdom teeth-related complaints induced by seasonal climate changes.

Patient-reported disease control versus overall symptom severity as global metrics of chronic rhinosinusitis disease status.

BACKGROUND: Overall symptom severity (OSS) and patient-reported chronic rhinosinusitis (CRS) control are global measures of CRS identified as consensus, essential criteria for CRS disease control assessment. We sought to determine the functional relationship between these two metrics. METHODS: Using an international multicenter mixed-methods design, 260 CRS patients were recruited. OSS score was measured using a visual analog scale. Patient-reported CRS control was measured as "controlled," "partly controlled," and "uncontrolled." Twelve participants underwent semi-structured interviews to discuss OSS and patient-reported CRS control. RESULTS: The majority of interviewed participants felt OSS and patient-reported CRS control measured different constructs-while OSS only measured symptoms, patient-reported CRS control was more global, including not only symptom severity but also concepts such as medication usage, activity impairment, and exacerbations. Nevertheless, OSS score was strongly correlated with (ρ = 0.67, p < 0.001) and highly predictive of patient-reported CRS control. OSS score of >4 (95% confidence interval [CI]: 1.8-4.2) had 74.7% sensitivity and 93.2% specificity in identifying patients reporting their CRS as not controlled. OSS score of >6.6 (95% CI: 4.1-7.1) had 77.0% sensitivity and 75.9% specificity in identifying patients reporting their CRS as uncontrolled. The 22-item Sinonasal Outcome Test score was also predictive of patient-reported CRS disease control but OSS was significantly more predictive. CONCLUSIONS: Patients conceptually view patient-reported CRS control as a more global measure that subsumes OSS. Quantitatively, however, OSS is highly correlated with patient-reported CRS control, possibly reflecting their redundancy. For ease of use, we recommend patient-reported CRS control be reflected by OSS <4 for controlled, 4 ≤ OSS < 7 for partly controlled, and OSS ≥7 for uncontrolled CRS.

Advances in Interventional Radiology Technology for the Treatment of Knee Osteoarthritis.

Minimally invasive interventional radiology procedures play an adjunctive role in treating the symptoms of osteoarthritis (OA) with the hopes of delaying total knee arthroplasty (TKA). However, currently available intra-articular injections offer only short-term benefits. This has led to evolution of new techniques such as genicular artery embolization and genicular nerve ablation, which show benefit in pain control and quality of life, especially for mild-to-moderate OA, positioning these techniques as potential alternatives to intra-articular injections to help delay TKA.

Nivolumab maintenance improves overall survival of patients with advanced melanoma who experience severe immune-related adverse events on nivolumab plus ipilimumab.

BACKGROUND: The combination of ipilimumab and nivolumab is a highly effective treatment for metastatic cutaneous melanoma. However, immune-related adverse events (irAEs) are common, often necessitating treatment interruption and the use of immunosuppressive agents. There is no data on the impact of resuming nivolumab on survival following recovery from the irAE and completion of immunosuppressive treatment. PATIENTS AND METHODS: In this retrospective analysis, we examined a cohort of patients treated with ipilimumab/nivolumab who developed irAEs requiring treatment interruption and immunosuppressive therapy. The differences in physician practice patterns at our institution allowed us to examine the survival effect of restarting single-agent nivolumab. A multivariate analysis of clinical factors associated with improved survival was performed. RESULTS: We identified 165 patients who were treated with ipilimumab/nivolumab and developed irAEs requiring treatment interruption and immunosuppressive therapy. Patients with the best overall response of progressive disease were excluded. Of the remaining 122 patients, 46 resumed single-agent nivolumab. When stratified by age and adjusted for sex, M-stage, lactate dehydrogenase (LDH), therapy duration, and irAE type, the effect of resumption of nivolumab on survival was highly significant (p=0.02). Patients who resumed nivolumab had a 68% reduction in the hazard of death compared with patients who had not yet or never resumed nivolumab (HR: 0.32, 95% CI: 0.12 to 0.84). Of the patients who resumed nivolumab, 12 (26%) patients had subsequent irAEs, with five patients having grade 3 irAEs. No grade 4 or 5 irAEs were noted. CONCLUSIONS: Resuming single-agent nivolumab following a treatment interruption for ipilimumab/nivolumab-associated irAE and completion of immunosuppressive therapy increased overall survival compared with discontinuing nivolumab permanently in patients with metastatic melanoma. Toxicity observed post-resumption of single-agent nivolumab was manageable with no severe irAEs observed.

Cost burden following esophagectomy: A single centre observational study.

BACKGROUND: Cost analyses of patients undergoing esophagectomy is valuable for identifying modifiable expenditure drivers to target and curtail costs while improving the quality of care. We aimed to define the cost-complication relationship after esophagectomy and delineate the incremental contributions to costs. AIM: To assess the relationship between the hospital costs and potential cost drivers post esophagectomy and investigate the relationship between the cost-driving variables (predicting variables) and hospital costs (dependent variable). METHODS: In this retrospective single center study, the severity of complications was graded using the Clavien-Dindo (CD) classification system. Key esophagectomy complications were categorized and defined according to consensus guidelines. Raw costing data included the in-hospital costs of the index admission and any unplanned admission within 30 postoperative days. We used correlation analysis to assess the relationship between key clinical variables and hospital costs (in United States dollars) to identify cost drivers. A mediation model was used to investigate the relationship between these variables and hospital costs. RESULTS: A total of 110 patients underwent primary esophageal resection. The median admission cost was $47822.7 (interquartile range: 35670.2-68214.0). The total effects on costs were $13593.9 (95%CI: 10187.1-17000.8, P < 0.001) for each increase in CD severity grade, $4781 (95%CI: 3772.7-5789.3, P < 0.001) for each increase in the number of complications, and $42552.2 (95%CI: 8309-76795.4, P = 0.015) if a key esophagectomy complication developed. Key esophagectomy complications drove the costs directly by $11415.7 (95%CI: 992.5-21838.9, P = 0.032). CONCLUSION: The severity and number of complications, and the development of key esophagectomy complications significantly contributed to total hospital costs. Continuous institutional initiatives and strategies are needed to enhance patient outcomes and minimize costs.

JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans.

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 is a peptide targeting the IL-23 receptor with high affinity (KD: 7.1 pM). In human cells, JNJ-77242113 potently and selectively inhibited proximal IL-23 signaling (IC50: 5.6 pM) without impacting IL-12 signaling. JNJ-77242113 inhibited IL-23-induced interferon (IFN)γ production in NK cells, and in blood from healthy donors and psoriasis patients (IC50: 18.4, 11 and 9 pM, respectively). In a rat trinitrobenzene sulfonic acid-induced colitis model, oral JNJ-77242113 attenuated disease parameters at doses ≥ 0.3 mg/kg/day. Pharmacologic activity beyond the gastrointestinal tract was also demonstrated. In blood from rats receiving oral JNJ-77242113, dose-dependent inhibition of ex vivo IL-23-stimulated IL-17A production was observed. In an IL-23-induced rat skin inflammation model, JNJ-77242113 inhibited IL-23-induced skin thickening and IL-17A, -17F and -22 gene induction. Oral dosing of JNJ-77242113 in healthy human volunteers inhibited ex vivo IL-23-stimulated IFNγ production in whole blood. Thus, JNJ-77242113 provided selective, systemic IL-23 pathway inhibition in preclinical models which translated to pharmacodynamic activity in healthy human volunteers, supporting the potential for JNJ-77242113 as a selective oral therapy for IL-23-driven immune-mediated diseases.

Trial of Converting Nursing Records into Simplified and Structured Information Utilizing ChatGPT-3.5.

In Japan, the excessive length of time required for nursing records has become a social problem. A shift to concise "bulleted" records is needed to apply speech recognition and to work with foreign caregivers. Therefore, using 96,000 descriptively described anonymized nursing records, we identified typical situations for each information source and attempted to convert them to "bulleted" records using ChatGPT-3.5(For return from the operating room, Status on return, Temperature control, Blood drainage, Stoma care, Monitoring, Respiration and Oxygen, Sensation and pain, etc.). The results showed that ChatGPT-3.5 has some usable functionality as a tool for extracting keywords in "bulleted" records. Furthermore, through the process of converting to a "bulleted" record, it became clear that the transition to a standardized nursing record utilizing the "Standard Terminology for Nursing Observation and Action (STerNOA)" would be facilitated.