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Multidimensional Nomogram to Predict Postoperative Pancreatic Fistula after Minimally Invasive Pancreaticoduodenectomy
No full textBackground: Clinically relevant postoperative pancreatic fistula (CR-POPF) is an inherently severe risk of pancreatic resection. Previous research has proposed models that identify risk factors and predict CR-POPF, although these are rarely applicable to minimally invasive pancreaticoduodenectomy (MIPD). This study aimed to evaluate the individual risks of CR-POPF and to propose a nomogram for predicting POPF in MIPD.
Patients and methods: We retrospectively reviewed the medical records of 429 patients who underwent MIPD. In the multivariate analysis, the Akaike information criterion stepwise logistic regression method was used to select the final model to develop the nomogram.
Results: Of 429 patients, 53 (12.4%) experienced CR-POPF. On multivariate analysis, pancreatic texture (p = 0.001), open conversion (p = 0.008), intraoperative transfusion (p = 0.011), and pathology (p = 0.048) were identified as independent predictors of CR-POPF. The nomogram was developed based on patient, pancreatic, operative, and surgeon factors by using the following four additional clinical factors as variables: American Society of Anesthesiologists class ≥ III, size of pancreatic duct, type of surgical approach, and < 40 cases of MIPD experience.
Conclusions: A multidimensional nomogram was developed to predict CR-POPF after MIPD. This nomogram and calculator can help surgeons anticipate, select, and manage critical complications.restrictio
A virtual memory CD8+ T cell-originated subset causes alopecia areata through innate-like cytotoxicity
No full textVirtual memory T (TVM) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although TVM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a TVM cell-originated CD44super-high(s-hi)CD49dlo CD8+ T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8+ TVM cells and can cause alopecia areata. Mechanistically, CD44s-hiCD49dlo CD8+ T cells could be induced from conventional TVM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44s-hiCD49dlo CD8+ T cells was mediated by NKG2D-dependent innate-like cytotoxicity, which was further augmented by IL-15 stimulation and triggered disease onset. Collectively, these data suggest an immunological mechanism through which TVM cells can cause chronic inflammatory disease by innate-like cytotoxicity.restrictio
Immediate Postoperative High Syndecan-1 is Associated with Short-Term Morbidity and Mortality After Robot-Assisted Esophagectomy: A Prospective Observational Study
No full textBackground: Disruption of the endothelial glycocalyx (EG) is associated with a poor prognosis in various clinical settings. This study aimed to determine the association between immediate postoperative serum syndecan-1 levels, a representative marker for EG degradation, and major postoperative morbidity and mortality in patients undergoing robot-assisted esophagectomy.
Methods: Patients who underwent robot-assisted esophagectomy between 2018 and 2022 were prospectively enrolled. The primary outcome was the association between immediate postoperative syndecan-1 levels and the occurrence of major postoperative morbidity and mortality within 30 days of surgery. Patients were classified into low and high syndecan-1 groups based on the optimal cut-off value of syndecan-1 for predicting major morbidity and mortality. A multivariable logistic regression analysis was performed to investigate the risk factors for major morbidity and mortality.
Results: A total of 207 patients were analyzed. Patients with high syndecan-1 levels (≥48 ng/mL) showed a significantly greater incidence of unexpected returns to the operating room and anastomotic leaks and longer durations of hospital and intensive care unit stays than patients with low syndecan-1 levels (<48 ng/mL). Immediate postoperative syndecan-1 levels ≥48 ng/mL (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.23-4.76), American Society of Anesthesiologists physical status ≥III (OR 3.36, 95% CI 1.56-7.22), and current smoker (OR 4.02, 95% CI 1.52-10.61) were independently associated with major morbidity and mortality within 30 days of esophagectomy.
Conclusions: Immediate postoperative syndecan-1 levels ≥48 ng/mL could be used for the early detection of patients at high risk of complications after robot-assisted esophagectomy.restrictio
Clinical Evaluation of BioFire COVID-19 Test, BioFire Respiratory Panel 2.1, and Cepheid Xpert Xpress SARS-CoV-2 Assays for Sample-to-Answer Detection of SARS-CoV-2
Get PDFBackground: Due to the extreme infectivity of SARS-CoV-2, sample-to-answer SARS-CoV-2 reverse transcription (RT) polymerase chain reaction (PCR) assays are urgently needed in order to facilitate infectious disease surveillance and control. The purpose of this study was to evaluate three sample-to-answer SARS-CoV-2 RT-PCR assays—BioFire COVID-19 Test, BioFire RP 2.1, and Cepheid Xpert Xpress SARS-CoV-2—using clinical samples. Methods: A total of 77 leftover nasopharyngeal swab (NP) swabs (36 positives and 41 negatives) confirmed by reference SARS-CoV-2 RT real-time (q) PCR assay were collected. The clinical sample concordance, as specified by their respective emergency use authorizations (EUAs), in comparison to the reference SARS-CoV-2 RT-qPCR assay, was assessed. Results: The results showed that all three sample-to-answer SARS-CoV-2 RT-PCR assays provided perfectly concordant results consistent with the reference SARS-CoV-2 RT-qPCR assay. The BioFire COVID-19 Test exhibited the best turnaround time (TAT) compared to the other assays, regardless of the test results, using one-way analysis of variance followed by Scheffe’s post hoc test (p < 0.001). The Xpert Xpress SARS-CoV-2 showed a shorter average TAT (mean ± standard deviation, 49.9 ± 3.1 min) in the positive samples compared to that (55.7 ± 2.5 min) of the negative samples. Conclusions: Our evaluation demonstrates that the BioFire COVID-19 Test, BioFire RP 2.1, and Cepheid Xpert Xpress SARS-CoV-2 assays compare favorably to the reference SARS-CoV-2 RT-qPCR assay, along with a 100% concordance in assay results for clinical samples and an acceptable analytical performance at their guaranteed limits of detection. The addition of a widely used simultaneous sample-to-answer SARS-CoV-2 RT-PCR assay will contribute to the number of medical laboratories able to test for COVID-19. © 2023 by the authors.ope
Ideal cardiovascular health metrics and the risk of nonalcoholic fatty liver disease in Korean adults
Get PDFBackground: The association between cardiovascular risk factors and nonalcoholic fatty liver disease (NAFLD) is well established, but whether cardiovascular health (CVH) metrics is associated with NAFLD had not been fully studied. Thus, we examined the association between CVH metrics and NAFLD in the middle-aged Korean population. Methods: We used data of 2,928 (851 men and 2,077 women) participants aged 30–64 years from the Cardiovascular and Metabolic Disease Etiology Research Center study. CVH metrics were measured using a modified version of Life’s Simple 7 by the American Heart Association. NAFLD diagnosis was based on the fatty liver index or liver-to-spleen ratio on computed tomography. A multiple logistic regression model was used to investigate the cross-sectional and longitudinal associations between CVH metrics and NAFLD. Results: In the cross-sectional analysis, the odds ratio for NAFLD was lower in participants with ideal CVH (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.08–0.18), while it was higher in individuals with poor CVH (OR, 2.87; 95% CI, 2.13–3.86). Similarly, the risk of new-onset NAFLD was lower in participants with ideal CVH (OR, 0.28; 95% CI, 0.11–0.74), and higher in individuals with poor CVH (OR, 2.20; 95% CI, 0.50–9.72) in the longitudinal analysis of a subgroup. Conclusions: Ideal CVH was associated with a lower risk of NAFLD while poor CVH was associated with a higher risk of NAFLD. These findings suggest that making efforts to encourage people to manage their CVH to the ideal level may prevent and manage NAFLD. © 2022, The Author(s).ope
Mesenchymal Stem-Like Cells Derived from the Ventricle More Effectively Enhance Invasiveness of Glioblastoma Than Those Derived from the Tumor
No full textPurpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM pa tient-derived cells.
Materials and Methods: The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo ex periments.
Results: After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investi gated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accel erated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLC induced increases in the invasiveness of GBM TSs.
Conclusion: Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates.ope
Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial
No full textImportance: In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy.
Objective: To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin.
Design, setting, and patients: Phase 3, 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries.
Interventions: Patients (n = 2067) were randomized to 1 of 24 treatment groups in 2 steps. Patients were initially randomized to a daily, moderate-intensity (atorvastatin [10 mg], simvastatin [40 mg], or rosuvastatin [5 mg]) or high-intensity (atorvastatin [80 mg], rosuvastatin [40 mg]) statin. After a 4-week lipid-stabilization period, patients (n = 1899) were randomized to compare evolocumab (140 mg every 2 weeks or 420 mg monthly) with placebo (every 2 weeks or monthly) or ezetimibe (10 mg or placebo daily; atorvastatin patients only) when added to statin therapies.
Main outcomes and measures: Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) level at the mean of weeks 10 and 12 and at week 12.
Results: Evolocumab reduced LDL-C levels by 66% (95% CI, 58% to 73%) to 75% (95% CI, 65% to 84%) (every 2 weeks) and by 63% (95% CI, 54% to 71%) to 75% (95% CI, 67% to 83%) (monthly) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups; the LDL-C reductions at week 12 were comparable. For moderate-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36%, 40%, and 39% of evolocumab-, ezetimibe-, and placebo-treated patients, respectively. The most common adverse events in evolocumab-treated patients were back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2%).
Conclusions and relevance: In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia, evolocumab added to moderate- or high-intensity statin therapy resulted in additional LDL-C lowering. Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering.restrictio
Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery
Get PDFThe aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery.The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommenda-tions. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an inter-vention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC. © 2023 by Korean Society of Otorhinolaryngology-Head and Neck Surgery.ope
Silmitasertib plus gemcitabine and cisplatin first-line therapy in locally advanced/metastatic cholangiocarcinoma: A Phase 1b/2 study
No full textBackground and Aims: This study aimed to investigate safety and efficacy of silmitasertib, an oral small molecule casein kinase 2 inhibitor, plus gemcitabine and cisplatin (G+C) versus G+C in locally advanced/metastatic cholangiocarcinoma.
Approach and Results: This work is a Phase 1b/2 study (S4‐13‐001). In Phase 2, patients received silmitasertib 1000 mg twice daily for 10 days with
G+C on Days 1 and 8 of a 21‐day cycle. Primary efficacy endpoint was progression‐free survival (PFS) in the modified intent‐to‐treat population
(defined as patients who completed at least one cycle of silmitasertib without dose interruption/reduction) from both phases (silmitasertib/G+C n = 55, G+C n = 29). The response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. The median PFS was 11.2 months (95% confidence
interval [CI], 7.6, 14.7) versus 5.8 months (95% CI, 3.1, not evaluable [NE])(p = 0.0496); 10‐month PFS was 56.1% (95% CI, 38.8%, 70.2%) versus
22.2% (95% CI, 1.8%, 56.7%); and median overall survival was 17.4 months(95% CI, 13.4, 25.7) versus 14.9 months (95% CI, 9.9, NE) with silmitasertib/G+C versus G+C. Overall response rate was 34.0% versus 30.8%; the disease control rate was 86.0% versus 88.5% with silmitasertib/G+C versus G+C. Almost all silmitasertib/G+C (99%) and G+C (93%) patients reported at least one treatment emergent adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib/G+C versus G+C were diarrhea (70% versus 13%), nausea (59% vs. 30%), fatigue (47% vs. 47%), vomiting (39% vs. 7%), and anemia (39% vs. 30%). Twelve patients (10%) discontinued
treatment because of TEAEs during the study.
Conclusions: Silmitasertib/G+C demonstrated promising preliminary evi?dence of efficacy for the first‐line treatment of patients with locally advanced/metastatic cholangiocarcinomarestrictio
Outpatient-based diagnostic criteria for partial ACL injury: clinical outcomes of non-operative treatment and radiographic predictor
No full textIntroduction This study aimed to (1) evaluate the short-term clinical outcomes of patients who underwent non-operative treatment for partial anterior cruciate ligament (ACL) tears diagnosed using the outpatient-based diagnostic criteria and (2) investigate the radiographic predictors distinguishing patients at risk of non-operative treatment failure. Methods From 2010 to 2019, patients diagnosed with partial ACL tears and treated with non-operative treatment were reviewed retrospectively. Patients were then classified into two groups: those who successfully responded to non-operative treatment (group S) and those who failed to respond to non-operative treatment and required surgical reconstruction within 6 months after injury (group F). ACL laxity, patient-reported outcomes (PROs), and several radiographic parameters were analyzed. To identify radiographic predictors related to clinical outcomes, radiographic parameters were compared between the groups, which were statistically matched for potential confounders (age and activity level) using inverse probability of treatment weighting. Results A total of 44 patients were analyzed (mean age, 28.7 +/- 8.7 years; 31 men), and classified into two groups (group S, 23 patients; group F, 21 patients). There were no significant differences in ACL laxity and PROs between the groups at 1 year after either non-operative treatment or surgical reconstruction. A comparison of radiographic parameters between the groups revealed significant differences in several parameters related to secondary signs of ACL injury. Subsequent regression analyses revealed that anterior tibial translation and extent of bone bruises were radiographic predictors related to clinical outcomes. Conclusion Non-operative treatment for partial ACL tears diagnosed using the outpatient-based diagnostic criteria can provide successful short-term clinical outcomes in selective patients. Secondary signs of ACL injuries, particularly the amount of anterior tibial translation and the extent of bone bruises, are radiographic predictors that could differentiate patients at risk of non-operative treatment failure.restrictio