Vitaliy Poylin

Role of glucocorticoids in the molecular regulation of muscle wasting.

Objective:To review glucocorticoid-regulated molecular mechanisms of muscle wasting. Design:Review of recent literature describing the role of glucocorticoids in the regulation of proteolytic mechanisms, transcription factors, and nuclear cofactors in skeletal muscle during various catabolic conditions. Main Results:Catabolic doses of glucocorticoids induce muscle atrophy both in vivo and in vitro by stimulating protein breakdown and inhibiting protein synthesis. Signaling pathways that regulate muscle protein synthesis at the translational level are inhibited by glucocorticoids. Glucocorticoids increase the expression and activity of the ubiquitin-proteasome pathway, a major proteolytic mechanism of muscle atrophy. The expression and activity of muscle wasting-related transcription factors, including C/EBP&bgr; and &dgr; and Forkhead box O 1, 3, and 4, as well as the nuclear cofactor p300, are up-regulated by glucocorticoid excess. Conclusions:Muscle wasting in various catabolic conditions is, at least in part, regulated by glucocorticoids. The role of glucocorticoids in muscle wasting is complex and reflects regulation at the molecular level of multiple mechanisms influencing both synthesis and degradation of muscle proteins.

Radiation Proctitis: Current Strategies in Management

Radiation proctitis is a known complication following radiation therapy for pelvic malignancy. The majority of cases are treated nonsurgically, and an understanding of the available modalities is crucial in the management of these patients. In this paper, we focus on the current treatments of radiation proctitis.

The NF-κB Inhibitor Curcumin Blocks Sepsis-Induced Muscle Proteolysis

We tested the hypothesis that treatment of rats with curcumin prevents sepsis-induced muscle protein degradation. In addition, we determined the influence of curcumin on different proteolytic pathways that are activated in septic muscle (i.e., ubiquitin-proteasome-, calpain-, and cathepsin L-dependent proteolysis) and examined the role of NF-κB and p38/MAP kinase inactivation in curcumin-induced inhibition of muscle protein breakdown. Rats were made septic by cecal ligation and puncture or were sham-operated. Groups of rats were treated with three intraperitoneal doses (600 mg/kg) of curcumin or corresponding volumes of solvent. Protein breakdown rates were measured as release of tyrosine from incubated extensor digitorum longus muscles. Treatment with curcumin prevented sepsis-induced increase in muscle protein breakdown. Surprisingly, the upregulated expression of the ubiquitin ligases atrogin-1 and MuRF1 was not influenced by curcumin. When muscles from septic rats were treated with curcumin in vitro, proteasome-, calpain-, and cathepsin L-dependent protein breakdown rates were reduced, and nuclear NF-κB/p65 expression and activity as well as levels of phosphorylated (activated) p38 were decreased. Results suggest that sepsis-induced muscle proteolysis can be blocked by curcumin and that this effect may, at least in part, be caused by inhibited NF-κB and p38 activities. The results also suggest that there is not an absolute correlation between changes in muscle protein breakdown rates and changes in atrogin-1 and MuRF1 expression during treatment of muscle wasting.

Medical Management of Spontaneous Celiac Artery Dissection : Case Report and Literature Review

Spontaneous visceral artery dissections are a rare occurrence. Here we report a case of spontaneous celiac artery dissection that was treated without surgery.

Obesity and bariatric surgery: A systematic review of associations with defecatory dysfunction

Aim  Background Obesity rates are rapidly growing in the developed world. While upper gastrointestinal disturbances and urinary incontinence are independently associated with obesity, the relationship between obesity and defecatory dysfunction is less well defined. Objectives To summarize the literature on faecal incontinence, diarrhoea and constipation in obese patients and its effects of bariatric surgery.

Experimental hyperthyroidism in rats increases the expression of the ubiquitin ligases atrogin‐1 and MuRF1 and stimulates multiple proteolytic pathways in skeletal muscle

Muscle wasting is commonly seen in patients with hyperthyroidism and is mainly caused by stimulated muscle proteolysis. Loss of muscle mass in several catabolic conditions is associated with increased expression of the muscle‐specific ubiquitin ligases atrogin‐1 and MuRF1 but it is not known if atrogin‐1 and MuRF1 are upregulated in hyperthyroidism. In addition, it is not known if thyroid hormone increases the activity of proteolytic mechanisms other than the ubiquitin–proteasome pathway. We tested the hypotheses that experimental hyperthyroidism in rats, induced by daily intraperitoneal injections of 100 µg/100 g body weight of triiodothyronine (T3), upregulates the expression of atrogin‐1 and MuRF1 in skeletal muscle and stimulates lysosomal, including cathepsin L, calpain‐, and caspase‐3‐dependent protein breakdown in addition to proteasome‐dependent protein breakdown. Treatment of rats with T3 for 3 days resulted in an approximately twofold increase in atrogin‐1 and MuRF1 mRNA levels. The same treatment increased proteasome‐, cathepsin L‐, and calpain‐dependent proteolytic rates by approximately 40% but did not influence caspase‐3‐dependent proteolysis. The expression of atrogin‐1 and MuRF1 remained elevated during a more prolonged period (7 days) of T3 treatment. The results provide support for a role of the ubiquitin–proteasome pathway in muscle wasting during hyperthyroidism and suggest that other proteolytic pathways as well may be activated in the hyperthyroid state. J. Cell. Biochem. 108: 963–973, 2009.

Reducing urinary tract infections in colon and rectal surgery.

BACKGROUND: Urinary tract infection is associated with increased morbidity, mortality, and healthcare costs. Colon and rectal surgery has been shown to be an independent risk factor for urinary tract infection. Decreased length of the indwelling urinary catheter may play a role in decreasing the rate of urinary tract infection. OBJECTIVE: The aim of this study was to investigate the effect of standardized indwelling urinary catheter management on urinary tract infection. DESIGN: This was a prospective cohort study. SETTINGS: This study was conducted in an urban academic tertiary care center. PATIENTS: All of the patients were undergoing colon or rectal resection from 2010 to 2012 at a single National Surgical Quality Improvement Program participating institution. INTERVENTIONS: Intervention 1 (group 1) included implementation of a daily electronic order prompt requiring justification for an indwelling urinary catheter for >24 hours. Intervention 2 (group 2) included intervention 1 plus sterile intraoperative placement of a urinary catheter after the antiseptic preparation and draping of the patient. MAIN OUTCOME MEASURES: The primary outcome measured was urinary tract infection rate. RESULTS: A total of 811 patients were identified (control = 215; group 1 = 476; group 2 = 120). Patient demographics and comorbidities were similar among the groups. No differences existed in the proportion of proctectomy among the groups. Urinary tract infection rate decreased significantly with the implementation of each intervention (control, 6.9%; group 1, 2.7%; group 2, 0.8%; p = 0.004). The lone urinary tract infection in group 2 involved ureteral reconstruction and stent placement at the time of surgery. LIMITATIONS: This study was limited by its small sample size and single institution design. CONCLUSIONS: The implementation of 2 low-cost practice interventions was associated with a statistically significant decrease in urinary tract infection in patients undergoing colorectal surgery at an academic tertiary care center.

Surgery for Ulcerative Colitis Is Associated with a High Rate of Readmissions at 30 Days

Background:Currently, the predictors of readmission after colectomy specifically for ulcerative colitis (UC) are poorly investigated. We sought to determine the rates and predictors of 30-day readmissions after colectomy for UC. Methods:Patients undergoing total proctocolectomy and end ileostomy, abdominal colectomy with end ileostomy, proctocolectomy with ileoanal pouch anastomosis (IPAA) formation and diverting ileostomy, one stage IPAA, or abdominal colectomy with ileorectal anastomosis at a tertiary care center between January 2002 and January 2012 for UC were included. Patients were identified using ICD-9 code 556.x. Each record was manually reviewed. The electronic record system was reviewed for demographic information, medical histories, UC history, medications, and data regarding the admission and discharge. Charts were reviewed for readmissions within 30 days of surgery. Univariate and multivariate analyses were performed using Stata v.13. Results:Two hundred nine patients with UC underwent a colectomy. Forty-three percent had a proctocolectomy with IPAA and diverting ileostomy and 32% had abdominal colectomy with end ileostomy. Seventy-six percent of surgeries were due to failure of medical therapy and 68% of patients were electively admitted for surgery. Thirty-two percent (n = 67/209) of the cohort was unexpectedly readmitted within 30 days. In multivariate model, proctocolectomy with IPAA and diverting ileostomy (odds ratio [OR] = 2.11; 95% CI, 1.06–4.19; P = 0.033) was the only significant predictor of readmission. Hospital length of stay >7 days (OR = 1.82; 95% CI, 0.98–3.41; P = 0.060), presence of limited UC (OR = 2.10; 95% CI, 0.93–4.74; P = 0.074), and steroid before admission (OR = 1.69; 95% CI, 0.90–3.2; P = 0.100) trended toward significance. Conclusions:Surgery for UC is associated with a high rate of readmission. Further prospective studies are necessary to determine the means to reduce these readmissions.

Gabapentin significantly decreases posthemorrhoidectomy pain: a prospective study

PurposeSurgery for hemorrhoidectomy remains a painful procedure despite advances in pain management. Gabapentin is widely used for control of acute and chronic pain. Our aim was to evaluate the effect of gabapentin on posthemorrhoidectomy pain and opioid use.MethodsA prospective, open-label study. Patients requiring hemorrhoid surgery were recruited to be in control (standard of care) or treatment group (standard of care plus daily gabapentin).ResultsTwenty-one treatment and 18 control patients were recruited. One patient from study group and two patients from control group were excluded due to failure to follow up. Pain levels for gabapentin group were significantly lower on postoperative days 1, 7, and 14 compared to the standard treatment group (3.68 vs. 6.82 p < 0.01, 2.68 vs. 5 p = 0.02 and 0.75 vs. 3.64 p < 0.001 respectively). There was a trend toward less opioids taken in gabapentin group for postoperative days 1, 7, and 14 (4.69 vs. 6.36; 2.13 vs. 2.73, and 0.125 vs. 0.9) but it did not reach statistical significance. The average hemorrhoidal grade and number of hemorrhoidal complexes removed was slightly higher in gabapentin group. Five control group patients experienced postoperative complications versus two gabapentin group patients. No gabapentin related complications were seen in the treatment group. The average cost of gabapentin course was

Complications Following Anorectal Surgery

5.34 per patient.ConclusionsDaily use of gabapentin in perioperative period significantly decreased reported levels of postoperative pain. This effective, inexpensive addition improves pain after hemorrhoid surgery. Randomized placebo-controlled studies would better define the usefulness of this medication for posthemorrhoidectomy pain.