Seasonal variations of empyema in Taiwan: A 10-year analysis.

BACKGROUND: Empyema is a serious infection in pleural space. Finding out seasonal variations of empyema and its pathogens can help in providing preventive measures, and implicating future researches. METHODS: This study is a 10-year observational study in a single center. Patients with empyema thoracis receiving thoracoscopic decortication between January 2012 and December 2021 were included in the study. RESULTS: There were 1082 empyema patients enrolled in this study. No seasonal variation was noted (spring = 25.7 %, summer =25.5 %, autumn = 24.8 %, winter = 24.0 %). However, we observed seasonal variations in pathogens. Streptococcus species had slightly higher prevalence in winter and spring than summer and autumn (54.3 % vs. 45.7 %) without significant difference (p = 0.251). On the contrary, Staphylococcus species occurred more often in summer and autumn than winter and spring (61.5 % vs. 38.5 %) (p = 0.035). Klebsiella species were more likely found in autumn (34.9 %) (p = 0.050), and Pseudomonas species showed no peak prevalence in any season (p = 0.423). The incidence of Streptococcus species increased over the years. CONCLUSIONS: Although no seasonal variation was found in severe empyema patients requiring surgery, there were seasonal variations for the pathogens in Taiwan. The medical community should focus on Streptococcus species in winter and spring and Staphylococcus species in summer and autumn.

Six years follow-up of type 1 retinopathy of prematurity (ROP) treated with intravitreal injection of ranibizumab and bevacizumab: Long-Term Outcomes of intravitreal injection in Type 1 ROP.

To investigate biometric and refractive results in patients with type 1 retinopathy of prematurity (ROP) treated by intravitreal injection (IVI) of ranibizumab (R) and bevacizumab (B) at the corrected age of 6. This is a single-center retrospective study. Infants diagnosed with type 1 ROP and treated with IVI of either R or B as the primary therapy were included. Data on axial length, anterior chamber depth (ACD), and lens thickness (LT) were obtained using A-scan ultrasound. Cycloplegic refraction, keratometry (K), and best-corrected visual acuity were also documented. Additionally, optical coherence tomography angiography was performed to assess the foveal avascular zone and the density of superficial and deep vessels. We analyzed the structural and functional differences between the 2 groups and compared them with findings from a previous study conducted when these children were between the ages of 1 and 3. The study included 60 eyes from 34 patients, with 34 eyes receiving B and 26 eyes receiving R injections for ROP. In biometric outcomes, there was still a deeper ACD (3.36 ±â€…0.24 mm in the B group; 3.52 ±â€…0.21 mm in the R group) and thinner LT (3.63 ±â€…0.16 mm in the B group; 3.53 ±â€…0.12 mm in the R group) in the R group, as previously reported at the age of 3. In the refractive aspect, the eyes treated with B had higher myopia at the ages of 1 and 3; however, at the age of 6, refractive errors did not differ significantly between the 2 groups. At the corrected age of 6, the eyes treated with IVI of R were associated with deeper ACD and thinner LT. Interestingly, the emmetropization process resulted in a similar incidence of high myopia at the age of 6, which was different from the outcomes observed at younger ages.

Prolactin Drives Iron Release from Macrophages and Uptake in Mammary Cancer Cells through CD44.

Iron is an essential element for human health. In humans, dysregulated iron homeostasis can result in a variety of disorders and the development of cancers. Enhanced uptake, redistribution, and retention of iron in cancer cells have been suggested as an "iron addiction" pattern in cancer cells. This increased iron in cancer cells positively correlates with rapid tumor growth and the epithelial-to-mesenchymal transition, which forms the basis for tumor metastasis. However, the source of iron and the mechanisms cancer cells adopt to actively acquire iron is not well understood. In the present study, we report, for the first time, that the peptide hormone, prolactin, exhibits a novel function in regulating iron distribution, on top of its well-known pro-lactating role. When stimulated by prolactin, breast cancer cells increase CD44, a surface receptor mediating the endocytosis of hyaluronate-bound iron, resulting in the accumulation of iron in cancer cells. In contrast, macrophages, when treated by prolactin, express more ferroportin, the only iron exporter in cells, giving rise to net iron output. Interestingly, when co-culturing macrophages with pre-stained labile iron pools and cancer cells without any iron staining, in an iron free condition, we demonstrate direct iron flow from macrophages to cancer cells. As macrophages are one of the major iron-storage cells and it is known that macrophages infiltrate tumors and facilitate their progression, our work therefore presents a novel regulatory role of prolactin to drive iron flow, which provides new information on fine-tuning immune responses in tumor microenvironment and could potentially benefit the development of novel therapeutics.

Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.

The bone marrow endothelial progenitor cell response to septic infection.

Early increase in the level of endothelial progenitor cells (EPCs) in the systemic circulation occurs in patients with septic infection/sepsis. The significance and underlying mechanisms of this response remain unclear. This study investigated the bone marrow EPC response in adult mice with septic infection induced by intravenous injection (i.v.) of Escherichia coli. For in vitro experiments, sorted marrow stem/progenitor cells (SPCs) including lineage(lin)-stem cell factor receptor (c-kit)+stem cell antigen-1 (Sca-1)-, lin-c-kit+, and lin- cells were cultured with or without lipopolysaccharides (LPSs) and recombinant murine vascular endothelial growth factor (VEGF) in the absence and presence of anti-Sca-1 crosslinking antibodies. In a separate set of experiments, marrow lin-c-kit+ cells from green fluorescence protein (GFP)+ mice, i.v. challenged with heat-inactivated E. coli or saline for 24 h, were subcutaneously implanted in Matrigel plugs for 5 weeks. Marrow lin-c-kit+ cells from Sca-1 knockout (KO) mice challenged with heat-inactivated E. coli for 24 h were cultured in the Matrigel medium for 8 weeks. The marrow pool of EPCs bearing the lin-c-kit+Sca-1+VEGF receptor 2 (VEGFR2)+ (LKS VEGFR2+) and LKS CD133+VEGFR2+ surface markers expanded rapidly following septic infection, which was supported by both proliferative activation and phenotypic conversion of marrow stem/progenitor cells. Increase in marrow EPCs and their reprogramming for enhancing angiogenic activity correlated with cell-marked upregulation of Sca-1 expression. Sca-1 was coupled with Ras-related C3 botulinum toxin substrate 2 (Rac2) in signaling the marrow EPC response. Septic infection caused a substantial increase in plasma levels of IFN-γ, VEGF, G-CSF, and SDF-1. The early increase in circulating EPCs was accompanied by their active homing and incorporation into pulmonary microvasculature. These results demonstrate that the marrow EPC response is a critical component of the host defense system. Sca-1 signaling plays a pivotal role in the regulation of EPC response in mice with septic infection.

Modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor for diabetic macular edema in Taiwan.

Given the rising prevalence of patients with diabetes and increasing treatment burden for patients with vision-threatening diabetic macular edema (DME), we aimed to explore the efficacy of modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor (VEGF) therapy under the Taiwan National Insurance Bureau reimbursement policy. We obtained data on 69 eyes treated with initial 4-monthly intravitreal injections of aflibercept or ranibizumab, plus individualized treat-and-extend regimen. At 12 months, the mean (SD) change in LogMAR best corrected visual acuity from baseline was - 0.28 (0.31) in all eyes, while that in the aflibercept and ranibizumab groups were - 0.30 (0.34) and - 0.25 (0.28), respectively. Central retinal thickness decreased by 137.2 (122.4) in all eyes, 138.1 (134.2) in the aflibercept group, and 136.2 (110.9) in the ranibizumab group. Additionally, the aflibercept group had a lower mean number of injections than the ranibizumab group (8.5 vs. 8.7). The last extended dosing interval of > 12 weeks was 31.0% and 16.7% of the eyes in the aflibercept and ranibizumab groups, respectively. The modified anti-VEGF regimens effectively managed DME in terms of functional and anatomical outcomes, and efficiently reduced the healthcare burden by reducing the number of injections and extending treatment intervals within 12 months.

ABCB1 Regulates Immune Genes in Breast Cancer.

Background: Resistance to standard chemotherapy is a critical problem for breast cancer patients. The ATP-binding cassette (ABC) superfamily transporters actively pump out drugs and play an important role in chemoresistance. ABCB1 (ABC subfamily B, member 1, also named as multidrug resistance protein 1, MDR1) and suppressive myeloid-derived suppressor cells (MDSCs) potentially involve in chemoresistance of breast cancer. The relationship between ABCB1 and immune genes in breast cancer has not been widely studied. Methods: Microarray and RNA sequencing data were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma in Genomic Data Commons Data Portal and Gene Expression Omnibus database. A patient-derived xenograft (PDX) model of HER2+ breast cancer was established to investigate the association between ABCB1 and immune genes in breast cancer. Results: Expression of ABCB1 increased in doxorubicin-selected MCF-7/ADR cells. High expression of ABCB1 mRNA is correlated with lymph-node metastasis and worse overall survival in patients with breast cancer. ABCB1 is positively correlated with IL6, CSF1, CSF3, and PTGS2. In the HER2+ stage IIA breast cancer PDX model, both doxorubicin and paclitaxel suppressed growth of P2 tumors. IL6, CSF1, CSF3, and PTGS2 expression were suppressed by paclitaxel but not doxorubicin. Intrasplenic MDSCs, including CD11b+Ly6G+ and CD11b+Ly6C+ cells, were more abundant than intratumor MDSCs in PDX-carrying nude mice. Clinically, the patient developed cancer recurrence after adjuvant chemotherapy with doxorubicin-based regimen and was well controlled after paclitaxel-trastuzumab combined therapy. Conclusion: ABCB1 was a poor predictor of HER2+ LN- breast cancer. Regulation of immune genes by ABCB1 contributed to cancer recurrence and treatment effect. The PDX model was suitable for investigation the expression of target genes and expansion of immune cells.

Adjuvant chemotherapy in pathological node-negative non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is associated with a poor survival rate, even for patients with early-stage cancer. Identifying patients with pathological N0 NSCLC who may benefit from adjuvant chemotherapy treatment after surgery is essential. We conducted a retrospective cohort study used data from the Surveillance, Epidemiology, and End Results database and included 26,380 patients with pathological N0 NSCLC after surgery between January 2018, and December 2019. Among 26,380 patients, 24,273 patients received surgery alone and the other 2107 patients received surgery plus adjuvant chemotherapy. After 1:1 propensity score matching, both groups contained 2107 patients. Adjuvant chemotherapy did not show significantly better 24-month survival in T2aN0 NSCLC patients (83.41% vs. 82.91%, p = 0.067), although it did for T2bN0 patients (86.36% vs. 81.70%, p = 0.028). Poorly-differentiated NSCLC remained a high-risk factor for pT2N0, and adjuvant chemotherapy provided better 24-month survival after matching (86.36% vs. 81.70%, p = 0.029). In conclusion, when treating pN0 NSCLC, adjuvant chemotherapy had a beneficial effect when the tumor size was larger than 4 cm. The effect when the tumor size was between 3 and 4 cm was not remarkable. Poorly-differentiated NSCLC was a high-risk factor in the pT2N0 stage.

LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis.

BACKGROUND: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. RESULTS: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. CONCLUSION: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.

Competitive Assay for the Ultrasensitive Detection of Organophosphate Pesticides Based on a Fiber-Optic Particle Plasmon Resonance Biosensor and an Acetylcholinesterase Binding Peptide.

An acetylcholinesterase (AChE) binding-based biosensor was developed for the ultrasensitive detection of organophosphate (OP) pesticides. The biosensor integrates the technique based on fiber-optic particle plasmon resonance detection and a synthetic AChE binding peptide conjugated with gold nanoparticles on the optical fiber surface via an AChE competitive binding assay. The OP pesticides present in the solution hinder the binding of AChE to the peptide on the biosensor by competing for the binding sites present in AChE. The limit of detection obtained for parathion using this method was observed to be 0.66 ppt (2.3 pM). This method shows a wide linear dynamic range of 6 orders. Furthermore, the use of the AChE binding peptide in the biosensor can better discriminate OPs against carbamates by using only a single biosensor. The practical application of this method was tested using spiked samples, which yielded good recovery and reproducibility. The spiked sample required minimal pretreatment before analysis; hence, this biosensor may also be used in the field.

Interplay Between Inflammatory-immune and Interleukin-17 Signalings Plays a Cardinal Role on Liver Ischemia-reperfusion Injury-Synergic Effect of IL-17Ab, Tacrolimus and ADMSCs on Rescuing the Liver Damage.

BACKGROUND: This study tested the hypothesis that inflammatory and interleukin (IL)-17 signalings were essential for acute liver ischemia (1 h)-reperfusion (72 h) injury (IRI) that was effectively ameliorated by adipose-derived mesenchymal stem cells (ADMSCs) and tacrolimus. METHODS: Adult-male SD rats (n = 50) were equally categorized into groups 1 (sham-operated-control), 2 (IRI), 3 [IRI + IL-17-monoclonic antibody (Ab)], 4 (IRI + tacrolimus), 5 (IRI + ADMSCs) and 6 (IRI + tacrolimus-ADMSCs) and liver was harvested at 72 h. RESULTS: The main findings included: (1) circulatory levels: inflammatory cells, immune cells, and proinflammatory cytokines as well as liver-damage enzyme at the time point of 72 h were highest in group 2, lowest in group 1 and significantly lower in group 6 than in groups 3 to 5 (all p < 0.0001), but they did not differ among these three latter groups; (2) histopathology: the liver injury score, fibrosis, inflammatory and immune cell infiltration in liver immunity displayed an identical pattern of inflammatory cells among the groups (all p < 0.0001); and (3) protein levels: upstream and downstream inflammatory signalings, oxidative-stress, apoptotic and mitochondrial-damaged biomarkers exhibited an identical pattern of inflammatory cells among the groups (all p < 0.0001). CONCLUSION: Our results obtained from circulatory, pathology and molecular-cellular levels delineated that acute IRI was an intricate syndrome that elicited complex upstream and downstream inflammatory and immune signalings to damage liver parenchyma that greatly suppressed by combined tacrolimus and ADMSCs therapy.

Prediction of Surgical Outcome by Tumor Volume Doubling Time via Stereo Imaging Software in Early Non-Small Cell Lung Cancer.

BACKGROUND: Volume doubling time (VDT) has been proven to be a powerful predictor of lung cancer progression. In non-small cell lung cancer patients receiving sublobar resection, the discussion of correlation between VDT and surgery was absent. We proposed to investigate the surgical outcomes according to VDT. METHODS: We retrospectively studied 96 cases post sublobar resection from 2012 to 2018, collecting two chest CT scans preoperatively of each case and calculating the VDT. The receiver operating characteristic curve was constructed to identify the optimal cut-off point of VDTs as 133 days. We divided patients into two groups: VDT < 133 days and VDT ≥ 133 days. Univariable and multivariable analyses were performed for comparative purposes. RESULTS: Univariable and multivariable analyses revealed that the consolidation and tumor diameter ratio was the factor of overall survival (OS), and VDT was the only factor of disease-free survival (DFS). The five year OS rates of patients with VDTs ≥ 133 days and VDTs < 133 days, respectively, were 89.9% and 71.9%, and the five year DFS rates were 95.9% and 61.5%. CONCLUSION: As VDT serves as a powerful prognostic predictor and provides an essential role in planning surgical procedures, the evaluation of VDT preoperatively is highly suggested.

Early and Dose-Dependent Xenogeneic Mesenchymal Stem Cell Therapy Improved Outcomes in Acute Respiratory Distress Syndrome Rodent Through Ameliorating Inflammation, Oxidative Stress, and Immune Reaction.

This study tested whether human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) treatment effectively protected the rat lung against acute respiratory distress syndrome (ARDS) injury, and benefits of early and dose-dependent treatment. Rat pulmonary epithelial cell line L2 (PECL2) were categorized into G1 (PECL2), G2 (PECL2 + healthy rat lung-derived extraction/50 mg/ml co-cultured for 24 h), G3 (PECL2 + ARDS rat lung-derived extraction/50 mg/ml co-cultured for 24 h), and G4 (condition as G3 + HUCDMSCs/1 × 105/co-cultured for 24 h). The result showed that the protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IkB/NF-κB/IL-1ß/TNF-α), oxidative-stress/mitochondrial-damaged (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/JNKs/JUN/cytosolic-cytochrome-C/cyclophilin-D/DRP1), and cell-apoptotic/fibrotic (cleaved-caspase 3/cleaved-PARP/TGF-ß/p-Smad3) biomarkers were significantly increased in G3 than in G1/G2 and were significantly reversed in G4 (all P < 0.001), but they were similar between G1/G2. Adult male rats (n = 42) were equally categorized into group 1 (normal control), group 2 (ARDS only), group 3 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 3 h after 48 h ARDS induction (i.e., early treatment)], group 4 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 24 h after 48 h ARDS induction (late treatment)], and group 5 [ARDS + HUCDMSCs/1.2 × 106 cells intravenous administration at 3 h/24 h after-48 h ARDS induction (dose-dependent treatment)]. By day 5 after ARDS induction, the SaO2%/immune regulatory T cells were highest in group 1, lowest in group 2, significantly lower in group 4 than in groups 3/5, and significantly lower in group 3 than in group 5, whereas the circulatory/bronchioalveolar lavage fluid inflammatory cells (CD11b-c+/LyG6+/MPO+)/circulatory immune cells (CD3-C4+/CD3-CD8+)/lung-leakage-albumin level/lung injury score/lung protein expressions of inflammatory (HMGB-1/TLR-2/TLR-4/MAL/TRAM/MyD88/TRIF/TRAF6/IκB-ß/p-NF-κB/IL-1ß/TNF-α)/fibrotic (p-SMad3/TGF-ß), apoptosis (mitochondrial-Bax/cleaved-caspase-3)/oxidative-cell-stress (NOX-1/NOX-2/ASK1/p-MKK4/p-MKK7/p-JNKs/p-cJUN)/mitochondrial damaged (cyclophilin-D/DRP1/cytosolic-cytochrome-C) biomarkers displayed an opposite pattern of SaO2% among the groups (all P < 0.0001). Early administration was superior to and two-dose counterpart was even more superior to late HUCDMSCs treatment for protecting the lung against ARDS injury.

Culture-Positive and Culture-Negative Empyema After Thoracoscopic Decortication: A Comparison of Short-term and Long-term Outcomes.

Background: Empyema thoracis is a serious infectious disease and is associated with high morbidity and mortality. The perioperative outcomes between culture-positive and culture-negative empyema after thoracoscopic decortication remained controversial, especially since there were no studies that reported the survival outcomes between culture-positive and culture-negative empyema. Methods: This single-institute study involved a retrospective analysis. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. Patients were grouped into a culture-positive group and a culture-negative group according to culture results obtained no later than 2 weeks after surgery. Results: A total of 1087 patients with empyema received surgery, and 824 were enrolled after exclusion. Among these, 366 patients showed positive culture results and 458 patients showed negative results. Longer intensive care unit stays (11.69 vs 5.64 days, P < .001), longer ventilator usage (24.70 vs 14.01 days, P = .002), and longer postoperative hospital stays (40.83 vs 28.37 days, P < .001) were observed in the culture-positive group. However, there was no significant difference in 30-day mortality between the 2 groups (5.2% in culture negative vs 5.0% in culture positive, P = .913). The 2-year survival was not significantly different between the 2 groups (P = .236). Conclusions: Patients with culture-positive or culture-negative empyema who underwent thoracoscopic decortication showed similar short-term and long-term survival outcomes. A higher risk of death was associated with advanced age, a higher Charlson Comorbidity Index score, phase III empyema, and a cause other than pneumonia.

How Cultural Behaviors and Superstitions Associate the Willingness to Undergo Cataract Surgery in Taiwan: A Nationwide Survey.

Background and Objectives: Cultural beliefs influence the conceptualization, adaptation, and coping strategies for diseases. This study aimed to investigate the impact of cultural beliefs and customs on the willingness to undergo cataract surgery in Taiwan. Materials and Methods: The data were retrospectively retrieved from the national Longitudinal Health Insurance Database 2000 (LHID2000). From the national database, we enrolled patients that were diagnosed with cataracts and underwent cataract surgery from 2001 to 2010. All the patients were stratified according to their gender and living area. Gender was categorized as male or female, and the living area was classified as urban or rural. We compared the difference in the number of surgeries between stratified patient groups in each Chinese lunar month. Results: The number of cataract surgeries decreased significantly in the seventh and twelfth lunar months for both genders. There was a significant reduction in cataract surgeries in both the urban and rural groups during the seventh lunar month. Interestingly, only the seventh lunar month had an association with sex in different living areas, which meant that in the seventh month, there was a gender-specific difference in the surgical numbers. Conclusions: The Taiwanese population holds a belief that surgical procedures, including cataract surgery, during the lunar ghost month is inauspicious. Citizens tend to avoid elective surgery due to cultural practice, resulting in a decrease in surgical numbers during the period of the Chinese New Year. The authorities should consider these cultural behaviors when developing medical policies and allocating resources. Healthcare providers should be aware of these superstitions and take them into account when providing medical care and advice to patients.

Safety and efficacy of intracoronary artery administration of human bone marrow-derived mesenchymal stem cells in STEMI of Lee-Sung pigs-A preclinical study for supporting the feasibility of the OmniMSC-AMI phase I clinical trial.

Background: This study tested whether early left intracoronary arterial (LAD) administration of human bone marrow-derived mesenchymal stem cells (hBMMSCs, called OmniMSCs) in acute ST-segment elevation myocardial infarction (STEMI) of Lee-Sung pigs induced by 90 min balloon-occluded LAD was safe and effective. Methods and results: Young male Lee-Sung pigs were categorized into SC (sham-operated control, n = 3), AMI-B (STEMI + buffer/21 cc/administered at 90 min after STEMI, n = 6), and AMI-M [acute myocardial infarction (AMI) + hBMMSCs/1.5 × 107/administered at 90 min after STEMI, n = 6] groups. By 2 and 5 months after STEMI, the cardiac magnetic resonance imaging demonstrated that the muscle scar score (MSS) and abnormal cardiac muscle exercise score in the infarct region were significantly increased in the AMI-B than in the SC group that were significantly reversed in the AMI-M group, whereas the left ventricular ejection function by each month (from 1 to 5) displayed an opposite pattern of MSS among the groups (all p < 0.001). By 5 months, histopathological findings of infarct and fibrosis areas and isolectin-B4 exhibited an identical pattern, whereas the cellular expressions of troponin-I/troponin-T/von Willebrand factor exhibited an opposite pattern of MSS among the groups (all p < 0.001). The ST-segment resolution (>80%) was significantly earlier (estimated after 6-h AMI) in the AMI-M group than in the AMI-B group (p < 0.001). The protein expressions of inflammation (IL-1ß/TNF-α/NF-κB)/oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptosis (cleaved caspase-3/cleaved PARP)/DNA damage (γ-H2AX) displayed an identical pattern to MSS among the groups, whereas the protein expressions of angiogenesis factors (SDF-1α/VEGF) were significantly and progressively increased from SC, AMI-B, to AMI-M groups (all p < 0.001). Conclusion: Early intra-LAD transfusion of OmniMSC treatment effectively reduced the infarct size and preserved LV function in porcine STEMI.

Different treatment efficacies and T790M acquisition of EGFR-TKIs on NSCLC patients with variable Del-19 subtypes of EGFR.

EGFR exon 19 deletion (Del-19) comprises multiple advanced NSCLC subtypes. EGFR-tyrosine kinase inhibitor (TKI) efficacy and T790M acquisition in various Del-19 subtypes is unknown. We prospectively collected tissue samples from patients harboring NSCLC with Del-19 between 2006 and 2020. We evaluated EGFR-TKI treatment effectiveness among the different Del-19 subtypes. We collected 1391 NSCLC samples from 892 patients with Del-19, and the most common subtype was del E746-A750 (67.5%). 741 patients had taken first- or second-generation EGFR-TKIs. There were no significant differences in response rates between patients with different Del-19 subtypes (P = .630). Patients with indel E746 had the longest median PFS (14.6 months), but those with non-LRE deletions had the shortest PFS (8.9 months; P = .002). For OS analysis, patients with indel E746 also had the longest OS (34.1 months), but those with non-LRE deletions had the shortest OS (21.1 months; P = .046). Patients with different Del-19 subtypes showed no significant differences in the T790M acquisition rates (P = .443). Among the 151 patients with acquired T790M who received third-generation EGFR-TKIs, the Del-19 subtype was not associated with different RR and PFS. In vitro cellular viability and activation of the EGFR pathway analysis were consistent with the clinical findings. In conclusion, compared with del E746-A750, indel E746 was associated with longer PFS and OS, but the non-LRE subtype was correlated with shorter survival prognosis. There were no significant differences in the acquired T790M rate and treatment effectiveness of subsequent third-generation EGFR-TKIs between various Del-19 subgroups.

Predictive Value of Flank Pain and Gross Hematuria on Long-Term Survival in Patients With Upper Tract Urothelial Carcinoma Treated by Radical Nephroureterectomy.

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P < .05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P < .001). The Cox multivariate regression analysis showed that "FP without GH" (P < .001), tumor multifocality (P = .005), and pathological stage (P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC.

The outcomes of thoracoscopic decortication between fungal empyema and bacterial empyema.

BACKGROUND: Fungal empyema is an uncommon disease and is associated with a high mortality rate. Surgical intervention is suggested in stage II and III empyema. However, there were no studies that reported the outcomes of surgery for fungal empyema. METHODS: This study is a retrospective analysis in a single institute. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. We separated the patients into a fungal empyema group and a bacterial empyema group according to culture results. We used 1:3 propensity score matching to reduce selection bias. RESULTS: There were 1197 empyema patients who received surgery. Of these, 575 patients showed positive culture results and were enrolled. Twenty-eight patients were allocated to the fungal empyema group, and the other 547 patients were placed in the bacterial empyema group. Fungal empyema showed significantly longer intensive care unit stay (16 days vs. 3 days, p = 0.002), longer median ventilator usage duration (20.5 days vs. 3 days, p = 0.002), longer hospital stay duration (40 days vs. 17.5 days, p < 0.001) and a higher 30-day mortality rate (21.4% vs. 5.9%, p < 0.001). Fungal empyema revealed significantly poorer 1-year survival rate than bacterial empyema before matching (p < 0.001) but without significant difference after matching. CONCLUSIONS: The fungal empyema patients had much worse surgical outcomes than the bacterial empyema patients. Advanced age and high Charlson Comorbidity Index score are independent predictors for poor prognosis. Prompt surgical intervention combined with the use of antifungal agents was the treatment choice for fungal empyema.