Episodic mandibular tremor in dogs: an idiopathic movement disorder or a manifestation of pain.

OBJECTIVE: Episodic mandibular tremor (EMT), manifested as teeth chattering, is not well described in dogs. The aim of this study was to describe clinical signs, MRI findings, and outcome of dogs with EMT. ANIMALS: 11 dogs retrospectively and 31 dogs in an online survey. METHODS: A retrospective multicenter study of dogs with EMT between 2018 and 2023 and prospective online questionnaire open to owners of pets with teeth chattering. RESULTS: All dogs had rapid and short-lasting (< 1 minute) episodes of EMT in the absence of other neurological signs. Lip smacking occasionally accompanied the tremor in 5 of 11 (45.5%) hospital dog cases. Excitement was a common trigger in 14 of 31 (45.2%) dogs from the survey. Cavalier King Charles Spaniel was the most common breed in both clinical and survey populations. Median age at presentation was 3 years for both hospital cases and the survey dogs. A concurrent medical condition was present in 8 of 11 (72.7%) hospital cases and 20 of 31 (64.5%) survey dogs. In 3 hospital dogs that underwent further investigations, no brain disease was present. CLINICAL RELEVANCE: EMT and its clinical features are presented for the first time, shedding light on a clinical sign that might resemble an idiopathic movement disorder or a manifestation of pain in dogs.

Imaging Findings of Primary Acinic Cell Carcinoma of the Breast: A Case Report.

Acinic cell carcinoma is a rare malignant tumor that accounts for 2%-3% of salivary gland tumors. Acinic cell carcinoma arising from the breast is extremely rare, with only approximately 70 cases reported to date. Owing to its rarity, previous studies have primarily focused on pathological findings. Herein, we present the clinical and radiological features of acinic cell carcinoma of the breast in a 33-year-old woman.

Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial.

BACKGROUND AND AIMS: We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer (BTC). APPROACH AND RESULTS: This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included treatment-naïve adults with locally advanced/metastatic BTC. Patients (N=297) were randomized to receive an intravenous infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m2+cisplatin 25 mg/m2 on days 1 and 8/3 wk; 8 cycles) (BA group, n=148) or placebo+GemCis (placebo group, n=149). The primary endpoint was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cut-off: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naïve, when 80 progression-free survival events had occurred and ≥19 weeks of follow-up had been completed (BA, n=73; placebo, n=77). Median OS (95% CI) for the BA (11.5 mo [9.3-not estimable, NE]) and placebo (11.5 mo [10.0-NE]) groups was comparable (hazard ratio 1.23 [95% CI 0.66-2.28]; p=0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively. CONCLUSIONS: BA+GemCis did not provide a clinically meaningful benefit compared to GemCis alone as first-line treatment for BTC and the study was discontinued early (terminated: August 20, 2021).

Atractylodes macrocephala Koidz Alleviates Symptoms in Zymosan-Induced Irritable Bowel Syndrome Mouse Model through TRPV1, NaV1.5, and NaV1.7 Channel Modulation.

(1) Background: Irritable bowel syndrome (IBS) is a common disease in the gastrointestinal (GI) tract. Atractylodes macrocephala Koidz (AMK) is known as one of the traditional medicines that shows a good efficacy in the GI tract. (2) Methods: We investigated the effect of AMK in a network pharmacology and zymosan-induced IBS animal model. In addition, we performed electrophysiological experiments to confirm the regulatory mechanisms related to IBS. (3) Results: Various characteristics of AMK were investigated using TCMSP data and various analysis systems. AMK restored the macroscopic changes and weight to normal. Colonic mucosa and inflammatory factors were reduced. These effects were similar to those of amitriptyline and sulfasalazine. In addition, transient receptor potential (TRP) V1, voltage-gated Na+ (NaV) 1.5, and NaV1.7 channels were inhibited. (4) Conclusion: These results suggest that AMK may be a promising therapeutic candidate for IBS management through the regulation of ion channels.

Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study.

BACKGROUND: In the preplanned interim analysis of the TOPAZ-1 study, durvalumab plus gemcitabine-cisplatin significantly improved overall survival versus placebo plus gemcitabine-cisplatin in participants with advanced biliary tract cancer. We aimed to report updated overall survival and safety data from TOPAZ-1 with additional follow-up and data maturity beyond the interim analysis. METHODS: TOPAZ-1 was a phase 3, randomised, double-masked, placebo-controlled, global study done at 105 sites in 17 countries. Participants aged 18 years or older with unresectable, locally advanced, or metastatic biliary tract cancer were randomly assigned (1:1) to durvalumab plus gemcitabine-cisplatin or placebo plus gemcitabine-cisplatin using a computer-generated randomisation scheme, stratified by disease status and primary tumour location. Participants received durvalumab (1500 mg) or placebo on day 1 of each cycle every 3 weeks for up to eight cycles, plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) intravenously on days 1 and 8 of each cycle every 3 weeks for up to eight cycles, followed by durvalumab (1500 mg) or placebo monotherapy every 4 weeks until disease progression or other discontinuation criteria were met. Investigators and participants were masked to study treatment. The primary endpoint was overall survival. TOPAZ-1 met its primary endpoint at the preplanned interim analysis, and the study is active but no longer recruiting participants. Updated overall survival and safety data from TOPAZ-1, with additional follow-up (data cutoff Feb 25, 2022) and data maturity beyond the interim analysis, are reported here. Efficacy was assessed in the full analysis set (all randomly assigned participants). Safety was assessed in the safety analysis set (all participants who received at least one dose of study treatment). The TOPAZ-1 study is registered with ClinicalTrials.gov, NCT03875235. FINDINGS: From April 16, 2019, to Dec 11, 2020, 914 participants were enrolled, 685 of whom were randomly assigned (341 to the durvalumab plus gemcitabine-cisplatin group and 344 to the placebo plus gemcitabine-cisplatin group). 345 (50%) participants were male and 340 (50%) were female. Median follow-up at the updated data cutoff was 23·4 months (95% CI 20·6-25·2) in the durvalumab plus gemcitabine-cisplatin group and 22·4 months (21·4-23·8) in the placebo plus gemcitabine-cisplatin group. At the updated data cutoff, 248 (73%) participants in the durvalumab plus gemcitabine-cisplatin group and 279 (81%) participants in the placebo plus gemcitabine-cisplatin group had died (median overall survival 12·9 months [95% CI 11·6-14·1] vs 11·3 months [10·1-12·5]; hazard ratio 0·76 [95% CI 0·64-0·91]). Kaplan-Meier-estimated 24-month overall survival rates were 23·6% (95% CI 18·7-28·9) in the durvalumab plus gemcitabine-cisplatin group and 11·5% (7·6-16·2) in the placebo plus gemcitabine-cisplatin group. Maximum grade 3 or 4 adverse events occurred in 250 (74%) of 338 participants in the durvalumab plus gemcitabine-cisplatin group and 257 (75%) of 342 in the placebo plus gemcitabine-cisplatin group. The most common maximum grade 3 or 4 treatment-related adverse events were decreased neutrophil count (70 [21%] vs 86 [25%]), anaemia (64 [19%] vs 64 [19%]), and neutropenia (63 [19%] vs 68 [20%]). INTERPRETATION: Durvalumab plus gemcitabine-cisplatin showed robust and sustained overall survival benefit with no new safety signals. Findings continue to support the regimen as a standard of care for people with untreated, advanced biliary tract cancer. FUNDING: AstraZeneca.

Structural study for substrate recognition of human N-terminal glutamine amidohydrolase 1 in the arginine N-degron pathway.

The N-degron pathway determines the half-life of proteins by selectively destabilizing the proteins bearing N-degrons. N-terminal glutamine amidohydrolase 1 (NTAQ1) plays an essential role in the arginine N-degron (Arg/N-degron) pathway as an initializing enzyme via the deamidation of the N-terminal (Nt) glutamine (Gln). However, the Nt-serine-bound conformation of hNTAQ1 according to the previously identified crystal structure suggests the possibility of other factors influencing the recognition of Nt residues by hNTAQ1. Hence, in the current study, we aimed to further elucidate the substrate recognition of hNTAQ1; specifically, we explored 12 different substrate-binding conformations of hNTAQ1 depending on the subsequent residue of Nt-Gln. Results revealed that hNTAQ1 primarily interacts with the protein Nt backbone, instead of the side chain, for substrate recognition. Here, we report that the Nt backbone of proteins appears to be a key component of hNTAQ1 function and is the main determinant of substrate recognition. Moreover, not all second residues from Nt-Gln, but rather distinctive and charged residues, appeared to aid in detecting substrate recognition. These new findings define the substrate-recognition process of hNTAQ1 and emphasize the importance of the subsequent Gln residue in the Nt-Gln degradation system. Our extensive structural and biochemical analyses provide insights into the substrate specificity of the N-degron pathway and shed light on the mechanism underlying hNTAQ1 substrate recognition. An improved understanding of the protein degradation machinery could aid in developing therapies to promote overall health through enhanced protein regulation, such as targeted protein therapies.

An interaction network in the polymerase active site is a prerequisite for Watson-Crick base pairing in Pol γ.

The replication accuracy of DNA polymerase gamma (Pol γ) is essential for mitochondrial genome integrity. Mutation of human Pol γ arginine-853 has been linked to neurological diseases. Although not a catalytic residue, Pol γ arginine-853 mutants are void of polymerase activity. To identify the structural basis for the disease, we determined a crystal structure of the Pol γ mutant ternary complex with correct incoming nucleotide 2'-deoxycytidine 5'-triphosphate (dCTP). Opposite to the wild type that undergoes open-to-closed conformational changes when bound to a correct nucleotide that is essential for forming a catalytically competent active site, the mutant complex failed to undergo the conformational change, and the dCTP did not base pair with its Watson-Crick complementary templating residue. Our studies revealed that arginine-853 coordinates an interaction network that aligns the 3'-end of primer and dCTP with the catalytic residues. Disruption of the network precludes the formation of Watson-Crick base pairing and closing of the active site, resulting in an inactive polymerase.

Optimizing Embryo Collection for Application of CRISPR/Cas9 System and Generation of Fukutin Knockout Rat Using This Method.

Rat animal models are widely used owing to their relatively superior cognitive abilities and higher similarity compared with mouse models to human physiological characteristics. However, their use is limited because of difficulties in establishing embryonic stem cells and performing genetic modifications, and insufficient embryological research. In this study, we established optimal superovulation and fertilized-egg transfer conditions, including optimal hormone injection concentration (≥150 IU/kg of PMSG and hCG) and culture medium (mR1ECM), to obtain high-quality zygotes and establish in vitro fertilization conditions for rats. Next, sgRNA with optimal targeting activity was selected by performing PCR analysis and the T7E1 assay, and the CRISPR/Cas9 system was used to construct a rat model for muscular dystrophy by inducing a deficiency in the fukutin gene without any off-target effect detected. The production of fukutin knockout rats was phenotypically confirmed by observing a drop-in body weight to one-third of that of the control group. In summary, we succeeded in constructing the first muscular dystrophy disease rat model using the CRISPR/CAS9 system for increasing future prospects of producing various animal disease models and encouraging disease research using rats.

Neoadjuvant chemotherapy is associated with improved disease-free survival in pancreatic cancer patients undergoing pancreaticoduodenectomy with vascular resection.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) is becoming favored for all pancreatic adenocarcinoma (PDAC). Patients with seemingly resectable disease infrequently still display vascular involvement intraoperatively. Outcomes following NAC versus upfront surgery in patients undergoing pancreaticoduodenectomy (PD) with vascular resection are unknown. METHODS: We performed a retrospective cohort study of PDAC patients who underwent PD with vascular resection between January 1, 2013, to December 31, 2020, within a single academic center. Clinicopathologic characteristics and disease-free survival (DFS) were compared between NAC versus upfront surgery cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. RESULTS: Eighty-one patients who underwent PD with vascular resection for PDAC were included. Forty-six patients (56%) received NAC. The NAC cohort more often had pathologic N0 status (47.8% vs. 8.6%, p < 0.001), had decreased vascular invasion (11% vs. 40%, p = 0.002), and completed chemotherapy (80% vs. 40%, p < 0.01). The NAC cohort demonstrated improved DFS (40.5 vs. 14.3 months, p = 0.007). In multivariable analysis, NAC remained independently associated with increased DFS (HR = 0.48, p = 0.02). CONCLUSIONS: NAC was associated with improved clinicopathologic outcomes and DFS in PD with vascular resection. These findings demonstrate the advantage of NAC in PDAC patients undergoing PD with vascular resection.

Outcomes of carotid endarterectomy in octogenarians compared to their younger counterparts: a retrospective observational study.

Purpose: This study was performed to analyze the association between age and outcomes of carotid endarterectomy (CEA) by comparing postoperative outcomes between octogenarians and younger patients. Methods: From November 1994 to December 2022, 1,585 internal carotid arteries of 1,434 patients were enrolled. Patients were stratified into 2 groups: octogenarians (≥80 years old) and non-octogenarians (<80 years old). Primary endpoints were early (≤30 days) outcomes of ipsilateral stroke, any stroke, myocardial infarction, death, and major adverse cardiovascular events (MACE). We also compared overall any stroke and death between the 2 groups. Results: One of 132 octogenarians (0.8%) and 17 of 1,453 non-octogenarians (1.1%) experienced ipsilateral stroke within 30 days. Thirty-day MACE occurred in 4 of 132 octogenarians (3%) and 44 of 1,453 non-octogenarians (3%). There were no significant differences in any early (≤30 days) outcomes. Symptomatic status was associated with increased 30-day MACE (odds ratio [OR], 2.610; 95% confidence interval [CI], 1.450-4.696; P = 0.003) and 30-day any stroke (OR, 3.999; 95% CI, 1.627-9.828; P = 0.003). Symptomatic status was also associated with overall any stroke (hazard ratio [HR], 2.885; 95% CI, 1.865-4.463; P < 0.001), but age of ≥80 years was not associated with 30-day MACE, 30-day any stroke, or overall stroke. Age of ≥80 years was only associated with overall survival (HR, 2.644; 95% CI, 1.967-3.555; P < 0.001). Conclusion: CEA would be a safe and effective treatment for octogenarians with low 30-day complications and long-term stroke rates, comparable with that of younger counterparts. Advanced age is not a contraindication for CEA.

Prevalence and Factors Influencing Post-Operative Complications following Tooth Extraction: A Narrative Review.

Background: Complications from dental extractions may result in multiple post-operative visits and adversely affect the patient's life. Preventing complications may decrease post-operative morbidity for the individual as well as lower societal costs, such as lost time from work and healthcare costs. Objectives: This narrative review aims to assess the prevalence and factors influencing post-operative complications following tooth extraction, helping clinicians minimise the risk. Data Sources. Cross-sectional studies. Study Eligibility and Participants. Patients undergoing dental extractions. Our exclusion criteria included in vitro studies, animal studies, terminally ill patients, and tooth loss not due to dental extraction. Literature was collected from "PubMed" and "Web of Science" through search criteria based on the "PICO" framework. Twenty articles were used to formulate a prevalence table, and 156 articles were included for the factors influencing complications. Study Appraisal and Synthesis Methods. This narrative review was reported using the SANRA (a scale for the quality assessment of narrative review articles) checklist. Due to the scope of our narrative review and its associated objectives, the quality of cross-sectional studies (AXIS) will be conducted from the studies outlining the prevalence. Results: Alveolar osteitis appears to be the most prevalent post-operative complication following tooth extraction. Predisposing factors can be significant in their ability to alter the risk of postoperative complications, and clinicians should provide patient-centred care to mitigate this risk. Limitations. Due to the breadth of context, a systematic review was not feasible, as it may have introduced heterogeneity. Conclusion: This narrative review has highlighted an array of factors which can influence the prevalence of post-operative complications. Future research would benefit from individually reporting post-operative complications, reducing the heterogeneity in definitions of the complications, and including greater detail on the predisposing factors studied.

Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study.

BACKGROUND: Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate approved by the US Food and Drug Administration and the European Medicines Agency for HER2-mutant non-small-cell lung cancer. Few treatment options exist for patients with HER2-mutant solid tumours beyond lung cancers. We investigated trastuzumab deruxtecan in metastatic solid tumours with specific activating HER2 mutations. METHODS: In this open-label, phase 2, basket study done in 29 centres in Asia, Europe, and North America, we investigated trastuzumab deruxtecan (5·4 mg/kg every 3 weeks by intravenous infusion) in patients aged 18 years or older with unresectable or metastatic solid tumours with specific activating HER2 mutations, an Eastern Cooperative Oncology Group performance status of 0 or 1, and disease progression following previous treatment (previous HER2-targeted therapy was permitted) or with no satisfactory alternative treatment options. The primary endpoint was confirmed objective response rate by independent central review. Anti-tumour activity and safety were analysed in all patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT04639219, and is active but no longer recruiting. FINDINGS: Between Dec 30, 2020, and Jan 25, 2023, 102 patients (62 [61%] female and 40 [39%] male; median age 66·5 years [IQR 58-72]; 51 [50%] White, two [2%] Black or African American, 38 [37%] Asian, and 11 [11%] did not have race information reported) with solid tumours with activating HER2 mutations received trastuzumab deruxtecan and were included in the anti-tumour activity and safety analyses sets. Patients had a median of three (IQR 2-4) previous treatment regimens. The median duration of follow-up was 8·61 months (IQR 3·71-12·68). The objective response rate by independent central review was 29·4% (95% CI 20·8-39·3; 30 of 102 patients). 52 (51%) patients had a treatment-emergent adverse event of grade 3 or worse; the most common events (in ≥5% of patients) were anaemia (16 [16%]) and neutrophil count decreased (eight [8%]). Drug-related treatment-emergent serious adverse events occurred in ten (10%) patients. Adjudicated drug-related interstitial lung disease or pneumonitis of any grade occurred in 11 patients (11%; three grade 1, five grade 2, one grade 3, and two grade 5); there were two (2%) cases of fatal adjudicated drug-related interstitial lung disease or pneumonitis. INTERPRETATION: Trastuzumab deruxtecan showed anti-tumour activity and durable responses in heavily pretreated patients across multiple tumour types with activating HER2 mutations, with no new safety signals. Prespecified HER2 mutations might be targeted by HER2-directed antibody-drug conjugates and our findings support further investigation of trastuzumab deruxtecan in the pan-tumour setting. FUNDING: AstraZeneca and Daiichi Sankyo.

Refining the CRiSPHe (checklist for reporting research using a simulated patient methodology in Health): a Delphi study.

OBJECTIVES: A recent applicability study highlighted the need for the existing checklist for reporting research using a simulated patient methodology (CRiSP) to be clearer and user-friendly. The aim of this study was to update the checklist to address these concerns. METHODS: A fourth round of the Delphi consensus study, used in the original checklist development work, was conducted. Previous participants, who had expertise in SP methodology, were invited to complete a questionnaire including a list of 13 checklist items developed in the previous study and revised following applicability testing. Closed questions were analysed for frequency. Consensus was predefined as >80% agreement. All items were discussed in a roundtable meeting and further modified as necessary. Responses to open questions were content analysed. KEY FINDINGS: Twenty-one authors participated. There was a statistical consensus in 12 out of 13 modified checklist items. CONCLUSIONS: A final reporting checklist for studies in health research using SP methodology has been developed using a consensus approach. Further refinements may be needed to increase the generalizability of the checklist in different contexts.

The Application of Virtual Reality in Shoulder Surgery Rehabilitation.

To achieve a positive functional prognosis in orthopedic surgery, particularly in shoulder surgeries, effective rehabilitation is essential. Recently, there has been growing interest in the use of virtual reality (VR) in the field of orthopedics, particularly for preoperative education and training, as well as clinical and home-based rehabilitation. This report describes the process of developing an application utilizing Meta Quest 2 VR technology (Meta, CA, USA) for rehabilitation after shoulder surgery. This application assists patients in performing postoperative exercises at home by wearing VR equipment tailored to their postoperative weeks. The advantages of VR rehabilitation lie in overcoming the limitations of traditional rehabilitation methods and providing patients with a better rehabilitation experience. Moreover, automating the rehabilitation process and reducing patients' visits to clinics can lead to cost savings. This report raises expectations for the potential and scalability of VR utilization, extending beyond orthopedics to other fields. In addition, it anticipates that with better feedback and motivation, the rehabilitation effects for patients can be further enhanced.

Use of acetate as substrate for sustainable production of homoserine and threonine by Escherichia coli W3110: A modular metabolic engineering approach.

Acetate, a promising yet underutilized carbon source for biological production, was explored for the efficient production of homoserine and threonine in Escherichia coli W. A modular metabolic engineering approach revealed the crucial roles of both acetate assimilation pathways (AckA/Pta and Acs), optimized TCA cycle flux and glyoxylate shunt activity, and enhanced CoA availability, mediated by increased pantothenate kinase activity, for efficient homoserine production. The engineered strain W-H22/pM2/pR1P exhibited a high acetate assimilation rate (5.47 mmol/g cell/h) and produced 44.1 g/L homoserine in 52 h with a 53% theoretical yield (0.18 mol/mol) in fed-batch fermentation. Similarly, strain W-H31/pM2/pR1P achieved 45.8 g/L threonine in 52 h with a 65% yield (0.22 mol/mol). These results represent the highest reported levels of amino acid production using acetate, highlighting its potential as a valuable and sustainable feedstock for biomanufacturing.

The influence of patients' beliefs about medicines and the relationship with suboptimal medicine use in community-dwelling older adults: a systematic review of quantitative studies.

BACKGROUND: Medication use in older adults is increasing, therefore, reducing the risk of suboptimal medicine use is imperative in achieving optimal therapeutic outcomes. Research suggests that factors such as personal beliefs and beliefs about medicines may be associated with non-adherence and inappropriate medicine use. AIM: To systematically review and identify quantitative research on the influence of beliefs about medicines and the relationship with suboptimal medicine use in older adults. METHOD: Searches were conducted on PubMed, EMBASE, CINAHL, and PsycINFO for quantitative studies (inception to March 2023). INCLUSION CRITERIA: (1) exposure: participants' beliefs (personal, cultural, and medication-related), (2) outcomes: polypharmacy, potentially inappropriate medicines use, or non-adherence, and (3) participants: community-dwelling adults 65 years or above. Study selection, data extraction and quality appraisal (Joanna Briggs Institute critical appraisal checklist) were completed independently by two investigators. Data were combined in a narrative synthesis and presented in a summary of findings table. RESULTS: Nineteen articles were included: 15 cross-sectional and four cohort studies. Outcomes of included papers were as follows; adherence (n = 18) and potentially inappropriate medicine use (n = 1). Ten studies found stronger beliefs in the necessity of medicines and/or fewer concerns led to better adherence, with one paper contradicting these findings. Three studies did not find associations between adherence and beliefs. One study confirmed an association between unnecessary drug use and a lack of belief in a "powerful other" (e.g. doctor). CONCLUSION: Further investigation is necessary to (1) ascertain the importance of necessity or concern beliefs in fostering adherence and, (2) examine the influence of beliefs on polypharmacy and inappropriate medicine use.

Conversion surgery for initially unresectable locally advanced biliary tract cancer: A multicenter collaborative study conducted in Japan and Korea.

BACKGROUND: Although surgical resection is the only curative treatment for biliary tract cancer, in some cases, the disease is diagnosed as unresectable at initial presentation. There are few reports of conversion surgery after the initial treatment for unresectable locally advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of conversion surgery in patients with initially unresectable locally advanced biliary tract cancer. METHODS: We retrospectively collected clinical data from groups of patients in multiple centers belonging to the Japanese Society of Hepato-Biliary-Pancreatic Surgery and Korean Association of Hepato-Biliary-Pancreatic Surgery. We analyzed two groups of prognostic factors (pretreatment and surgical factors) and their relation to the treatment outcomes. RESULTS: A total of 56 patients with initially unresectable locally advanced biliary tract cancer were enrolled in this study of which 55 (98.2%) patients received chemotherapy, and 16 (28.6%) patients received additional radiation therapy. The median time from the start of the initial treatment to resection was 6.4 months. Severe postoperative complications of Clavien-Dindo grade III or higher occurred in 34 patients (60.7%), and postoperative mortality occurred in five patients (8.9%). Postoperative histological results revealed CR in eight patients (14.3%). The median survival time from the start of the initial treatment in all 56 patients who underwent conversion surgery was 37.7 months, the 3-year survival rate was 53.9%, and the 5-year survival rate was 39.1%. CONCLUSIONS: Conversion surgery for initially unresectable locally advanced biliary tract cancer may lead to longer survival in selected patients. However, more precise preoperative safety evaluation and careful postoperative management are required.

Electronic health records and e-prescribing in Australia: An exploration of technological utilisation in Australian community pharmacies.

OBJECTIVE: This study aimed to assess the utilisation, benefits, and challenges associated with Electronic Health Records (EHR) and e-prescribing systems in Australian Community Pharmacies, focusing on their integration into daily practice and the impacts on operational efficiency, while also gathering qualitative insights from community pharmacists. METHODS: A mixed-methods online survey was carried out among community pharmacists throughout Australia to assess the utilisation of EHR and e-prescribing systems, including the benefits and challenges associated with their use. Data was analysed based on pharmacists' age, gender, and practice location (metropolitan vs. regional). The chi-square test was applied to examine the relationship between these demographic factors and the utilisation and operational challenges of EHR and e-prescribing systems. RESULTS: The survey engaged 120 Australian community pharmacists. Of the participants, 67 % reported usability and efficiency issues with EHR systems. Regarding e-prescribing, 58 % of pharmacists faced delays due to slow software performance, while 42 % encountered errors in data transmission. Despite these challenges, the benefits of e-prescribing were evident, with 79 % of respondents noting the elimination of illegible prescriptions and 40 % observing a reduction in their workload. Issues with prescription quantity discrepancies and the reprinting process were highlighted, indicating areas for improvement in workflow and system usability. The analysis revealed no significant statistical relationship between the utilisation and challenges of EHR and e-prescribing systems with the demographic variables of age, gender and location (p > 0.05), emphasising the necessity for healthcare solutions that address the needs of all pharmacists regardless of specific demographic segments. CONCLUSION: In Australian community pharmacies, EHR and e-prescribing may enhance patient care but come with challenges such as data completeness, technical issues, and usability concerns. Implementing successful integration relies on user-centric design, standardised practices, and robust infrastructure. While demanding for pharmacists, the digital transition improves efficiency and quality of care. Ensuring user-friendly tools is crucial for the smooth utilisation of digital health.