Decreased Serum Albumin Levels Research Articles

Sex-specific modulation of renal epigenetic and injury markers in aging kidney.

Sex differences in renal physiology and pathophysiology are well established in rodent models and humans. While renal epigenetics play a crucial role in injury, the impact of biological sex on aging kidney epigenome is less known, as most of the studies are from male rodents. We sought to determine the influence of sex and age on kidney epigenetic and injury markers, using male and female mice at 4-month (4M; young), 12-month (12M), and 24-month (24M; aged) of age. Females exhibited a significant increase in kidney and body weight and serum creatinine and decreased serum albumin levels from ages 4M to 24M, whereas minor changes were observed in male mice. Males exhibited higher levels of circulating histone 3 (H3; damage-associated molecular pattern molecules) compared with age-matched females. Kidney injury molecule-1 levels increased in serum and renal tissues from 12M to 24M in both sexes. Overall, females had markedly high histone acetyltransferase activity than age-matched males. Aged females had substantially decreased H3 methylation at lysine 9 and 27 and histone methyltransferase activity compared to aged males. Klotho levels were significantly higher in young males than females and decreased with age in males, whereas epigenetic repressor of Klotho, H3K27me3 and its enzyme, EZH2 augmented with age in both sexes. Proinflammatory NF-κB (p65) signaling increased with age in both sexes. Taken together, our data suggest that renal aging may lie in a range between normal and diseased kidneys, but differ between female and male mice, highlighting sex-specific regulation of renal epigenome in aging.

Development rat models of nephrotoxic: A pre-clinical test model to discover nephroprotective agents

Background: The use of drugs, including aminoglycoside drugs and anticancer drugs, is one of the things that can cause toxicity to the kidneys. Therefore, the development of agents that function as nephroprotectors continues to be researched. Objective: This study aims to obtain a nephrotoxic experimental animal model for testing nephroprotective agents. Method: The treatment was normal group, groups given a single dose of Cisplatin 7 mg/kgBW i.p (Cis), Doxorubicin single dose 25 mg/kgBW i.p (Dox-25), Doxorubicin repeated dose 4 mg/kgBW i.p twice/week for two weeks (Dox-4 repeated dose), and Gentamicin single dose 112 mg/kgBW i.p (Gen). The nephrotoxic effect was assessed by the parameters of kidney weight ratio, Ureum, Creatinine and Albumin levels in rat serum. Result: The nephrotoxic effect was indicated by an increase in the renal weight ratio of the Cisplatin; Dox-25, Dox-4 repeated, and Gen groups than normal, respectively. There was an increase in serum BUN levels, an increase in serum creatinine, and a decrease in serum albumin levels compared to the normal group. Conclusion: Cisplatin, Doxorubicin and Gentamicin have nephrotoxic effects. The administration of a single dose of cisplatin at 7 mg/kg BW gave the strongest nephrotoxic effect, making it appropriate as a model of acute nephrotoxicity in rats.

Open distal pancreatectomy stump closure by linear stapling versus continuous suturing: a retrospective–prospective comparative study

Background Distal pancreatectomy (DP), performed for removing pancreatic lesions located to the left of the superior mesenteric vein, accounts for ~25% of all pancreatic resections. Most recently reported overall mortality rate of DP is less than 3%. However, albeit technically simpler to perform than pancreaticoduodenectomy, morbidity rate of DP remains substantial. Postoperative pancreatic fistulas (POPFs), which may result in numerous clinically significant and potentially life-threatening complications such as intraabdominal abscess, hemorrhage, and surgical site infection, is the leading cause of morbidity after DP, with an incidence of ~30–60%. Risk factors associated with POPFs after DP include decreased serum albumin levels, concurrent splenectomy, increased body weight, increased duration of surgery, higher American Society of Anesthesiologists score, and impaired renal function. Furthermore, POPFs often translate to significant increases in hospitalization costs. Objective To compare the technique of DP stump closure in two groups of patients; a group underwent stump closure with linear stapling technique and the other group underwent stump closure with continuous suturing technique. Patients and methods This was a retrospective–prospective clinical trial that was conducted at General Surgery Department, Ain Shams University Hospitals on 30 patients who were admitted to specialized hepatobiliary units in Cairo, Egypt for open DP. Between January 2020 and June 2022 with postoperative follow-up period of 2 months. In our study, there were 30 patients (15 in the continuous suturing technique group and 15 in the linear stapling technique group) with a mean age of 45.37±10.662 years. Groups were similar in demographic and clinical characteristics (P>0.05). Results In our study, 13.33% patients in continuous suturing technique group developed clinically relevant POPF (grade B and grade C POPF), whereas 33.33% patients in stapling technique group develop POPF (P=1.00). The amount of the blood loss which was found to be statistically significant as the P value was found less than 0.05 and the t test was found to be −2.396 which mean that the amount of the blood lost was more in the stapler group. There was no statistically significant difference in the rate of clinically relevant POPF (grade B and grade C POPF) with suture closure compared with stapler closure (13.33 vs. 33.33%). There was no statistically significant difference in the risk of intraabdominal abscess. There were three (20%) patients with a biochemical leak in continuous suturing technique group. In stapling technique group, three (20%) patients developed biochemical leaks. There was no significant in difference between groups in terms of biochemical leak. In our study, mortality rates did not differ between stapler and suture closure techniques. Conclusion Our study showed no significant difference between suture and stapler closure of DP stump with respect to POPF or intraabdominal collection after DP. The amount of the blood lost was more in the stapler group.

Nephrotic syndrome due to focal segmental glomerulosclerosis complicating scleroderma: a case report

BackgroundSystemic scleroderma (SSc) is an insidious autoimmune connective tissue disorder with multiorgan involvement. Renal involvement is one of the important causes of morbidity and mortality in scleroderma; however, nephrotic syndrome is reported rarely in association with SSc. We present a patient with SSc who developed focal segmental glomerulosclerosis (FSGS) as a complication of scleroderma.Case presentationA 59 year old Caucasian female patient, with a known history of diffuse systemic sclerosis from 8 years, presented to our clinic with symptoms of anasarca and weight gain. Her physical examination was unremarkable except for periorbital and extremity edema. Her biochemistry assessment revealed decreased serum albumin levels and elevated serum creatinine levels. A renal biopsy was performed, which showed histopathological patterns of FSGS type of nephrotic syndrome. After administration of high doses of steroid and rituximab in the course of her treatment for 6 months, her symptoms and proteinuria were improved without the occurrence of scleroderma renal crises.ConclusionSSc is a complex multisystemic autoimmune disorder. SRC is the most prominent renal involvement in SSc, but other renal pathologies may also occur. Each patient should be precisely investigated since managing these renal conditions can differ significantly. Nephrotic syndrome is a rare complication of SSc, which could be managed with prompt diagnosis and steroid administration.

The Impact of Medium Cut-Off Dialyzers on Malnutrition-Inflammation Scores in Maintenance Hemodialysis Patients

Introduction: Medium cut-off (MCO) membranes may be able to remove middle-large uremic toxins that are retained in the body, which has been linked to various risk factors including malnutrition-inflammation score (MIS). The effect of MCO dialyzers on MIS has been studied. Methods: This single-center exploratory prospective observational study enrolled maintenance hemodialysis patients who underwent dialysis using either MCO (Theranova 400) or high-flux (FX80) membranes as part of their regular care. Measurements of MIS, body weight, height, body mass index, and various biochemical markers were taken at the beginning and conclusion of the study. Results: This study included 50 patients who were treated with either the Theranova 400 (n = 25) or the FX80 (n = 25) for a period of 6 months. The two groups were similar in terms of demographics, duration of hemodialysis treatment, and baseline biochemical test results. Theranova 400 had no significant impact on the median MIS (6 [6–10] vs. 7 [5-10], p 0.575) and serum albumin levels (4.07 [3.92–4.22] vs. 4.04 [3.85–4.30], p 0.689), while the FX80 resulted in a significant increase in MIS (6 [5–8] vs. 8 [6–10], p 0.033) and a significant decrease in serum albumin levels (4.23 [4.03–4.36] vs. 3.98 [3.77–4.12], p 0.027) at the end of the study. Discussion/Conclusion: After 6 months of treatment, the MCO dialyzer did not demonstrate a statistically significant difference in the MIS when compared to the high-flux dialyzer. However, MIS worsening was significantly less in the MCO group, indicating the potential benefits of MCO membranes in maintaining nutritional status. Further research is required to validate these results.

Identification of risk factors for disseminated cryptococcosis in non-hiv patients: a retrospective analysis

ObjectiveThis study aimed to investigate the potential risk factors associated with disseminated cryptococcosis in HIV-negative individuals.MethodsA total of 106 HIV-negative patients with cryptococcal disease were enrolled. The observation group consisted of patients with disseminated cryptococcosis (DC), whereas the control groups included patients with pulmonary cryptococcosis (PC) and cryptococcal meningitis (CM). Univariate and multivariate logistic regression algorithms were used to explore the significant clinical and laboratory characteristics that affect the progression of cryptococcal infections. Finally, receiver operating characteristics (ROC) curves are applied to assess the diagnostic value of identified risk factors.LE: Kindly check the edit made in the title.I agreeResultsOf the 106 patients, 57 were diagnosed with pulmonary cryptococcosis, 22 with cryptococcal meningitis, and 27 with disseminated cryptococcosis. The logistic regression equation included five variables: diabetes, decompensated liver cirrhosis, long-term use of immunosuppressive agents, decreased serum albumin level, and elevated plasma cytokine IL-10 level. The ROC curves showed that albumin (AUC > 0.7), IL-10 (AUC > 0.7) and decompensated liver cirrhosis (AUC > 0.6) have relatively high diagnostic capacity in predicting the progression of Cryptococcus.ConclusionThis study identified elevated IL-10 levels as an independent risk factor for developing disseminated cryptococcosis in the control groups. Furthermore, decompensated liver cirrhosis and decreased serum albumin independently affected the progression of cryptococcosis in the CM and PC groups, respectively.

Impact of perioperative decreased serum albumin level on anastomotic leakage in esophageal squamous cell carcinoma patients treated with neoadjuvant chemotherapy followed by minimally invasive esophagectomy

BackgroundAnastomotic leakage (AL) is a severe complication following esophagectomy with high mortality. Perioperative decreased serum albumin level is considered a predictive of AL, however, its impact on AL incidence in patients treated with neoadjuvant chemotherapy (NCT) followed by minimally invasive esophagectomy (MIE) is not well defined.MethodsThe data of 318 consecutive esophageal cancer patients who underwent MIE were collected retrospectively from January 2021 to December 2021. The perioperative level of albumin was detected and the baseline of altering levels for albumin was established. The incidence of postoperative complications and survival rate were analyzed between groups.ResultsAfter exclusion, 137 patients were enrolled and assigned to more decreased albumin (MA) and less decreased albumin (LA) groups. The levels of albumin descended significantly after MIE (p < 0.0001). There was no significant difference in the clinicopathologic characteristics or surgical outcomes between groups. The incidence of postoperative AL was 10.2% in MA group and 1.4% in LA group (p = 0.033). Three patients died due to AL in MA group, while no mortality was observed in LA group (p = 0.120). The rate of other postoperative complications was similar between groups. Progression-free survival (PFS) in LA group was a little higher than that in MA group, but it was no significant difference (p = 0.853). Similarly, no difference was observed in overall survival (OS) between groups (p = 0.277).ConclusionsSeverely deficient serum albumin after MIE was an indicator of AL in esophageal cancer patients treated with NCT.Trial registrationChinese clinical trial registry: ChiCTR2200066694, registered December14th,2022. https://www.chictr.org.cn/edit.aspx?pid=185067&htm=4.

Postoperative volume maintenance rate of microvascular free flap in oral and maxillofacial region: Systematic review and meta-analysis

Background and objectivesThe resorption of flap's volume can be frequently observed in the transplantation of microvascular free flaps, which could significantly affect postoperative function. Therefore, it's essential to comprehend the postoperative flap volume and the mechanisms behind before making clinical decisions. MethodsLiterature search was conducted from database on PubMed, EMBASE, Cochrane Library, Chinese database and Google Scholar. A random effects model meta-analyses and descriptive systematic review were performed. ResultsThe search identified 420 articles, of which 9 studies included in meta-analysis and 14 studies included in descriptive systematic review. Postoperative flap volume maintenance rate is used to represent the volume change. The pooled mean postoperative flap volume maintenance rate was 62.82 % for soft tissue flap (95 %CI: 58.83 to 66.82, p = 0.076, I2=56.3 %) and 85.96 % for bone flap (95 %CI: 84.19 to 87.73, p = 0.274, I2=20.4 %). Weight loss, muscle atrophy, and decreased serum albumin levels are risk factors for postoperative volume reduction of soft tissue flaps. The bone resorption rate of bone flaps in women is higher than that in men. ConclusionWhen designing microvascular free flaps for oral and maxillofacial surgery, soft tissue flaps should consider an anticipated postoperative shrinkage of 37 %, while bone flaps should consider an anticipated postoperative shrinkage of 14 %.

Bypass Surgery Provides Better Outcomes Compared with Endovascular Therapy in Patients with Chronic Limb-Threatening Ischemia Classified as Indeterminate Category According to the Global Vascular Guidelines

The present study aimed to determine the preferred initial revascularization procedure between bypass surgery and endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI) categorized as indeterminate according to the Global Vascular Guidelines (GVG). We retrospectively analyzed the multicenter data of patients who underwent infrainguinal revascularization for CLTI categorized as indeterminate according to the GVG between 2015 and 2020. The end point was the composite of relief from rest pain, wound healing, major amputation, reintervention, or death. A total of 255 patients with CLTI and 289 limbs were analyzed. Of the 289 limbs, 110 (38.1%) and 179 (61.9%) underwent bypass surgery and EVT, respectively. The 2-year event-free survival rates with respect to the composite end point were 63.4% and 28.7% in the bypass and EVT groups, respectively (P<0.01). Multivariate analysis revealed that increased age (P=0.03); decreased serum albumin level (P=0.02); decreased body mass index (P=0.02); dialysis-dependent end-stage renal disease (P<0.01); increased Wound, Ischemia, and foot Infection (WIfI) stage (P<0.01); Global Limb Anatomic Staging System (GLASS) III (P=0.04); increased inframalleolar grade (P<0.01); and EVT (P<0.01) were independent risk factors for the composite end point. In the WIfI-GLASS 2-III and 4-II subgroups, bypass surgery was superior to EVT with regard to 2-year event-free survival (P<0.01). Bypass surgery is superior to EVT in terms of the composite end point in patients classified as indeterminate according to the GVG. Bypass surgery should be considered an initial revascularization procedure, especially in the WIfI-GLASS 2-III and 4-II subgroups.

Prognostic Value of Regular Nutritional Treatment in Patients With Amyotrophic Lateral Sclerosis.

Malnutrition adversely affects the prognosis of amyotrophic lateral sclerosis (ALS). The aim of this study was to evaluate the effect of regular nutrition treatment and follow-up in clinical nutrition outpatient clinic (CNOC) on survival in ALS patients. The study included 55 ALS patients who were admitted and followed up in CNOC. Malnutrition was diagnosed using ESPEN criteria and nutrition treatment was planned according to needs of each patient. Nutritional status was followed up by body mass index (BMI), bioelectrical impedence analysis, and serum albumin. During the follow-up, survivors and nonsurvivors were compared according to their nutrition treatment success and changes in the anthropometric and laboratory measurements. Body weight, BMI, and fat free mass were decreased during the follow-up in both survivors and nonsurvivors (P<0.01). The decrease in the serum albumin and BMI were significantly higher in nonsurvivors (P<0.01). Mortality rate was lower in those with higher adherence to nutrition treatment (P<0.01) and patients with lower adherence to nutrition treatment showed more significant decrease in serum albumin levels (P<0.01). A personalized nutrition treatment combined with increased nutritional adherence in CNOC can decrease mortality in ALS patients.

Treatment outcomes between bypass surgery and endovascular therapy in patients with chronic limb-threatening ischemia classified as bypass-preferred category based on Global Vascular Guidelines

ObjectiveThe aim of this study was to examine outcomes between bypass surgery and endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI), classified as bypass-preferred according to the Global Vascular Guidelines (GVG). MethodsWe retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) Stage 3 to 4 and Global Limb Anatomical Staging System (GLASS) Stage III, which is classified as bypass-preferred category by the GVG between 2015 and 2020. The endpoints were limb salvage and wound healing. ResultsWe analyzed 301 patients and 339 limbs following 156 bypass surgeries and 183 EVTs. The 2-year limb salvage rates were 92.2% in the bypass surgery group and 76.3% in the EVT group, respectively (P < .01). The 1-year wound healing rates were 86.7% in the bypass surgery group and 67.8% in the EVT group (P < .01). Multivariate analysis shows decreased serum albumin level (P < .01), increased wound grade (P = .04), and EVT (P < .01) were risk factors for major amputation. Decreased serum albumin level (P < .01), increased wound grade (P < .01), GLASS infrapopliteal grade (P = .02), inframalleolar (IM) P grade (P = .01), and EVT (P < .01) were risk factors for impaired wound healing. Subgroup analysis of limb salvage in patients after EVT, decreased serum albumin level (P < .01), increased wound grade (P = .03), increased IM P grade (P = .04), and congestive heart failure (P < .01) were risk factors for major amputation. According to scoring by existence of these risk factors, 2-year limb salvage rates following EVT were 83.0% and 42.8% for the total score of 0 to 2 and of 3 to 4, respectively (P < .01). ConclusionsBypass surgery provides better limb salvage and wound healing in patients with WIfI Stage 3 to 4 and GLASS Stage III, which is classified as bypass-preferred category by the GVG. In patients after EVT, serum albumin level, wound grade, IM P grade, and congestive heart failure were related to major amputation. Although bypass surgery may be considered as initial revascularization procedure in patients classified as bypass-preferred category, in case that EVT has to be selected, relatively acceptable outcomes can be expected in patients with less of these risk factors.

The Preventive Effect of Specific Collagen Peptides against Dexamethasone-Induced Muscle Atrophy in Mice.

Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, therapeutic options for muscle atrophy are limited, so studies to develop therapeutic agents for muscle loss are always required. For this study, we investigated how orally administered specific collagen peptides (CP) affect muscle atrophy and elucidated its molecular mechanism using an in vivo model. We treated mice with dexamethasone (DEX) to induce a muscular atrophy phenotype and then administered CP (0.25 and 0.5 g/kg) for four weeks. In a microcomputed tomography analysis, CP (0.5 g/kg) intake significantly increased the volume of calf muscles in mice with DEX-induced muscle atrophy. In addition, the administration of CP (0.25 and 0.5 g/kg) restored the weight of the gluteus maximus and the fiber cross-sectional area (CSA) of the pectoralis major and calf muscles, which were reduced by DEX. CP significantly inhibited the mRNA expression of myostatin and the phosphorylation of Smad2, but it did not affect TGF-β, BDNF, or FNDC5 gene expression. In addition, AKT/mTOR, a central pathway for muscle protein synthesis and related to myostatin signaling, was enhanced in the groups that were administered CP. Finally, CP decreased serum albumin levels and increased TNF-α gene expression. Collectively, our in vivo results demonstrate that CP can alleviate muscle wasting through a multitude of mechanisms. Therefore, we propose CP as a supplement or treatment to prevent muscle atrophy.

Clinical symptoms of patients with Kawasaki disease include smoldering fever.

Persistent low-grade fever has been observed in some patients during intravenous immunoglobulin (IVIG) therapy for Kawasaki disease (KD); however, smoldering fever (SF) has not previously been reported in patients with KD. This study aimed to clarify the clinical characteristics of SF in patients with KD. A single-center retrospective cohort study, which included a total of 621 patients who received IVIG therapy, was conducted. Patients with a fever of 37.5-38°C lasting ≥3 days after 2 days of the initial-IVIG were defined as the SF group. Patients were divided into four groups according to the fever course: SF (n = 14), biphasic fever (BF, n = 78), non-fever after initial-IVIG (NF, n = 384), and persistent fever (PF, n = 145). The clinical features of SF were described and compared between the groups. The median duration of fever in the SF group was 16 days, which was longer than that in any other group. The neutrophil fraction after IVIG therapy in the SF group was higher than that in the BF and NF groups but similar to that in the PF group. Repeated IVIG administration in the SF group resulted in increased IgG levels but decreased serum albumin levels. In the SF group, 29% of the patients had coronary artery lesions at 4 weeks. The frequency of SF in KD was 2.3%. Patients with SF continued to have moderate inflammatory responses. Repeated administration of IVIG doses was not effective in treating SF, and acute coronary artery lesions were occasionally observed. Active therapeutic intervention was needed.

Serum ANGPTL4 and FGF2, energy-related blood biochemicals, cytokine responses and oxidative stress in dairy cows with subclinical ketosis

In this study, it was aimed to investigate the serum levels of ANGPTL4, FGF21, IL-1β, IL-6, SOD, MDA, and serum biochemical and hematological parameters in cows with subclinical ketosis. The mean serum β-hydroxybutyric acid (BHB) level was 1.37 ± 0.04 mmol/L in 10 dairy cows aged 3-5 years that were &amp;lt;21 days postpartum and diagnosed with subclinical ketosis. The mean serum BHB level was 0.40 ± 0.08 mmol/L in 10 healthy dairy cows in the same period and in the same age range. An increase in serum AST (P&amp;lt;0.001) and a decrease in serum albumin levels (P&amp;lt;0.05) indicated altered liver functions. An increase in serum non-esterified fatty acid (P&amp;lt;0.001) and decreases in serum HDL, triglyceride, and total cholesterol levels (P&amp;lt;0.05) were interpreted as indicators of increased metabolic pathology risk due to negative energy balance. Increases in serum ANGPTL4, FGF2, IL-1β, IL-6, and MDA (P&amp;lt;0.001) and SOD levels (P&amp;lt;0.05) were evaluated as indicators of the development of effective metabolic, inflammatory, and oxidative stress.It was concluded that significant increases in serum ANGPTL4, FGF2, IL-1β, IL-6, and MDA and SOD levels in dairy cows with subclinical ketosis were associated with negative energy balance, effective cytokine responses, and oxidative stress.

Mitigation of Sarcopenia after Peritoneovenous Shunt Placement in Patients with Refractory Ascites

PurposeTo evaluate the effect of peritoneonvenous shunt placement on metrics of sarcopenia in patients with refractory ascites. Materials and MethodsAn institutional review board–approved single-institution retrospective analysis of all patients who underwent peritoneovenous shunt (Denver Shunt; BD, Franklin Lakes, New Jersey) placement (N = 29) and a comparator cohort of patients with cirrhosis who underwent serial paracentesis (N = 42) from 2009 to 2019 with baseline and follow-up cross-sectional imaging of at least 3 months was performed. Axial muscle area measurements (psoas, paraspinal, and total abdominal wall) were performed using free-hand region-of-interest technique. Patient records were reviewed for demographic characteristics, referring indication, laboratory studies, and performance status. Statistical analyses were performed with Student t test, Welch unequal variances, Fisher exact test, and Wilcoxon signed rank test. ResultsThe most common indications for peritoneovenous shunt placement were metastatic disease or cirrhosis. In the shunt cohort, there were no significant differences in the aggregate psoas muscle area (13.4 vs 14.0 cm2; P = .223) or paraspinal muscle area (43.0 vs 42.2 cm2; P = .471). In the paracentesis cohort, there were significant decreases in aggregate psoas (18.1 vs 15.7 cm2; P < .0001) and erector spinae (43.4 vs 39.9 cm2; P < .0001) muscle area. In addition, there was a significant decrease in serum albumin level (3.2 vs 3.0 g/dL; P = .015) and Eastern Cooperative Oncology Group performance status score (1.0 vs 1.3; P < .0001) in the paracentesis group, compared with no significant changes in the shunt cohort. ConclusionsIn patients with refractory ascites who are not candidates for transjugular intrahepatic portosystemic shunt placement, peritoneovenous shunt mitigates loss of truncal muscle and, in some instances, promotes muscle growth.

Nomogram for prediction of severe community-acquired pneumonia development in diabetic patients: a multicenter study

BackgroundDiabetic patients with community-acquired pneumonia (CAP) have an increased risk of progressing to severe CAP. It is essential to develop predictive tools at the onset of the disease for early identification and intervention. This study aimed to develop and validate a clinical feature-based nomogram to identify diabetic patients with CAP at risk of developing severe CAP.MethodA retrospective cohort study was conducted between January 2019 to December 2020. 1026 patients with CAP admitted in 48 hospitals in Shanghai were enrolled. All included patients were randomly divided into the training and validation samples with a ratio of 7:3. The nomogram for the prediction of severe CAP development was established based on the results of the multivariate logistic regression analysis and other predictors with clinical relevance. The nomogram was then assessed using receiver operating characteristic curves (ROC), calibration curve, and decision curve analysis (DCA).ResultsMultivariate analysis showed that chronic kidney dysfunction, malignant tumor, abnormal neutrophil count, abnormal lymphocyte count, decreased serum albumin level, and increased HbA1c level at admission was independently associated with progression to severe CAP in diabetic patients. A nomogram was established based on these above risk factors and other predictors with clinical relevance. The area under the curve (AUC) of the nomogram was 0.87 (95% CI 0.83–0.90) in the training set and 0.84 (95% CI 0.78–0.90). The calibration curve showed excellent agreement between the predicted possibility by the nomogram and the actual observation. The decision curve analysis indicated that the nomogram was applicable with a wide range of threshold probabilities due to the net benefit.ConclusionOur nomogram can be applied to estimate early the probabilities of severe CAP development in diabetic patients with CAP, which has good prediction accuracy and discrimination abilities. Since included biomarkers are common, our findings may be performed well in clinical practice and improve the early management of diabetic patients with CAP.

Inhibition of induced-hepatic cancer in vivo through IQGAP1-shRNA gene therapy and modulation of TRAIL-induced apoptosis pathway.

BackgroundLiver cancer is the deadliest malignancy among common tumors. It is the top cause of cancer-related deaths in Egypt, and it is characterized by increasing occurrence among the population. The objective of this study was to determine the outcome of pre-treatment of IQGAP1-shRNA on induced mouse hepatocellular carcinoma model and evaluate the potency of this IQGAP1-shRNA plasmid to recover hepatic cancer as a new tool of cancer therapy. Therefore, we will use RNA interference (RNAi) technology to silence IQGAP1 oncogene to completely recover the chemically induced models for hepatic cancer by designing short RNAi specific for IQGAP1 gene in HCC cells in vivo and construct new vectors suitable for this purpose. We assigned mice into three groups: the first negative control group (NC) was injected with saline, the second control group was injected with shRNA (shNC), the third positive control group was injected with diethylnitrosamine (DENAA), and the fourth group was treated with the IQGAP1-shRNA prior to its exposure to DENA.ResultsOur results revealed that the treated group with IQGAP1-shRNA with DENA developed very few cases of hepatic cancer when compared with the positive control group. The positive control group exhibited significant increases in the liver function level as well as a decrease in serum albumin levels when compared to both the treated and the negative control groups. The altered levels of the serum α-fetoprotein as well as of the tumor necrosis factor-alpha, and interleukin-4 in DENA-treated mice were significantly ameliorated by IQGAP1-shRNA administration. Flow cytometer analyses have indicated that the silencing of IQGAP1 cannot significantly modulate DENA-induced apoptosis in the circulating blood cells. Moreover, the elevated mRNA expression levels of IQGAP1, IQGAP3, KRas, HRas, interleukin-8, nuclear factor kappa B, caspase-3, caspase-9 and Bcl-2, were significantly decreased by the IQGAP1-shRNA treatment. However, the IQGAP2, DR4, DR5, p53 and BAX genes were found to be significantly up-regulated post-therapy. In agreement with these findings, IQGAP1-shRNA was able to modulate the DENA-induced histological changes in the mice liver which were represented by severe necrosis and hydropic degenerative changes.ConclusionOur study revealed that IQGAP1-shRNA was able to preserve hepatocyte integrity and the liver histological architecture through the regulation of the expression of IQGAPs, Ras, TRAILs and IL-8 receptors, as well as of pro-apoptotic and anti-apoptotic genes. Therefore, the silencing of IQGAP1 could be part of a promising therapeutic strategy against hepatic cancer.

The role of cardiometabolic risk factors and endothelial dysfunction in serum albumin levels and capillary leak syndrome of patients with COVID-19

Abstract Background Growing evidence focuses on the role of hypoalbuminemia in the COVID-19 course and the role of vascular inflammation in the progression to Capillary Leak Syndrome (CLS). CLS may be mediated by a derangement of endothelial barrier following vascular endothelial dysfunction. We investigated the role of cardiometabolic risk factors in the association of hypoalbuminemia with endothelial dysfunction of hospitalized COVID-19 patients. Methods In this cross-sectional study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled. Medical history and laboratory examinations were collected while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD) between the first 24–72 hours of their admission to the hospital. According to the body mass index, history of hypertension, dyslipidemia, and diabetes mellitus, COVID-19 patients were categorized in those with Cardiometabolic Risk Factors (CRFact) or without CRFact (no-CRFact). From the study population, we excluded subjects with established cardiovascular disease. Results Sixty-six patients with COVID-19 (37% admitted in ICU) were recruited. From the study population, 41 were in the group of CRFact and 25 in the no-CRFact. Patients with CFRact were older (65±9 years vs. 53±14 years, p&amp;lt;0.001), had more impaired FMD (1.16±2.13% vs. 2.60±2.44%, p=0.01), and lower serum albumin levels (3.10±0.68 g/dL vs. 3.52±0.26 g/dL, p=0.006) compared to the no-CRFact group. Between CRFact and no-CRFact, there was no difference in CRP and IL-6 levels. Interestingly, serum albumin in patients with CRFact was significantly lower than the lower reference limit (LRL) (=3.5 g/dl) of albumin (p=0.001), while no such finding was noted in subjects with no CRFact (p=0.64). Furthermore, regression analysis revealed that, even after adjustment for age, the presence of CRFact was associated with decreased serum albumin levels by 0.31mg/dl (95% CI 0.08 to 0.63, p=0.04). In the CRFact population, there was a correlation of albumin with FMD (R=0.29, p=0.05) and an inverse correlation with CRP (rho=−0.48, p=0.02) and IL-6 (rho=−0.66, p&amp;lt;0.001), while in the no-CRFact group no such correlation were observed (p=NS for all). Conclusion COVID-19 patients with cardiometabolic risk factors present with low serum albumin levels early at the course of the disease, which may be driven by endothelial dysfunction and vascular inflammation. This data gives insights into the potential association of a dysfunctional endothelial layer and the progression to capillary leak syndrome. Funding Acknowledgement Type of funding sources: None.

Hypoalbuminemia in COVID-19 Patients: A Predictor of Disease Severity and Guarded Outcome

Background: Pandemic of COVID-19 is spreading in all continents. There have been lots of article published on different aspects of this infection. Finding low Albumin levels in the patients of COVID-19 disease regardless of their degree of severity of infection has surprised us from the beginning. Aim: To review the hypoalbuminemia and its extent in local population presented with COVID-19 and to determine the relationship of degree of hypoalbuminemia with the severity of infection. Place and duration of study: Bahria International Hospital Lahore and Services Institute of Medical Sciences, Lahore from 1st May 2021 to 30th September 2021. Methodology: Medical records 400 COVID-19 patient’s related symptoms such as cough, flu, fever, headache, tiredness, distress in breathing were included. Serum Albumin, AST and ALT as clinical bioindicators in COVID-19 patients were reviewed. Results: A significant decrease in serum albumin levels with the means and standard deviation (2.692±0.302), (χ²=344.69, df=16, p&lt;0.001) was recorded. Whereas, a significant increase AST (U/L) and ALT (U/L) with the means and standard deviations (45.130±31.138), (χ²=214.30, df=72, p&lt;0.001) was also noted. Analysis between survivors and non-survivors shows the level of albumin and AST/ALT was inversely proportional. Conclusion: Low albumin is associated with disease severity and poor outcomes in terms of prolonged admissions and worse respiratory failure due to alveolar endothelial damage in COVID-19. Keywords: COVID-19, Albumin, Transaminases, ALT, AST, Alveolar endothelial damage

The effect of urinary essential and non-essential elements on serum albumin: Evidence from a community-based study of the elderly in Beijing.

Background & aimsFew epidemiological studies have investigated the relationships of urinary essential and non-essential elements with serum albumin, an indicator of nutritional status, especially for the elderly in China.MethodsA community-based study among elderly participants (n = 275) was conducted in Beijing from November to December 2016. We measured 15 urinary elements concentrations and serum albumin levels. Three statistical methods including the generalized linear model (GLM), quantile g-computation model (qgcomp) and bayesian kernel machine regression (BKMR) were adapted.ResultsIn GLM analysis, we observed decreased serum albumin levels associated with elevated urinary concentrations of aluminum, arsenic, barium, cobalt, chromium, copper, iron, manganese, selenium, strontium, and zinc. Compared with the lowest tertile, the highest tertile of cadmium and cesium was also negatively associated with serum albumin. Urinary selenium concentration had the most significant negative contribution (30.05%) in the qgcomp analysis. The negative correlations of element mixtures with serum albumin were also observed in BKMR analysis.ConclusionsOur findings suggested the negative associations of essential and non-essential elements with serum albumin among the elderly. Large-scare cohort studies among the general population are required to validate our findings and elucidate the relevant underlying mechanisms.