Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures.

JOURNAL/nrgr/04.03/01300535-202501000-00034/figure1/v/2024-05-14T021156Z/r/image-tiff Certain amino acids changes in the human Na+/K+-ATPase pump, ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1), cause Charcot-Marie-Tooth disease type 2 (CMT2) disease and refractory seizures. To develop in vivo models to study the role of Na+/K+-ATPase in these diseases, we modified the Drosophila gene homolog, Atpα, to mimic the human ATP1A1 gene mutations that cause CMT2. Mutations located within the helical linker region of human ATP1A1 (I592T, A597T, P600T, and D601F) were simultaneously introduced into endogenous DrosophilaAtpα by CRISPR/Cas9-mediated genome editing, generating the AtpαTTTF model. In addition, the same strategy was used to generate the corresponding single point mutations in flies (AtpαI571T, AtpαA576T, AtpαP579T, and AtpαD580F). Moreover, a deletion mutation (Atpαmut) that causes premature termination of translation was generated as a positive control. Of these alleles, we found two that could be maintained as homozygotes (AtpαI571T and AtpαP579T). Three alleles (AtpαA576T, AtpαP579 and AtpαD580F) can form heterozygotes with the Atpαmut allele. We found that the Atpα allele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila. Flies heterozygous for AtpαTTTF mutations have motor performance defects, a reduced lifespan, seizures, and an abnormal neuronal morphology. These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Proposal of a revised 3-tier "2 mm" risk classification model for postoperative pancreatic fistula in robotic pancreatoduodenectomy.

BACKGROUND: The recent International Study Group for Pancreatic Surgery (ISGPS) risk classification for postoperative pancreatic fistula (grade B/C) was developed based on data from open and mixed minimally invasive pancreatoduodenectomy. The ISGPS risk classification model has not been validated specifically for POPF after robotic pancreatoduodenectomy (RPD). METHODS: We calculated the rate of POPF (ISGPS 2016 definition, grade B/C) by analyzing consecutive patients after RPD by surgeons after their learning curves (80 RPDs per surgeon). The validation of the ISGPS 4-tier and the simplified 3-tier risk classification was conducted using the area under the receiver operating curve (AUC). RESULTS: From 2019 to 2023, 187 patients after RPD were included. Neither the ISGPS 4-tier nor the simplified 3-tier classification model showed robust discrimination (AUC: 0.696 and 0.685, respectively). Moreover, both risk classifications failed to differentiate the rates of POPF and major complications among subgroups. Multivariate analysis suggested that soft pancreatic texture and pancreatic duct ≤ 2 mm were independent risk factors for POPF after RPD. After adjusting the duct size's cutoff from 3 to 2 mm, the revised 4-tier "2 mm" classification model showed no significant difference between risk categories B and C (6.7% vs. 9.4%, P = 0.063). The revised 3-tier "2 mm" classification model stratified patients into A (n = 54), B (n = 68), and C (n = 65) groups, with corresponding POPF rates of 0.0%, 8.8%, and 23.1% (P < 0.001), and major complication rates of 5.6, 14.7, and 24.6% (P = 0.014), respectively. Compared to the simplified 3-tier classification model, the revised 3-tier "2 mm" classification model showed improved discrimination (AUC: 0.753 vs. 0.685, P = 0.034) and clinical utility. CONCLUSIONS: The current ISGPS 4-tier and the simplified 3-tier classification models lacked sufficient discrimination in patients after RPD. We propose a revised 3-tier "2 mm" risk classification model for RPD with a robust discrimination, which requires further international validation with prospectively obtained data.

Consensus, debate, and prospective on pancreatic cancer treatments.

Pancreatic cancer remains one of the most aggressive solid tumors. As a systemic disease, despite the improvement of multi-modality treatment strategies, the prognosis of pancreatic cancer was not improved dramatically. For resectable or borderline resectable patients, the surgical strategy centered on improving R0 resection rate is consensus; however, the role of neoadjuvant therapy in resectable patients and the optimal neoadjuvant therapy of chemotherapy with or without radiotherapy in borderline resectable patients were debated. Postoperative adjuvant chemotherapy of gemcitabine/capecitabine or mFOLFIRINOX is recommended regardless of the margin status. Chemotherapy as the first-line treatment strategy for advanced or metastatic patients included FOLFIRINOX, gemcitabine/nab-paclitaxel, or NALIRIFOX regimens whereas 5-FU plus liposomal irinotecan was the only standard of care second-line therapy. Immunotherapy is an innovative therapy although anti-PD-1 antibody is currently the only agent approved by for MSI-H, dMMR, or TMB-high solid tumors, which represent a very small subset of pancreatic cancers. Combination strategies to increase the immunogenicity and to overcome the immunosuppressive tumor microenvironment may sensitize pancreatic cancer to immunotherapy. Targeted therapies represented by PARP and KRAS inhibitors are also under investigation, showing benefits in improving progression-free survival and objective response rate. This review discusses the current treatment modalities and highlights innovative therapies for pancreatic cancer.

Trans-aconitic acid assimilation system as a widespread bacterial mechanism for environmental adaptation.

The ability of bacteria to use natural carbon sources greatly affects their growth and survival in the environment. Bacteria have evolved versatile abilities to use environmental carbon sources, but their diversity and assimilation pathways remain largely unexplored. Trans-aconitic acid, a geometric isomer of cis-aconitic acid involved in the tricarboxylic acid cycle, has long been considered a natural carbon source metabolizable by bacteria. However, its catabolism and ecological role in linking bacterial interactions with the environments remain unclear. Here, we identify a regulatory system in Bacillus velezensis FZB42 that is capable of sensing and catabolizing trans-aconitic acid. The system consists of a tar operon, an adjacent positive regulatory gene tarR, and a shared promoter. After receiving the trans-aconitic acid signal, the TarR protein interacts directly with the promoter, initiating the expression of the membrane transporter TarB and aconitate isomerase TarA encoded by the operon, which function in importing the trans-aconitic acid and isomerizing it into the central intermediate cis-aconitic acid. Subsequent soil colonization experiments reveal that trans-aconitic acid assimilating ability can give its coding bacteria a growth and competitive advantage. Bioinformatics analyses coupled with bacterial isolation experiments further show that the assimilation system of trans-aconitic acid is widely distributed in the bacterial domain, and its assimilating bacteria also extensively distributed in nature, indicating an important role of trans-aconitic acid metabolism in bacterial carbon acquisition. This work emphasizes the importance of metabolic adaptation to environmental carbon sources for bacterial survival and may provide inspiration for engineering microbes with enhanced environmental competitiveness.

Mycorrhizal Symbiosis Increases Plant Phylogenetic Diversity and Regulates Community Assembly in Grasslands.

The intricate mechanisms controlling plant diversity and community composition are cornerstone of ecological understanding. Yet, the role of mycorrhizal symbiosis in influencing community composition has often been underestimated. Here, we use extensive species survey data from 1315 grassland sites in China to elucidate the influence of mycorrhizal symbiosis on plant phylogenetic diversity and community assembly. We show that increasing mycorrhizal symbiotic potential leads to greater phylogenetic dispersion within plant communities. Mycorrhizal species predominantly influence deterministic processes, suggesting a role in niche-based community assembly. Conversely, non-mycorrhizal species exert a stronger influence on stochastic processes, highlighting the importance of random events in shaping community structure. These results underscore the crucial but often hidden role of mycorrhizal symbiosis in driving plant community diversity and assembly. This study provides valuable insights into the mechanisms shaping ecological communities and the way for more informed conservation that acknowledges the complex interplay between symbiosis and community dynamics.

Simulation-Guided Molecular Modeling of Nisin and Lipid II Assembly and Membrane Pore Formation.

The lantibiotic pore-forming peptide nisin is a promising candidate in the fight against multidrug-resistant bacteria due to its unique structure, which allows it to disrupt bacteria in two distinct ways─Lipid II trafficking and transmembrane pore formation. However, exactly how nisin and Lipid II assemble into oligomeric pore structures in the bacterial membrane is not known. Spontaneous peptide assembly into pores is difficult to observe in even the very long-time scale molecular dynamics (MD) simulations. In this study, we adopted an MD-guided modeling approach to investigate the nisin-nisin and nisin-Lipid II associations in the membrane environment. Through extensive microsecond-time scale all-atom MD simulations, we established that nisin monomers dimerize by forming ß-sheets in a POPE:POPG lipid bilayer and oligomerize further to form stable transmembrane channels. We determined that these nisin dimers use Lipid II as a dimer interface to incur enhanced stability. Our results provide a clearer understanding of the self-assembly of nisin monomers within the membrane and insights into the role of Lipid II in the structural integrity of oligomeric structures.

Patterns of Recurrence after Curative Intent Hepatic Resection for Colorectal Liver Metastasis.

BACKGROUND: Improved surgical techniques and more intensive systemic therapy have increased the number of oligometastatic colorectal cancer patients eligible for resection, but a significant percentage of these patients will ultimately recur. Furthermore, distinct recurrence patterns have been associated with different outcomes. METHODS: Data for 195 patients who underwent curative-intent colorectal liver metastasis (CRLM) resection from 2016-2022 at Johns Hopkins Hospital were retrospectively collected. Cox regression univariate and multivariate analysis identified features associated with survival outcomes. Association between risk factors and site of recurrences was conducted via logistic regression with initial recurrences grouped into intrahepatic-only, extrahepatic-only, and concurrent intra- and extrahepatic recurrence. RESULTS: The 1- and 2-year recurrence free survival (RFS) rates were 46% and 22% respectively. The 1- and 2-year overall survival (OS) rates were 95% and 88% respectively. Median OS was 71.7 months. Multivariate analysis identified age <60 years old, N2 nodal status, R1 liver margin, and higher preoperative carcinoembryonic antigen as top prognostic factors for worse RFS. Additionally, patients with left-sided primary tumors had higher risk of intrahepatic-only recurrence while mutant KRAS was associated with higher risk of extrahepatic recurrence with or without liver recurrence. DISCUSSION OR CONCLUSION: These results from a recent cohort of patients treated with current standard of care therapies identifies features associated with elevated recurrence risk and specific recurrence patterns. These insights into CRLM recurrence patterns support a larger prospective study to identify subgroups of patients who may require additional therapies to prevent recurrence.

Effect of tDCS combined with virtual reality for post-stroke cognitive impairment: a randomized controlled trial study protocol.

BACKGROUND: Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. METHODS: This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects' speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. DISCUSSION: Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Promising therapeutic targets for tumor treatment: Cleaved activation of receptors in the nucleus.

A new fate of cell surface receptors, cleaved activation in the nucleus, is summarized. The intracellular domain (ICD) of cell surface receptors, cleaved by enzymes like γ-secretase, translocates to the nucleus to form transcriptional complexes participating in the onset and development of tumors. The fate is clinically significant, as inhibitors of cleavage enzymes have shown effectiveness in treating advanced tumors by reducing tumorigenic ICDs. Additionally, the construction of synthetic receptors also conforms with the fate mechanism. This review details each step of cleaved activation in the nucleus, elucidates tumorigenic mechanisms, explores application in antitumor therapy, and scrutinizes possible limitations.

PRELP inhibits colorectal cancer progression by suppressing epithelial-mesenchymal transition and angiogenesis via the inactivation of the FGF1/PI3K/AKT pathway.

Proline/arginine-rich end and leucine-rich protein (PRELP) is identified as a small proteoglycan in the extracellular matrix that has been tightly associated with cell adhesion. At present, the role of PRELP in colorectal cancer (CRC) remains largely unknown. PRELP expression in human CRC tissue samples was analyzed by qRT-PCR and immunochemistry. CCK-8, colony formation, transwell, and tube formation assays were utilized to determine the influences of PRELP on the malignant phenotypes of CRC cells. Mouse xenograft and tumor metastasis models were constructed to further validate the function of PRELP. Furthermore, we investigated the efficacy of PRELP combined with bevacizumab treatment in a mouse xenograft model of CRC. Additionally, RNA-seq was performed to analyze the potential signaling pathways regulated by PRELP. Immunofluorescence staining and coimmunoprecipitation were conducted to confirm the interaction between PRELP and fibroblast growth factor 1 (FGF1). In this study, we found that PRELP exerted a tumor-suppressive effect on CRC. The expression level of PRELP was significantly reduced in CRC tissues and cell lines. Both in vivo and in vitro experiments confirmed that PRELP inhibited CRC cell proliferation, promoted apoptosis, and suppressed migration and invasion via a reduction in the epithelial-mesenchymal transition and attenuated angiogenesis, thereby dampening tumor progression. In addition, PRELP markedly potentiated the efficacy of bevacizumab in a mouse xenograft model. Mechanistically, PRELP bound to FGF1 and reduced the stability of the FGF1 protein, accompanied by an increase in its degradation, which subsequently inactivated the PI3K/AKT/mTOR pathway, thereby leading to reduction in tumor angiogenesis and metastasis. Our study for the first time unveiled the tumor-suppressive role of PRELP in CRC and provided a potential effective strategy for the treatment of CRC.

A few-shot learning framework for the diagnosis of osteopenia and osteoporosis using knee X-ray images.

OBJECTIVE: We developed a few-shot learning (FSL) framework for the diagnosis of osteopenia and osteoporosis in knee X-ray images. METHODS: Computer vision models containing deep convolutional neural networks were fine-tuned to enable generalization from natural images (ImageNet) to chest X-ray images (normal vs. pneumonia, base images). Then, a series of automated machine learning classifiers based on the Euclidean distances of base images were developed to make predictions for novel images (normal vs. osteopenia vs. osteoporosis). The performance of the FSL framework was compared with that of junior and senior radiologists. In addition, the gradient-weighted class activation mapping algorithm was used for visual interpretation. RESULTS: In Cohort #1, the mean accuracy (0.728) and sensitivity (0.774) of the FSL models were higher than those of the radiologists (0.512 and 0.448). A diagnostic pipeline of FSL model (first)-radiologists (second) achieved better performance (0.653 accuracy, 0.582 sensitivity, and 0.816 specificity) than radiologists alone. In Cohort #2, the diagnostic pipeline also showed improved performance. CONCLUSIONS: The FSL framework yielded practical performance with respect to the diagnosis of osteopenia and osteoporosis in comparison with radiologists. This retrospective study supports the use of promising FSL methods in computer-aided diagnosis tasks involving limited samples.

Informing Decision-making for Transected Margin Reresection in Intraductal Papillary Mucinous Neoplasm-derived PDAC: An International Multicenter Study.

OBJECTIVE: To assess the prognostic impact of margin status in patients with resected intraductal papillary mucinous neoplasms (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and to inform future intraoperative decision-making on handling differing degrees of dysplasia on frozen section. SUMMARY BACKGROUND DATA: The ideal oncologic surgical outcome is a negative transection margin with normal pancreatic epithelium left behind. However, the prognostic significance of reresecting certain degrees of dysplasia or invasive cancer at the pancreatic neck margin during pancreatectomy for IPMN-derived PDAC is debatable. METHODS: Consecutive patients with resected and histologically confirmed IPMN-derived PDAC (2002-2022) from six international high-volume centers were included. The prognostic relevance of a positive resection margin (R1) and degrees of dysplasia at the pancreatic neck margin were assessed by log-rank test and multivariable Cox-regression for overall survival (OS) and recurrence-free survival (RFS). RESULTS: Overall, 832 patients with IPMN-derived PDAC were included with 322 patients (39%) having an R1-resection on final pathology. Median OS (mOS) was significantly longer in patients with an R0 status compared to those with an R1 status (65.8 vs. 26.3 mo P<0.001). Patients without dysplasia at the pancreatic neck margin had similar OS compared to those with low-grade dysplasia (mOS: 78.8 vs. 66.8 months, P=0.344). However, high-grade dysplasia (mOS: 26.1 mo, P=0.001) and invasive cancer (mOS: 25.0 mo, P<0.001) were associated with significantly worse OS compared to no or low-grade dysplasia. Patients who underwent conversion of high-risk margins (high-grade or invasive cancer) to a low-risk margin (low-grade or no dysplasia) after intraoperative frozen section had significantly superior OS compared to those with a high-risk neck margin on final pathology (mOS: 76.9 vs. 26.1 mo P<0.001). CONCLUSIONS: In IPMN-derived PDAC, normal epithelium or low-grade dysplasia at the neck have similar outcomes while pancreatic neck margins with high-grade dysplasia or invasive cancer are associated with poorer outcomes. Conversion of a high-risk to low-risk margin after intraoperative frozen section is associated with survival benefit and should be performed when feasible.

More sensitive microbial responses to the interactive effects of warming and altered precipitation in subsoil than topsoil of an alpine grassland ecosystem.

Subsoil is a large organic carbon reservoir, storing more than half of the total soil organic carbon (SOC) globally. Conventionally, subsoil is assumed to not be susceptible to climate change, but recent studies document that climate change could significantly alter subsoil carbon cycling. However, little is known about subsoil microbial responses to the interactive effects of climate warming and altered precipitation. Here, we investigated carbon cycling and associated microbial responses in both subsoil (30-40 cm) and topsoil (0-10 cm) in a Tibetan alpine grassland over 4 years of warming and altered precipitation. Compared to the unchanged topsoil carbon (ß = .55, p = .587), subsoil carbon exhibited a stronger response to the interactive effect of warming and altered precipitation (ß = 2.04, p = .021), that is, warming decreased subsoil carbon content by 28.20% under decreased precipitation while warming increased subsoil carbon content by 18.02% under increased precipitation.Furthermore, 512 metagenome-assembled genomes (MAGs) were recovered, including representatives of phyla with poor genomic representation. Compared to only one changed topsoil MAG, 16 subsoil MAGs were significantly affected by altered precipitation, and 5 subsoil MAGs were significantly affected by the interactive effect of warming and precipitation. More than twice as many populations whose MAG abundances correlated significantly with the variations of carbon content, components and fluxes were observed in the subsoil than topsoil, suggesting their potential contribution in mediating subsoil carbon cycling. Collectively, our findings highlight the more sensitive responses of specific microbial lineages to the interactive effects of warming and altered precipitation in the subsoil than topsoil, and provide key information for predicting subsoil carbon cycling under future climate change scenarios.

Modified Chitosan-Based Coating/Packaging Composites with Enhanced Antibacterial, Antioxidant, and UV-Resistant Properties for Fresh Food Preservation.

Chitosan-based biomass packaging materials are a promising material for food preservation, but their limited solubility, antioxidant capacity, UV resistance, and mechanical properties severely restrict their application. In this study, we developed a novel chitosan-based coating/packaging composite (QCTO) using quaternary ammonium salt and tannic acid (TA)-modified chitosan (QCS-TA) and oxidized chitosan (OCS). The introduction of quaternary ammonium salt and TA effectively improves the water solubility and antibacterial, antioxidant, and UV-resistant properties of chitosan. The Schiff-base bond formed between OCS and QCS-TA, along with the TA-mediated multiple interactions, conferred the prepared composite film with good mechanical properties (69.9 MPa tensile strength) and gas barrier performance to water (14.3 g·h-1·m-2) and oxygen (3.5 g·mm·m-2·h-1). Meanwhile, the prepared QCTO composites demonstrate excellent biocompatibility and safety and are applied as coatings for strawberries and bananas as well as packaging films for mushrooms. These preservation experiments demonstrated that the prepared composites are able to effectively reduce weight loss, prevent microbial growth, maintain color, and significantly prolong the shelf life of fresh products (bananas, strawberries, and mushrooms extended shelf life by 6, 5, and 6 days, respectively). Therefore, the developed QCTO coating/packaging film shows great potential for applications in the field of food preservation and packaging.

Poor Prognostic Factors in Long-Term Survivors of Resected Pancreatic Ductal Adenocarcinoma: An International, Multicenter Cohort Study.

OBJECTIVE: To measure the rate of LTS in resected PDAC and determine the association between predictors of OS and LTS. SUMMARY BACKGROUND DATA: Long-term survival (>5 y, LTS) remains rare in pancreatic ductal adenocarcinoma (PDAC). Multiple predictors of overall survival (OS) are known but their association with LTS remains unclear. METHODS: An international, multicenter retrospective study was conducted. Included were patients from 2012-2019 with resected PDAC. Excluded were those with metastases at diagnosis or resection, R2 resections, and 90-day mortality. Predictors of OS were identified using multivariable Cox regression and their prevalence in patients with LTS assessed. LTS was calculated by excluding patients with shorter follow-up and predictors of LTS were identified using multivariable logistic regression. RESULTS: 3,003 patients were included (27.4% received neoadjuvant chemotherapy). Elevated baseline CA19-9, high tumor grade, nodal disease, and perineural and lymphovascular invasion were negative independent predictors of OS, while receipt of adjuvant chemotherapy predicted improved OS (all P<0.05). LTS was observed in 220/2,436 patients (9.0%), of whom 198 (90%) harbored poor prognostic factors: elevated baseline CA19-9 (58.1%), poor tumor differentiation (51.0%), nodal disease (46.8%), and perineural invasion (76.0%). Of those without any of these four features, 50.0% achieved LTS as compared to 21.3%, 13.3%, 5.2%, and 3.5% in those with 1, 2, 3, or 4 features. CONCLUSIONS: This bi-national cohort demonstrates a true LTS rate of 9.0% in resected PDAC. Clinicians should remain aware that presence of poor prognostic factors does not preclude LTS.

Initiation of a robotic pancreatoduodenectomy program using virtual collaboration.

BACKGROUND: Adoption of robotic pancreatoduodenectomy (RPD) is growing, although there are challenges for safe introduction of this technique, including limitations in on-site expert proctoring. We developed and implemented a structured approach for safe introduction of a new RPD program using virtual collaboration. METHODS: A structured framework for introducing a RPD program was designed; key steps included obtaining additional training, identifying required resources, establishing a dedicated team, and patient safety considerations. Virtual collaboration with a proctor for bidirectional communication was utilized for remote operative guidance. In the initial cohort, perioperative data and postoperative outcomes were extracted from a prospectively maintained database. RESULTS: From August 2020 to December 2023, 68 patients underwent RPD. The median operative time was 407 min with an estimated blood loss of 150 mL. Median length of stay was 8 days. Negative margins were obtained in 90% of resections. Operative time was significantly shorter in the second half of cases compared to the first (380min vs 441min, p < 0.01) and rate of conversion decreased (6% vs 21%). CONCLUSION: The safe initiation of a structured RPD program is feasible through virtual expert collaboration. With careful consideration and an appropriate environment, excellent perioperative outcomes are achievable even for initial cases.

Total versus Partial Pancreatectomy in Patients with Pancreatic Cancer Arising from Multifocal or Diffuse Intraductal Papillary Mucinous Neoplasia - A Multicenter Observational Study.

AIM: To investigate the impact of total pancreatectomy (TP) on oncological outcomes for patients at high-risk of local recurrence or secondary progression in the remnant gland after partial pancreatectomy (PP) for IPMN-associated cancer. SUMMARY BACKGROUND DATA: Major risk factors for invasive progression in the remnant gland include multifocality, diffuse main duct dilation, and the presence of invasive cancer. In these high-risk patients, a TP may be oncologically beneficial. However, current guidelines discourage TP, especially in elderly patients. METHODS: This international multicenter study compares TP versus PP in patients with adenocarcinoma arising from multifocal or diffuse IPMN (2002-2022). Log-rank test and multivariable Cox-analysis with interaction analysis was performed to assess overall survival (OS), disease-free survival (DFS), and local-DFS. RESULTS: Of 359 included patients, 162 (45%) were treated with TP, whereas 197 (55%) underwent PP. Despite TP and PP having similar R0-rates (59% vs. 58%, P=0.866), patients undergoing a TP had significantly longer local-DFS compared to PP (P=0.039). However, no difference in OS was observed between the two surgical approaches (P=0.487). In a multivariable analysis, young age (optimal cut-off ≤63.6 yrs) was associated with an OS benefit derived from TP (HR:0.44, 95%CI:0.22-0.89), whereas no significant difference was observed in elderly patients (HR:1.24, 95%CI:0.92-1.67, Pinteraction=0.007). CONCLUSION: Since overall, patients with diffuse or multifocal IPMN with an invasive component do not benefit from TP in terms of OS, the indication for TP may be individualized to young patients who have sufficient life expectancy to benefit from the prevention of secondary progression or local recurrence.

Treatment of acute dacryocystitis by translacrimal canalicular drainage and D-silicone intubation.

AIM: To demonstrate the outcomes of translacrimal canalicular drainage using a lacrimal probe and intranasal drainage by D-silicone intubation for acute dacryocystitis (AD). METHODS: This retrospective study included 23 patients with AD and had undergone abscess decompression with the use of lacrimal probe and intranasal drainage by D-silicone intubation between January 2019 and December 2022. Patients received abscess decompression and systemic antibiotic-corticosteroid from the time of diagnosis. D-silicone tube was inserted within 10d after diagnosis and removed 3-6mo after intubation. The procedure and outcomes of this method were evaluated. RESULTS: All patients showed improvement of signs and symptoms of AD within 72h. No intraoperative and postoperative complications were observed. No recurrence of lacrimal sac abscesses occurred after D-silicone tube removed. CONCLUSION: Lacrimal probe and D-silicone intubation appear to be a feasible, minimally invasive, safe, and effective method, which could be a reasonable choice in the treatment of AD.

Physicochemical and microbiological evaluation of treated Gastrodia elata with combination of slightly acidic electrolyzed water and lithium magnesium silicate under certain temperatures and different storage periods.

This study aimed to investigate the impact of slightly acidic electrolyzed water combined with lithium magnesium silicate hydrosol on the quality of fresh slices of Gastrodia elata under varying storage temperatures, including room temperature fresh slices of Gastrodia elata 25 °C and 37 °C. Fresh slices of Gastrodia elata 25 and 37 samples were stored for 13 days and extensively analyzed for color, weight loss, decay index, bacterial count, vitamin C, and polysaccharide contents during different storage periods. The findings revealed that the slightly acidic electrolyzed water + hydrosol treatment notably decreased weight loss and decay index compared to distilled water and slightly acidic electrolyzed water treatments. Moreover, fresh slices of Gastrodia elata treated with slightly acidic electrolyzed water + hydrosol exhibited untraceable bacterial counts after 3 days, with counts starting to increase after 7 days of storage. The bacterial counts rose from 3.25 to 5.36 and from 4.13 to 5.79 log CFU/g under both storage conditions. The application of slightly acidic electrolyzed water + hydrosol resulted in reduced chromaticity values of L*, a*, and b* on the Gastrodia elata surface, along with a lower percentage loss of polysaccharide contents and vitamin C compared to distilled water and slightly acidic electrolyzed water treatments. These results suggested that Gastrodia elata treated with slightly acidic electrolyzed water + hydrosol maintained its quality characteristics and nutritional attributes, exhibiting greater stability during storage.