Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.

BACKGROUND: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers. METHODS: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified. RESULTS: Of the total 3895 patients, 99 (2.5 %) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2 % (27/1350) of patients with colorectal cancer, followed by 3.48 % (32/920) of patients with gastric cancer and 3.88 % (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3 % (27/99) had a concomitant KRAS mutation. More than 50 % of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1 % (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9 %, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1. CONCLUSIONS: Of the 3895 patients with metastatic solid tumors, 99 (2.5 %) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.

CDK4/6 inhibition to resensitize BRAF/EGFR inhibitor in patient-derived BRAF/PTEN-mutant colon cancer cells.

Background: In v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant colorectal cancer (CRC), encorafenib-cetuximab has been established as standard second-line therapy, but not all patients respond and the duration of response is relatively short. Overcoming intrinsic or acquired resistance to BRAF/EGFR inhibitors is crucial for enhancing treatment outcomes in metastatic BRAF-mutated CRC. The aim of the study is to investigate the resistance mechanisms in BRAF-mutant CRC patient refractory to BRAF/EGFR targeted therapy. Methods: We established patient-derived cells (PDCs) from a patient with BRAF/PTEN-mutant metastatic colon cancer who progressed rapidly on encorafenib plus cetuximab. To explore potential treatment options for inherent resistance caused by simultaneous PTEN mutation in BRAF-mutated CRC, we conducted cell viability assays using PDCs treated with encorafenib-cetuximab in combination with a cyclin-dependent kinase-4 and 6 (CDK4/6) inhibitor. Results: The patient's tumor had concurrent PTEN loss-of-function alteration at diagnosis and PDCs were generated from ascites after resistance to the BRAF/EGFR inhibitor. The PDCs were resistant to the encorafenib-cetuximab combination even at a high concentration of cetuximab (up to 500 µg/mL). Adding the CDK4/6 inhibitor, ribociclib, to encorafenib-cetuximab showed a synergistic effect in a proliferation assay. Ribociclib plus encorafenib-cetuximab represented a significantly lower expression of Ki-67 compared to the dual combination alone. An MTS assay showed that triplet therapy with ribociclib, encorafenib, and cetuximab suppressed cell viability more efficiently than the two-drug combinations. Investigating the combined effect of triplet therapy using the calculated combination index (CI) showed that ribociclib had a synergistic effect with encorafenib-cetuximab when applied to PDCs with a concurrent BRAF/PTEN mutation. Conclusions: Our results suggest that combining the CDK4/6 inhibitor with the BRAF/EGFR inhibitor might be a novel treatment strategy for concomitant BRAF and PTEN-mutant CRC.

Intraoperative Fluorescent Navigation of the Ureters, Vessels, and Nerves during Robot-Assisted Sacrocolpopexy.

In this study, we aimed to demonstrate the feasibility and safety of navigating the ureters, middle sacral artery (MSA), and superior hypogastric nerve (SHN) using indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during robot-assisted sacrocolpopexy (RSCP). Overall, 15 patients who underwent RSCP for apical vaginal prolapse were retrospectively enrolled. All patients underwent cystoscopic intraureteric instillation of 5 cc ICG (2.5 mg/mL) before RSCP and intravenous injection of 3 cc ICG during presacral dissection and mesh fixation. In all patients, the fluorescent right ureter was clearly identified in real time. The MSA was visualized on ICG-NIRF images in 80% (13/15) of patients. The mean time from ICG injection to MSA visualization was 43.7 s; the mean duration of the arterial phase was 104.3 s. Fluorescent SHN was detected in 73.3% (11/15) of patients. The time from ICG injection to SHN fluorescence was 48.4 s; the duration of fluorescence was 177.2 s. There was no transfusion, iatrogenic ureteral injury, or bowel or urinary dysfunction. Our results indicated that intraoperative ureter, MSA, and SHN mapping using ICG-NIRF images during RSCP is a valuable and safe technique to avoid iatrogenic ureteral, vascular, and neural injuries and to simplify surgical procedures. Nonetheless, further studies are required.

Revealing the Filler-Matrix Interfacial Interactions: Real-Time Observation with Mechano-Responsive Spiropyran Microbeads.

Interfacial interactions between polymers and fillers play a crucial role in determining the performance of composite materials. In this study, mechano-responsive spiropyran (SP) beads, which exhibit fluorescence changes under stress, serve as force probes to evaluate force transfer efficiency across two types of interfaces: noncovalent and covalent. These interfaces are engineered by respectively employing physical blending and grafting polymerization to integrate hydroxyl SP beads with a polyurethane (PU) matrix. A custom-built in situ opto-mechanical setup quantitatively assesses force transfer by monitoring changes in fluorescence intensity and peak wavelength during specimen stretching. The analysis reveals that the covalent interface significantly outperforms the noncovalent interface, demonstrating a 100% improvement in force magnitude and transfer rate from the PU matrix to the SP beads. Direct observation of SP beads within the PU matrix during tension unveils that enhanced force transfer efficiency is closely linked to changes in the SP beads' aspect ratio. Fluorescence changes in SP beads are solely a function of aspect ratio, making them effective independent force probes.

Recurrence-Free Survival after Postoperative Hormone Therapy for Catamenial Pneumothorax.

Background: Catamenial pneumothorax (CP) is a rare form of spontaneous pneumothorax that is linked to endometriosis; thus, it predominantly manifests in women of reproductive age. Considerable research has explored the potential benefits of postoperative hormone therapy following various surgical interventions. This study was performed to examine the clinical implications of postoperative hormone treatment in patients with CP. Methods: The study included patients who underwent surgical intervention for CP between November 2009 and February 2023. These procedures included wedge resection, diaphragm resection, and total pleural coverage. Recurrence-free survival was analyzed using the Kaplan-Meier log-rank test to assess the impact of hormone therapy. Additionally, Cox proportional hazards analysis was employed to identify risk factors associated with postoperative CP recurrence. Results: The study included 41 patients, with a median age of 38.4 years. Among them, 27 individuals received hormone therapy, 8 of whom experienced recurrence during a median follow-up period of 1 year. Patients who received hormone therapy exhibited a lower rate of recurrence than those who did not; however, the difference was not statistically significant, likely due to the small sample size. Side effects of hormone therapy included depression (6.8%), excessive sweating (3.4%), and headache (3.4%). In the analysis of risk factors for postoperative recurrence, diaphragm resection emerged as a protective factor (hazard ratio, 0.16; 95% confidence interval, 0.03-0.77; p=0.022). Conclusion: Hormone treatment combined with surgery did not significantly impact recurrence in patients with CP. The application of diaphragm resection was the sole factor that displayed significance in preventing CP recurrence.

Cesium lead bromide perovskite nanocrystals synthesized via supersaturated recrystallization at room temperature: comparison of one-step and two-step processes.

Over more than a decade, lead halide perovskites (LHPs) have been popular as a next-generation semiconductor for optoelectronics. Later, all-inorganic CsPbX3 (X = Cl, Br, and I) nanocrystals (NCs) were synthesized via supersaturated recrystallization (SR) at room temperature (RT). However, compared to the hot injection (HI) method, the formation mechanism of NCs via SR-RT has not been well studied. Hence, this study will contribute to elucidating SR-RT based on the LaMer model and Hansen solubility parameter. Herein, we also demonstrate the entropy-driven mixing between two dissimilar polar-nonpolar (DMF-toluene) solvents. Next, we find that, in a poor solvent (toluene ≫ DMF in volume), ∼60 nm sized CsPbBr3 NCs were synthesized in one step, whereas in a marginal solvent (toluene ≈ DMF), ∼3.5 nm sized NCs were synthesized in two steps, indicating the importance of solvent polarity, specifically the 'solubility parameter'. In addition, in the presence of a CuBr2 additive, high-quality cubic NCs (with ∼3.8 nm and ∼21.4 nm edge sizes) were synthesized. Hence, through this study, we present a 'solubility parameter-based nanocrystal-size control model' for SR-RT processes.

Relationships of Jugular Bulb Parameters with Cerebral Perfusion and Metabolism After Resuscitation from Cardiac Arrest: A Post-Hoc Analysis of Experimental Studies Using a Minipig Model.

BACKGROUND: Cerebral blood flow (CBF) decreases in the first few hours or days following resuscitation from cardiac arrest, increasing the risk of secondary cerebral injury. Using data from experimental studies performed in minipigs, we investigated the relationships of parameters derived from arterial and jugular bulb blood gas analyses and lactate levels (jugular bulb parameters), which have been used as indicators of cerebral perfusion and metabolism, with CBF and the cerebral lactate to creatine ratio measured with dynamic susceptibility contrast magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. METHODS: We retrospectively analyzed 36 sets of the following data obtained during the initial hours following resuscitation from cardiac arrest: percent of measured CBF relative to that at the prearrest baseline (%CBF), cerebral lactate to creatine ratio, and jugular bulb parameters, including jugular bulb oxygen saturation, jugular bulb lactate, arterial-jugular bulb oxygen content difference, cerebral extraction of oxygen, jugular bulb-arterial lactate content difference, lactate oxygen index, estimated respiratory quotient, and arterial-jugular bulb hydrogen ion content difference. Linear mixed-effects models were constructed to examine the effects of each jugular bulb parameter on the %CBF and cerebral lactate to creatine ratio. RESULTS: The arterial-jugular bulb oxygen content difference (P = 0.047) and cerebral extraction of oxygen (P = 0.030) had a significant linear relationship with %CBF, but they explained only 12.0% (95% confidence interval [CI] 0.002-0.371) and 14.2% (95% CI 0.005-0.396) of the total %CBF variance, respectively. The arterial-jugular bulb hydrogen ion content difference had a significant linear relationship with cerebral lactate to creatine ratio (P = 0.037) but explained only 13.8% (95% CI 0.003-0.412) of the total variance in the cerebral lactate to creatine ratio. None of the other jugular bulb parameters were related to the %CBF or cerebral lactate to creatine ratio. CONCLUSIONS: In conclusion, none of the jugular bulb parameters appeared to provide sufficient information on cerebral perfusion and metabolism in this setting.

Acute kidney injury as a prognostic predictor of in-hospital mortality and neurological outcomes in patients after extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly being applied to patients with refractory cardiac arrest, but the survival rate to hospital discharge is only approximately 29%. Because ECPR requires intensive resources, it is important to predict outcomes. We therefore investigated the prognostic association between acute kidney injury (AKI) and ECPR to confirm the performance of AKI as a prognostic predictor of in-hospital mortality and neurological outcomes in ECPR. METHODS: We conducted a retrospective observational study on patients undergoing ECPR for cardiac etiology at Chonnam National University Hospital from 2015 to 2021. The group diagnosed with AKI in any KDIGO category within the first 48 h after ECPR was compared to that without AKI, and the primary outcome of the study was in-hospital mortality. RESULTS: Of 138 enrolled patients, 83 were studied. Hospital mortality occurred in 49 patients (59%), and 55 (66.3%) showed poor neurological outcomes. The AKI group displayed significantly elevated in-hospital mortality (77.8% vs 24.1%) and poor neurological outcomes (81.5% vs 37.9%) compared to the non-AKI group (p < 0.001). Regression analysis showed that AKI was associated with significantly higher rates of both in-hospital mortality (odds ratio (OR) range 10.75-12.88) and neurologic outcomes (OR range 5.9-6.22). CONCLUSIONS: There was a significant association of AKI with both in-hospital mortality and poor neurologic outcome in patients after ECPR, and AKI can be used as an early prognostic predictor in these patients.

TLR2 immunotherapy suppresses neuroinflammation, tau spread, and memory loss in rTg4510 mice.

In Alzheimer's disease, chronic neuroinflammation is accompanied by amyloid and tau pathologies. Especially, aberrant microglial activation is known to precede the regional tau pathology development, but the mechanisms how microglia affect tau spread remain largely unknown. Here, we found that toll-like receptor 2 (TLR2) in microglia recognizes oligomeric tau as a pathogenic ligand and induces inflammatory responses. Knockout of TLR2 reduced tau pathology and microglial activation in rTg4510 tau transgenic mice. Treatment of oligomeric tau induced TLR2 activation and increased inflammatory responses in microglial cells. TLR2 further mediated the tau-induced microglial activation and promoted tau uptake into neurons in neuron-microglia co-culture system and in mouse hippocampus after intracranial tau injection. Importantly, treatment with anti-TLR2 monoclonal antibody Tomaralimab blocked TLR2 activation and inflammatory responses in a dose-dependent manner, and significantly reduced tau spread and memory loss in rTg4510 mice. These results suggest that TLR2 plays a crucial role in tau spread by causing aberrant microglial activation in response to pathological tau, and blocking TLR2 with immunotherapy may ameliorate tau pathogenesis in Alzheimer's disease.

TMEM9 activates Rab9-dependent alternative autophagy through interaction with Beclin1.

Transmembrane protein 9 (TMEM9) is a transmembrane protein that regulates lysosomal acidification by interacting with the v-type ATPase complex. However, the role of TMEM9 in the lysosome-dependent autophagy machinery has yet to be identified. In this study, we demonstrate that the lysosomal protein TMEM9, which is involved in vesicle acidification, regulates Rab9-dependent alternative autophagy through its interaction with Beclin1. The cytosolic domain of TMEM9 interacts with Beclin1 via its Bcl-2-binding domain. This interaction between TMEM9 and Beclin1 dissociates Bcl-2, an autophagy-inhibiting partner, from Beclin1, thereby activating LC3-independent and Rab9-dependent alternative autophagy. Late endosomal and lysosomal TMEM9 apparently colocalizes with Rab9 but not with LC3. Furthermore, we show that multiple glycosylation of TMEM9, essential for lysosomal localization, is essential for its interaction with Beclin1 and the activation of Rab9-dependent alternative autophagy. These findings reveal that TMEM9 recruits and activates the Beclin1 complex at the site of Rab9-dependent autophagosome to induce alternative autophagy.

Clipless internal mammary artery harvesting for minimally invasive coronary artery bypass grafting using the shear-tip harmonic scalpel.

Background: The internal mammary artery (IMA) is the most commonly used graft in coronary artery bypass grafting (CABG) because of its superior long-term patency rate. However, its small diameter poses challenges in handling, and any vascular damage that may occur during harvesting can significantly affect surgical outcomes. The primary focus during IMA harvesting is to ensure safe and effective hemostasis without direct vascular injury, while ensuring secure and reliable ligation of the vascular branches. Various methods using multiple surgical instruments have been used for this purpose. Unlike traditional instruments, the shear-tip Harmonic scalpel offers more precise vessel branching control, while minimizing damage to surrounding tissues. In this study, we assessed the utility of the shear-tip Harmonic scalpel in patients undergoing minimally invasive coronary artery bypass grafting (MICABG). Methods: From April 2019 to May 2023, a total of 40 patients underwent MICABG. The IMA was harvested using the shear-tip Harmonic scalpel with a clipless skeletonized technique. In this cohort, 5 patients underwent complete endoscopic harvesting, while 34 patients underwent direct visualization harvesting through minimal thoracotomy. Graft patency was assessed by measuring a Doppler flowmeter in the bypass conduit. Results: Successful graft patency was achieved in all patients. The mean duration of IMA harvesting was 87 min. In total, 38 of the 40 patients underwent MICABG without the need for cardiopulmonary bypass, ensuring a stable procedure. There were no graft-related events or complications observed in any of the patients, and all were discharged without any issues. During a median follow-up period of 15.2 months, only one patient experienced graft occlusion necessitating intervention. Conclusions: The utilization of shear-tip Harmonic scalpel for IMA harvesting in MICABG is feasible and yields stable early results.

Early single session of hyperbaric oxygen therapy mitigates renal apoptosis in lipopolysaccharides-induced endotoxemia in rats.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often resulting in adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, offers potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms. Methods: A lipopolysaccharide (LPS)-induced endotoxemia model was established using 8-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a group of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements. Results: Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis. Additionally, HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis by impeding p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor beta (TGF-ß)/Smad4 and alpha smooth muscle actin expressions were significantly reduced in the LPS + HBOT group. Conclusion: An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by suppressing p53 activation and cytochrome C levels to mitigate apoptosis. The observed TGF-ß decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

Imatinib in c-KIT-mutated metastatic solid tumors: A multicenter trial of Korean Cancer Study Group (UN18-05 Trial).

INTRODUCTION: We conducted an open-label, single-arm, multi-center phase II trial to evaluate the efficacy and safety of imatinib chemotherapy-refractory or metastatic solid tumor patients with c-KIT mutations and/or amplification. METHODS: c-KIT mutations and amplification were detected using NGS. Imatinib (400 mg daily) was administered continuously in 28-day cycles until disease progression, unacceptable adverse events, or death by any cause. The primary endpoint was the objective response rate (ORR). RESULT: In total, 18 patients were enrolled on this trial. The most common tumor type was melanoma (n = 15, 83.3%), followed by ovarian cancer, breast cancer, and metastasis of unknown origin (MUO) (each n = 1, 5.5%). The total number of evaluable patients was 17, of which one patient had a complete response, six patients had partial response, and two patients had stable disease. The overall response rate (ORR) of 41.2% (95% CI 17.80-64.60) and a disease control rate of 52.9% (95% CI 29.17-76.63). The median progression-free survival was 2.2 months (95% CI 1.29-3.20), and median overall survival was 9.1 months (95% CI 2.10-16.11). The most common adverse events were edema (31.3%), anorexia (25.0%), nausea (18.8%), and skin rash (18.8%). CONCLUSION: Imatinib demonstrated modest anti-tumor activity and a manageable safety profile in chemotherapy-refractory solid tumors with c-KIT mutation, especially in melanoma patients.

Effect of intravenous palonosetron on hypotension induced by spinal anesthesia for cesarean section: A randomized controlled trial.

BACKGROUND: The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section. METHODS: Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery. RESULTS: No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 µg [interquartile range, 291.3-507.8 µg versus 428.0 µg [interquartile range, 305.0-507.0 µg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes. CONCLUSION: Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.

Catheter detection by transthoracic echocardiography during placement of peripherally inserted central catheters: a real-time method for eliminating misplacement.

BACKGROUND: Although guidelines and protocols are available for central venous access, existing methods lack specificity and sensitivity, especially when placing peripherally inserted central catheters (PICCs). We evaluated the feasibility of catheter detection in the right atrial cavity using transthoracic echocardiography (TTE) during PICC placement. METHODS: This single-center, retrospective study included consecutive patients who underwent PICC placement between January 2022 and March 2023. TTE was performed to detect the arrival of the catheter in the right atrial cavity. Catheter misplacement was defined as an aberrant catheter position on chest x-ray (CXR). The primary endpoint was predicting catheter misplacement based on catheter detection in the right atrial cavity. The secondary endpoint was optimizing catheter placement and examining catheter-associated complications. RESULTS: Of the 110 patients identified, 10 were excluded because of poor echogenicity and vein access failure. The remaining 100 patients underwent PICC placement with TTE. The catheter was visualized in the right atrial cavity in 90 patients. CXR exams revealed catheter misplacement in seven cases. Eight patients with catheter misplacement underwent the same procedure in the other arm. In two patients, PICC placement failed due to anatomical reasons. Catheter misplacement was detected using TTE with sensitivity, specificity, positive predictive value, and negative predictive value of 97% confidence interval (CI; 91.31%-99.36%), 90% CI (55.50%-99.75%), 99%, and 75%, respectively. CONCLUSIONS: TTE is a reliable tool for detecting catheter misplacement and optimizing catheter tip positioning during PICC placement.

All-in-one platform: Versatile, Easy, and User-friendly System (VEUS) based on automated and expert-independent antibody immobilization and immunoassay by utilizing customized movement of magnetic particles.

The ELISA is the most worldwide method for immunoassay. However, the ELISA is losing ground due to low reproducibility of manual experimental processes in both R&D and IVD areas. An automated platform is a good solution, but there are still limitations owning to extremely high cost and requiring large space to set up especially for a small size laboratory. Here, we present a novel all-in-one platform called "VEUS" settable on the laboratory table that offers comprehensive automation of the entire multiplex immunoassay process by exploiting antibody conjugated magnetic particles, quality control and then immunoanalytical reaction, thereby enhancing detection sensitivity and high reproducibility. As a proof of concept, the system exhibits a sensitive LOD of 0.6 and 3.1 pg mL-1 within 1 h run, comparable precision that of molecular diagnostic systems based on PCR method, enabling rapid multiplex diagnosis of Influenza A, Influenza B, and COVID-19 viruses with similar symptoms. Through automation by the all-in-one system, it can be used by novice users, something innovative for immunoassays, relying heavily on user experience. Furthermore, it can contribute to streamline entire immunoassay processes of diverse biomarkers with high reproducibility and convenience in laboratories.

The safety and efficacy outcomes of Minnelide given alone or in combination with paclitaxel in advanced gastric cancer: A phase I trial.

Minnelide is a water-soluble disodium salt variant of triptolide, an HSP70 inhibitor that can prevent tumor progression and induce apoptosis. Maximum tolerated dose (MTD), safety, and antitumor activity of Minnelide alone and its combination with paclitaxel were evaluated in this open-label, single-center, dose-escalation phase I study (NCT05566834) in patients who were previously treated for advanced gastric cancer (AGC). Minnelide was administered orally using a 3 + 3 dose-escalation design as monotherapy (Regimen A), and in combination with paclitaxel (Regimen B & C). Our results show that no patients experienced dose limiting toxicity (DLT) in the combination group (Regimen B& C) while 2 patients experienced DLT from the Regimen A group (n = 11) (Minnelide 1.5 mg). The MTD was Minnelide 1.25 mg once daily for 21days Q4 weeks as monotherapy. The most common Grade ≥3 AEs were neutropenia (19.4 %) and abdominal pain (11.1 %). In Regimen C, 71.5 % achieved either a partial response or a stable disease with the median PFS of 4.5 months, and the median OS of 10.7 months. The combination of Minnelide plus paclitaxel as salvage treatment in AGC patients showed meaningful clinical activity with a manageable safety profile. Based on these encouraging results, a phase II study is being initiated to test the effectiveness of the combination regimen in patients with advanced gastric cancer.

Robotic Single-Site Plus One-Port Myomectomy versus Robotic Single-Site Plus Two-Port Myomectomy: A Propensity Score Matching Analysis.

PURPOSE: Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes. MATERIALS AND METHODS: The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups' surgical outcomes were compared using propensity score matching (PSM) analysis. RESULTS: In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p=0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p=0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients' baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p=0.001) compared to the RSTM group. CONCLUSION: Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM.

Management of chronic rhinosinusitis with nasal polyps in the Asia-Pacific region and Russia: Recommendations from an expert working group.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition of the nasal and paranasal tissues, characterized by the presence of bilateral nasal polyps. An expert panel of specialists from the Asian-Pacific region and Russia was convened to develop regional guidance on the management of CRSwNP through a consensus approach. The present article presents the chief observations and recommendations from this panel to provide guidance for clinicians in these areas. Etiology and pathogenetic mechanisms in CRSwNP are heterogeneous and complex. In many patients, CRSwNP is primarily driven by type 2 inflammation, although this may be less important in Asian populations. Frequent comorbidities include asthma and other inflammatory diseases such as non-steroidal anti-inflammatory drug (NSAID)/aspirin-exacerbated respiratory disease or atopic dermatitis. Clinical management of CRSwNP is challenging, and a multidisciplinary approach to evaluation and treatment is recommended. While many patients respond to medical treatment (topical irrigation and intranasal corticosteroids, and adjunctive short-term use of systemic corticosteroids), those with more severe/uncontrolled disease usually require endoscopic sinus surgery (ESS), although outcomes can be unsatisfactory, requiring revision surgery. Biological therapies targeting underlying type 2 inflammation offer additional, effective treatment options in uncontrolled disease, either as an alternative to ESS or for those patients with persistent symptoms despite ESS.