Impact of neoadjuvant chemotherapy on short-term outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases: A propensity-score matched and coarsened exact matched study.

BACKGROUND: In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. METHODS: A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. RESULTS: 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. CONCLUSION: Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases.

Association of Basal Forebrain Volume with Amyloid, Tau, and Cognition in Alzheimer's Disease.

Background: Degeneration of cholinergic basal forebrain (BF) neurons characterizes Alzheimer's disease (AD). However, what role the BF plays in the dynamics of AD pathophysiology has not been investigated precisely. Objective: To investigate the baseline and longitudinal roles of BF along with core neuropathologies in AD. Methods: In this retrospective cohort study, we enrolled 113 subjects (38 amyloid [Aß]-negative cognitively unimpaired, 6 Aß-positive cognitively unimpaired, 39 with prodromal AD, and 30 with AD dementia) who performed brain MRI for BF volume and cortical thickness, 18F-florbetaben PET for Aß, 18F-flortaucipir PET for tau, and detailed cognitive testing longitudinally. We investigated the baseline and longitudinal association of BF volume with Aß and tau standardized uptake value ratio and cognition. Results: Cross-sectionally, lower BF volume was not independently associated with higher cortical Aß, but it was associated with tau burden. Tau burden in the orbitofrontal, insular, lateral temporal, inferior temporo-occipital, and anterior cingulate cortices were associated with progressive BF atrophy. Lower BF volume was associated with faster Aß accumulation, mainly in the prefrontal, anterior temporal, cingulate, and medial occipital cortices. BF volume was associated with progressive decline in language and memory functions regardless of baseline Aß and tau burden. Conclusions: Tau deposition affected progressive BF atrophy, which in turn accelerated amyloid deposition, leading to a vicious cycle. Also, lower baseline BF volume independently predicted deterioration in cognitive function.

Novel figure-of-eight reconstruction with free tendon graft for unrepairable collateral ligament of the thumb metacarpophalangeal joint.

OBJECTIVES: This study aimed to report surgical technique and clinical outcomes for a novel figure-of-eight collateral ligament reconstruction technique using palmaris longus autograft for chronic irreparable collateral ligament injury of the thumb metacarpophalangeal joint. MATERIAL AND METHODS: The Jobe elbow collateral ligament reconstruction method was adapted for thumb metacarpophalangeal joint collateral ligament reconstruction. Sixteen reconstructions (7 ulnar collateral ligament, 9 radial collateral ligament) using palmaris longus autograft were reviewed retrospectively. Surgery was performed at a mean 12 months post-injury. All 16 patients were followed up for more than 1 year. Metacarpophalangeal joint radial and ulnar deviation, metacarpophalangeal and interphalangeal joint range of motion, key pinch and grip strength, Glickel functional grade and QuickDASH score were evaluated. RESULTS: Preoperative radial or ulnar deviation improved from 19.3° to 5.3° postoperatively. Metacarpophalangeal range of motion improved from 31.5° to 46.6°, and interphalangeal range of motion from 48.4° to 65.6°. Preoperative key pinch and grip strength were respectively 49% and 81% of contralateral values and improved to 82% and 87%. On Glickel grade, 9 cases were excellent and 7 good. CONCLUSION: The novel Jobe-like figure-of-eight reconstruction technique using palmaris longus graft was useful for reconstructing irreparable thumb metacarpophalangeal joint instability without an incision on the opposite side or an additional implant. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer.

BACKGROUND: There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. METHODS: Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. RESULTS: Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT were administered in 167 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response (HR 3.11, 95% CI 1.73-5.58, P <0.001) based on cut-off value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels <37 IU/L (median survival; 35.5 vs. 20.9 mo, P <0.001) and CA19-9 levels ≥37 IU/L (median survival; 34.3 vs. 17.8 mo, P =0.03). In patients suspected to be Lewis antigen negative, predictive performance of MTV was found to be limited ( P =0.84). CONCLUSION: Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.

Discrimination between ventricular tachycardia and wide-QRS preexcited tachycardia.

BACKGROUND: To develop a new algorithm to differentiate ventricular tachycardia (VT) from preexcited tachycardia (pre-ET) according to left bundle branch block (LBBB) and right bundle branch block (RBBB) patterns. METHODS: This study included 67 electrocardiograms (ECGs) with VT and 63 ECGs with pre-ET, collected from our hospital and through PubMed. Of those, 64 were allocated to the derivation cohort and the rest to the validation cohort. The diagnoses of the ECGs were confirmed using an electrophysiological study. Parameters and classifiers from prior algorithms along with the propagation speeds in the early portion of the QRS complex (initial deflection index) in leads V1, V6, aVR, II, and III were manually measured. The performance of the new algorithm was compared with that of prior algorithms. RESULTS: The initial deflection index in lead III was the strongest predictor of pre-ET in LBBB-pattern wide-QRS tachycardia (p = 0.003, AUC 0.805). The initial deflection index in lead V1 was the most powerful predictor of pre-ET in RBBB-pattern wide-QRS tachycardia (p = 0.001, AUC 0.848). Compared to earlier algorithms, those using the initial deflection indexes: lead III in LBBB patterns (cutoff value >0.3) and lead V1 in RBBB patterns (cutoff value ≤0.48), demonstrated superior performance in screening VT, with AUC values of 0.828. The initial deflection indexes proved effective as discriminators between VT and pre-ET in the validation cohort. CONCLUSIONS: In LBBB-pattern wide-QRS tachycardia, the early propagation speed of pre-ET was faster than that in VT. Conversely, in RBBB-pattern wide-QRS tachycardia, it was slower.

Deep learning-based prediction of post-pancreaticoduodenectomy pancreatic fistula.

Postoperative pancreatic fistula is a life-threatening complication with an unmet need for accurate prediction. This study was aimed to develop preoperative artificial intelligence-based prediction models. Patients who underwent pancreaticoduodenectomy were enrolled and stratified into model development and validation sets by surgery between 2016 and 2017 or in 2018, respectively. Machine learning models based on clinical and body composition data, and deep learning models based on computed tomographic data, were developed, combined by ensemble voting, and final models were selected comparison with earlier model. Among the 1333 participants (training, n = 881; test, n = 452), postoperative pancreatic fistula occurred in 421 (47.8%) and 134 (31.8%) and clinically relevant postoperative pancreatic fistula occurred in 59 (6.7%) and 27 (6.0%) participants in the training and test datasets, respectively. In the test dataset, the area under the receiver operating curve [AUC (95% confidence interval)] of the selected preoperative model for predicting all and clinically relevant postoperative pancreatic fistula was 0.75 (0.71-0.80) and 0.68 (0.58-0.78). The ensemble model showed better predictive performance than the individual ML and DL models.

AraDQ: an automated digital phenotyping software for quantifying disease symptoms of flood-inoculated Arabidopsis seedlings.

BACKGROUND: Plant scientists have largely relied on pathogen growth assays and/or transcript analysis of stress-responsive genes for quantification of disease severity and susceptibility. These methods are destructive to plants, labor-intensive, and time-consuming, thereby limiting their application in real-time, large-scale studies. Image-based plant phenotyping is an alternative approach that enables automated measurement of various symptoms. However, most of the currently available plant image analysis tools require specific hardware platform and vendor specific software packages, and thus, are not suited for researchers who are not primarily focused on plant phenotyping. In this study, we aimed to develop a digital phenotyping tool to enhance the speed, accuracy, and reliability of disease quantification in Arabidopsis. RESULTS: Here, we present the Arabidopsis Disease Quantification (AraDQ) image analysis tool for examination of flood-inoculated Arabidopsis seedlings grown on plates containing plant growth media. It is a cross-platform application program with a user-friendly graphical interface that contains highly accurate deep neural networks for object detection and segmentation. The only prerequisite is that the input image should contain a fixed-sized 24-color balance card placed next to the objects of interest on a white background to ensure reliable and reproducible results, regardless of the image acquisition method. The image processing pipeline automatically calculates 10 different colors and morphological parameters for individual seedlings in the given image, and disease-associated phenotypic changes can be easily assessed by comparing plant images captured before and after infection. We conducted two case studies involving bacterial and plant mutants with reduced virulence and disease resistance capabilities, respectively, and thereby demonstrated that AraDQ can capture subtle changes in plant color and morphology with a high level of sensitivity. CONCLUSIONS: AraDQ offers a simple, fast, and accurate approach for image-based quantification of plant disease symptoms using various parameters. Its fully automated pipeline neither requires prior image processing nor costly hardware setups, allowing easy implementation of the software by researchers interested in digital phenotyping of diseased plants.

Edible insects in food.

Edible insects, with their high protein and lipid content, offer a safe and cost-effective alternative to traditional protein sources. They are environmentally friendly, emitting fewer greenhouse gases and requiring less water than livestock farming. Their rapid reproduction, efficiency, and labor-saving qualities make them attractive for industry. However, the unappealing appearance of edible insects hinders consumer acceptance. To overcome this, materialization technologies should be developed, and negative perceptions addressed with objective data. Promoting the nutritional value, safe rearing, disease prevention, and cost-efficiency of edible insects can boost consumer interest. Commercializing various insect products is crucial to revitalize their integration into the food industry.

Methods to Isolate Muscle Stem Cells for Cell-Based Cultured Meat Production: A Review.

Cultured meat production relies on various cell types, including muscle stem cells (MuSCs), embryonic stem cell lines, induced pluripotent cell lines, and naturally immortalized cell lines. MuSCs possess superior muscle differentiation capabilities compared to the other three cell lines, making them key for cultured meat development. Therefore, to produce cultured meat using MuSCs, they must first be effectively separated from muscles. At present, the methods used to isolate MuSCs from muscles include (1) the pre-plating method, using the ability of cells to adhere differently, which is a biological characteristic of MuSCs; (2) the density gradient centrifugation method, using the intrinsic density difference of cells, which is a physical characteristic of MuSCs; and (3) fluorescence- and magnetic-activated cell sorting methods, using the surface marker protein on the cell surface of MuSCs, which is a molecular characteristic of MuSCs. Further efficient and valuable methods for separating MuSCs are expected to be required as the cell-based cultured meat industry develops. Thus, we take a closer look at the four methods currently in use and discuss future development directions in this review.

International consensus guidelines on robotic pancreatic surgery in 2023.

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Effect of Crude Polysaccharides from Ecklonia cava Hydrolysate on Cell Proliferation and Differentiation of Hanwoo Muscle Stem Cells for Cultured Meat Production.

Ecklonia cava, a brown seaweed native to the East Asian coast, is known for its unique composition, including polysaccharides, polyphenols, and phlorotannins. Fucoidan is a sulfated polysaccharide widely used as a functional ingredient in foods. This study obtained crude polysaccharides (ECC_CPS) from E. cava celluclast enzymatic hydrolysate using ethanol precipitation. ECC_CPS increased cell viability during the proliferation of Hanwoo muscle satellite cells (HMSCs). The effect of ECC_CPS on the expression of proliferation-related markers was confirmed as MYF5 and MYOD expression significantly increased, whereas PAX7 expression was maintained. The evaluation of cell migration activity has a major impact on cell proliferation and differentiation, and the cell migration index significantly increased with ECC_CPS treatment (p < 0.01). This was related to the HGF/MET pathway and FAK pathway. Treatment with ECC_CPS promoted differentiation at the cell differentiation stage, thereby increasing the expression of differentiation markers, such as MYH2, MYH7, and MYOG (p < 0.001 or p < 0.01). Therefore, our findings imply that crude polysaccharide obtained from E. cava can be an additive ingredient that enhances the proliferation and differentiation of muscle satellite cells used in the manufacture of cultured meat products.

Effects of Early Initiation of Polymyxin B Hemoperfusion Therapy in Patients with Cancer with Refractory Septic Shock.

Background: We aimed to analyze the correlation between in-hospital mortality and hemodynamic changes, using polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) initiation time in patients with cancer with refractory septic shock. Methods: Forty-six patients with cancer who received PMX-DHP for refractory septic shock were retrospectively analyzed and classified into early (≤3 h between refractory septic shock and PMX-DHP; n = 17) and late (>3 h; n = 29) initiation groups. The vasopressor inotropic score (VIS), sequential organ failure assessment (SOFA) score, and lactate clearance before and 24 h post-PMX-DHP were compared. Results: Overall, 52.17% died from multiple organ dysfunction, with a lower mortality rate in the early initiation group. The VIS and SOFA score decreased in both groups, but the magnitude of decrease was not significant. Lactate clearance improved in both groups, with greater improvement in the early initiation group. Univariable analysis identified associations of in-hospital mortality with early initiation, ΔC-reactive protein, lactate clearance, ΔSOFA score, and ΔVIS. Multivariable analysis demonstrated associations of in-hospital mortality risk with ΔSOFA score and early PMX-DHP initiation. Overall survival was higher in the early initiation group. Early initiation of PMX-DHP in patients with cancer with refractory septic shock reduced in-hospital mortality and improved lactate clearance.

Real-world outcome of patients with extensively pretreated multiple myeloma who were treated with selinexor and dexamethasone: a Korean multicenter retrospective analysis.

The outcomes of patients with myeloma after exposed to penta-classes are extremely poor. Selinexor is the first approved exportin inhibitor for those patients, but intractable toxicities may limit its use. This retrospective study evaluated the real-world efficacy and safety of selinexor plus dexamethasone (XD) and involved 48 patients with multiple myeloma, who were treated from November 2020 to October 2022. Their median age was 64 years, and the median number of prior lines of therapy was 6. The overall response rate was 25%, and the median progression-free survival (PFS) was 2.1 months (95% confidence interval (CI), 1.7-2.5). Patients on a reduced initial dose, delayed treatment, and dose reduction had better PFS. After XD treatment failure, 17 patients received subsequent therapy and had a median PFS of 2.4 months. The median overall survival was 4.6 months (95% CI, 2.3-6.9). Among the patients, 12 (25%) and 17 (35%) experienced dose reduction and delayed treatment, respectively. Our data show that the real-world efficacy of XD treatment in heavily pretreated patients was modest and that improving treatment adherence through reducing initial doses or delaying treatments may improve patient outcomes.

Quantitative cistern effacement and reduced gray to white matter ratio for prognostication in early brain computed tomography of patients with cardiac arrest.

Background: The impact of cerebral edema on brain cells and ventricles in cardiac arrest patients can manifest as effacement of cortical sulci, diminished ventricle size, altered gray matter to white matter ratio (GWR), and increased optic nerve sheath diameter (ONSD) in brain CT scans. However, a complete investigation of GWR in whole lobes, quantitative cistern size, and comprehensive comparison of various brain CT parameters has not been conducted. This study aimed to comprehensively compare various early brain CT parameters along with conventional significant variables in relation to poor neurological outcome and diffuse cortical necrosis. Methods: This retrospective study included 86 adult patients with cardiac arrest who underwent brain CT/MRI. GWRs, the distance of the posterior ambient cistern, and ONSD in early brain CT and regions of interest (ROIs) in brain MRI were measured and analyzed along with clinical characteristics. Results: ROIs in the putamen and parietal white matter showed significant differences (p = 0.05, p = 0.022, respectively). The distance of the posterior ambient cistern and the GWR of the putamen and parietal white matter were newly developed predictors that were not used previously and demonstrated a significant correlation with the presence of diffuse cortical necrosis (OR 0.4, p = 0.006, AUC 0.637; OR 0.478, p = 0.02, AUC 0.603, respectively) or poor neurological outcomes (AUC 0.637, AUC 0.603, respectively), but were not more significant than pupil reflex (OR 0.06, p < 0.001). ONSD was not significantly associated with the outcomes. Conclusions: Quantitative cistern effacement and reduced GWR of the putamen and parietal white matter in early brain CT measurements of cardiac arrest patients were promising predictors in early brain CT for prognostication, but compared with clinical characteristics, the clinical significance of the CT predictors was not considerable. The relationship and clinical significance between the parameters in early brain CT and the outcomes might have to be separately considered.

A Multicenter Analysis of Clinical Features and Long-Term Outcomes of POEMS Syndrome in Korea.

BACKGROUND: POEMS syndrome is a rare form of plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes. Owing to its low incidence, there are few reports regarding this syndrome. This multicenter study included 84 patients diagnosed with POEMS syndrome in South Korea. METHODS: We retrospectively evaluated 84 patients diagnosed with POEMS syndrome at 8 hospitals in South Korea between January 2000 and October 2022. The clinical characteristics and treatment outcomes were analyzed. RESULTS: The median patient age was 53 years (range, 26-77 years), and 63.1% of the patients were male. All patients had peripheral neuropathy, and 81 (96.4%) had monoclonal plasma cell proliferation. Plasma vascular endothelial growth factor levels were available for 32 patients with a median of 821 pg/mL (range, 26-12,900 pg/mL). Other common features included skin changes (54.2%), volume overload (71.4%), and organomegaly (72.6%). Of the 84 patients, 75 received initial treatment (local radiotherapy, 6 [8.0%]; chemotherapy, 17 [22.7%]; both chemotherapy and local radiotherapy, 9 [12.0%]), upfront autologous stem cell transplantation (ASCT), 43 (57.3%; with induction chemotherapy, n = 12, 16.0%; without induction chemotherapy, n = 31, 41.3%). The median follow-up duration was 40.7 months. The 5-year overall survival (OS) was 78%, and the 5-year progression-free survival (PFS) was 55%. Patients who underwent upfront ASCT and were diagnosed after 2014 had a longer OS and PFS. CONCLUSION: The demographics of Korean patients with POEMS syndrome were similar to those reported previously. Because of the introduction of new treatment agents and the reduced rate of transplant-related mortality related to ASCT, the treatment outcomes of Korean patients with POEMS syndrome have improved in recent years.

Anti-inflammatory effect of pepper extract with high polyamine levels; inhibition of ERK/MAPK pathway in mice.

Polyamines have been reported to have cell proliferative and anti-inflammatory effects on normal metabolism in the body. This study aimed to investigate polyamine content of AIG01 pepper and the anti-inflammatory effect of AIG01 pepper extract (PAE) in mice. Polyamine content was analyzed by HPLC after acid hydrolysis of peppers with different acidic solvents. AIG01 pepper has the highest total polyamine content at about 1.5 mg/g. In LPS-stimulated RAW264.7, PAE inhibits nitric oxide production in a concentration-dependent manner and decreased the levels of pro-inflammatory cytokines. PAE has been shown to inhibit phosphorylation of MAPK/ERK. In TPA-stimulated Balb/C, PAE treatment showed tissue-level reductions in pro-inflammatory cytokines, reductions in ear thickness, and inhibition of neutrophil invasion. The polyamine content, polyamine extraction efficiency and anti-inflammatory effect of AIG01 obtained in this study suggest that it is useful as a raw material for the treatment of inflammatory diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01333-x.

Carfilzomib, thalidomide, and dexamethasone is safe and effective in relapsed and/or refractory multiple myeloma: final report of the single arm, multicenter phase II ALLG MM018/AMN002 study.

This multicentre, phase II study of the Australian Lymphoma and Leukaemia Group (ALLG) and the Asian Myeloma Network (AMN) investigated fixed-duration (18-month) treatment with carfilzomib (K), thalidomide (T), and dexamethasone (d; KTd) in patients with relapsed and/or refractory multiple myeloma and 1-3 prior lines of therapy. Patients received induction with up to twelve 28-day cycles of K [20mg/m2 IV cycle 1 day 1 and 2, 56mg/m2 (36mg/m2 for patients ≥75 years) from day 8 onwards), T 100mg PO nocte and weekly dexamethasone 40mg (20mg for patients ≥75 years). During maintenance T was omitted, while K continued on days 1,2,15,16 with fortnightly dexamethasone. The primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate, overall survival (OS), duration of response, safety, and tolerability. Ninety-three patients (median age 66.3 years (41.9 - 84.5)) were enrolled with a median follow-up of 26.4 (1.6 - 54.6) months. The median PFS was 22.3 months (95% CI 15.7 - 25.6) with a 46.3% (95% CI 35.1 - 52.8) 2-year PFS. Median OS was not reached and was 73.8% (95% CI 62.9 - 81.9) at 2 years. The overall response rate was 88% (≥ VGPR 73%). There was no difference in the depth of response, PFS or OS comparing Asian and Non-Asian cohorts (p=0.61). The safety profile for KTd was consistent with each individual drug. KTd is well tolerated and effective in patients with RRMM irrespective of Asian or non-Asian ethnicity and provides an alternative option particularly where use of KRd is limited by access, cost, or renal impairment.

Clinical implication of the geometric location (fundal end versus cystic ductal end) of gallbladder cancer.

BACKGROUND: Management of early-stage gallbladder cancer is becoming more important as the rate of early detection is increasing. Although there have been many studies about the clinical implication of the invasion depth or peritoneal/hepatic location of gallbladder cancers, there is no study on the clinical implication of the geometric location of cancer along the longitudinal length of the gallbladder. METHODS: The location of gallbladder cancer was defined as the geometric center of the primary site of a tumour, which lies on the longitudinal diameter of the surgical specimens. We compared the oncologic outcomes following surgery between gallbladder cancers located on the fundal end and those located on the cystic ductal end. We also analysed patients with stage 1 gallbladder cancer who recurred after surgery. RESULTS: A total of 575 patients with gallbladder cancer were included in this study. Patients with gallbladder cancer on the cystic ductal end had significantly lower rates of recurrence-free survival (P = 0.016) and overall survival (P = 0.023) compared to those with gallbladder cancer on the fundal end. Among 90 patients with stage 1 gallbladder cancer, three patients had a recurrence, all of whom had cystic ductal end gallbladder cancer and showed cystic duct invasion or concomitant xanthogranulomatous cholecystitis in permanent pathology. CONCLUSIONS: Gallbladder cancers on the cystic ductal end had worse postoperative oncologic outcomes compared with those on the fundal end.

Intravenous dexamethasone does not prolong the duration of pudendal nerve block in infants and children undergoing hypospadias surgery: A randomized clinical trial.

BACKGROUND: The administration of intravenous dexamethasone increases the duration of neuraxial block and improves the quality of analgesia. However, little is known about these effects of dexamethasone on peripheral nerve blocks in children. AIMS: In this study, we aimed to investigate the benefit of intravenous dexamethasone for enhancing the effect of pudendal block on postoperative analgesia in children who underwent hypospadias surgery. METHODS: In total, 46 children aged 6-36 months who underwent hypospadias surgery were randomly allocated to either a control group (normal saline, group C) or dexamethasone group (0.5 mg/kg, group D). Pudendal block was performed before the surgery using 0.3 mL/kg of 0.225% ropivacaine on both sides. Parents were instructed to press the patient-controlled analgesia bolus button when their children's pain score was >4 points. The primary outcome measure was the time at which the first patient-controlled analgesia by proxy bolus dose was administered. The secondary outcome measures were pain score, number of patient-controlled analgesia administration by proxy bolus attempts, number of rescue analgesics required, total amount of fentanyl administered, and overall parental satisfaction. RESULTS: The time of first patient-controlled analgesia bolus administration by proxy was not different between the control and dexamethasone groups (5.6 [5.2, 8.8] h versus 6.5 [5.4, 8.1] h, hazard ratio 0.8, 95% confidence intervals 0.43 to 1.47, p = .46). There were no statistically significant differences among the secondary outcomes. CONCLUSIONS: Administration of intravenous dexamethasone did not enhance the duration of pudendal nerve block in infants and children aged 6-36 months who underwent hypospadias surgery.