Relationship between recurrence and age in the diffuse sclerosing variant of papillary thyroid carcinoma: clinical significance in pediatric patients.

Background: The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC. Methods: We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV. Results: Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group. Conclusions: This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC.

Reduced cell-mediated immune response in hyperglycemic NOD mice following influenza vaccination.

Due to the higher risk of medical complications posed by influenza infection, patients with type 1 diabetes (T1D) are strongly recommended to receive the influenza vaccine. However, it remains unclear if hyperglycemia in patients with T1D affects vaccine-induced immune responses. In this study, we investigated the humoral and cellular immune responses of prediabetic and diabetic, nonobese diabetic (NOD) mice following influenza vaccination to determine the effects of hyperglycemia on influenza vaccine-induced responses. In diabetic NOD mice, vaccine-specific IgG and IgM levels, as well as IgG-producing cells, were comparable to those in prediabetic NOD mice. However, the diabetic NOD mice exhibited reduced percentages of memory T cells and activated T cells in the spleen, along with reduced number of vaccine-specific interferon (IFN)-γ-secreting cells. Thus, these findings suggest that in patients with T1D, hyperglycemia could lead to impaired cell-mediated immune responses following influenza vaccination.

Contributions of Brain Microstructures and Metabolism to Visual Field Loss Patterns in Glaucoma Using Archetypal and Information Gain Analyses.

Purpose: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures. Methods: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with 16 archetypal VF loss patterns. We also ranked neuroimaging, ophthalmic, and demographic attributes in terms of their information gain to determine their importance to glaucoma. Results: In dMRI, decreasing fractional anisotropy, radial kurtosis, and tortuosity and increasing radial diffusivity correlated with greater overall VF loss bilaterally. Regionally, decreasing intra-axonal space and extra-axonal space diffusivities correlated with greater VF loss in the superior-altitudinal area of the right eye and the inferior-altitudinal area of the left eye. In MRS, both early and advanced glaucoma patients had lower gamma-aminobutyric acid (GABA), glutamate, and choline levels than healthy controls. GABA appeared to associate more with superonasal VF loss, and glutamate and choline more with inferior VF loss. Choline ranked third for importance to early glaucoma, whereas radial kurtosis and GABA ranked fourth and fifth for advanced glaucoma. Conclusions: Our findings highlight the importance of non-invasive neuroimaging biomarkers and analytical modeling for unveiling glaucomatous neurodegeneration and how they reflect complementary VF loss patterns.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

The Diagnostic Accuracy of SPECT Imaging in Patients With Suspected Pulmonary Embolism: Systematic Review and Network Meta-analysis.

BACKGROUND: This meta-analysis and systematic review assessed the diagnostic accuracy of lung SPECT compared with lung planar imaging in patients with suspected acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension. PATIENTS AND METHODS: A search of Medline, Embase, and Cochrane databases identified suitable articles published before October 2023. Meta-analyses were performed to determine the diagnostic accuracy of SPECT imaging modalities, including perfusion (Q) SPECT, ventilation (V)/Q SPECT, Q SPECT/CT, and V/Q SPECT/CT. Network meta-analyses were performed to compare the diagnostic accuracy of SPECT and planar imaging in paired-design studies. RESULTS: Twenty-four articles (total n = 6576) were included in the analysis. For suspected acute PE, the respective sensitivity and specificity of SPECT imaging modalities were as follows: Q SPECT, 0.93 (95% confidence interval [CI], 0.87-0.99; I2 = 49%) and 0.72 (95% CI, 0.54-0.95; I2 = 94%); V/Q SPECT, 0.96 (95% CI, 0.94-0.98; I2 = 51%) and 0.95 (95% CI, 0.92-0.98; I2 = 80%); Q SPECT/CT, 0.93 (95% CI, 0.87-0.98; I2 = 66%) and 0.82 (95% CI, 0.70-0.96; I2 = 87%); and V/Q SPECT/CT, 0.97 (95% CI, 0.93-1.00; I2 = 7%) and 0.98 (95% CI, 0.97-1.00; I2 = 31%). The relative sensitivity and specificity of SPECT compared with planar imaging were 1.17 (95% CI, 1.06-1.30; P < 0.001) and 1.14 (95% CI, 1.00-1.29; P = 0.05), respectively. For suspected chronic thromboembolic pulmonary hypertension, the pooled sensitivity and specificity of SPECT imaging were 0.97 (95% CI, 0.95-1.00; I2 = 0%) and 0.91 (95% CI, 0.87-0.94; I2 = 0%), respectively. CONCLUSIONS: SPECT exhibited superior diagnostic performance for PE. V/Q SPECT/CT was the most accurate modality.

Efficacy of Empirical 131 I Radioiodine Therapy in Well-Differentiated Thyroid Carcinoma Patients With Thyroglobulin-Elevated Negative Iodine Scintigraphy Syndrome : A Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to perform a systematic review and meta-analysis on the efficacy of empirical high-dose radioiodine therapy in treating differentiated thyroid cancer patients with thyroglobulin (Tg)-elevated negative iodine scintigraphy (TENIS) syndrome. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify relevant studies published until April 2022. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and registered in an international prospective register of systematic reviews (PROSPERO). Meta-analyses of proportions and odds ratios were performed to assess the beneficial effect of empirical high-dose radioiodine therapy in patients with TENIS syndrome. Subgroup analysis was also performed according to the presence of micrometastasis or macrometastasis. RESULTS: We identified 14 studies including 690 patients who received empirical high-dose radioiodine therapy for TENIS syndrome. Those who had micrometastasis exhibited additional lesions not previously observed on diagnostic whole-body scan (prop = 0.64, 95% confidence interval [CI], 0.51-0.77) and had reduced serum Tg levels (prop = 0.69; 95% CI, 0.52-0.84) after empirical radioiodine treatment. No such findings were observed among patients with macrometastasis. Moreover, we found that the empirical radioiodine treatment group had lower serum Tg levels than did controls (odds ratio = 0.27; 95% CI, 0.09-0.87), which suggests a lower risk of disease progression. CONCLUSIONS: Our findings indicate that empirical high-dose radioiodine therapy promoted beneficial effects and could be recommended for patients with TENIS syndrome, especially those with micrometastasis.

Dosing Strategy of Ramosetron to Prevent Postoperative Nausea and Vomiting and Development of Prediction Models Using Data Obtained From Randomized Controlled Trials: A Comparative Study.

PURPOSE: The study aimed to compare the postoperative nausea and vomiting (PONV) preventive effect of repeated administration of ramosetron with the standard treatment group and compare models to predict the incidence of PONV using machine-learning techniques. METHODS: A total of 261 patients scheduled for breast surgery were analyzed to evaluate the effectiveness of repeated intravenous administration of ramosetron. All patients were administered 0.3 mg ramosetron just before the end of surgery. For the repeated dose of ramosetron group, an additional dose of 0.3 mg was administered at 4, 22, and 46 hours after the end of the surgery. Postoperative nausea, vomiting, and retching were evaluated using the Rhodes Index of Nausea, Vomiting, and Retching at 6, 24, and 48 hours postoperatively. Previously published randomized controlled data were combined with the data of this study to create a new dataset of 1390 patients, and machine-learning-based PONV prediction models (classification tree, random forest, extreme gradient boosting, and neural network) was constructed and compared with the Apfel model. FINDINGS: Fifty patients (38.5%) and 60 patients (45.8%) reported nausea, vomiting, or retching 48 hours postoperatively in the standard and repeated-dose groups, respectively (P = 0.317, χ2 test). Median sensitivity, specificity, and accuracy of the Apfel model analyzed using the training set were 0.815, 0.344, and 0.495, respectively. IMPLICATIONS: The repeated administration of ramosetron did not reduce the incidence of PONV. The Apfel model had high sensitivity, however, its specificity and accuracy were lower than that in machine-learning-based models.

Combination of red ginseng and velvet antler extracts prevents skin damage by enhancing the antioxidant defense system and inhibiting MAPK/AP-1/NF-κB and caspase signaling pathways in UVB-irradiated HaCaT keratinocytes and SKH-1 hairless mice.

Background: Studies have reported that the combination of two or more therapeutic compounds at certain ratios has more noticeable pharmaceutical properties than single compounds and requires reduced dosage of each agent. Red ginseng and velvet antler have been extensively used in boosting immunity and physical strength and preventing diseases. Thus, this study was conducted to elucidate the skin-protective potentials of red ginseng extract (RGE) and velvet antler extract (VAE) alone or in combination on ultraviolet (UVB)-irradiated human keratinocytes and SKH-1 hairless mice. Methods: HaCaT cells were preincubated with RGE/VAE alone or in combination for 2 h before UVB (30 mJ/cm2) irradiation. SKH-1 mice were orally given RGE/VAE alone or in combination for 15 days before exposure to single dose of UVB (600 mJ/cm2). Treated cells and treated skin tissues were collected and subjected to subsequent experiments. Results: RGE/VAE pretreatment alone or in combination significantly prevented UVB-induced cell death, apoptosis, reactive oxygen species production, and DNA damage in keratinocytes and SKH-1 mouse skins by downregulating mitogen-activated protein kinases/activator protein 1/nuclear factor kappa B and caspase signaling pathways. These extracts also strengthened the antioxidant defense systems and skin barriers in UVB-irradiated HaCaT cells and SKH-1 mouse skins. Furthermore, RGE/VAE co-administration appeared to be more effective in preventing UVB-caused skin injury than these extracts used alone. Conclusion: Overall, these findings suggest that the consumption of RGE/VAE, especially in combination, offers a protective ability against UVB-caused skin injury by preventing inflammation and apoptosis and enhancing antioxidant capacity.

Routine Ureteral Stenting in Kidney Transplant Reduces Postoperative Hydronephrosis and Percutaneous Ureteral Interventions: A Single-Center Experience.

OBJECTIVES: The effect of routine ureteral stenting on postoperative hydronephrosis and percutaneous ureteral intervention in kidney transplant remains unknown. This study aimed to evaluate the effects of routine ureteral stenting on hydronephrosis and percutaneous ureteral intervention and the cost benefit of ureteral stenting in kidney transplant. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent kidney transplant at a tertiary institution between 2005 and 2021. We adopted a ureteral stentingprotocol in2017, anda comparisonwas performed with previous patients without stents. RESULTS: In total, 539 patients underwent kidney transplant(271 with stents [51.3%], 268 without stents [49.7%]). Hydronephrosis was detected in 16 cases (5.9%) and 30 cases (11.2%) of groups with and without stents,respectively (P = .041). Among patients with hydronephrosis, the number of patients who underwent percutaneous ureteral intervention was significantly lower in the stent group than in the nostent group (1 [6.25%] vs 10 [33.33%]; P= .014).Twenty patients (3.71%) experienced major urologic complications (19 [7.1%] in the no-stent group, and 1 [0.4%] in the stent group; P = .001). No significant differences between the groups were shown in the incidence of urinary tract infections within 3 months of transplant (24 [8.9%] vs 22 [8.2%]; P = .846). No differences were shown between the groups in ureterovesical anastomosis time (24.4 vs 24.03 min; P = .699) or 1-year graft survival (97% vs 97.8%; P = .803). The healthcare cost was significantly lower in the stent group than in the no-stent group by $1702.05 ($15000.89 vs $16702.95; P < .001). CONCLUSIONS: Routine ureteral stenting in kidney transplant significantly decreased the incidence of postoperative hydronephrosis and percutaneous ureteral intervention. Stenting did notlead to increased urinary tract infections and was cost-effective.

Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131 I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer : A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer. PATIENTS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria. RESULTS: Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01-1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88-1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78-1.44). CONCLUSIONS: rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.

Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Treatment of walled-off necrosis using lumen-apposing metal stents versus plastic stents: a systematic review and meta-analysis of data from randomized trials.

BACKGROUND: Walled-off necrosis (WON) is highly morbid disease most effectively managed by endoscopic drainage with lumen-apposing metal stents (LAMSs) or plastic stents, with or without necrosectomy. This meta-analysis compared the clinical outcomes of patients included in randomized trials treated using LAMSs or plastic stents. METHODS: The MEDLINE and EMBASE databases were searched to identify all data collected from randomized trials comparing LAMSs and plastic stents for the treatment of WON. The primary outcome measure was need for endoscopic necrosectomy. RESULTS: Three studies comprising 206 patients met inclusion criteria. Except for procedure duration, which was significantly shorter for LAMSs (standardized mean difference [SMD] -1.22, 95%CI -1.64 to -0.79), there was no significant difference in need for necrosectomy (38.5% vs. 41.2%; risk ratio [RR] 1.07, 95%CI 0.79-1.45), number of interventions (SMD -0.09, 95%CI -0.40 to 0.22), treatment success (90.7% vs. 94.5%; RR 0.96, 95%CI 0.87-1.06), recurrence (4.6% vs. 0.6%; RR 3.73, 95%CI 0.42-33.0), readmission (42.6% vs. 50.2%; RR 0.84, 95%CI 0.62-1.14), length of hospitalization (SMD -0.06, 95%CI -0.55 to 0.43), mortality (8.5% vs. 9.8%; RR 0.70, 95%CI 0.30-1.66), new-onset organ failure (10.6% vs. 14.6%; RR 0.72, 95%CI 0.16-3.32), bleeding (11.0% vs. 10.7%; RR 1.09, 95%CI 0.34-3.44), procedural adverse events (23.6% vs. 19.2%; RR 1.38, 95%CI 0.82-2.33), or overall costs (SMD -0.04, 95%CI -0.31 to 0.24) between LAMSs and plastic stents, respectively. CONCLUSIONS: Except for procedure duration, there is no significant difference in clinical outcomes for patients with WON treated using LAMSs or plastic stents.

Impact of endoprosthesis type on inflammatory response in patients undergoing endoscopic drainage of pancreatic fluid collections.

OBJECTIVE: To study the impact of endoprosthesis type on inflammatory response in patients undergoing endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFC). METHODS: Patients undergoing EUS-guided PFC drainage and treated using lumen-apposing metal stents (LAMS) or plastic endoprostheses constituted the study cohort. The primary outcome was the presence of systemic inflammatory response syndrome (SIRS) after index intervention. Secondary outcomes were persistent organ failure, new onset organ failure, duration of hospitalization, and treatment success. RESULTS: In all, 303 patients were treated using LAMS (n = 247) or plastic stents (n = 56). At 48 h postintervention, the presence of SIRS (25.0 vs. 14.2%, P = 0.047), new onset SIRS (10.0 vs. 1.8%, P = 0.017), and new organ failure (5.4 vs. 0.4%, P = 0.003) were significantly higher in the plastic stent cohort compared to LAMS. On multivariable logistic regression analysis, the use of plastic stents (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2-6.0, P = 0.014), patients receiving high-acuity care (OR 5.1, 95% CI 2.5-10.4, P < 0.001) and the presence of ≥33% of necrosis (OR 4.5, 95% CI 2.0-10.0, P < 0.001) were significantly associated with the presence of SIRS or new organ failure. While there was no significant difference in treatment success (96.4 vs. 95.5%, P = 0.77), duration of hospitalization was significantly longer for the plastic stent cohort (mean [standard deviation] 12.5 [17.8] vs. 7.9 [10.1] days, P = 0.009). CONCLUSIONS: Use of plastic stents as compared to LAMS was associated with a higher proportion of SIRS and new organ failure that prolonged hospital stay. Therefore, placement of LAMS is recommended in sick patients and those with ≥33% necrosis to minimize inflammatory response.

Clinical Implications of Adding SPECT/CT to Radioiodine Whole-Body Scan in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to determine the usefulness of adding SPECT/CT to radioiodine whole-body scans (WBSs) for the treatment of differentiated thyroid cancer (DTC). PATIENTS AND METHODS: A systematic review and meta-analysis were performed following the PRISMA guidelines (PROSPERO registration: CRD42022341732) to compare the feasibility of conclusive readings and the frequency of changes in treatment plans in patients with DTC undergoing WBS + SPECT/CT versus WBS. MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles concerning thyroid cancer, radioactive iodine, and SPECT/CT or SPECT, published before August 16, 2023. Studies not comparing WBS + SPECT/CT with WBS, those lacking target outcomes, and those not involving human subjects were excluded. The risk of bias was assessed using the RoBANS 2.0 (Risk of Bias Assessment Tool for Nonrandomized Studies) tool. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the quality of evidence and strength of recommendations. RESULTS: A total of 30 studies (prospective n = 9, retrospective n = 21) were included in the meta-analyses. Adding SPECT/CT to WBS was shown to increase conclusive readings for cervical lesions, extracervical lesions, and all regions. Lesion-based analyses showed improvements of 14%, 20%, and 18%, respectively, whereas scan-based analyses showed improvements of 27%, 9%, and 34%. The addition of SPECT/CT to WBS led to changes in 30% of treatment plans after diagnostic scans and 9% of treatment plans after posttherapeutic scans. The quality of evidence and strength of recommendations were low. CONCLUSIONS: Compelling evidence demonstrates that the addition of SPECT/CT to WBS improves lesion localization, diagnostic performance, and therapy plan for patients with DTC.

Upfront endoscopic necrosectomy or step-up endoscopic approach for infected necrotising pancreatitis (DESTIN): a single-blinded, multicentre, randomised trial.

BACKGROUND: Although the preferred management approach for patients with infected necrotising pancreatitis is endoscopic transluminal stenting followed by endoscopic necrosectomy as step-up treatment if there is no clinical improvement, the optimal timing of necrosectomy is unclear. Therefore, we aimed to compare outcomes between performing upfront necrosectomy at the index intervention versus as a step-up measure in patients with infected necrotising pancreatitis. METHODS: This single-blinded, multicentre, randomised trial (DESTIN) was done at six tertiary care hospitals (five hospitals in the USA and one hospital in India). We enrolled patients (aged ≥18 years) with confirmed or suspected infected necrotising pancreatitis with a necrosis extent of at least 33% who were amenable to endoscopic ultrasound-guided drainage. By use of computer-generated permuted block randomisation (block size four), eligible patients were randomly assigned (1:1) to receive either upfront endoscopic necrosectomy or endoscopic step-up treatment. Endoscopists were not masked to treatment allocation, but participants, research coordinators, and the statistician were. Lumen-apposing metal stents (20 mm diameter; 10 mm saddle length) were used for drainage in both groups. In the upfront group, direct necrosectomy was performed immediately after stenting in the same treatment session. In the step-up group, direct necrosectomy or additional drainage was done at a subsequent treatment session if there was no clinical improvement (resolution of any criteria of systemic inflammatory response syndrome or sepsis or one or more organ failure and at least a 25% percentage decrease in necrotic collection size) 72 h after stenting. The primary outcome was the number of reinterventions per patient to achieve treatment success from index intervention to 6 months' follow-up, which was defined as symptom relief in conjunction with disease resolution on CT. Reinterventions included any endoscopic or radiological procedures performed for necrosectomy or additional drainage after the index intervention, excluding the follow-up procedure at 4 weeks for stent removal. All endpoints and safety were analysed by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT05043415 and NCT04113499, and recruitment and follow-up have been completed. FINDINGS: Between Nov 27, 2019, and Oct 26, 2022, 183 patients were assessed for eligibility and 70 patients (24 [34%] women and 46 [66%] men) were randomly assigned to receive upfront necrosectomy (n=37) or step-up treatment (n=33) and included in the intention-to-treat population. At the time of index intervention, seven (10%) of 70 patients had organ failure and 64 (91%) patients had walled-off necrosis. The median number of reinterventions was significantly lower for upfront necrosectomy (1 [IQR 0 to 1] than for the step-up approach (2 [1 to 4], difference -1 [95% CI -2 to 0]; p=0·0027). Mortality did not differ between groups (zero patients in the upfront necrosectomy group vs two [6%] in the step-up group, difference -6·1 percentage points [95% CI -16·5 to 4·5]; p=0·22), nor did overall disease-related adverse events (12 [32%] patients in the upfront necrosectomy group vs 16 [48%] patients in the step-up group, difference -16·1 percentage points [-37·4 to 7·0]; p=0·17), nor procedure-related adverse events (four [11%] patients in the upfront necrosectomy group vs eight [24%] patients in the step-up group, difference -13·4 percentage points [-30·8 to 5·0]; p=0·14). INTERPRETATION: In stabilised patients with infected necrotising pancreatitis and fully encapsulated collections, an approach incorporating upfront necrosectomy at the index intervention rather than as a step-up measure could safely reduce the number of reinterventions required to achieve treatment success. FUNDING: None.

Orlando Protocol for single session ductal clearance of common bile duct stones at endosopic retrograde cholangiopancreatography.

OBJECTIVES: Approach to management of common bile duct stones (CBDS) by endoscopic retrograde cholangiopancreatography (ERCP) is not standardized. We examined outcomes by applying predetermined protocol for CBDS management. METHODS: When standard extraction techniques failed at ERCP, presence of tapered bile duct and stone-duct ratio were calculated. Large balloon sphincteroplasty (LBS) and/or mechanical/single-operator cholangioscopy-guided lithotripsy was performed based on presence of tapered bile duct and stone-duct mismatch. Primary outcome was single-session ductal clearance. Secondary outcome was adverse events. RESULTS: Of 409 patients treated over 16 months, 321 (78.5%) had no tapered bile duct or stone-duct mismatch, and single-session ductal clearance was achieved using standard techniques in 99.7% over median duration of 14 min (interquartile range [IQR] 9-21 min). Of 88 (21.5%) patients with difficult CBDS, tapered duct was seen in 79 (89.8%) and/or stone-duct mismatch in 36 (40.9%). Single-session ductal clearance was achieved in all 88 patients (100%) by LBS in 79 (89.8%), mechanical lithotripsy in 20 (22.7%), and single-operator cholangioscopy-guided lithotripsy in 16 (18.2%) over a median duration of 29 min (IQR 17-47 min). Overall, single-session ductal clearance was achieved in 99.8% with adverse events in 17 (4.2%) that included perforation in two, postsphincterotomy bleeding in one, and mild/moderate post-ERCP pancreatitis in 14 patients. CONCLUSIONS: A predetermined protocol optimized outcomes by enabling single-session ductal clearance of CBDS with high technical success and low adverse events.

Impact of Slim Linear Echoendoscope on the Practice of EUS.

BACKGROUND: Standard linear echoendoscopes have a large distal tip and bending radius, which can preclude adequate examination in some patients. OBJECTIVE: We examined the impact of having available slim linear echoendoscopes (SLE) on our endoscopic ultrasound (EUS) practice. MATERIALS AND METHODS: As a quality improvement measure, data on the need for the use of SLE were documented in 2000 consecutive procedures performed over a 10-month period from February to November 2022. When examination using a standard size echoendoscope failed due to technical limitations, the procedure was reattempted in the same session using a SLE. The main outcome was the impact of SLE, which was defined as the establishment of a new diagnosis or if findings altered treatment plan. RESULTS: A complete EUS examination failed in 23 of 2000 procedures (1.15%, 95% CI, 0.73-1.72%) performed using standard size echoendoscope (14 male, median age 73 y [IQR 66 to 79]). The examination was technically successful when using SLE in 22 of 23 (95.6%) patients. SLE impacted clinical management in all 22 patients (100%) by establishing tissue diagnosis in 19 and/or altering subsequent treatment plan in 5. Adverse event of transient hypoxia was observed in one patient (4.3%). CONCLUSIONS: A very experienced EUS team required SLE in 1.1% of consecutive examinations. Our findings suggest that when used, 95% of patients benefitted as it had a significant impact on their clinical management.