Cardiometabolic benefits of fenofibrate in heart failure related to obesity and diabetes.

BACKGROUND: Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy. METHODS AND RESULTS: We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate's beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824-0.998). CONCLUSIONS: The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.

Integrative single-cell transcriptome analysis provides new insights into post-COVID-19 pulmonary fibrosis and potential therapeutic targets.

The global COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 virus has resulted in a significant number of patients experiencing persistent symptoms, including post-COVID pulmonary fibrosis (PCPF). This study aimed to identify novel therapeutic targets for PCPF using single-cell RNA-sequencing data from lung tissues of COVID-19 patients, idiopathic pulmonary fibrosis (IPF) patients, and a rat transforming growth factor beta-1-induced fibrosis model treated with antifibrotic drugs. Patients with COVID-19 had lower alveolar macrophage counts than healthy controls, whereas patients with COVID-19 and IPF presented with elevated monocyte-derived macrophage counts. A comparative transcriptome analysis showed that macrophages play a crucial role in IPF and COVID-19 development and progression, and fibrosis- and inflammation-associated genes were upregulated in both conditions. Functional enrichment analysis revealed the upregulation of inflammation and proteolysis and the downregulation of ribosome biogenesis. Cholesterol efflux and glycolysis were augmented in both macrophage types. The study suggests that antifibrotic drugs may reverse critical lung fibrosis mediators in COVID-19. The results help clarify the molecular mechanisms underlying pulmonary fibrosis in patients with severe COVID-19 and IPF and highlight the potential efficacy of antifibrotic drugs in COVID-19 therapy. Collectively, all these findings may have significant implications for the development of new treatment strategies for PCPF.

A single-center prospective study regarding time to return to activities of daily living after craniotomy for brain tumors.

BACKGROUND: There are few studies on the time to return to activities of daily living (ADL) after craniotomy in patients with brain tumors. This study aimed to investigate the duration before returning to ADLs after craniotomy for brain tumors and present data that can provide information and guidelines on the appropriate time needed. METHODS: Patients (n = 183 of 234) who underwent craniotomy for brain tumors between April 2021 and July 2021 capable of self-care upon discharge were enrolled, and data of 158 were collected. The start time of 85 ADL items was prospectively investigated for 4 months postoperatively, using the self-recording sheet. RESULTS: Over 89% and 87% of the patients performed basic ADL items within a month and instrumental ADL items within 2 months (medians: within 18 days), except for a few. Regarding work, 50% of the patients returned within 4 months. Washing hair with a wound was performed at 18 days of median value, after 4 months of dyeing/perming hair, 6 days of drinking coffee/tea, after 4 months of air travel, and 40 days of complementary and alternative medicine. In patients with infratentorial tumors or surgical problems, return times were much later for various items. CONCLUSIONS: It is possible to provide practical information and guidelines on the duration to return to ADL after craniotomy in brain tumor patients. These study findings also reduce uncertainty about recovery and daily life and help patients return to their daily life at the appropriate time, thereby maintaining function and daily well-being after surgery.

Peripheral Artery Bypass Graft for the Treatment of Ischemic Ulcer or Severe Pain of Hand in Connective Tissue Diseases.

ABSTRACT: Chronic ischemia of the hands and feet is a rare medical condition that requires surgical revascularization. In particular, digital ischemia resulting from connective tissue diseases (CTDs) is among the most important manifestations that negatively affect patients' quality of life. Here, we describe a bypass graft technique for treating digital ischemia. This study aimed to share the considerable benefits of surgical intervention for CTD and present a treatment algorithm. From 2009 to 2020, bypass graft surgery was performed on 10 patients with CTD to relieve their ischemic symptoms or ulceration. Preoperative angiography was performed, and blood distribution patterns were analyzed in detail. Based on the angiographic 4-level analysis, bypass graft surgeries were performed accordingly. The postoperative follow-up was 15 to 72 months. Pain in the hands that underwent the bypass graft surgery improved immediately after surgery. All ulcerations healed and the mean time recorded for ulceration healing was 45.7 days. Here, we propose an appropriate surgical treatment algorithm for managing CTD using arterial bypass graft surgery, and its positive long-term results demonstrate that it is an appropriate option for treating digital ischemia. In conclusion, strict measures with precise preoperative planning can provide satisfactory long-term results in patients with CTD.

The Effect of Epiphysiodesis on the Longitudinal Bone Growth of Hands or Feet in Children With Macrodactyly Based on Long-term Quantitative Analysis.

BACKGROUND: Treatment protocols for macrodactyly have not been elucidated due to its rarity and variety of clinical manifestations. This study aims to share our long-term clinical results of epiphysiodesis in children with macrodactyly. METHODS: A retrospective chart review was performed for 17 patients with isolated macrodactyly treated with epiphysiodesis over 20 years. Length and width of each phalanx in both the affected finger and the corresponding unaffected finger in the contralateral hand were measured. Results were presented in ratios of the affected to unaffected side for each phalanx. Measuring of length and width of phalanx was performed preoperatively and postoperatively at 6, 12, and 24 months, and the last follow-up session. Postoperative satisfaction scoring was done with visual analogue scale. RESULTS: The mean follow-up period was 7 years and 2 months. In the proximal phalanx, length ratio significantly decreased compared with preoperative state at after more than 24 months, in the middle phalanx after 6 months, in the distal phalanx after 12 months. When classified by the growth patterns, the progressive type showed significant decrease in length ratio at after 6 months, and the static type after 12 months. Patients were overall satisfied with the results. CONCLUSION: Epiphysiodesis effectively regulated longitudinal growth with different degree of control for different phalanges in the long-term follow-up.

Effectiveness and Safety of Fufang Danshen Dripping Pill (Cardiotonic Pill) on Blood Viscosity and Hemorheological Factors for Cardiovascular Event Prevention in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.

Background and Objectives: Diabetes can cause various vascular complications. The Compounded Danshen-Dripping-Pill (CDDP) is widely used in China. This study aimed to analyze the effectiveness and safety of CDDP in the blood viscosity (BV) with type 2 diabetes mellitus (T2DM). Materials and Methods: We conducted a systematic search of seven databases from their inception to July 2022 for randomized controlled trials that used CDDP to treat T2DM. To evaluate BV, we measured low shear rate (LSR), high shear rate (HSR), and plasma viscosity (PV). Homocysteine and adiponectin levels were also assessed as factors that could affect BV. Results: We included 18 studies and 1532 patients with T2DM. Meta-analysis revealed that CDDP significantly reduced LSR (mean difference [MD] -2.74, 95% confidence interval [CI] -3.77 to -1.72), HSR (MD -0.86, 95% CI -1.08 to -0.63), and PV (MD -0.37, 95% CI -0.54 to -0.19) compared to controls. CDDP also reduced homocysteine (MD -8.32, 95% CI -9.05 to -7.58), and increased plasma adiponectin (MD 2.72, 95% CI 2.13 to 3.32). Adverse events were reported less frequently in the treatment groups than in controls. Conclusions: CDDP is effective in reducing BV on T2DM. However, due to the poor design and quality of the included studies, high-quality, well-designed studies are required in the future.

Coronary CTA With AI-QCT Interpretation: Comparison With Myocardial Perfusion Imaging for Detection of Obstructive Stenosis Using Invasive Angiography as Reference Standard.

BACKGROUND. Deep learning frameworks have been applied to interpretation of coronary CTA performed for coronary artery disease (CAD) evaluation. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of myocardial perfusion imaging (MPI) and coronary CTA with artificial intelligence quantitative CT (AI-QCT) interpretation for detection of obstructive CAD on invasive angiography and to assess the downstream impact of including coronary CTA with AI-QCT in diagnostic algorithms. METHODS. This study entailed a retrospective post hoc analysis of the derivation cohort of the prospective 23-center Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) trial. The study included 301 patients (88 women and 213 men; mean age, 64.4 ± 10.2 [SD] years) recruited from May 2014 to May 2017 with stable symptoms of myocardial ischemia referred for nonemergent invasive angiography. Patients underwent coronary CTA and MPI before angiography with quantitative coronary angiography (QCA) measurements and fractional flow reserve (FFR). CTA examinations were analyzed using an FDA-cleared cloud-based software platform that performs AI-QCT for stenosis determination. Diagnostic performance was evaluated. Diagnostic algorithms were compared. RESULTS. Among 102 patients with no ischemia on MPI, AI-QCT identified obstructive (≥ 50%) stenosis in 54% of patients, including severe (≥ 70%) stenosis in 20%. Among 199 patients with ischemia on MPI, AI-QCT identified nonobstructive (1-49%) stenosis in 23%. AI-QCT had significantly higher AUC (all p < .001) than MPI for predicting ≥ 50% stenosis by QCA (0.88 vs 0.66), ≥ 70% stenosis by QCA (0.92 vs 0.81), and FFR < 0.80 (0.90 vs 0.71). An AI-QCT result of ≥ 50% stenosis and ischemia on stress MPI had sensitivity of 95% versus 74% and specificity of 63% versus 43% for detecting ≥ 50% stenosis by QCA measurement. Compared with performing MPI in all patients and those showing ischemia undergoing invasive angiography, a scenario of performing coronary CTA with AIQCT in all patients and those showing ≥ 70% stenosis undergoing invasive angiography would reduce invasive angiography utilization by 39%; a scenario of performing MPI in all patients and those showing ischemia undergoing coronary CTA with AI-QCT and those with ≥ 70% stenosis on AI-QCT undergoing invasive angiography would reduce invasive angiography utilization by 49%. CONCLUSION. Coronary CTA with AI-QCT had higher diagnostic performance than MPI for detecting obstructive CAD. CLINICAL IMPACT. A diagnostic algorithm incorporating AI-QCT could substantially reduce unnecessary downstream invasive testing and costs. TRIAL REGISTRATION. Clinicaltrials.gov NCT02173275.

Pediatric Cases of Recurrent Skull Giant Osteoma Misdiagnosed as Fibrous Dysplasia.

ABSTRACT: Osteomas are benign mature bone tumors that typically arise in the skull. Osteomas larger than 3 cm in diameter are considered giant osteomas. Giant osteomas of the skull vault are very rare, especially in children; therefore, only a few cases have been reported in the literature. Although osteomas are usually asymptomatic, a large skull mass can cause headache, as well as esthetic disfigurement of the forehead. it can be misdiagnosed as other conditions, such as fibrous dysplasia, ossifying cephalhematoma, or other malignant bone tumors. Herein, the authors report 2 rare pediatric cases of giant osteomas mimicking fibrous dysplasia and their successful surgical excision. These cases showed good results without recurrence or complications on long-term follow-up after complete excision.

Evaluating the Association of Anesthesia Type With Postoperative Complications in Patients Undergoing Ankle Fracture Repair.

General and neuraxial anesthesia are both successful anesthesia techniques used in many orthopedic procedures. The purpose of this study was to compare the complications and length of hospital stay between patients who underwent general anesthesia versus neuraxial anesthesia during the repair of ankle fractures. Patients undergoing open reduction and internal fixation for ankle fracture from 2014 to 2018 were identified in the National Surgical Quality Improvement Program database. Patients were stratified into 2 cohorts: general anesthesia and neuraxial anesthesia. In this analysis, demographics data, comorbidities, and postoperative complications were collected and compared between the two cohorts. Bivariate analyses and multivariable logistical regression were performed. Of 3585 patients who underwent operative treatment for ankle fracture, 3315 patients (92.5%) had general anesthesia and 270 (7.5%) had neuraxial anesthesia. On bivariate analyses, patients who had neuraxial anesthesia were more likely to develop pulmonary complications (p = .173) or extended length of stay more than 5 days (p = .342) compared to the general anesthesia group. Following adjustment on multivariate analyses, the neuraxial anesthesia cohort no longer had increased likelihood of pulmonary complications or extended length of stay compared to the general anesthesia group. Healthy ankle fracture patients could also benefit from neuraxial anesthetic methods, and they should be considered for this anesthetic type regardless of their lack of comorbidities.

A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis.

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.

Comparative Transcriptome Profiling of Young and Old Brown Adipose Tissue Thermogenesis.

Brown adipose tissue (BAT) is a major site for uncoupling protein 1 (UCP1)-mediated non-shivering thermogenesis. BAT dissipates energy via heat generation to maintain the optimal body temperature and increases energy expenditure. These energetic processes in BAT use large amounts of glucose and fatty acid. Therefore, the thermogenesis of BAT may be harnessed to treat obesity and related diseases. In mice and humans, BAT levels decrease with aging, and the underlying mechanism is elusive. Here, we compared the transcriptomic profiles of both young and aged BAT in response to thermogenic stimuli. The profiles were extracted from the GEO database. Intriguingly, aging does not cause transcriptional changes in thermogenic genes but upregulates several pathways related to the immune response and downregulates metabolic pathways. Acute severe CE upregulates several pathways related to protein folding. Chronic mild CE upregulates metabolic pathways, especially related to carbohydrate metabolism. Our findings provide a better understanding of the effects of aging and metabolic responses to thermogenic stimuli in BAT at the transcriptome level.

Effect of 222-nm krypton-chloride excilamp treatment on inactivation of Escherichia coli O157:H7 and Salmonella Typhimurium on alfalfa seeds and seed germination.

We examined the control effect of a 222-nm KrCl excilamp on foodborne pathogens on alfalfa seeds and compared it with a conventional 254-nm low-pressure (LP) Hg lamp. When the 222-nm KrCl excilamp treated seeds at 87, 174 and 261 mJ/cm2, the log reductions of Escherichia coli O157:H7 (E. coli O157:H7) were 0.85, 1.77, and 2.77, respectively, and Salmonella Typhimurium (S. Typhimurium) experienced log reductions of 1.22, 2.27, and 3.04, respectively. When the 254-nm LP Hg lamp was applied at 87, 174, and 261 mJ/cm2, the log reductions of E. coli O157: H7 were 0.7, 1.16, and 1.43, respectively, and those of S. Typhimurium were 0.75, 1.15, and 1.85, respectively. Therefore, it was shown that the 222-nm KrCl excilamp was more effective than the 254-nm LP Hg lamp in reducing foodborne pathogens. The germination rate decreased to less than 80% after 261 mJ/cm2 treatment with the 254-nm LP Hg lamp, while more than 90% was maintained with 261 mJ/cm2 222-nm KrCl excilamp treatment. DNA damage assay showed that the difference in germination rate was due to DNA damage resulting from 254-nm LP Hg lamp treatment. However, 222 nm KrCl excilamp treatment did not cause DNA damage, resulting in no difference in germination rate compared to that of non-treated alfalfa seeds. Overall, these results demonstrate the utility of the 222-nm KrCl excilamp as a foodborne pathogen control intervention for the alfalfa seed industry.

Type I interferon signaling regulates myeloid and T cell crosstalk in the glioblastoma tumor microenvironment.

Downstream interferon signaling through the type I interferon (IFN) receptor, IFNAR, is crucial for the proper production of type I IFNs in mounting anti-tumor immune responses. Our study investigates the role of type I IFN signaling in the glioblastoma (GBM) tumor microenvironment by leveraging single-cell RNA sequencing to analyze tumor-infiltrating lymphocytes. We investigate how type I IFN signaling within the myeloid compartment contributes to the crosstalk with T cells in the tumor microenvironment. Through the use of the Gl261 murine GBM model, we find that the lack of proper type I IFN response results in enhanced PD-L1 interactions among myeloid cells, thereby affecting T cell functionality. Additionally, we also characterize how anti-PD1 treatment induces transcriptional changes in tumor-associated monocytes and macrophages by analyzing intercellular communication networks and propose how immune checkpoint blockade therapy could possibly relieve some of the immunosuppression derived from the lack of proper type I IFN production.

Advanced Flexible Physical Sensors with Independent Detection Mechanisms of Pressure and Strain Stimuli for Overcoming Signal Interference.

Flexible and wearable physical sensors have gained significant interest owing to their potential in attachable devices, electronic skin, and multipurpose sensors. The physical stimuli of these sensors typically consist of vertically and horizontally applied pressures and strains, respectively. However, owing to their similar response characteristics, interference occurs between the two types of signals detected, complicating the distinction between pressure and strain stimuli, leading to inaccurate data interpretation and reduced sensor specificity. Therefore, we developed a dual-sensing-mode physical sensor with separate response mechanisms for the two types of physical stimuli based on a unique structural design that can independently induce changes in the piezocapacitance and piezoresistance for pressure and strain stimuli, respectively. The asterisk-shaped piezoresistive pathway (electrode), designed for multifunctionality, effectively detected the intensity and direction of tensile deformation, and an elastomeric sponge structure positioned between the two electrodes detected the pressure signals via changes in capacitance. This dual-sensing-mode sensor offers clearer signal differentiation and enhanced multifunctionality compared to those of traditional single-mode sensors. Additionally, extensive experimentation demonstrated that our sensor has a good sensitivity, high linearity, and stability in detecting signals, proving its applicability for sophisticated monitoring and control tasks that require the differential detection between pressure and deformation signals.

Spatial profiling of non-small cell lung cancer provides insights into tumorigenesis and immunotherapy response.

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment. Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI). In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment. In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated. Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity. Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue. Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis. These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients.

Efficacy of Antibiotic Regimens for Pneumonia in Young Infants Aged 0-59 Days: A Systematic Review.

CONTEXT: Pneumonia is a leading cause of death in young infants. OBJECTIVES: To evaluate the efficacy of different antibiotic regimens to treat young infant pneumonia on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization (WHO) Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials of young infants aged 0 to 59 days with pneumonia (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. LIMITATIONS: Trials were heterogeneous, which precluded data pooling. RESULTS: Of 2601 publications screened, 10 randomized controlled trials were included. Seven trials were hospital-based (n = 869) and 3 were nonhospital-based (n = 4329). No hospital-based trials evaluated WHO-recommended first-choice regimens. One trial found the WHO-recommended second-choice antibiotic, cefotaxime, to have similar rates of treatment success as non-WHO-recommended regimens of either amoxicillin-clavulanate (RR 0.99, 95% confidence interval 0.82-1.10) or amoxicillin-clavulanate/cefotaxime (RR 1.02, 95% confidence interval 0.86-1.12). Among 3 nonhospital-based trials comparing oral amoxicillin to alternate regimens to treat isolated tachypnea among infants aged 7-59 days, there were no differences in treatment failure between amoxicillin and alternate regimens. Certainty of evidence was low or very low for all primary outcomes. CONCLUSIONS: We found limited evidence to support the superiority of any single antibiotic regimen over alternate regimens to treat young infant pneumonia.

Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma.

BACKGROUND: Certain cancers present challenges for treatment because they are resistant to immune checkpoint blockade (ICB), attributed to low tumor mutational burden and the absence of T cell-inflamed features. Among these, glioblastoma (GBM) is notoriously resistant to ICB. To overcome this resistance, the identification of T cells with heightened stemness marked by T-cell factor 1 (TCF1) expression has gained attention. Several studies have explored ways to preserve stem-like T cells and prevent terminal exhaustion. In this study, we investigate a target that triggers stem-like properties in CD8 T cells to enhance the response to ICB in a murine GBM model. METHODS: Using Fcgr2b-/- mice and a murine GL261 GBM model, we confirmed the efficacy of anti-programmed cell death protein-1 (PD-1) immunotherapy, observing improved survival. Analysis of immune cells using fluorescence-activated cell sorting and single-cell RNA sequencing delineated distinct subsets of tumor-infiltrating CD8 T cells in Fcgr2b-/- mice. The crucial role of the stem-like feature in the response to anti-PD-1 treatment for reinvigorating CD8 T cells was analyzed. Adoptive transfer of OT-I cells into OVA-expressing GL261 models and CD8 T cell depletion in Fcgr2b-/- mice confirmed the significance of Fcgr2b-/- CD8 T cells in enhancing the antitumor response. Last, S1P1 inhibitor treatment confirmed that the main source of tumor antigen-specific Fcgr2b-/- CD8 T cells is the tumor-draining lymph nodes (TdLNs). RESULTS: In a murine GBM model, anti-PD-1 monotherapy and single-Fc fragment of IgG receptor IIb (FcγRIIB) deletion exhibit limited efficacy. However, their combination substantially improves survival by enhancing cytotoxicity and proliferative capacity in tumor-infiltrating Fcgr2b-/- CD8 T cells. The improved response to anti-PD-1 treatment is associated with the tumor-specific memory T cells (Ttsms) exhibiting high stemness characteristics within the tumor microenvironment (TME). Ttsms in the TdLN thrives in a protective environment, maintaining stem-like characteristics and serving as a secure source for tumor infiltration. This underscores the significance of FcγRIIB ablation in triggering Ttsms and enhancing ICB therapy against GBM. CONCLUSIONS: Deletion of FcγRIIB on CD8 T cells leads to the generation of a Ttsms, which is localized in TdLN and protected from the immunosuppressive TME. Incorporating these highly stemness-equipped Ttsms enhances the response to anti-PD-1 therapy in immune-suppressed brain tumors.

Efficacy of Antibiotic Regimens for Sepsis or Possible Serious Bacterial Infection in Young Infants Aged 0 to 59 Days: A Systematic Review and Meta-analysis.

CONTEXT: Sepsis is a leading cause of young infant mortality. OBJECTIVE: To evaluate the efficacy of different antibiotic regimens to treat young infant sepsis or possible serious bacterial infection (PSBI) on clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants 0 to 59 days with sepsis or PBSI (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We performed random-effects meta-analysis, and used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. RESULTS: Of 2390 publications, we included 41 RCTs (n = 18 054). Thirty-five trials were hospital-based and 6 were nonhospital-based. Meta-analysis of 4 trials demonstrated similar rates of treatment success with intramuscular/intravenous third generation cephalosporins versus intramuscular/intravenous penicillin or ampicillin + gentamicin (RR 1.03, 95% CI 0.93-1.13]; n = 1083; moderate certainty of evidence). Meta-analysis of 3 trials demonstrated similar rates of treatment failure with oral amoxicillin + intramuscular gentamicin versus intramuscular penicillin + gentamicin for nonhospital treatment of clinical severe illness (RR 0.86, 95% CI 0.72-1.02]; n = 5054; low certainty of evidence). Other studies were heterogeneous. LIMITATIONS: RCTs evaluated heterogeneous regimens, limiting our ability to pool data. CONCLUSIONS: We found limited evidence to support any single antibiotic regimen as superior to alternate regimens to treat young infant sepsis or PSBI.

Double-edged sword: γδ T cells in mucosal homeostasis and disease.

The mucosa is a tissue that covers numerous body surfaces, including the respiratory tract, digestive tract, eye, and urogenital tract. Mucosa is in direct contact with pathogens, and γδ T cells perform various roles in the tissue. γδ T cells efficiently defend the mucosa from various pathogens, such as viruses, bacteria, and fungi. In addition, γδ T cells are necessary for the maintenance of homeostasis because they select specific organisms in the microbiota and perform immunoregulatory functions. Furthermore, γδ T cells directly facilitate pregnancy by producing growth factors. However, γδ T cells can also play detrimental roles in mucosal health by amplifying inflammation, thereby worsening allergic responses. Moreover, these cells can act as major players in autoimmune diseases. Despite their robust roles in the mucosa, the application of γδ T cells in clinical practice is lacking because of factors such as gaps between mice and human cells, insufficient knowledge of the target of γδ T cells, and the small population of γδ T cells. However, γδ T cells may be attractive targets for clinical use due to their effector functions and low risk of inducing graft-versus-host disease. Therefore, robust research on γδ T cells is required to understand the crucial features of these cells and apply these knowledges to clinical practices.

γδ T cells as a potential therapeutic agent for glioblastoma.

Although γδ T cells comprise a small population of T cells, they perform important roles in protecting against infection and suppressing tumors. With their distinct tissue-localizing properties, combined with their various target recognition mechanisms, γδ T cells have the potential to become an effective solution for tumors that do not respond to current therapeutic procedures. One such tumor, glioblastoma (GBM), is a malignant brain tumor with the highest World Health Organization grade and therefore the worst prognosis. The immune-suppressive tumor microenvironment (TME) and immune-evasive glioma stem cells are major factors in GBM immunotherapy failure. Currently, encouraged by the strong anti-tumoral function of γδ T cells revealed at the preclinical and clinical levels, several research groups have shown progression of γδ T cell-based GBM treatment. However, several limitations still exist that block effective GBM treatment using γδ T cells. Therefore, understanding the distinct roles of γδ T cells in anti-tumor immune responses and the suppression mechanism of the GBM TME are critical for successful γδ T cell-mediated GBM therapy. In this review, we summarize the effector functions of γδ T cells in tumor immunity and discuss current advances and limitations of γδ T cell-based GBM immunotherapy. Additionally, we suggest future directions to overcome the limitations of γδ T cell-based GBM immunotherapy to achieve successful treatment of GBM.