Prevention of methylprednisolone acetate-induced osteoporosis with calcium administration in rat model

Glucocorticoid steroids are widely used as anti-inflammatory and immunosuppressive medications and are well known to induce osteoporosis. In Present study 24 rats were randomly divided into four groups (n=6): Group A (control), Group B (sham)that was treated only by normal saline for 1 month.Group C that was treated by methylprednisolone acetate alone (0.2 mg/kg) for 1 month. Group D that was treated by methylprednisolone acetate (0.2 mg/kg) and oral calcium supplementation (15 mg/kg) for 1 month. Changes in concentration of bone metabolic markers such as osteocalcine, acid phosphatase and calcium were evaluated before and after treatment. Bone mineral density (BMD) of lumbar vertebrae was also measured by dual energy X ray absorptiometry (DEXA). The results showed that concentration mean of serum acid phosphatase was increased significantly (P � 0.05) in C and D groups in compared to A and B groups. The concentration mean of serum osteocalcine in group C was decreased significantly (P � 0.05) in comparison to A and B groups but increased significantly in the group D in comparison to group C. The concentration mean of serum calcium was decreased significantly (P � 0.05) in C and D groups in compared to A and B groups. The bone mineral density (g/cm2) was decreased significantly (P � 0.05) in group C in compared to A and B groups. This increased significantly in group D in compared to group C. These results are compatible with the view that low doses of methylprednisolone acetate decreases bone formation and increase bone resorption in the lumbar vertebrae of rats. Calcium administration decreased effects of methylprednisolone. © 2009 Tehran University of Medical Sciences. All rights reserved

Robotic multiquadrant colorectal procedures: A single-center experience and a systematic review of the literature

Purpose: Robotic surgery has been progressively implemented for colorectal procedures but is still limited for multiquadrant abdominal resections. The present study aims to describe our experience in robotic multiquadrant colorectal surgeries and provide a systematic review and meta-analysis of the literature investigating the outcomes of robotic total proctocolectomy (TPC), total colectomy (TC), subtotal colectomy (STC), or completion proctectomy (CP) compared to laparoscopy. Methods: At our institution 16 consecutive patients underwent a 2- or 3-stage totally robotic total proctocolectomy (TPC) with ileal pouch-anal anastomosis. A systematic review of the literature was performed to select studies on robotic and laparoscopic multiquadrant colorectal procedures. Meta-analyses were used to compare the two approaches. Results: In our case series, 14/16 patients underwent a 2-stage robotic TPC for ulcerative colitis with a mean operative time of 271.42 (SD:37.95) minutes. No conversion occurred. Two patients developed postoperative complications. The mean hospital stay was 8.28 (SD:1.47) days with no readmissions. Mortality was nil. All patients underwent loop-ileostomy closure, and functional outcomes were satisfactory. The literature appraisal was based on 23 retrospective studies, including 736 robotic and 9,904 laparoscopic multiquadrant surgeries. In the robotic group, 36 patients underwent STC, 371 TC, 166 TPC, and 163 CP. Pooled data analysis showed that robotic TC and STC had a lower conversion rate (OR = 0.17;95% CI, 0.04–0.82; p = 0.03) than laparoscopic TC and STC. The robotic approach was associated with longer operative time for TC and STC (MD = 104.64;95% CI, 18.42–190.87; p = 0.02) and TPC and CP (MD = 38.8;95% CI, 18.7–59.06; p = 0.0002), with no differences for postoperative complications and hospital stay. Reports on urological outcomes, sexual dysfunction, and quality of life were missing. Conclusions: Our experience and the literature suggest that robotic multiquadrant colorectal surgery is safe and effective, with low morbidity and mortality rates. Nevertheless, the overall level of evidence is low, and functional outcomes of robotic approach remain largely unknown. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022303016

Predictors of mortality following emergency open colectomy for ischemic colitis: A single-center experience

Background: Ischemic colitis (IC) is a severe emergency in gastrointestinal surgery. The aim of the present study was to identify the predictors of postoperative mortality after emergent open colectomy for IC treatment. Additionally, we compared postoperative outcomes of patients undergoing emergent colectomy due to aortic surgery-related IC (AS-IC group) vs. other IC etiologies (Other-IC group). Methods: We analyzed records of consecutive patients who underwent emergency open colectomy for IC between 2008 and 2019. Logistic regression analysis was performed to identify clinical and operative parameters associated with postoperative mortality. The AS-IC and Other-IC groups were compared for mortality, morbidity, ICU stay, hospital stay, and survival. Results: During the study period, 94 patients (mean age, 67.4 ± 13.7 years) underwent emergent open colectomy for IC. In the majority of cases, IC involved the entire colon (53.2%) and vasopressor agents were required preoperatively (63.8%) and/or intraoperatively (78.8%). Thirty-four patients underwent surgery due to AS-IC, whereas 60 due to Other-IC causes. In the AS-IC group, 9 patients had undergone endovascular aortic repair and 25 open aortic surgery; 61.8% of patients needed aortic surgery for ruptured abdominal aortic aneurism (AAA). Overall, 66 patients (70.2%) died within 90 days from surgery. The AS-IC and Other-IC groups showed similar operative outcomes and postoperative complication rates. However, the duration of the ICU stay (19 days vs. 11 days; p = 0.003) and of the total hospital stay (22 days vs. 16 days; p = 0.016) was significantly longer for the AS-IC group than for the Other-IC group. The rate of intestinal continuity restoration at 1 year after surgery was higher for the Other-IC group than for the AS-IC group (58.8% vs. 22.2%; p = 0.05). In the multivariate model, preoperative increased lactate levels, a delay between signs/symptoms' onset and surgery > 12 h, and the occurrence of postoperative acute kidney injury were statistically associated with postoperative mortality. Neither IC etiology (aortic surgery vs. other etiology) nor ruptured AAA was associated with postoperative mortality. Conclusion: Emergency open colectomy for IC is associated with high postoperative mortality, which appears to be unrelated to the IC etiology. Preoperative lactate levels, > 12-h delay to surgery, and postoperative acute kidney injury are independent predictors of postoperative mortality

Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses

The immune system plays a central role in the onset and progression of cancer. A better understanding of transcriptional changes in immune cell-related genes associated with cancer progression, and their significance in disease prognosis, is therefore needed. NanoString-based targeted gene expression profiling has advantages for deployment in a clinical setting over RNA-seq technologies. We analysed NanoString PanCancer Immune Profiling panel gene expression data encompassing 770 genes, and overall survival data, from multiple previous studies covering 10 different cancer types, including solid and blood malignancies, across 515 patients. This analysis revealed an immune gene signature comprising 39 genes that were upregulated in those patients with shorter overall survival; of these 39 genes, three (MAGEC2, SSX1 and ULBP2) were common to both solid and blood malignancies. Most of the genes identified have previously been reported as relevant in one or more cancer types. Using Cibersort, we investigated immune cell levels within individual cancer types and across groups of cancers, as well as in shorter and longer overall survival groups. Patients with shorter survival had a higher proportion of M2 macrophages and γδ T cells. Patients with longer overall survival had a higher proportion of CD8+ T cells, CD4+ T memory cells, NK cells and, unexpectedly, T regulatory cells. Using a transcriptomics platform with certain advantages for deployment in a clinical setting, our multi-cancer meta-analysis of immune gene expression and overall survival data has identified a specific transcriptional profile associated with poor overall survival

Microbial Dysbiosis in Colorectal Cancer (CRC) Patients

The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis

Potential of fecal microbiota for early-stage detection of colorectal cancer

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism

Spatial interplay of lymphocytes and fibroblasts in estrogen receptor-positive HER2-negative breast cancer

In estrogen-receptor-positive, HER2-negative (ER+HER2−) breast cancer, higher levels of tumor infiltrating lymphocytes (TILs) are often associated with a poor prognosis and this phenomenon is still poorly understood. Fibroblasts represent one of the most frequent cells in breast cancer and harbor immunomodulatory capabilities. Here, we evaluate the molecular and clinical impact of the spatial patterns of TILs and fibroblast in ER+HER2− breast cancer. We used a deep neural network to locate and identify tumor, TILs, and fibroblasts on hematoxylin and eosin-stained slides from 179 ER+HER2− breast tumors (ICGC cohort) together with a new density estimation analysis to measure the spatial patterns. We clustered tumors based on their spatial patterns and gene set enrichment analysis was performed to study their molecular characteristics. We independently assessed the spatial patterns in a second cohort of ER+HER2− breast cancer (N = 630, METABRIC) and studied their prognostic value. The spatial integration of fibroblasts, TILs, and tumor cells leads to a new reproducible spatial classification of ER+HER2− breast cancer and is linked to inflammation, fibroblast meddling, or immunosuppression. ER+HER2− patients with high TIL did not have a significant improved overall survival (HR = 0.76, P = 0.212), except when they had received chemotherapy (HR = 0.447). A poorer survival was observed for patients with high fibroblasts that did not show a high level of TILs (HR = 1.661, P = 0.0303). Especially spatial mixing of fibroblasts and TILs was associated with a good prognosis (HR = 0.464, P = 0.013). Our findings demonstrate a reproducible pipeline for the spatial profiling of TILs and fibroblasts in ER+HER2− breast cancer and suggest that this spatial interplay holds a decisive role in their cancer-immune interactions

Probiotic treatment reduces appetite and glucose level in the zebrafish model.

The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation

Potential role of endocrine gastrin in the colonic adenoma carcinoma sequence

The role of hyper-gastrinaemia in the incidence of colonic cancer remains to be clarified. The aim of this study was to determine whether cholecystokinin-2 (CCK-2) receptor expression predicts the sensitivity of human colonic adenomas to the proliferative effects of serum hyper-gastrinaemia. Gene expression of the classical (74 kDa) CCK-2 receptor in human colonic adenoma specimens and cell lines, was quantified by real-time PCR. Western blotting, using a CCK-2 receptor antiserum, confirmed protein expression. A transformed human colonic adenoma was grown in SCID mice, with hyper-gastrinaemia induced by protein pump inhibitors. CCK-2 receptor blockade was achieved by using neutralising antiserum. Both human colonic adenoma cell lines and biopsies expressed CCK-2 receptor mRNA at levels comparable with CCK-2 receptor transfected fibroblasts and oxyntic mucosa. Western blotting confirmed immunoreactive CCK-2 receptor bands localised to 45, 74 and 82.5 kDa. Omeprazole and lansoprazole-induced hyper-gastrinaemia (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively) significantly increased the weight of the human adenoma grafts (43% (P=0.016) and 70% (P=0.014), respectively). The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor. Hyper-gastrinaemia may promote proliferation of human colonic adenomas that express CCK-2 receptor isoforms