Ching-Chuan Hsieh

INTRODUCTION: Few studies have examined outcomes of laparoscopic cholecystectomy for acute cholecystitis in patients with heart failure (HF). This study was to assess the impact of HF on cholecystectomy outcomes. METHODS: Data from the United States Nationwide Inpatient Sample (NIS) from 2016 to 2020 were examined. Adults 20 years and older diagnosed with acute cholecystitis who underwent laparoscopic cholecystectomy were included. Patients were categorized into groups with and without pre-existing HF. RESULTS: Outcomes assessed included inhospital mortality, nonroutine discharge, length of hospital stay, total hospital cost, and complications. Propensity score matching at a 1:1 ratio was conducted to balance between-group characteristics. Associations between HF and the outcomes were determined using univariate and multivariable regression analyses. After propensity score matching, 11,646 patients were included in the analysis: 5,823 with HF and 5,823 without. Patients with HF had significantly elevated risks of inhospital mortality (adjusted odds ratio [aOR] = 2.14, 95% confidence interval [CI]: 1.44–3.17), nonroutine discharge (aOR = 1.80, 95% CI: 1.61–2.01), and complications (aOR = 1.51, 95% CI: 1.40–1.63). Patients with HF also had longer length of hospital stay (1.52 days, 95% CI: 1.45–1.60) and higher total hospital costs (16.64 thousand USD, 95% CI: 15.58–17.70). The outcomes of patients with HF were seen in those with HF reduced ejection fraction and HF with preserved ejection fraction. DISCUSSION: Patients with HF, either HF reduced ejection fraction or HF with preserved ejection fraction, have increased risk of adverse inpatient outcomes after laparoscopic cholecystectomy for acute cholecystitis. This emphasizes the importance of tailored perioperative care to optimize patient outcomes.

Purpose Obesity is associated with complications in surgical procedures and postoperative outcomes. This study aims to compare in-hospital outcomes of robotic inguinal hernia repair (RIHR) and laparoscopic inguinal hernia repair (LIHR) in obese patients. Methods Data from the National Inpatient Sample (NIS) from 2005 to 2020 were used in this study. Inclusion criteria were ≥ 18 years old with obesity (body mass index ≥ 30 kg/m²) who underwent either RIHR or LIHR. Data were analyzed for in-hospital mortality, length of stay (LOS), total hospital costs, and complications. Results A total of 647 patients were included. Multivariable analysis showed RIHR was associated with a significantly lower risk of any complications (adjusted odds ratio [aOR] = 0.53, 95% confidence interval [CI]: 0.36, 0.77), shorter LOS (adjusted Beta [aBeta] = -0.94, 95%CI: -1.02, -0.86), and higher total hospital costs (aBeta = 5.62, 95%CI: 4.80, 6.44). Stratified analysis revealed that the lower risk of complications with RIHR was consistent across most subgroups, including age < 60 years (aOR = 0.56) and ≥ 60 years (aOR = 0.53), non-smokers (aOR = 0.53) and smokers (aOR = 0.48), non-hypertensive (aOR = 0.27) and hypertensive patients (aOR = 0.66), and non-diabetic (aOR = 0.53) and diabetic patients (aOR = 0.44), as well as patients admitted during 2017–2020 (aOR = 0.50). Conclusions RIHR is associated with lower complication risk and shorter LOS, but higher hospital costs compared to LIHR for obese patients. These findings suggest that RIHR may offer better short-term outcomes for obese patients, which should be considered in surgical decision-making. Given the retrospective nature of this analysis and the potential for selection bias and residual confounding, future randomized controlled trials are warranted to confirm these findings and provide more robust evidence to guide surgical decision-making.

Intricate signaling cascades involving chemokines and their cognate receptors on neoplastic and immune constituents within tumor microenvironment have garnered substantial research interest. Our investigation delineates the contribution of Chemokine (C-C motif) ligand 16 (CCL16) to the clinico-pathological features and tumorigenesis of hepatocellular carcinoma (HCC). Analysis of 237 pairs of HCC specimens unraveled a significant association between CCL16 expression and vascular invasion, early-stage clinicopathological features, and diminished recurrence-free survival among HCC patients. Immunohistochemical (IHC) assays of the clinical HCC specimens indicated elevated CCL16 in tumorous versus normal hepatic tissues. Our in vivo experiments demonstrated CCL16 overexpression fostered tumor proliferation, whereas in vitro assays elucidated that CCL16-mediated chemotactic recruitment of monocytes and M2 macrophages was orchestrated via CCR1 and CCR5. In contrast to previous claims that CCL16 is physiologically irrelevant and has minimal affinity for its receptors (CCR1, CCR2, CCR5, CCR8), our findings unravel that inhibition of CCL16/CCR1 and CCL16/CCR5 interactions through receptor-specific antagonists markedly impeded CCL16-directed chemotaxis, migration, adhesion, and leukocyte recruitment. Moreover, CCL16-overexpression in HCCs significantly augmented levels of several cytokines implicated in tumor progression, namely IL-6, IL-10 and VEGFA. IHC analysis of CCL16-overexpressing xenografts elicited greatly enhanced levels of VEGFA and IL-6, while assessments of HCC specimens confirmed a positive correlation between CCL16 expression and IL-6 and VEGFA levels. Collectively, our study highlights oncogenic role of CCL16 in hepatocarcinogenesis and provides a foundational basis for novel therapeutic interventions targeting the CCL16/CCR1/CCR5 axis.

Type 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. This study presents an ex vivo procedure to develop MDSCs from bone marrow cells propagated from granulocyte–macrophage-colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-1β cytokines expressing immature morphology and high immunosuppression of T-cell proliferation. The adoptive transfer of cytokine-induced MDSCs (cMDSCs) improved the hyperglycemic state and prolonged the diabetes-free survival of nonobese diabetic (NOD) mice with severe combined immune deficiency (SCID) induced by reactive splenic T cells harvested from NOD mice. In addition, the application of cMDSCs reduced fibronectin production in the renal glomeruli and improved renal function and proteinuria in diabetic mice. Moreover, cMDSCs use mitigated pancreatic insulitis to restore insulin production and reduce the levels of HbA1c. In conclusion, administering cMDSCs propagated from GM-CSF, IL-6, and IL-1β cytokines provides an alternative immunotherapy protocol for treating diabetic pancreatic insulitis and renal nephropathy.

Chronic kidney disease (CKD) is a serious public health problem. Due to a high variability in the speed of CKD progression to end-stage renal disease (ESRD) and the critical involvement of Wnt/β-catenin signaling in CKD, we investigated the role of the Wnt antagonist Dickkopf-1 (DKK1) in CKD progression. Our data revealed that patients with CKD stages 4–5 had higher DKK1 levels in their serum and renal tissues than the control subjects. In an 8-year follow-up, the serum DKK1-high group in the enrolled CKD patients showed a faster progression to ESRD than the serum DKK1-low group. Using a rat model of 5/6 nephrectomy (Nx)-induced CKD, we consistently detected elevated serum levels and renal production of DKK1 in 5/6 Nx rats compared to sham-operated rats. Importantly, the knockdown of the DKK1 levels in the 5/6 Nx rats markedly attenuated the CKD-associated phenotypes. Mechanistically, we demonstrated that the treatment of mouse mesangial cells with recombinant DKK1 protein induced not only the production of multiple fibrogenic proteins, but also the expression of endogenous DKK1. Collectively, our findings suggest that DKK1 acts as a profibrotic mediator in CKD, and elevated levels of serum DKK1 may be an independent predictor of faster disease progression to ESRD in patients with advanced CKD.

Redox is a constant phenomenon in organisms. From the signaling pathway transduction to the oxidative stress during the inflammation and disease process, all are related to reduction-oxidation (redox). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor targeting many antioxidant genes. In non-stressed conditions, NRF2 maintains the hemostasis of redox with housekeeping work. It expresses constitutively with basal activity, maintained by Kelch-like-ECH-associated protein 1 (KEAP1)-associated ubiquitination and degradation. When encountering stress, it can be up-regulated by several mechanisms to exert its anti-oxidative ability in diseases or inflammatory processes to protect tissues and organs from further damage. From acute kidney injury to chronic kidney diseases, such as diabetic nephropathy or glomerular disease, many results of studies have suggested that, as a master of regulating redox, NRF2 is a therapeutic option. It was not until the early termination of the clinical phase 3 trial of diabetic nephropathy due to heart failure as an unexpected side effect that we renewed our understanding of NRF2. NRF2 is not just a simple antioxidant capacity but has pleiotropic activities, harmful or helpful, depending on the conditions and backgrounds.

Diabetic nephropathy is a complication of diabetes that leads to end-stage kidney disease and is a major health burden worldwide. Prenylflavonoid compounds extracted from Macaranga tanarius (MTE) exhibit anti-inflammation, anti-oxidant, and anti-bacterial properties. However, the effects of these compounds on diabetic nephropathy remain unclear. The effects of MTE on diabetic nephropathy were investigated in vitro by using mouse renal mesangial cells and in vivo by using a db/db knockout mouse model. No overt alteration in proliferation was observed in mouse renal mesangial cells treated with 0–1 μg/mL MTE. Western blot analysis indicated that MTE dose-dependently attenuated the expression of fibronectin, α-smooth muscle actin, and collagen IV. Administration of MTE ameliorated renal albumin loss in db/db mice. Immunohistochemical staining revealed that MTE mitigated diabetes-induced fibronectin and collagen IV expression. Periodic acid–Schiff (PAS) and trichrome staining also showed that administration of MTE reduced the renal fibrosis phenomenon. MTE significantly ameliorated diabetes-induced nephropathy.

Background Type 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. Immunotherapy is a method of disease treatment that involves stimulating or suppressing an immune response. Although the spleens and blood of tumor-bearing mice are the most common MDSC source for immunotherapy, many safety precautions must be considered. Methods Cytokine-induced MDSCs were propagated from bone marrow cells cultured with mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-1β. Arginase-1 and inducible NO synthase (iNOS) expressions of MDSCs were evaluated using quantitative reverse-transcriptase PCR. Diabetes was diagnosed as a sustained blood sugar level > 350 mg/dL. The immunized T cells harvested from the spleens of nonobese diabetic (NOD) mice cotransplanted with cMDSCs were injected intravenously to the NOD mice with severe combined immune deficiency (SCID), twice a week for 5 consecutive weeks. Diabetes-free survival of NOD–SCID mice was measured. Fibronectin expressions of the renal glomerulus and insulin production of the pancreas were analyzed using immunohistochemistry studies. Results This study presents an ex vivo procedure to develop MDSCs from bone marrow cells propagated from GM-CSF, IL-6, and IL-1β cytokines expressing less costimulatory and more inhibitory surface markers as well as considerably high levels of the iNOS enzyme through the signal transducer and activator of transcription 1 (STAT1) signaling pathway. In addition, the MDSCs also displayed immature morphology and strong immunosuppression of T cell proliferation. The adoptive transfer of cMDSCs improved the hyperglycemic state in and prolonged the diabetes-free survival of NOD-SCID mice induced by reactive splenic T cells harvested from NOD mice. In addition, cMDSC use reduced fibronectin production in the renal glomeruli and improved pancreatic insulitis in the NOD–SCID mice. Conclusions The administration of cMDSCs propagated from GM-CSF, IL-6, and IL-1β cytokines provides an alternative immunotherapy protocol for the treatment of diabetic pancreatic insulitis and renal nephropathy.

Background: Malnutrition in patients with tuberculosis (TB) is associated with poor outcomes. This study assessed the validity of the patient-generated subjective global assessment (PG-SGA) in adult TB patients and examined the association of the PG-SGA score with adverse outcomes. Methods: This is a retrospective chart review study compared with the well-nourished and malnourished TB patients. The nutritional status was determined using the PG-SGA for adult patients (n = 128). Clinical outcomes included liver injury and mortality. Adverse outcomes included hepatitis during anti-tuberculosis therapy. Results: By comparing nutritional status using global assessment, well-nourished patients had a significantly higher body weight index (p = 0.002), a lower PG-SGA score (p < 0.001), and lower diabetic rate (p = 0.029). Malnourishment was a risk factor (p = 0.022) for liver injury and fatal outcomes (p < 0.001). A higher PG-SGA score was a risk factor for liver injury (p = 0.002) and an independent risk factor for fatal outcomes (p = 0.031). ROC analysis for outcome prediction showed that a PG-SGA score of 5.5 points yielded the most appropriate sensitivity (61.5%) and specificity (64.7%). Conclusion: Both global assessment and the total PG-SGA score were related to tuberculosis outcome and liver injury during anti-TB treatment.