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BMJ Open Diabetes Research & Care May 2024ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing...
INTRODUCTION
ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.
RESEARCH DESIGN AND METHODS
Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.
RESULTS
The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.
CONCLUSIONS
Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.
TRIAL REGISTRATION NUMBER
UMIN000011525.
Topics: Humans; Male; Female; Diabetic Nephropathies; Angiotensin-Converting Enzyme 2; Biomarkers; Middle Aged; Glomerular Filtration Rate; Peptidyl-Dipeptidase A; Aged; Prognosis; Disease Progression; Follow-Up Studies
PubMed: 38816205
DOI: 10.1136/bmjdrc-2024-004237 -
The Journal of Biological Chemistry May 2024Infiltration of monocyte-derived cells to sites of infection and injury is greater in males than in females, due in part, to increased chemotaxis, the process of...
Infiltration of monocyte-derived cells to sites of infection and injury is greater in males than in females, due in part, to increased chemotaxis, the process of directed cell movement toward a chemical signal. The mechanisms governing sexual dimorphism in chemotaxis are not known. We hypothesized a role for the store-operated calcium entry (SOCE) pathway in regulating chemotaxis by modulating leading and trailing edge membrane dynamics. We measured the chemotactic response of bone marrow derived macrophages (BMDMs) migrating towards complement component 5a (C5a). Chemotactic ability was dependent on sex and inflammatory phenotype (M0, M1, M2), and correlated with SOCE. Notably, females exhibited a significantly lower magnitude of SOCE than males. When we knocked out the SOCE gene, stromal interaction molecule 1 (STIM1), it eliminated SOCE and equalized chemotaxis across both sexes. Analysis of membrane dynamics at the leading and trailing edges showed that STIM1 influences chemotaxis by facilitating retraction of the trailing edge. Using BTP2 to pharmacologically inhibit SOCE mirrored the effects of STIM1 knockout, demonstrating a central role of STIM/Orai-mediated calcium signaling. Importantly, by monitoring the recruitment of adoptively transferred monocytes in an in vivo model of peritonitis, we show that increased infiltration of male monocytes during infection is dependent on STIM1. These data support a model in which STIM1-dependent SOCE is necessary and sufficient for mediating the sex difference in monocyte recruitment and macrophage chemotactic ability by regulating trailing edge dynamics.
PubMed: 38815866
DOI: 10.1016/j.jbc.2024.107422 -
Turkish Journal of Medical Sciences 2023Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it...
BACKGROUND/AIM
Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it was aimed herein to investigate the effect of intraperitoneal surfactant application on preventing postoperative peritoneal adhesion formation in a uterine horn adhesion model.
MATERIALS AND METHODS
Twenty-one Wistar albino rats were randomly divided into 3 groups (G1-G3), as follows: G1 (n = 7): control group. The abdomen was opened and then closed; G2 (n = 7): adhesion group. The abdomen was opened. Then, a 2-cm linear incision was made over the right uterine horn, 2 mL of isotonic saline was administered intraperitoneally, and the abdomen was closed; and G3 (n = 7): treatment group. The abdomen was opened, a 2-cm linear incision was made over the right uterine horn, 2 mL (70 mg/kg) of surfactant was administered intraperitoneally, and the abdomen was closed. After 15 days, the rats were euthanized, the abdomens were reopened, and adhesion scoring was performed. After the right uterine horns were removed and fixed with 10% formalin, appropriate sections were taken from the traumatized tissue, stained with Masson's trichrome, and fibrosis and inflammation scoring were performed.
RESULTS
The adhesion area and intensity were significantly higher in G2 than in G1 and G3 (p = 0.001) and were similar in G1 and G3 (p = 0.165). While fibrosis and inflammation were significantly higher in G2 than in G1 and G3 (p = 0.001), there was no difference between G1 and G3 (p = 0.5).
CONCLUSION
Intraperitoneal surfactant administration at a dose of 70 mg/kg was found to be effective in preventing intraabdominal adhesion formation in a rat uterine horn model.
Topics: Animals; Tissue Adhesions; Rats, Wistar; Female; Surface-Active Agents; Rats; Postoperative Complications; Injections, Intraperitoneal; Uterus; Disease Models, Animal
PubMed: 38813488
DOI: 10.55730/1300-0144.5752 -
Heliyon May 2024No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation....
INTRODUCTION
No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation. We hypothesize that dialysate CypA can be a marker for historical peritonitis (at least 3 months free from peritonitis).
METHOD
An enzyme-linked immunosorbent assay kit was used to measure the concentration of dialysate CypA. Clinical and laboratory data were collected to correlate with historical peritonitis. Mann-Whitney test and -square test were used for analysis. Receiver operating characteristic (ROC) analysis was used to evaluate predictive power.
RESULTS
Out of a total of 31 patients who had undergone PD for at least 2 years, 18 had no history of PD-related peritonitis, while 13 had experienced PD-related peritonitis at least once. Overall, the patients in this population were in good health (normal white blood cell count, no anemia, normal electrolyte and serum albumin levels). There were no significant differences between patients with and without a history of peritonitis, except for blood white blood cell count (5650.6 ± 1848.4 vs. 7154.6 ± 2056.8, p = 0.032) and dialysate CypA value (24.27 ± 22.715 vs. 54.41 ± 45.63, p = 0.020). In the univariate analysis, only the dialysate CypA level showed a statistically significant association with historical peritonitis (HR = 1.030, 95 % CI = 1.010-1.062, p = 0.046). The AUC for dialysate CypA (>34.83 ng/mL) was 0.748, with a sensitivity of 0.615 and specificity of 0.833.
CONCLUSION
PD peritonitis poses a significant threat to the long-term use of peritoneal dialysis. Based on our study, even in the absence of concurrent infection, dialysate CypA can serve as a predictive marker for historical peritonitis, demonstrating high predictive power along with fair sensitivity and good specificity.
PubMed: 38813216
DOI: 10.1016/j.heliyon.2024.e31021 -
EClinicalMedicine Jun 2024Caesarean section (CS) is the most performed major surgery worldwide. Surgical techniques used for CS vary widely and there is no internationally accepted... (Review)
Review
BACKGROUND
Caesarean section (CS) is the most performed major surgery worldwide. Surgical techniques used for CS vary widely and there is no internationally accepted standardization. We conducted an overview of systematic reviews (SR) of randomized controlled trials (RCT) to summarize the evidence on surgical techniques or procedures related to CS.
METHODS
Searches were conducted from database inception to 31 January 2024 in Cochrane Database of Systematic Reviews, PubMed, EMBASE, Lilacs and CINAHL without date or language restrictions. AMSTAR 2 and GRADE were used to assess the methodological quality of the SRs and the certainty of evidence at outcome level, respectively. We classified each procedure-outcome pair into one of eight categories according to effect estimates and certainty of evidence. The overview was registered at PROSPERO (CRD 42023208306).
FINDINGS
The analysis included 38 SRs (16 Cochrane and 22 non-Cochrane) published between 2004-2024 involving 628 RCT with a total of 190,349 participants. Most reviews were of low or critically low quality (AMSTAR 2). The SRs presented 345 procedure-outcome comparisons (237 procedure versus procedure, 108 procedure versus no treatment/placebo). There was insufficient or inconclusive evidence for 256 comparisons, clear evidence of benefit for 40, possible benefit for 17, no difference of effect for 13, clear evidence of harm for 14, and possible harm for 5. We found no SRs for 7 pre-defined procedures. Skin cleansing with chlorhexidine, Joel-Cohen-based abdominal incision, uterine incision with blunt dissection and cephalad-caudal expansion, cord traction for placental extraction, manual cervical dilatation in pre-labour CS, changing gloves, chromic catgut suture for uterine closure, non-closure of the peritoneum, closure of subcutaneous tissue, and negative pressure wound therapy are procedures associated with benefits for relevant outcomes.
INTERPRETATION
Current evidence suggests that several CS surgical procedures improve outcomes but also reveals a lack of or inconclusive evidence for many commonly used procedures. There is an urgent need for evidence-based guidelines standardizing techniques for CS, and trials to fill existing knowledge gaps.
FUNDING
UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO).
PubMed: 38812964
DOI: 10.1016/j.eclinm.2024.102632 -
Therapeutic Advances in Gastroenterology 2024Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE);...
INTRODUCTION
Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been suggested that it may play a crucial role in reducing infections in these populations.
AIM
To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections [spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia], e infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug.
METHODS
A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching.
RESULTS
We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 [95% confidence interval (CI) (0.47-0.89); = 0.008]. However, no discernible impact on mortality outcome was observed [IRR 1.9, 95% CI (0.9-4.0); = 0.09]. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects.
CONCLUSION
The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis.
PubMed: 38812703
DOI: 10.1177/17562848241254267 -
Radiology Case Reports Aug 2024A jejunal intussusception as a presentation of retroperitoneal liposarcoma (RLPS) is a rare occurrence. The majority of RLPS are presented as an abdominal mass, however,...
A jejunal intussusception as a presentation of retroperitoneal liposarcoma (RLPS) is a rare occurrence. The majority of RLPS are presented as an abdominal mass, however, having a jejunal obstruction is an interesting case. The aim is to describe the management of jejunal intussusception secondary to atypical lipomatous tumours with concurrent RLPS. A 61-year-old lady presented with a sudden onset of intestinal obstruction with 1 month of constitutional symptoms and an enlarging right lumbar mass. Computed tomography showed a small bowel intussusception with diffuse peritoneal and retroperitoneal lipomatosis. Emergency exploratory laparotomy, segmental bowel resection, and partial excision of intraperitoneal mesenteric lipoma were performed. A stage En-bloc resection of the RLPS and right nephrectomy was done later. However, she refused for subsequent surgery. A complete resection is the gold standard in managing RLPS. In this report, the management is rendered not to the standard as the patient first presented with intestinal obstruction requiring emergency reduction with a piecemeal resection. A stage surgery was required to determine a promising prognosis, but the patient refused such surgery. A small bowel intussusception in adults is rare but is mostly caused by a tumor or neoplasm. Early recognition of the complexity of the case should be preempted and referred to the tertiary team for further definitive surgery. Patient exhaustion from the subsequent surgery might hamper the only management available for the case.
PubMed: 38812591
DOI: 10.1016/j.radcr.2024.04.021 -
Frontiers in Veterinary Science 2024This report describes a case of transmural migration of a gossypiboma from the peritoneum into the urinary bladder in a 4-year-old, female spayed, mixed-breed dog. The...
This report describes a case of transmural migration of a gossypiboma from the peritoneum into the urinary bladder in a 4-year-old, female spayed, mixed-breed dog. The dog was presented on an emergency basis for complete urethral obstruction with radiographic evidence of urocystolithiasis. An exploratory laparotomy was performed and a 4-5 cm mass was identified which was confluent with the apex of the urinary bladder. The mass and bladder were exteriorized and isolated, and an apical, partial cystectomy was performed to remove the mass and gain access to the uroliths within the lumen of the bladder. A 4×4 surgical sponge was identified within the trigone of the bladder, it had multiple uroliths; another sponge was also found within the mass itself. This case demonstrates an atypical cause of urethral obstruction and serves as the first reported case of transmural migration of a gossypiboma into the urinary bladder of a dog. It also illustrates the importance of establishing routine operating procedures including gauze counts and the use of radiopaque-labeled surgical gauze.
PubMed: 38812558
DOI: 10.3389/fvets.2024.1394052 -
IScience Jun 2024Cancer-mesothelial cell interactions are critical for multiple solid tumors to colonize the surface of peritoneal organs. Understanding mechanisms of mesothelial barrier...
Cancer-mesothelial cell interactions are critical for multiple solid tumors to colonize the surface of peritoneal organs. Understanding mechanisms of mesothelial barrier dysfunction that impair its protective function is critical for discovering mesothelial-targeted therapies to combat metastatic spread. Here, we utilized a live cell imaging-based assay to elucidate the dynamics of ovarian cancer spheroid transmesothelial migration and mesothelial-generated mechanical forces. Treatment of mesothelial cells with the adenylyl cyclase agonist forskolin strengthens cell-cell junctions, reduces actomyosin fibers, contractility-driven matrix displacements, and cancer spheroid transmigration in a protein kinase A (PKA)-dependent mechanism. We also show that inhibition of the cytoskeletal regulator Rho-associated kinase in mesothelial cells phenocopies the anti-metastatic effects of forskolin. Conversely, upregulation of contractility in mesothelial cells disrupts cell-cell junctions and increases the clearance rates of ovarian cancer spheroids. Our findings demonstrate the critical role of mesothelial cell contractility and mesothelial barrier integrity in regulating metastatic dissemination within the peritoneal microenvironment.
PubMed: 38812549
DOI: 10.1016/j.isci.2024.109950 -
JAMA Network Open May 2024People with kidney failure receiving maintenance dialysis visit the emergency department (ED) 3 times per year on average, which is 3- to 8-fold more often than the...
IMPORTANCE
People with kidney failure receiving maintenance dialysis visit the emergency department (ED) 3 times per year on average, which is 3- to 8-fold more often than the general population. Little is known about the factors that contribute to potentially preventable ED use in this population.
OBJECTIVE
To identify the clinical and sociodemographic factors associated with potentially preventable ED use among patients receiving maintenance dialysis.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used linked administrative health data within the Alberta Kidney Disease Network to identify adults aged 18 years or older receiving maintenance dialysis (ie, hemodialysis or peritoneal dialysis) between April 1, 2010, and March 31, 2019. Patients who had been receiving dialysis for more than 90 days were followed up from cohort entry (defined as dialysis start date plus 90 days) until death, outmigration from the province, receipt of a kidney transplant, or end of study follow-up. The Andersen behavioral model of health services was used as a conceptual framework to identify variables related to health care need, predisposing factors, and enabling factors. Data were analyzed in March 2024.
MAIN OUTCOMES AND MEASURES
Rates of all-cause ED encounters and potentially preventable ED use associated with 4 kidney disease-specific ambulatory care-sensitive conditions (hyperkalemia, heart failure, volume overload, and malignant hypertension) were calculated. Multivariable negative binomial regression models were used to examine the association between clinical and sociodemographic factors and rates of potentially preventable ED use.
RESULTS
The cohort included 4925 adults (mean [SD] age, 60.8 [15.5] years; 3071 males [62.4%]) with kidney failure receiving maintenance hemodialysis (3183 patients) or peritoneal dialysis (1742 patients) who were followed up for a mean (SD) of 2.5 (2.0) years. In all, 3877 patients had 34 029 all-cause ED encounters (3100 [95% CI, 2996-3206] encounters per 1000 person-years). Of these, 755 patients (19.5%) had 1351 potentially preventable ED encounters (114 [95% CI, 105-124] encounters per 1000 person-years). Compared with patients with a nonpreventable ED encounter, patients with a potentially preventable ED encounter were more likely to be in the lowest income quintile (38.8% vs 30.9%; P < .001); to experience heart failure (46.8% vs 39.9%; P = .001), depression (36.6% vs 32.5%; P = .03), and chronic pain (60.1% vs 54.9%; P = .01); and to have a longer duration of dialysis (3.6 vs 2.6 years; P < .001). In multivariable regression analyses, potentially preventable ED use was higher for younger adults (incidence rate ratio [IRR], 1.69 [95% CI, 1.33-2.15] for those aged 18 to 44 years) and patients with chronic pain (IRR, 1.35 [95% CI, 1.14-1.61]), greater material deprivation (IRR, 1.57 [95% CI, 1.16-2.12]), a history of hyperkalemia (IRR, 1.31 [95% CI, 1.09-1.58]), and historically high ED use (ie, ≥3 ED encounters in the prior year; IRR, 1.46 [95% CI, 1.23-1.73).
CONCLUSIONS AND RELEVANCE
In this study of adults receiving maintenance dialysis in Alberta, Canada, among those with ED use, 1 in 5 had a potentially preventable ED encounter; reasons for such encounters were associated with both psychosocial and medical factors. The findings underscore the need for strategies that address social determinants of health to avert potentially preventable ED use in this population.
Topics: Humans; Male; Female; Emergency Service, Hospital; Middle Aged; Renal Dialysis; Aged; Alberta; Adult; Cohort Studies; Kidney Failure, Chronic
PubMed: 38809552
DOI: 10.1001/jamanetworkopen.2024.13754