Long-Term Prognostic Value of Infarct Transmurality Determined by Contrast-Enhanced Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction.

The long-term prognostic significance of maximal infarct transmurality evaluated by contrast-enhanced cardiac magnetic resonance (CE-CMR) in ST-segment elevation myocardial infarction (STEMI) patients has yet to be determined. This study aimed to see if maximal infarct transmurality has any additional long-term prognostic value over other CE-CMR predictors in STEMI patients, such as microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). The study included 112 consecutive patients who underwent CE-CMR after STEMI to assess established parameters of myocardial injury as well as the maximal infarct transmurality. The primary clinical endpoint was the occurrence of major adverse cardiac events (MACE), which included all-cause death, non-fatal reinfarction, and new heart failure hospitalization. The MACE occurred in 10 patients over a median follow-up of 7.9 years (IQR, 5.8 to 9.2 years) (2 deaths, 3 nonfatal MI, and 5 heart failure hospitalization). Patients with MACE had significantly higher rates of transmural extent of infarction, infarct size >5.4 percent, MVO, and IMH compared to patients without MACE. In stepwise multivariable Cox regression analysis, the transmural extent of infarction defined as 75 percent or more of infarct transmurality was an independent predictor of the MACE after correction for MVO and IMH (hazard ratio 8.7, 95% confidence intervals [CIs] 1.1-71; p=0.043). In revascularized STEMI patients, post-infarction CE-CMR-based maximal infarct transmurality is an independent long-term prognosticator. Adding maximal infarct transmurality to CE-CMR parameters like MVO and IMH could thus identify patients at high risk of long-term adverse outcomes in STEMI.

Incidence and Characteristics of Cerebral Infarction After Microsurgical Clipping of Unruptured Anterior Circulation Cerebral Aneurysms: Diffusion-Weighted Imaging-Based Analysis of 600 Patients.

BACKGROUND AND OBJECTIVES: Postclipping cerebral infarction (PCI) remains a major concern after treatment for unruptured intracranial aneurysms (UIAs). However, studies of microsurgical clipping based on diffusion-weighted imaging are limited. We aimed to present the incidence, risk factors, and types of PCI and its radiological and clinical characteristics. METHODS: This was a retrospective single-center study in which patients were scheduled to undergo microsurgical clipping for anterior circulation UIAs. The overall incidence and risk factors were calculated. Based on the operation and relevant artery, we categorized PCI on diffusion-weighted imaging into 4 types and presented their radiological and clinical characteristics. RESULTS: We reviewed the radiological and clinical data of 605 patients. The overall incidence of PCI was 16.7% (101/605), of which asymptomatic infarction was 14.9% (90/605) and symptomatic infarction was 1.8% (11/605). Hypertension (adjusted odds ratio [aOR], 2.258; 95% confidence interval [CI]: 1.330-3.833), temporary clipping (aOR, 1.690; 95% CI: 1.034-2.760), multiple aneurysm locations (aOR, 1.832; 95% CI: 1.084-3.095), and aneurysm dome size (aOR, 1.094; 95% CI: 1.006-1.190) were independent risk factors for PCI. Type II (perianeurysmal perforator) infarction was the most common type of PCI (48.6%) and the most common cause of symptomatic infarction (72.7%). Types II and III (distal embolic) infarctions correlated with atherosclerotic changes in the aneurysm wall and temporary clipping (62.4% and 70.6%, respectively). The type IV (unrelated) infarction group had a higher incidence of systemic atherosclerosis (55%). CONCLUSION: Microsurgical clipping is a safe and viable option for the treatment of anterior circulation UIAs. However, modification of the surgical technique, preoperative radiological assessment, and patient selection are required to reduce the incidence of PCI.

Pharmacologic management of trigeminal nerve injury after endodontic treatment: A retrospective analysis.

BACKGROUND: Trigeminal nerve injury following endodontic treatment, leading to unpleasant sensations or partial sensory loss in the face or oral mucosa, is uncommon but significant when it occurs. OBJECTIVE: This study analysed the pharmacological management of trigeminal nerve injuries (TNI) in a university-based hospital. METHODS: We conducted a retrospective analysis of 47 patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital, Seoul, Korea, after TNI following endodontic procedures in primary clinics. Both objective tests and subjective evaluations, assessed the extent and duration of sensory injury during the initial visit. The patient's initial symptoms, presumed cause of TNI, referral delay (time interval between TNI and the first visit to our clinic), and medications were analysed to determine whether these factors affected the outcomes. RESULTS: Most patients with TNI experienced dysesthesia with hypoesthesia (70.2%). The mandibular molars were predominantly affected (72.3%), with the inferior alveolar nerve (IAN), lingual nerve (LN), both IAN and LN, and maxillary nerve compromised in 83.0, 12.8, 2.1, and 2.1% of cases, respectively. Causes of TNI included local anaesthesia (29.8%), overfilling/over-instrumentation (25.5%), endodontic surgery (17.0%), and unknown factors (27.7%). A shorter referral delay was associated with better outcomes, with an average delay of 8.6 weeks for symptom improvement compared with 44.1 weeks for no change. The medication regimens included steroids, NSAIDs, topical lidocaine, vitamin B complex, Adenosine Triphosphate (ATP), antiepileptics, antidepressants, and opioids administered alone or in combination, with a mean duration of 20.7 weeks. 53.2% of the patients reported improvement in their symptoms, 27.7% experienced no significant change, and 19.1% had unknown outcomes. CONCLUSIONS: Swift referral to an orofacial pain specialist is recommended for effective recovery in cases of TNI arising from endodontic treatment.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Effectiveness and Safety of Carbon Ion Radiotherapy in Solid Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to investigate the effectiveness of carbon ion radiotherapy (CIRT) compared to that of conventional radiotherapy in patients with various types of solid tumors. MATERIALS AND METHODS: We systematically searched eight electronic databases from inception until August 2022 in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The comparative effectiveness of the different treatment options was assessed by a random-effects meta-analysis. RESULTS: This review included 34 comparative studies and three treatment groups. Overall, the meta-analysis indicated comparable local control rates between the CIRT and control groups [pooled risk ratio (RR)=1.02, 95% confidence interval (CI) 0.90-1.15]. The local control rate in the CIRT group was higher than that in the photon therapy group, but slightly lower than that in the proton radiation therpy (PRT) group. Additionally, the CIRT group had significantly higher overall survival (OS) (RR=1.19, 95% CI=1.01-1.42) and progression-free survival (PFS) (RR=1.50, 95% CI=1.01-2.21) rates compared to the control group. In the subgroup analysis, survival rates were similar between the CIRT and PRT groups. CONCLUSION: CIRT was associated with improved toxicity, local tumor control, OS, and PFS compared to conventional treatments. Therefore, CIRT was found to be a safe and effective option for achieving local control in patients with solid tumors.

Dietary effects of protected fat, glycerol, and soybean meal on performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions.

OBJECTIVE: This study aimed to determine the effects of increasing energy and protein levels in diets by including protected fat (PF), glycerol (GL), and soybean meal (SBM) on growth performance, physiological parameters, carcass characteristics, and behavioral measurements of late-fattening Hanwoo steers under heat stress conditions. METHODS: Thirty-six steers (initial body weight, 724.9±58.3 kg; age, 25.5±0.4 month) were assigned into control (total digestible nutrient [TDN] 76%, crude protein [CP] 15%), PF (TDN 83.6%, CP 15%), PF+GL (TDN 83.6%, CP 15%) and PF+GL+SBM (TDN 83.6%, CP 16.5%) by randomized complete block design for a total of 16 weeks with division of 4-week periods. The average temperature-humidity index was 87.0 (1st period; severe), 82.8 (2nd; moderate), 71.4 (3rd; comfort), and 68.1 (4th; comfort). RESULTS: The dry matter intake (DMI) showed no treatments differences during the whole experiment. However, DMI in 1st and 2nd period decreased by approximately 30% and 10% compared to 4th period, respectively. Higher average daily gain and feed conversion ratio were noted for treatments compared to control at both 1st and 2nd period (p<0.05). There were no treatment effects on rectal temperature (RT), cortisol, and behaviors during the entire experiment. However, both RT and cortisol in 0, 1st and 2nd period were higher than those of 3rd and 4th period (p<0.05). Carcass yield and grade remained unaffected by increasing TDN and CP levels. Behavioral changes in the hot season (1st period) included reduced lying (43%), increased standing (48%), decreased walking (62%), and decreased eating (38%) (p<0.05), with an increase in drinking by 54%. Rumination during standing was 53% higher, while rumination during lying was about 33% lower compared to the post-hot season (3rd period) (p<0.05). CONCLUSION: Dietary supplementation of protected fat in late-fattening Hanwoo steers under heat stress had a positive effect on preventing a reduction in performance.

Glutamine-derived aspartate is required for eIF5A hypusination-mediated translation of HIF-1α to induce the polarization of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are vital contributors to the growth, metastasis, and therapeutic resistance of various cancers, including hepatocellular carcinoma (HCC). However, the exact phenotype of TAMs and the mechanisms underlying their modulation for therapeutic purposes have not been determined. Here, we present compelling evidence that glutamine-derived aspartate in TAMs stimulates spermidine production through the polyamine synthesis pathway, thereby increasing the translation efficiency of HIF-1α via eIF5A hypusination. Consequently, augmented translation of HIF-1α drives TAMs to undergo an increase glycolysis and acquire a metabolic phenotype distinct from that of M2 macrophages. Finally, eIF5A levels in tumor stromal lesions were greater than those in nontumor stromal lesions. Additionally, a higher degree of tumor stromal eIF5A hypusination was significantly associated with a more advanced tumor stage. Taken together, these data highlight the potential of inhibiting hypusinated eIF5A by targeting glutamine metabolism in TAMs, thereby opening a promising avenue for the development of novel therapeutic approaches for HCC.

The effect of Schizophyllan on the differentiation of osteoclasts and osteoblasts.

Schizophyllan (SPG), a ß-glucan from Schizophyllum commune, is recognized for its antioxidant, immunoregulatory, and anticancer activities. In this study, its effects on bone cells, particularly osteoclasts and osteoblasts, were examined. We demonstrated that SPG dose-dependently inhibited osteoclastogenesis and reduced gene expression associated with osteoclast differentiation. SPG also decreased bone resorption and F-actin ring formation. This inhibition could have been due to the downregulation of transcription factors c-Fos and nuclear factor of activated T cells 1 (NFATc1) via the MAPKs (JNK and p38), IκBα, and PGC1ß/PPARγ pathways. In coculture, SPG lowered osteoclastogenic activity in calvaria-derived osteoblasts by reducing macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) expression. In addition, SPG slightly enhanced osteoblast differentiation, as evidenced by increased differentiation marker gene expression and alizarin red staining. It also exhibited antiresorptive effects in a lipopolysaccharide-induced calvarial bone loss model. These results indicated a dual role of SPG in bone cell regulation by suppressing osteoclastogenesis and promoting osteoblast differentiation. Thus, SPG could be a therapeutic agent for bone resorption-related diseases such as osteoporosis, rheumatoid arthritis, and periodontitis.

Acesulfame potassium upregulates PD-L1 in HCC cells by attenuating autophagic degradation.

Artificial sweeteners, which contain no or few calories, have been widely used in various foods and beverages, and are regarded as safe alternatives to sugar by the Food and Drug Administration. While several studies suggest that artificial sweeteners are not related to cancer development, some research has reported their potential association with the risk of cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether acesulfame potassium (Ace K), a commonly used artificial sweetener, induces immune evasion of HCC cells by upregulating programmed death ligand-1 (PD-L1). Ace K elevated the protein levels of PD-L1 in HCC cells without increasing its mRNA levels. The upregulation of PD-L1 protein levels in HCC cells by Ace K was induced by attenuated autophagic degradation of PD-L1, which was mediated by the Ace K-stimulated ERK1/2-mTORC1 signaling pathway. Ace K-induced upregulation of PD-L1 attenuated T cell-mediated death of HCC cells, thereby promoting immune evasion of HCC cells. In summary, the present study suggests that Ace K promotes HCC progression by upregulating the PD-L1 protein level.

Impact of the COVID-19 pandemic on mortality and loss to follow-up among patients with dementia receiving anti-dementia medications.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted vulnerable groups, such as patients with dementia. We examined changes in mortality and loss to follow-up in patients with dementia using data from the Korean National Health Insurance Service research database. Patients with dementia who visited a medical institution with a recorded dementia-related diagnostic code, including Alzheimer's disease, and who received anti-dementia medication between February 2018 and January 2020 were included in this study. We divided patients with dementia receiving anti-dementia medications into two cohorts: those newly diagnosed with dementia between February 2018 and January 2019 (n = 62,631) and those diagnosed between February 2019 and January 2020 (n = 54,494). Then, we conducted a one-year follow-up of their records, tracking the cohort diagnosed between February 2018 and January 2019 from February 2019 to January 2020, as well as the cohort diagnosed between February 2019 and January 2020 from February 2020 to January 2021. There was a significant increase in follow-up loss among patients newly diagnosed with dementia during the COVID-19 outbreak, from 42.04% in 2019 to 45.89% in 2020. Female sex, younger age, fewer comorbidities, diagnosis of dementia at the Department of Neurology or Psychiatry, and higher income were associated with decreased follow-up loss and mortality. This study highlights the importance of paying extra attention to patients with dementia receiving anti-dementia medications, particularly during pandemics, given their increased risk of loss to follow-up.

Gene expression regulation by modulating Hfq expression in coordination with tailor-made sRNA-based knockdown in Escherichia coli.

The tailor-made synthetic sRNA-based gene expression knockdown system has demonstrated its efficacy in achieving pathway balancing in microbes, facilitating precise target gene repression and fine-tuned control of gene expression. This system operates under a competitive mode of gene regulation, wherein the tailor-made synthetic sRNA shares the intrinsic intracellular Hfq protein with other RNAs. The limited intracellular Hfq amount has the potential to become a constraining factor in the post-transcription regulation of sRNAs. To enhance the efficiency of the tailor-made sRNA gene expression regulation platform, we introduced an Hfq expression level modulation-coordinated sRNA-based gene knockdown system. This system comprises tailor-made sRNA expression cassettes that produce varying Hfq expression levels using different strength promoters. Modulating the expression levels of Hfq significantly improved the repressing capacity of sRNA, as evidenced by evaluations with four fluorescence proteins. In order to validate the practical application of this system, we applied the Hfq-modulated sRNA-based gene knockdown cassette to Escherichia coli strains producing 5-aminolevulinic acid and L-tyrosine. Diversifying the expression levels of metabolic enzymes through this cassette resulted in substantial increases of 74.6% in 5-aminolevulinic acid and 144% in L-tyrosine production. Tailor-made synthetic sRNA-based gene expression knockdown system, coupled with Hfq copy modulation, exhibits potential for optimizing metabolic fluxes through biosynthetic pathways, thereby enhancing the production yields of bioproducts.

Psychotic Symptoms in Patients With Major Neurological Diseases.

Neurological diseases often manifest with neuropsychiatric symptoms such as depression, emotional incontinence, anger, apathy and fatigue. In addition, affected patients may also experience psychotic symptoms such as hallucinations and delusions. Various factors contribute to the development of psychotic symptoms, and the mechanisms of psychosis are similar, but still differ among various neurological diseases. Although psychotic symptoms are uncommon, and have been less well investigated, they may annoy patients and their families as well as impair the patients' quality of life and increase the caregiver burden. Therefore, we need to appropriately identify and treat these psychotic symptoms in patients with neurological diseases.

Seven-year follow-up of endovascular treatment of iatrogenic brachioradial artery injury complicating percutaneous coronary intervention: a case report.

The radial artery has been used increasingly for percutaneous coronary intervention because of its safety and feasible access route. Nevertheless, transradial complications are possible because of the variation in radial artery anatomy. We experienced a case of the brachioradial artery injury secondary to catheterization, presenting as hypovolemic shock. A 76-year-old woman presented at our emergency department complaining of effort-induced angina. Coronary angiography via the right radial artery showed critical stenosis in the middle of the left anterior descending coronary artery. After wiring into this vessel, balloon angioplasty using a 6-Fr Judkin left guiding catheter was performed with the deployment of the zotarolimus-eluting stent. There was difficulty in negotiating the guidewire and balloons in that resistance was experienced while passing the catheter in the upper arm. Therefore, retrograde radial arteriography was performed to determine any injury to radial artery. This showed contrast extravasation in the brachioradial artery. Initially, manual compression was tried. However, 2 hours later, the patient developed cold sweating and went into a stupor. Laboratory findings showed a decline in hemoglobin, leading to suspicion of hemorrhagic shock. We applied over 30 minutes of balloon inflation, but this was ineffective. While surgical repair was not available, a 6.0 × 50 mm Viabahn stent was placed over the axillary artery. Subsequent angiography showed no further leakage or occlusion of the brachioradial artery. The postprocedural period was uneventful, and the patient was discharged with dual antiplatelet agents. At a 7-year clinical follow-up, the patient was free from limb ischemia symptoms.

Light emitting diode (LED) irradiation of liposomes enhances drug encapsulation and delivery for improved cancer eradication.

Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.

16S rRNA Next-Generation Sequencing May Not Be Useful for Examining Suspected Cases of Spontaneous Bacterial Peritonitis.

Background and Objectives: Ascites, often associated with liver cirrhosis, poses diagnostic challenges, particularly in detecting bacterial infections. Traditional methods have limitations, prompting the exploration of advanced techniques such as 16S rDNA next-generation sequencing (NGS) for improved diagnostics in such low-biomass fluids. The aim of this study was to investigate whether the NGS method enhances detection sensitivity compared to a conventional ascites culture. Additionally, we aimed to explore the presence of a microbiome in the abdominal cavity and determine whether it has a sterile condition. Materials and Methods: Ten patients with clinically suspected spontaneous bacterial peritonitis (SBP) were included in this study. A traditional ascites culture was performed, and all ascites samples were subjected to 16S ribosomal RNA gene amplification and sequencing. 16S rRNA gene sequencing results were interpreted by comparing them to positive and negative controls for each sample. Results: Differential centrifugation was applied to all ascites samples, resulting in very small or no bacterial pellets being harvested. The examination of the 16S amplicon sequencing libraries indicated that the target amplicon products were either minimally visible or exhibited lower intensity than their corresponding negative controls. Contaminants present in the reagents were also identified in the ascites samples. Sequence analysis of the 16S rRNA gene of all samples showed microbial compositions that were akin to those found in the negative controls, without any bacteria isolated that were unique to the samples. Conclusions: The peritoneal cavity and ascites exhibit low bacterial biomass even in the presence of SBP, resulting in a very low positivity rate in 16S rRNA gene sequencing. Hence, the 16S RNA sequencing method does little to enhance the rate of positive samples compared to traditional culture methods, including in SBP cases.

Nano-chemical priming strategy to enhance TGF-ß resistance and anti-tumor activity of natural killer cells.

Immunotherapy based on adoptive transfer of natural killer (NK) cells is a promising strategy for circumventing the limitations of cancer treatments. However, components of the immunosuppressive tumor microenvironment (TME), such as transforming growth factor-beta (TGF-ß), compromise the therapeutic efficacy of NK cells significantly. To address these limitations, we developed a novel method of engineering NK cells for adaptive transfer. The method is based on nanogels that serve two functions: (1) they overcome the TGF-ß-mediated stress environment of the TME, and (2) they enhance the direct anti-tumor activity of NK cells. Previously, we demonstrated that cationic compounds such as 25 K branched polyethylenimine (25 K bPEI) prime NK cells, putting them in a 'ready-to-fight' state. Based on these findings, we designed nanogels that have two primary characteristics: (1) they encapsulate galunisertib (Gal), which is used clinically to inhibit TGF-ß receptor activity, thereby blocking TGF-ß signaling; and (2) they provide cells with a surface coating of 25 K bPEI. When grown in culture medium containing TGF-ß, nanogel-treated NK cells demonstrated greater migration ability, degranulation activity, and cytotoxicity towards cancer cells than untreated NK cells. Additionally, the in vivo efficacy of nanogel-treated NK cells against PC-3 xenografts was significantly greater than that of Chem_NK cells primed by 25 K bPEI alone. These findings suggest that Gal-loaded 25 K bPEI-coated nanogels exert anti-tumor effects via chemical priming, as well suppressing the effects of TGF-ß on NK cells. We also expect 25 K bPEI-based nanogels to have great potential to overcome the suppressive effects of the TME through their NK cell-priming activity and delivery of the desired chemicals.

Case Report of Efficacy of Skin Perfusion After Hyperbaric Oxygen Therapy Following Peripheral Tissue Injury due to Usage of Inotropes and Vasopressors.

Hyperbaric Oxygen Therapy (HBOT) has garnered significant attention as a therapeutic principle with potential benefits across a variety spectrum of medical conditions, ranging from wound healing and ischemic conditions to neurologic disorders and radiation-induced tissue damage. HBOT involves the administration of 100% oxygen at higher atmospheric pressures, leading to increased oxygen dissolved in bodily fluids and tissues. The elevated oxygen levels are proposed to facilitate tissue repair, reduce inflammation, and promote angiogenesis. This case report presents a compelling instance of the usefulness of HBOT in promoting skin perfusion and healing following peripheral tissue injury resulting from the administration of inotropic and vasopressor agents in septic shock patients.

Clinical Outcome after Everolimus-Eluting Stent Implantation for Small Vessel Coronary Artery Disease: XIENCE Asia Small Vessel Study.

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270). Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.