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The article describes a case of emphysematous pyelonephritis in a 42-year-old woman with uncontrolled diabetes mellitus who complained of fever, nausea, dysuria and left flank pain when presented to the emergency department.

This study investigated the effects of weight reduction and/or calcitriol administration on regulating CD4 T cell subsets and renin-angiotensin system (RAS)-associated acute lung injury (ALI) in obese mice with sepsis. Half of the mice were fed a high-fat diet for 16 weeks, half of them had high-fat diet for 12 weeks then were transferred to a low-energy diet for 4 weeks. After feeding the respective diets, cecal ligation and puncture (CLP) were performed to induce sepsis. There were four sepsis groups: OSS group, obese mice injected with saline; OSD group, obese mice given calcitriol; WSS group, mice with weight reduction and saline; WSD group, mice with weight reduction and calcitriol. Mice were sacrificed after CLP. The findings showed that CD4 T subsets distribution did not differ among the experimental groups. Calcitriol-treated groups had higher RAS-associated AT2R, MasR, ACE2, and angiopoietin 1–7 (Ang(1–7)) levels in the lungs. Also, higher tight junction proteins were noted 12 h after CLP. At 24 h post-CLP, weight reduction and/or calcitriol treatment reduced plasma inflammatory mediator production. Calcitriol-treated groups had higher CD4/CD8, T helper (Th)1/Th2 and lower Th17/regulatory T (Treg) ratios than the groups without calcitriol. In the lungs, calcitriol-treated groups had lower AT1R levels, whereas the RAS anti-inflammatory protein levels were higher than those groups without calcitriol. Lower injury scores were also noted at this time point. These findings suggested weight reduction decreased systemic inflammation. However, calcitriol administration produced a more-balanced Th/Treg distribution, upregulated the RAS anti-inflammatory pathway, and attenuated ALI in septic obese mice. [Display omitted] • Obesity and low vitamin D levels may aggravate immune dysregulation and organ injury in sepsis. • Weight reduction before and/or IV calcitriol treatment after sepsis can attenuate the systemic inflammatory response. • The influences of weight reduction on blood CD4+ T cell polarization and RAS-associated pathway in the lungs are minimal. • Calcitriol treatment upregulates RAS anti-inflammatory pathway and alleviates lung injury in septic obese mice. [ABSTRACT FROM AUTHOR]

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is a common liver comorbidity with considerable global consequences. This study explores the efficacy of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor primarily used to manage type 2 diabetes, in reducing liver steatosis among NAFLD patients., Methods: This randomized, open-label, two-arm, parallel-group trial enrolled patients with NAFLD and a controlled attenuation parameter (CAP) score of ≥ 252 dB/m. Participants were randomized (1:1) into either the control or dapagliflozin groups. The primary outcome was the change in CAP scores, measured with FibroScan after 24 weeks., Results: The trial included 150 patients, 20 of whom (13%) had type 2 diabetes. In week 24, the dapagliflozin group had significantly lower CAP score and fatty liver grade than did the control group (266.3 ± 57.8 50 vs 298.6 ± 59.0 dB/m, respectively [p = 0.002]; 1.7 ± 0.7 vs 2.2 ± 0.8, respectively [p < 0.001]). Liver stiffness, waist circumference, and alanine transaminase levels decreased in both the dapagliflozin and control groups, but the between-group differences were nonsignificant (1.0 ± 0.3 vs 1.1 ± 0.3 [p = 0.678], 94.2 ± 12.7 vs 92.4 ± 11.1 [p = 0.382], and 28.8 ± 18.3 vs 28.3 ± 14.2 U/L [p = 0.856], respectively). In the multivariate analysis, a reduction in CAP was associated with dapagliflozin treatment (p = 0.01) and changes in BMI (p = 0.007). No adverse events were observed., Conclusion: Dapagliflozin can reduce CAP score and fatty liver grade in patients with moderate to severe NAFLD, regardless of their diabetes status., Competing Interests: Declarations. Conflict of interest: Meng-Tzu Weng, Po-Jen Yang, Pan-Fu Liu, Chin-Hao Chang, Hsuan-Shu Lee, Jin-Chuan Sheu and Hsiao-Ching Nien declare that they have no conflicts of interest to disclose regarding the publication of this article. Ethical approval: This study was approved by the Research Ethics Committee of the National Taiwan University Hospital (approval number: 202104098MIPC) and performed in accordance with the ethical standards as laid down in the Helsinki Declaration of 1975, as revised in 2008. All participants signed informed consent for the study. Consent for publication: All authors approved the manuscript for publication., (© 2024. Asian Pacific Association for the Study of the Liver.)

Background/purpose: Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for patients with morbid obesity, but the optimal gastric volume (GV) for resection remains unclear. Accordingly, we aimed to determine the optimal percentage of excised stomach that could engender significant weight loss and improve fatty liver., Methods: This prospective study included 63 patients. Computed tomography (CT) scans were performed before and 1 year after LSG to evaluate the gastric lumen (GL) and GV. Specifically, the stomach was distended with effervescent powder, following water-contrast mixture (20:1) and assessed by three-dimensional reconstruction. The correlations of reduced gastric lumen/volume (RGL/RGV) with total body weight (BW) loss and liver-spleen density ratio (LSDR) changes were analyzed, and optimal RGL/RGV associated with significant BW and fatty liver changes were determined., Results: We noted a positive correlation between the percentage of RGV/RGL (%RGV/%RGL) and percentage of total weight loss (%TWL; r = 0.359, p = 0.004 and r = 0.271, p = 0.032). Furthermore, a %RGL value of >78.2% and %RGV value of >75.3% were associated with more significant BW loss than did limited excision (both p < 0.01). On the other hand, LSDR values increased significantly after LSG, corresponding to the improvement of fatty liver disease at %RGL and %RGV values of >59.1% and >56.4% (both p < 0.01), respectively., Conclusion: %RGV and %RGL were determined to be factors affecting LSG outcomes. LSG engendered significantly more BW loss when %RGV was >75.3% and resulted in fatty liver disease improvement when %RGV was >56.4%., Competing Interests: Declaration of competing interest None. All authors declare no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Diabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus (T2DM) that leads to systemic inflammation. Maternally expressed gene 3 (MEG3) is a tumor suppressor that is involved in inflammation regulation. The current study investigated the association between DKD and the prevalence of the single-nucleotide polymorphisms (SNPs) of MEG3., Methods: A total of 706 and 735 patients were included in the DKD and non-DKD groups, respectively. The five SNPs of MEG3, namely rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G), and rs11160608 (A/C), were genotyped using TaqMan allelic discrimination., Results: Our results revealed that, in the DKD group, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.703, 95% CI: 0.506-0.975, P = 0.035). In addition, in the pre-ESRD DKD subgroup, the distribution of the TG + GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.637, 95% CI: 0.421-0.962, P = 0.032). In addition, among men in the DKD subgroup, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.630, 95% CI: 0.401-0.990, P = 0.045). Glycated hemoglobin (HbA1c) level was significantly higher in all T2DM patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.020). In addition, HbA1c levels were significantly higher in male patients and male DKD patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.032 and 0.031, respectively)., Conclusion: MEG3 SNP rs3087918 is significantly less prevalent in patients with DKD, and the SNP rs3087918 of MEG3 is associated with lower HbA1c levels., (© 2024. The Author(s).)

Diabetic kidney disease (DKD) is the gradual loss of renal function occurring in patients with diabetes. Stromal cell-derived factor-1 (SDF-1, encoded by SDF-1 gene) is a chemokine that binds to its receptor, CXCR4, to mediate many aspects of renal biology. To test the potential impact of SDF-1/CXCR4 gene variations on the risk for DKD, single-nucleotide polymorphisms (SNPs) of SDF-1/CXCR4 genes were genotyped in 388 DKD patients and 335 DKD-free diabetic controls. Among 6 SNPs examined, we demonstrated that rs1801157 of SDF-1 gene was associated with an increased risk for DKD (GA vs GG, AOR=2.252, p =0.035; GA+AA vs GG, AOR=2.156, p =0.036). Further stratification revealed that the correlation of rs1801157 with DKD was particularly detected in diabetic patients with early CKD but not in those with severe renal impairment. Instead, another SNP of SDF-1 gene, rs266085, was found in association with the advanced form of DKD (TC vs TT, AOR=2.106, p =0.027; TC+CC vs TT, AOR=2.130, p =0.019), indicating differential impacts of SDF-1 gene polymorphisms on the progressive loss of renal function in diabetic patients. Moreover, preliminary survey of public gene expression datasets showed that rs1801157 and rs266085 modulated SDF-1 expression in many human tissues, and SDF-1/CXCR4 levels were elevated in renal tissues of DKD patients. These data suggest that allele-specific expression of SDF-1 gene may influence DKD progression., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, whose complex etiology involves a genetic component. Growth arrest-specific 5 (GAS5), a long noncoding RNA (lncRNA) gene, has been recently shown to regulate renal fibrosis. Here, we aimed to explore the potential role of GAS5 gene polymorphisms in the predisposition to DKD. One single-nucleotide (rs55829688) and one insertion/deletion polymorphism (rs145204276) of GAS5 gene were surveyed in 778 DKD cases and 788 DKD-free diabetic controls. We demonstrated that diabetic subjects who are heterozygous at rs55829688 (TC; AOR, 1.737; 95% CI, 1.028-2.937; p=0.039) are more susceptible to advanced DKD but not early-staged DKD, as compared to diabetic subjects who are homozygous for the major allele of rs55829688 (TT). Carriers of at least one minor allele (C) of rs55829688 (TC and CC; AOR, 1.317; 95% CI, 1.023-1.696; p=0.033) more frequently suffer from advanced DKD than do those homozygotes for the major allele (TT). Furthermore, in comparison to those who do not carry the minor allele of rs55829688 (TT), advanced DKD patients possessing at least one minor allele of rs55829688 (TC and CC) exhibited a lower glomerular filtration rate, revealing an impact of rs55829688 on renal co-morbidities of diabetes. In conclusion, our data indicate an association of GAS5 gene polymorphisms with the progression of DKD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The Sodium-glucose co-transporter 2 (SGLT2) inhibitor is an anti-glycemic agent that frequently used in type 2 diabetes mellitus (T2DM) with antioxidant effects. Endometrial cancer (EC) is a common gynecological malignancy that correlates with oxidative stress. The aim in the present study is to survey the potential association between the SGLT2 inhibitor administration and the incidence of EC by the application of the National Health Insurance Research Database (NHIRD) of Taiwan. A retrospective cohort study was directed and the T2DM participants were divided into the SGLT2 inhibitors users and non-SGLT2 inhibitors users. After matching, a total of 163,668 and 327,336 participants were included into the SGLT2 inhibitors and control groups, respectively. The primary outcome is regarded as the development of EC according to the diagnostic, image, and procedure codes. Cox proportional hazard regression was employed to generate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of EC between the two groups. There were 422 and 876 EC events observed in the SGLT2 inhibitors and control groups, respectively. The SGLT2 inhibitors group demonstrated a significantly lower incidence of EC formation compared to the control groups (aHR: 0.87, 95% CI: 0.76-0.99). In the subgroup analysis, the correlation between SGLT2 inhibitor administration and lower rate of EC existed in the T2DM individuals with aged under 60. Moreover, the association between SGLT2 inhibitor administration and lower EC incidence only presented in the T2DM population with SGLT2 inhibitor administration under one year (aHR: 0.58, 95% CI: 0.45-0.73). In conclusion, the administration of SGLT2 inhibitors correlates to lower incidence of EC in T2DM population., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Lung adenocarcinoma (LUAD) is the most frequent histological subtype of lung cancer, which is the most common malignant tumor and the main cause of cancer-related mortality globally. Recent reports revealed that long non-coding RNA (lncRNA) of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in tumorigenesis and metastasis development in lung cancer. However, the contribution of MALAT1 genetic variants to the development of LUAD is unclear, especially in epidermal growth factor receptor (EGFR) mutation status. In this study, 272 LADC patients with different EGFR status were recruited to dissect the allelic discrimination of the MALAT1 polymorphisms at rs3200401, rs619586, and rs1194338. The findings of the study showed that MALAT1 polymorphisms rs3200401, rs619586, and rs1194338 were not associated to LUAD susceptibility; however, rs3200401 polymorphisms was significantly correlated to EGFR wild-type status and tumor stages in LUAD patients in dominant model (p=0.016). Further analyses using the datasets from The Cancer Genome Atlas (TCGA) revealed that lower MALAT1 mRNA levels were associated with the advanced stage, and lymph node metastasis in LADC patients. In conclusion, our results showed that MALAT1 rs3200401 polymorphisms dramatically raised the probability of LUAD development.

Background: The superior effects of gastric bypass surgery in preventing cardiovascular diseases compared with sleeve gastrectomy are well-established. However, whether these effects are independent of weight loss is not known., Methods: In this retrospective cohort study, we compared the change in cardiometabolic risks of 1073 diabetic patients undergoing Roux-en-Y gastric bypass (RYGB) (n = 265), one-anastomosis gastric bypass (OAGB) (n = 619), and sleeve gastrectomy (SG) (n = 189) with equivalent weight loss from the Min-Shen General Hospital. Propensity score-weighting, multivariate regression, and matching were performed to adjust for baseline differences., Results: After 12 months, OAGB and, to a lesser extent, RYGB exhibited superior effects on glycemic control compared with SG in patients with equivalent weight loss. The effect was significant in patients with mild-to-modest BMI reduction but diminished in patients with severe BMI reduction. RYGB and OAGB had significantly greater effects in lowering total and low-density lipoprotein cholesterol than SG, regardless of weight loss. The results of matching patients with equivalent weight loss yielded similar results. The longer length of bypassed biliopancreatic (BP) limbs was correlated with a greater decrease in glycemic levels, insulin resistance index, lipids, C-reactive protein (CRP) levels, and creatinine levels in patients receiving RYBG. It was correlated with greater decreases in BMI, fasting insulin, insulin resistance index, and C-reactive protein levels in patients receiving OAGB., Conclusion: Diabetic patients receiving OAGB and RYGB had lower glucose and cholesterol levels compared with SG independent of weight loss. Our results suggest diabetic patients with cardiovascular risk factors such as hypercholesterolemia to receive bypass surgery., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Sepsis is a lethal syndrome with T-cell dysregulation, imbalanced inflammatory reactions, and gastrointestinal dysfunction. Obesity coexistent with sepsis can cause more-deleterious disease outcomes. Vitamin D is a nutrient with immunomodulatory ability and helps maintain intestinal homeostasis. This study investigated treatment with calcitriol on mesenteric lymph node (MLN) CD4 + T-cell polarization and intestinal injury in obese mice with sepsis., Methods: Mice received a high-fat diet for 10 weeks; then, mice were separated into an obese control group without sepsis and sepsis groups that underwent cecal ligation and puncture (CLP). Septic mice were subdivided into a group that was injected with saline (SS group) or a group that was injected with calcitriol (SD group) via a tail vein 1 h after CLP. Obese mice with sepsis were euthanized at 12 or 24 h post CLP., Results: Sepsis resulted in increased percentages of type 2 T helper (Th2), Th17, and regulatory T (Treg) cells in MLNs. Also, inflammation-associated genes were upregulated and tight junction genes downregulated in the intestines after CLP. Compared with the SS group, the SD group exhibited reduced Th2, Th17, and Treg percentages in MLNs. Also, intestinal inflammatory chemokine expressions were reduced, whereas MUC2, ZO-1, and occludin had increased after CLP. Lower inflammatory cytokine levels in peritoneal lavage fluid in the ileum were also noted in the SD group., Conclusions: Intravenous calcitriol treatment after sepsis can elicit more-balanced CD4 T-cell subsets in lymph nodes near the intestines and alleviate intestinal inflammation and injury in obese mice complicated with sepsis., (© 2022 American Society for Parenteral and Enteral Nutrition.)

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4 + T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4 + T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4 + T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4 + T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4 + T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis.

Background: Continuous ambulatory peritoneal dialysis is one of the main treatments for end-stage renal disease. To correct mechanical outflow obstruction after open surgical methods of catheter insertion, laparoscopic techniques are widely employed. ♢, Methods: Between January 2001 and December 2006, 228 open Tenckhoff catheter implantations were carried out by mini-laparotomy in 218 patients at our medical center. The procedures were all performed by an experienced surgeon, and the postoperative care, patient education, and long-term follow-up were all conducted by the same peritoneal dialysis team. ♢, Results: Infection of the exit site or tunnel was the most common complication (27/228, 11.8%), followed by peritonitis (18/228, 7.9%) and refractory mechanical catheter obstruction (9/228, 3.9%). The main causes of catheter removal were successful renal transplantation (21/228, 9.2%), peritonitis (18/228, 7.9%), and infection of the exit site or tunnel (7/228, 3.1%). In the 9 cases of refractory mechanical catheter obstruction, laparoscopic surgery was performed to identify the pathology and to rescue the catheter at the same time. Omental wrapping was the major cause (8/9) of catheter obstruction, with blood clot in the lumen and tube migration occurring in the remaining case (1/9). Partial omentectomy was performed in 5 patients to prevent recurrent obstruction. Neither technique failure nor operation-related complications were noted in our laparoscopic rescue group. For 20 of the 25 patients with refractory infection of the exit site or tunnel, the salvage technique of partial re-plantation was performed, with an 85% (17/20) technique survival rate. ♢, Conclusions: With an experienced surgeon and a good postoperative care team, open paramedian placement is a simple, safe, and effective method for Tenckhoff catheter insertion, with a low complication rate. Laparoscopic surgery is effective as rescue for mechanical obstruction, and partial re-plantation is effective as salvage for exit-site or tunnel infection.

Gastrojejunostomy is often performed to relieve the symptoms of gastric outlet obstruction. The recent trend is toward minimally-invasive procedures to reduce recovery time and increase quality of life. However, several problems and complications have been reported using gas-filled laparoscopy, especially in the elderly and patients with poor cardiopulmonary function. Consequently, we developed a new gasless laparoscopy-assisted gastrojejunostomy procedure to eliminate the cardiopulmonary risks of gas-filled laparoscopic surgery. The working cavity is created by lifting the mini-laparotomy incision using a self-supporting retractor that we designed, and two to three additional working ports are created. Antecolic side-to-side gastrojejunostomy is performed using an endostapler. Eleven patients (3 males and 8 females) underwent this new procedure between April 2005 and May 2006. Their median age was 75 years (range 34 to 85), and eight of the eleven had more than three comorbid conditions. The median duration of postoperative flatus was 2 days (1-10 days), and the median hospital stay 10 days (5-28 days). No postoperative leakage occurred. However, one patient with postoperative gastrostasis and another with ileus due to cancer-related peritonitis were noted; fortunately, both responded to conservative medical management. In conclusion, our gasless, laparoscopy-assisted gastrojejunostomy procedure appears to be both safe and effective in patients with gastric outlet obstruction.