Lung ultrasound diagnosis of pulmonary edema resulting from excessive fluid absorption during hysteroscopic myomectomy: a case report.

BACKGROUND: Hysteroscopic surgery is a safe procedure used for diagnosing and treating intrauterine lesions, with a low rate of intraoperative complications. However, it is important to be cautious as fluid overload can still occur when performing any hysteroscopic surgical technique. CASE PRESENTATION: In this case report, we present a unique instance where lung ultrasound was utilized to diagnose pulmonary edema in a patient following a hysteroscopic myomectomy procedure. The development of pulmonary edema was attributed to the excessive absorption of fluid during the surgical intervention. By employing lung ultrasound as a diagnostic tool, we were able to promptly identify and address the pulmonary edema. As a result, the patient received timely treatment with no complications. This case highlights the importance of utilizing advanced imaging techniques, such as lung ultrasound, in the perioperative management of patients undergoing hysteroscopic procedures. CONCLUSIONS: This case report underscores the significance of early detection and intervention in preventing complications associated with fluid overload during hysteroscopic myomectomy procedures.

Correlation between anesthetic concentration and low Apgar scores in neonates born via Cesarean sections under general anesthesia.

OBJECTIVES: This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. METHODS: Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. RESULTS: There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8-56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3-69.0). The prediction model was: probability = 1/(e­Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer-Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. CONCLUSIONS: There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

High Areal Capacity, Long Cycle Life Li-Air Batteries Enabled by Nano/Micro Hierarchical Porous Cathode.

The limited cycle life of Li-air batteries (LABs) with high areal capacity remains the chief challenge that hinders their practical applications. Here, the study proposes a hierarchical porous electrode (HPE) design strategy, in which porous MnO nanoflowers are built into mesopore/macropore electrodes through a combination of chemical dealloying and physical de-templating procedures. The MnO nanoflowers with 10-30 nm pore provides active sites to catalyze the O2 reduction and decomposition of discharged products. The 5-10 µm macroscopic pores in the cathode serve as channels of O2 transportation and facilitate the electrolyte permeation. The proposed HPE exhibits a full discharge capacity of 17.49 mAh cm-2 and stable cycle life >2000 h with a limited capacity of 6 mAh cm-2 . These results suggest that the HPE design strategy for LABs can simultaneously provide large capacity and robust cycle life, which is promising for advanced metal-air batteries.

DeepLensNet: Deep Learning Automated Diagnosis and Quantitative Classification of Cataract Type and Severity.

PURPOSE: To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs. DESIGN: DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset. PARTICIPANTS: A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants). METHODS: Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students. MAIN OUTCOME MEASURES: Mean squared error (MSE). RESULTS: On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC. CONCLUSIONS: DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.

Analgesic effect of ultrasound-guided erector spinae plane block (espb) in general anesthesia for cesarean section: a randomized controlled trial.

BACKGROUND: The analgesic effects of erector spinae plane block in general anesthesia for cesarean section and recovery from puerperae remain unclear. METHODS: Sixty patients with contraindications for spinal anesthesia who required general anesthesia for cesarean section were enrolled and randomly divided into the erector spinal plane block (ESPB) combined with the general anesthesia group (group E) and general anesthesia group (group G). Group E received bilateral ESPB (20 ml of 0.25% ropivacaine on each side) under ultrasound guidance 30 min before general anesthesia. The primary outcomes were the number of patient-controlled intravenous analgesia (PCIA) boluses, and Bruggemann comfort scale (BCS) scores at 2 h, 6 h, 12 h, and 24 h after operation. The second outcome was intraoperative anesthesia dosage, fetal delivery time, puerperae emergence time, visual analog scale (VAS) at 2 h, 6 h, 12 h, and 24 h after operation, and incidence of nausea and vomiting. Heart rate (HR) and mean arterial pressure (MAP) were recorded 10 min before the start of anesthesia (T0), at the induction of anesthesia (T1), at skin incision (T2), and fetal delivery (T3), and immediately after surgery (T4). RESULTS: The number of PCIA boluses was lower in group E than in group G (P < 0.001). The BCS score increased at 2 h and 6 h after the operation in group E (P < 0.05), while the VAS score significantly decreased in group E at the same time (P < 0.05). Compared with group G, the doses of propofol and remifentanil were significantly decreased in group E (P < 0.001), the emergence time of puerperae was shortened (P = 0.003), and the incidence of nausea and vomiting was significantly decreased (P = 0.014). CONCLUSION: Ultrasound-guided ESPB applied to general anesthesia for a cesarean section can significantly reduce the required dose of general anesthetic drugs, shorten the recovery time of the puerperae, and improve postoperative analgesia. TRIAL REGISTRATION: www. CLINICALTRIALS: gov under the number ChiCTR2200056337 (04-02-2022).

STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases.

AIMS: Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis. METHODS AND RESULTS: Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-ß) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP. CONCLUSION: Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.

Deep learning-based natural language processing in ophthalmology: applications, challenges and future directions.

PURPOSE OF REVIEW: Artificial intelligence (AI) is the fourth industrial revolution in mankind's history. Natural language processing (NLP) is a type of AI that transforms human language, to one that computers can interpret and process. NLP is still in the formative stages of development in healthcare, with promising applications and potential challenges in its applications. This review provides an overview of AI-based NLP, its applications in healthcare and ophthalmology, next-generation use case, as well as potential challenges in deployment. RECENT FINDINGS: The integration of AI-based NLP systems into existing clinical care shows considerable promise in disease screening, risk stratification, and treatment monitoring, amongst others. Stakeholder collaboration, greater public acceptance, and advancing technologies will continue to shape the NLP landscape in healthcare and ophthalmology. SUMMARY: Healthcare has always endeavored to be patient centric and personalized. For AI-based NLP systems to become an eventual reality in larger-scale applications, it is pertinent for key stakeholders to collaborate and address potential challenges in application. Ultimately, these would enable more equitable and generalizable use of NLP systems for the betterment of healthcare and society.

Ferrous hemoglobin and hemoglobin-based oxygen carriers acting as a peroxidase can inhibit oxidative damage to endothelial cells caused by hydrogen peroxide.

Oxidative damage caused by the ferryl hemoglobin is one of the major clinical adverse reactions of hemoglobin-based oxygen carriers (HBOCs), while the production of reactive oxygen species in a pathological state can oxidize hemoglobin (HbFe2+ ) to ferryl Hb, which can then enter the pseudoperoxidase cycle, making hemoglobin highly toxic. In this study, we found that ferrous hemoglobin and polymerized porcine hemoglobin (one of the HBOCs) have the peroxidase activity different from the pseudoperoxidase activity of ferric hemoglobin. Ferrous hemoglobin can catalyze the reaction of tyrosine (Tyr) with hydrogen peroxide. In addition, the results also indicated that ferrous hemoglobin and pPolyHb have a strong inhibitory effect on the pseudoperoxidase activity of ferric hemoglobin. Therefore, hydrogen peroxide was consumed in a large amount, which greatly prevented hemoglobin from becoming oxidized and entering the pseudoperoxidase cycle, thus inhibiting ferryl Hb toxicity. We further cultured human umbilical vein endothelial cells and monitored cell morphology, viability, cell cycle, apoptosis, lactate dehydrogenase (LDH) release, and malondialdehydes (MDAs) formation when incubated with H2 O2 , Tyr, and HbFe2+ . HbFe2+ and pPolyHb reduced cell cycle arrest, apoptosis, LDH release, and MDA formation. These results showed that reducing oxidative damage induced by H2 O2 and converted hemoglobin from a molecule that is toxic to one that inhibits oxidative damage, suggesting a new strategy for development of a safer HBOCs.

Flexible Lithium-Air Battery in Ambient Air with an In†Situ Formed Gel Electrolyte.

Flexible Li-air batteries (LABs) have been considered as promising power sources for wearable electronics owing to its higher energy density. However, when operated in ambient air, problems arise, such as Li anode passivation, poor cycle life as well as leakage of liquid electrolyte. Herein, we present a LAB with a tetraethylene glycol dimethyl ether (TEGDME, G4) gel electrolyte, in which the gel is formed in situ through a cross-linking reaction between the liquid G4 and the lithium ethylenediamine (LiEDA) grown on the surface of Li anode. We demonstrate that the gel can efficiently alleviate the corrosion of the Li anode, and thus the LAB shows a cycle performance over 1175 hours (humidity: 10 % to 40 %), which is much superior to previous reports. Furthermore, the in situ formed gel enhances the electrode/electrolyte interfacial contact, which thus enables the cable-type LAB to exhibit a great flexibility.

Ankyrin exposure induced by activated protein kinase C plays a potential role in erythrophagocytosis.

BACKGROUND: In physiological and pathological conditions activated protein kinace C (PKC) has been observed in the erythrocytes. Externalization of ankyrin followed by Arg-Gly-Asp (RGD)/integrin recognition also triggers erythrophagocytosis. In the present study, to test whether activated PKC is associated with ankyrin exposure in erythrophagocytosis. METHODS: Phorbol 12-myristate-13-acetate (PMA)-induced PKC activation and ankyrin phosphorylation were tested, and under different treatment conditions the subpopulation of erythrocytes with ankyrin exposure and the levels of intracellular calcium were analyzed by flow cytometry. RESULTS: Results showed that treatment of erythrocytes with PMA in a calcium-containing buffer led to ankyrin exposure. In the absence of extracellular calcium, no ankyrin exposure was observed. PKC inhibition with calphostin C, a blocker of the PMA binding site, completely prevented the calcium entry, protein phosphorylation and ankyrin exposure. PKC inhibition with chelerythrine chloride, an inhibitor of the active site, diminished the level of ankyrin-exposing cells and ankyrin phosphorylation; however it even led to a higher percentage of cells with increased levels of calcium than with PMA treatment alone. Although PKC was activated and ankyrin phosphorylation occurred, no ankyrin exposure was observed in the absence of extracellular calcium. CONCLUSION: Analyses of results suggested that PMA induces calcium influx into the erythrocytes, leading to the activation of calcium-dependent enzymes and the phosphorylation of membrane proteins, ultimately inducing ankyrin exposure and erythrophagocytosis. This study may provide insights into the molecular mechanisms of removing aged or diseased erythrocytes.

Calpastatin counteracts pathological angiogenesis by inhibiting suppressor of cytokine signaling 3 degradation in vascular endothelial cells.

RATIONALE: Janus kinase/signal transducer and activator of transcription (JAK/STAT) signals and their endogenous inhibitor, suppressor of cytokine signaling 3 (SOCS3), in vascular endothelial cells (ECs) reportedly dominate the pathological angiogenesis. However, how these inflammatory signals are potentiated during pathological angiogenesis has not been fully elucidated. We suspected that an intracellular protease calpain, which composes the multifunctional proteolytic systems together with its endogenous inhibitor calpastatin (CAST), contributes to the JAK/STAT regulations. OBJECTIVE: To specify the effect of EC calpain/CAST systems on JAK/STAT signals and their relationship with pathological angiogenesis. METHODS AND RESULTS: The loss of CAST, which is ensured by several growth factor classes, was detectable in neovessels in murine allograft tumors, some human malignant tissues, and oxygen-induced retinopathy lesions in mice. EC-specific transgenic introduction of CAST caused downregulation of JAK/STAT signals, upregulation of SOCS3 expression, and depletion of vascular endothelial growth factor (VEGF)-C, thereby counteracting unstable pathological neovessels and disease progression in tumors and oxygen-induced retinopathy lesions in mice. Neutralizing antibody against VEGF-C ameliorated pathological angiogenesis in oxygen-induced retinopathy lesions. Small interfering RNA-based silencing of endogenous CAST in cultured ECs facilitated µ-calpain-induced proteolytic degradation of SOCS3, leading to VEGF-C production through amplified interleukin-6-driven STAT3 signals. Interleukin-6-induced angiogenic tube formation in cultured ECs was accelerated by CAST silencing, which is suppressible by pharmacological inhibition of JAK/STAT signals, antibody-based blockage of VEGF-C, and transfection of calpain-resistant SOCS3, whereas transfection of wild-type SOCS3 exhibited modest angiostatic effects. CONCLUSIONS: Loss of CAST in angiogenic ECs facilitates µ-calpain-induced SOCS3 degradation, which amplifies pathological angiogenesis through interleukin-6/STAT3/VEGF-C axis.

Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice.

BACKGROUND & AIM: Hydrogen peroxide-inducible clone-5 (Hic-5), also named as transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was found to be induced by TGF-ß. Previous studies have shown that TGF-ß is a principal mediator of hepatic stellate cell (HSC) activation in liver fibrosis. However, this process remains elusive. In this study, we aimed to define the role of Hic-5 in HSC activation and liver fibrosis. METHODS: We examined the expression levels of Hic-5 during HSCs activation and in fibrotic liver tissues by quantitative real-time reverse transcriptase polymerase chain reaction, Western blot and immunohistochemistry. Hic-5 knockout (KO) and wild-type (WT) mice were subjected to bile duct ligation (BDL) or carbon tetrachloride (CCl4) injection to induce liver fibrosis. RESULTS: Hic-5 expression was strongly upregulated in activated HSCs of the human fibrotic liver tissue and BDL or CCl4-induced mouse liver fibrosis. Hic-5 deficiency significantly attenuated mouse liver fibrosis and HSC activation. Furthermore, Hic-5 knockdown by siRNA in vivo repressed CCl4-induced liver fibrosis in mice. Mechanistically, the absence of Hic-5 significantly inhibited the TGF-ß/Smad2 signaling pathway, proved by increasing Smad7 expression, resulting in reduced collagen production and α-smooth muscle actin expression in the activated HSCs. CONCLUSION: Hic-5 deficiency attenuates the activation of HSCs and liver fibrosis though reducing the TGF-ß/Smad2 signaling by upregulation of Smad7. Thus, Hic-5 can be regarded as a potential therapeutic target for liver fibrosis.

NADPH oxidase deficiency exacerbates angiotensin II-induced abdominal aortic aneurysms in mice.

OBJECTIVE: Although nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) is reportedly essential for phagocyte host defenses, it has been found to aggravate atherosclerosis in apolipoprotein E (Apoe)-null mice through excess production of superoxide. We therefore assessed the role of NOX2 in an experimental model of abdominal aortic aneurysm (AAA) and assessed the mechanism of NOX2 action in AAA. APPROACH AND RESULTS: AAA was induced in low-density lipoprotein receptor-null (Ldlr(-/-)) mice by infusing angiotensin II. Nox2 expression was elevated in the abdominal aortae of these mice during infusion of angiotensin II, with enhanced Nox2 expression mainly because of the recruitment of NOX2-enriched macrophages into AAA lesions. Unexpectedly, systemic Nox2 deficiency promoted AAA development but reduced the level of reactive oxygen species in AAA lesions. Nox2 deficiency stimulated macrophage conversion toward the M1 subset, enhancing expression of interleukin (IL)-1ß and matrix metalloproteinase-9/12 mRNA. Administration of neutralizing antibody against IL-1ß abolished AAA development in Nox2-deficient mice. Bone marrow transplantation experiments revealed that AAA aggravation by Nox2 deficiency is because of bone marrow-derived cells. Isolated bone marrow-derived macrophages from Nox2-null mice could not generate reactive oxygen species. In contrast, IL-1ß expression in peritoneal and bone marrow-derived macrophages, but not in peritoneal neutrophils, was substantially enhanced by Nox2 deficiency. Pharmacological inhibition of Janus kinase/signal transducers and activators of transcription signaling inhibited excess IL-1ß expression in Nox2-deficient macrophages, whereas matrix metalloproteinase-9 secretion was constitutively stimulated via nuclear factor-κB signals. CONCLUSIONS: Nox2 deficiency enhances macrophage secretion of IL-1ß and matrix metalloproteinase-9, disrupting tissue-remodeling functions in AAA lesions. These actions are unfavorable if NOX2 is to serve as a molecular target for AAA.

Effects of different doses of alfentanil combined with target-controlled infusion (TCI) of propofol for daytime hysteroscopy.

Background: Daytime hysteroscopy requires anesthesia that offers rapid onset and clearance, with minimal respiratory and cardiovascular suppression. This study compared the effects of different doses of alfentanil combined with propofol target-controlled infusion (TCI) for such procedures. Methods: We randomized 240 patients undergoing daytime hysteroscopy into three groups to receive alfentanil at doses of 5 µg/kg, 10 µg/kg, and 15 µg/kg, combined with propofol TCI. We meticulously recorded complications and perioperative vitals to evaluate the safety and efficacy of each dosage regimen. Results: The 10 µg/kg dose of alfentanil, used in conjunction with propofol, required lower propofol dosages and resulted in quicker recovery time and fewer intraoperative movements. However, higher doses of 15 µg/kg led to a significant increase in hypoxemia and instability in hemodynamics and oxygenation. Conclusion: Combining alfentanil at 10 µg/kg with propofol TCI for daytime hysteroscopy results in high effectiveness. A lower incidence of complications, a reduced propofol requirement, and rapid emergence from sedation characterize this regimen.

Comparison of a single intravenous infusion of alfentanil or sufentanil combined with target-controlled infusion of propofol for daytime hysteroscopy: a randomized clinical trial.

Background: The administration of either alfentanil or sufentanil as a single injection, combined with target-controlled infusion (TCI) of propofol, represents a frequently employed anesthetic regimen for daytime hysteroscopy. Objectives: This study was designed to evaluate and compare the safety and efficacy of alfentanil and sufentanil in the context of daytime hysteroscopy. Design: A total of 160 patients, scheduled for daytime hysteroscopy, were randomly allocated into two groups: Group A and Group S respectively received alfentanil 10 µg/kg or sufentanil 0.15 µg/kg as a single intravenous injection. Both groups were given propofol with TCI for sedation. Methods: Monitoring of vital signs was conducted from pre-anesthesia through to 2 h postoperatively. The primary outcome measured was hypoxemia, defined as SpO2 levels below 92% for a duration of 30 s, which necessitated manual positive pressure ventilation. Secondary outcomes included various perioperative complications, such as postoperative nausea and vomiting (PONV) occurring 2 h after surgery, as well as hemodynamic indicators, NRS scores for pain, and other anesthesia-related data. This comprehensive dataset was meticulously documented and subsequently analyzed for comparative purposes. Results: The analyses revealed that Group A had a significantly lower incidence of hypoxemia (p = 0.002) and PONV (p = 0.021). Additionally, group A demonstrated overall more stable blood pressure and heart rate, as well as higher SpO2 levels. Conclusion: For daytime hysteroscopy, alfentanil at a dose of 10 µg/kg is safer than sufentanil at a dose of 0.15 µg/kg when combined with propofol TCI. Trial registration: This study was registered with the Chinese Clinical Trial Registry (The URL of registration is https://www.chictr.org.cn/showproj.html?proj=177784; registration number: ChiCTR2200063939). The date of first registration was September 21, 2022.

Alfentanil combined with propofol is safer and more suitable for daytime hysteroscopy Why was the study done? Hysteroscopy is a procedure to look inside the uterus, and managing pain and safety is crucial. The study was conducted to compare the safety and effectiveness of two pain relief medications, alfentanil and sufentanil, used during daytime hysteroscopy. What did the researchers do? We included 160 patients scheduled for daytime hysteroscopy. And we divided these patients into two groups: Group A: Received a single injection of 10 µg/kg of alfentanil. Group S: Received a single injection of 0.15 µg/kg of sufentanil. Both groups were also given propofol, a sedative, during the procedure. What did the researchers find? Group A (alfentanil): Fewer patients experienced low oxygen levels (hypoxemia) and postoperative nausea and vomiting. They also had more stable blood pressure and heart rate. Group S (sufentanil): More patients experienced hypoxemia and postoperative nausea and vomiting. What do the findings mean? The findings suggest that alfentanil at 10 µg/kg is safer and just as effective for pain relief during daytime hysteroscopy compared to sufentanil at 0.15 µg/kg. It leads to fewer breathing problems and other side effects, making it a better option for patients undergoing this procedure.

Effect of prophylactic noninvasive oxygen therapy after planned extubation on extubation failure in high-risk patients: a retrospective propensity score-matched cohort study.

Background: Extubation failure (EF) is common in the intensive care unit (ICU) and is associated with poor prognosis, especially in high-risk patients. However, the efficacy of prophylactic noninvasive oxygen therapy (NIT), including noninvasive ventilation (NIV) and high-flow nasal cannula (HFNC), in reducing EF in high-risk patients remains controversial. Therefore, we aimed to evaluate the effect of post-extubation prophylactic NIT on EF in high-risk patients. Methods: This was a retrospective observational study conducted in the ICU from March 2018 to December 2023. We included adult patients at high risk for reintubation who were mechanically ventilated for over 24 h and successfully passed the spontaneous breathing trial (SBT). Immediately after extubation, patients underwent NIT or conventional oxygenation therapy (COT). The primary outcome was the EF rate within 7 days after extubation. Results: There were 440 patients in the NIT group and 274 in the COT group. After propensity-score matching, 227 subjects were enrolled in each group. NIT reduced the rate of EF (18.0% vs. 34.3%, p < 0.001) and reintubation (10.5% vs. 18.2% p = 0.003) compared with COT, which was confirmed in propensity-matched cohort (17.6% vs. 32.2%, p < 0.001; 11.5% vs. 19.8%, p = 0.014). Multivariate logistic regression analysis indicated that prophylactic NIT (p = 0.001) and higher ROX index (p = 0.022) were associated with reduced risk of EF. While higher fluid balance (p = 0.013), higher RSBI (p < 0.001), and the occurrence of delirium (p = 0.032) may be the risk factors for EF. Subgroup analysis showed that post-extubation NIT was more effective in elderly patients, and HFNC was non-inferior to NIV in reducing EF. While HFNC had a tendency to reduce the incidence of delirium. Conclusion: Post-extubation prophylactic NIT is effective in reducing EF in high-risk patients, especially in the elderly patients. HFNC is an alternative treatment to NIV. Fluid balance, RSBI, ROX index, and delirium are associated with the occurrence of EF.

CHRM3 (rs2165870) gene polymorphism is related to postoperative vomiting in female patients undergoing laparoscopic surgery. Prospective observational study.

BACKGROUND: Postoperative nausea and vomiting are common complications after surgery, and female patients are more likely to experience these adverse events. The goal of this study was to explore the relationship between the CHRM3 rs2165870 polymorphism and postoperative vomiting incidence in female patients who underwent laparoscopic surgery. METHODS: Two hundred female patients who underwent elective laparoscopic surgery with subsequent patient-controlled intravenous analgesia using dexmedetomidine and sufentanil were prospectively enrolled. The CHRM3 rs2165870 and KCNB2 rs349358 polymorphisms were genotyped using MassARRAY SNP typing technology. Demographic data and preoperative laboratory results of all patients were recorded. Postoperative analgesia-related information, incidence of postoperative nausea and vomiting, and other adverse events were followed up and recorded for analysis. RESULTS: No significant differences were observed in any of the demographic characteristics of these patients among the different genotype carriers (P>0.05). The percentages of patients with each genotype of CHRM3 were 67% (GG), 28.5% (GA) and 4.5% (AA). We found that the AA or A allele of the CHRM3 rs2165870 polymorphism elevated the risk of postoperative vomiting (AA versus GG; OR, 6.94; 95% CI, 1.49-32.46; P = 0.014; A versus G; OR, 2.52; 95% CI, 1.22-5.19; P = 0.012). The percentages of patients with each genotype of KCNB2 were 84.5% (TT), 15.5% (CT) and 0% (CC). There were no significant differences in the postoperative nausea or vomiting rate across the KCNB2 rs349358 polymorphisms (P>0.05). CONCLUSION: The CHRM3 rs2165870 polymorphism is associated with the occurrence of postoperative vomiting in female patients who have undergone laparoscopic surgery. The AA genotype or A allele of the CHRM3 rs2165870 polymorphism elevates the risk of postoperative vomiting. TRIAL REGISTRATION: www.chictr.org.cn, registration number: ChiCTR2200062425.

Favorable efficacy of S-1 treatment for locoregionally advanced cutaneous squamous cell carcinoma in the head and neck region.

Cutaneous squamous cell carcinoma is usually treated with surgery; however, locoregionally advanced cutaneous squamous cell carcinoma can be difficult to resect. Although recent guidelines from Western countries recommend using anti-programmed cell death protein 1 (PD-1) antibodies, including cemiplimab and pembrolizumab, there are no approved anti-PD-1 antibodies for locoregional cutaneous squamous cell carcinoma in Asian countries. S-1 is an oral drug with a low incidence of severe toxicity that can be used for head and neck cancers, including head and neck locoregional cutaneous squamous cell carcinoma, in Japan. We retrospectively evaluated patients with head and neck locoregional cutaneous squamous cell carcinoma treated with S-1 at two Japanese institutions (2008-2022). The initial dosage was determined by the body surface area (<1.25 m2 : 80 mg/day, 1.25-1.5 m2 : 100 mg/day, ≥1.5 m2: 120 mg/day) for 28 consecutive days. The outcome measures were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Fourteen patients were included. The ORR was 78%, and the complete response (CR) rate was 64.3%. The median PFS and OS were not reached (NR) (95% confidence interval [CI], 5.9 months-NR) and NR (95% CI, 13.8 months-NR), respectively. The 12-month PFS and OS rates were 51% and 85%, respectively. Six of the nine patients who achieved CR showed no recurrence during the follow-up period (median follow-up, 24.7 months). After CR, three patients experienced recurrence. Among these, two resumed S-1 treatment and subsequently underwent salvage surgery, resulting in a sustained absence of recurrence. One patient developed lung metastasis and died, although S-1 therapy was resumed. Only one patient (7.1%) developed grade 3 anemia. S-1 showed favorable efficacy and low toxicity in patients with head and neck locoregionally advanced cutaneous squamous cell carcinoma. S-1 may be a good alternative to the anti-PD-1 antibody for treating head and neck locoregionally advanced squamous cell carcinoma.

Hic-5 antisense oligonucleotide inhibits advanced hepatic fibrosis and steatosis in vivo.

Background & Aims: Chronic liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH), pose a significant global health burden. Progressive liver fibrosis can lead to severe outcomes; however, there is a lack of effective therapies targeting advanced fibrosis. Hydrogen peroxide-inducible clone-5 (Hic-5), an adaptor protein in focal adhesion, is critical for promoting liver fibrosis in hepatic stellate cells. This study investigated its clinical applicability by examining hepatic Hic-5 expression in human fibrotic tissues, exploring its association with MASH, and assessing the therapeutic potential of antisense oligonucleotides (ASOs) targeting Hic-5 in a MASH mouse model. Methods: Hepatic Hic-5 expression in human fibrotic tissues underwent pathological image analysis and single-cell RNA sequencing. ASOs targeting Hic-5 were developed and tested using in vitro cell models. An in vivo MASH mouse model was used to evaluate the effects of anti-Hic-5 ASOs on advanced fibrosis and steatosis. Results: Hepatic Hic-5 expression increased with the progression of fibrosis, particularly in advanced stages. Single-cell RNA sequencing revealed Hic-5 expression primarily in hepatic stellate cells. In MASH-associated fibrosis, Hic-5 expression correlated with the expression of fibrotic genes. In the MASH mouse model, hepatic Hic-5 expression increased with disease progression. Anti-Hic-5 ASOs effectively suppressed Hic-5 expression in vitro and attenuated advanced fibrosis and steatosis in vivo, indicating their therapeutic potential. Conclusions: Hepatic Hic-5 expression is associated with advanced liver fibrosis and MASH. Anti-Hic-5 ASOs are promising therapeutic interventions for MASH accompanied by advanced fibrosis. These findings provide valuable insights into potential clinical treatments for advanced liver fibrosis. Impact and implications: This study investigated the role of Hic-5 in liver fibrosis and steatohepatitis, highlighting its potential as a therapeutic target. We developed an antisense oligonucleotide (ASO) that was particularly transportable to the liver, and targeted Hic-5. Anti-Hic-5 ASO exhibited therapeutic efficacy for liver fibrosis and steatosis in vivo, indicating its therapeutic potential for liver fibrosis and steatosis. ASOs have already achieved dramatic therapeutic effects as approved nucleic acid drugs. Thus, anti-Hic-5 ASO is expected to lead the direct generation of seed compounds for the clinical development of drugs for liver fibrosis and steatosis.

Comparative Analysis of Vision Transformers and Conventional Convolutional Neural Networks in Detecting Referable Diabetic Retinopathy.

Objective: Vision transformers (ViTs) have shown promising performance in various classification tasks previously dominated by convolutional neural networks (CNNs). However, the performance of ViTs in referable diabetic retinopathy (DR) detection is relatively underexplored. In this study, using retinal photographs, we evaluated the comparative performances of ViTs and CNNs on detection of referable DR. Design: Retrospective study. Participants: A total of 48 269 retinal images from the open-source Kaggle DR detection dataset, the Messidor-1 dataset and the Singapore Epidemiology of Eye Diseases (SEED) study were included. Methods: Using 41 614 retinal photographs from the Kaggle dataset, we developed 5 CNN (Visual Geometry Group 19, ResNet50, InceptionV3, DenseNet201, and EfficientNetV2S) and 4 ViTs models (VAN_small, CrossViT_small, ViT_small, and Hierarchical Vision transformer using Shifted Windows [SWIN]_tiny) for the detection of referable DR. We defined the presence of referable DR as eyes with moderate or worse DR. The comparative performance of all 9 models was evaluated in the Kaggle internal test dataset (with 1045 study eyes), and in 2 external test sets, the SEED study (5455 study eyes) and the Messidor-1 (1200 study eyes). Main Outcome Measures: Area under operating characteristics curve (AUC), specificity, and sensitivity. Results: Among all models, the SWIN transformer displayed the highest AUC of 95.7% on the internal test set, significantly outperforming the CNN models (all P < 0.001). The same observation was confirmed in the external test sets, with the SWIN transformer achieving AUC of 97.3% in SEED and 96.3% in Messidor-1. When specificity level was fixed at 80% for the internal test, the SWIN transformer achieved the highest sensitivity of 94.4%, significantly better than all the CNN models (sensitivity levels ranging between 76.3% and 83.8%; all P < 0.001). This trend was also consistently observed in both external test sets. Conclusions: Our findings demonstrate that ViTs provide superior performance over CNNs in detecting referable DR from retinal photographs. These results point to the potential of utilizing ViT models to improve and optimize retinal photo-based deep learning for referable DR detection. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.