Botulinum toxin infusion into the mesenteric artery has selective action on peristalsis in a rat model: experimental research.

OBJECTIVE: Botulinum toxin type A (BoNT/A) reversibly blocks neurotransmission at voluntary and autonomic cholinergic nerve terminals, inducing paralysis. The aim of this study was to block panenteric peristalsis in rats through BoNT/A administration into the superior mesenteric artery (SMA) and to understand whether the toxin's action is selectively restricted to the perfused territory. MATERIALS AND METHODS: Rats were infused through a 0.25-mm surgically inserted SMA catheter with different doses of BoNT/A (10 U, 20 U, 40 U BOTOX®, Allergan Inc.) or with saline for 24 h. Animals were free to move on an unrestricted diet. As a sign of bowel peristalsis impairment, body weight and oral/water intake were collected for 15 days. Statistical analysis was conducted with nonlinear mixed effects models to study the variation over time of the response variables. In three 40 U-treated rats, the selectivity of the intra-arterial delivered toxin action was studied by examining bowel and voluntary muscle samples and checking the presence of BoNT/A-cleaved SNAP-25 (the smoking gun of the toxin action) using the Immunofluorescence (IF) method through a specific antibody recognition. RESULTS: While control rats exhibited an increasing body weight, treated rats showed an initial dose-dependent weight reduction (p<0.001 control vs. treated) with recovery after Day 11 for 10 and 20 U-treated rats. Food and water intake over time showed significantly different half-saturation constants with rats treated with higher doses who reached half of the maximum achievable in a greater number of days (p<0.0001 control vs. treated rats). BoNT/A-cleaved SNAP-25 was identified in bowel wall NMJs and not in voluntary muscles, demonstrating the remarkable selectivity of arterially infused BoNT/A. CONCLUSIONS: Blockade of intestinal peristalsis, can be induced in rats by slow infusion of BoNT/A into the SMA. The effect is long-lasting, dose-dependent and selective. BoNT/A delivery into the SMA through a percutaneous catheter could prove clinically useful in the treatment of entero-atmospheric fistula by temporarily reducing fistula output.

Closed incision Negative Pressure Therapy (ciNPT): does depression affect underlying tissues?

OBJECTIVE: Closed incision Negative Pressure Therapy (ciNPT) has become a widespread practice in recent years. Described benefits concern the rate of wound infection, based on the assumption that negative pressure spreads inside the wound removing collections and edema. The study aims to clarify this technical point, on which experimental scientific evidence is lacking in literature. MATERIALS AND METHODS: In the experimental animal (newly sacrificed pig), the pressure was measured for hours at the bottom of three surgical abdominal wounds sutured by planes and dressed in negative pressure therapy commercial sets. RESULTS: The depression applied to the surface of the sutured wounds (ciNPT) is not transmitted to the underlying tissues. The blue dye deposited in the deep layer of the wounds didn't surface as an effect of ciNPT. CONCLUSIONS: The possible benefits deriving from the application of negative pressure on sutured wounds must depend on a different mechanism from the diffusion of depression in the wound planes and in the underlying tissues.

Percutaneous cholecystostomy in the treatment of acute cholecystitis: is there still a role? A 20-year literature review.

OBJECTIVE: Percutaneous cholecystostomy (PC) is used for the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. The evidence for this strategy is unclear. MATERIALS AND METHODS: We searched PubMed and the Cochrane databases for English-language studies published from January 1979 through December 31, 2019, for randomized clinical trials (RCTs), meta-analyses, systematic reviews, and observational studies. RESULTS: The two randomized studies that have compared PC with cholecystectomy (CCY) or conservative treatment have shown that the clinical outcomes did not differ significantly between the groups. Similar results have been found in the large majority of retrospective cohorts or single-center studies that have compared PC with CCY. CONCLUSIONS: PC does not seem to offer any benefit compared with CCY in the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. A large, prospective, randomized study that compares percutaneous PC and CCY in patients with high surgical risk and/or moderate to severe cholecystitis is warranted.

Regulatory mechanism of TGF-ß1/SGK1 pathway in tubulointerstitial fibrosis of diabetic nephropathy.

OBJECTIVE: The aim of this study was to clarify the potential function of transforming growth factor-ß1/serum/glucocorticoid-regulated kinase 1 (TGF-ß1/SGK1) pathway in diabetic nephropathy-induced tubulointerstitial fibrosis. MATERIALS AND METHODS: Type 2 diabetes mellitus (T2DM) model was successfully established in rats by high-sucrose-high-fat diet combined with streptozotocin (STZ) induction. Subsequently, blood glucose level, renal function and pathological changes in kidneys of T2DM and control rats were evaluated. Western blot and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) were conducted to determine the protein and mRNA expression levels of TGF-ß1, SGK1, fibronectin (FN) and α-smooth muscle actin (α-SMA) in rat kidney tissues, respectively. RESULTS: Blood glucose (BG), glycosylated hemoglobin (GHb), serum creatinine (Scr) and blood urea nitrogen (BUN) in T2DM rats were significantly higher than those of control rats (p<0.05). The morphology of glomeruli and renal tubules in rats of control group were normal. In contrast, T2DM rats showed significant lesions in glomeruli, renal tubules, and renal interstitium. Furthermore, the relative expression levels of TGF-ß1, SGK1, FN, and α-SMA in kidney tissues of T2DM rats were remarkably higher than those of controls (p<0.05). CONCLUSIONS: The TGF-ß1/SGK1 pathway is closely related to tubulointerstitial fibrosis in T2DM rats.

Lack of accountability in upholding authorship standards in prominent medical oncology clinical trials.

Authorship in biomedical publications is critical for establishing accountability and contribution toward clinical and scientific research. We examined the frequency of discordance in authorship between presentations of clinical trial data at annual meetings of the American Society of Clinical Oncology and the subsequent peer-reviewed publications. We found that more than 70% of subsequent publications had additional authors not originally present on the abstract despite there being no changes in trial accrual or trial design. This pervasive discordance in authorship demonstrates a lack of uniformity and accountability in authorship reporting standards.

Role of surgical setting and patients-related factors in predicting the occurrence of postoperative pulmonary complications after abdominal surgery.

OBJECTIVE: The aim of this retrospective study was to evaluate the role of surgical setting (urgent vs. elective) and approach (open vs. laparoscopic) in affecting postoperative pulmonary complications (PPCs) prevalence in patients undergoing abdominal surgery. PATIENTS AND METHODS: After local Ethical Committee approval, 409 patients who had undergone abdominal surgery between January and December 2014 were included in the final analysis. PPCs were defined as the development of one of the following new findings: respiratory failure, pulmonary infection, aspiration pneumonia, pleural effusion, pneumothorax, atelectasis on chest X-ray, bronchospasm or un-planned urgent re-intubation. RESULTS: PPCs prevalence was greater in urgent (33%) vs. elective setting (7%) (χ2 with Yates correction: 44; p=0.0001) and in open (6%) vs. laparoscopic approach (1.9%) (χ2 with Yates correction: 12; p=0.0006). PPCs occurrence was positively correlated with in-hospital mortality (Biserial Correlation r=0.37; p=0.0001). Logistic regression showed that urgent setting (p=0.000), Ariscat (Assess Respiratory Risk in Surgical Patients in Catalonia) score (p=0.004), and age (p=0.01) were predictors of PPCs. A cut-off of 23 for Ariscat score was also identified as determining factor for PPCs occurrence with 94% sensitivity and 29% specificity. CONCLUSIONS: Patients undergoing abdominal surgery in an urgent setting were exposed to a higher risk of PPCs compared to patients scheduled for elective procedures. Ariscat score fitted with PPCs prevalence and older patients were exposed to a higher risk of PPCs. Prospective studies are needed to confirm these results.

Comparison of cholecystectomy and percutaneous cholecystostomy in acute cholecystitis: results of a retrospective study.

OBJECTIVE: To retrospectively compare the clinical outcomes of percutaneous cholecystostomy (PC) and cholecystectomy in patients with acute cholecystitis admitted to an urban University Hospital. PATIENTS AND METHODS: We studied 646 patients with acute cholecystitis. Ninety patients had placement of a PC at their index hospitalization, and 556 underwent cholecystectomy. Of the 90 patients with PC, 13 underwent subsequent elective cholecystectomy. RESULTS: Overall, in-hospital mortality and postoperative complications were significantly higher in patients who received PC than in those who underwent cholecystectomy. In the ASA score 1-2 group, patients with PC were significantly older and had a longer postoperative stay while their mortality and morbidity were similar to patients who underwent cholecystectomy. In patients with ASA score of 3, PC and cholecystectomy did not differ significantly for demographic variables and clinical outcomes such as hospital stay, in-hospital mortality, postoperative complications and distribution of complications according to the classification of Clavien-Dildo. In mild, moderate, and severe cholecystitis, patients who underwent PC were significantly older than those who received cholecystectomy. In general, in mild, moderate and severe cholecystitis, the clinical outcomes did not differ significantly between patients who received PC and cholecystectomy. Morbidity was higher in patients with mild cholecystitis who underwent PC. Of the 77 patients dismissed from the hospital with drainage, 12 (15.6%) developed biliary complications and 5 needed substitutions of the drainage itself. CONCLUSIONS: PC does not offer advantages compared to cholecystectomy in the treatment of acute cholecystitis. Its routine use is therefore questioned. There is need of an adequate, randomized study that compares PC and cholecystectomy in high-risk patients with moderate-severe cholecystitis.

Negative pressure wound therapy (NPWT) in duodenal breakdown fistulas: negative pressure fistula therapy (NPFT)?

OBJECTIVE: To describe for the first time in literature the specific methodology of use of negative pressure wound therapy (NPWT) for duodenal fistula through clinical cases. The constant increase of use of NPWT for complex surgical situations imposes tailored previously undescribed solutions for the technique. PATIENTS AND METHODS: Herein, three cases of high output duodenal fistula successfully treated with Negative Pressure Wound Therapy (NPWT) are reported. The technical details for the application of NPWT to these fistulas are discussed and described. RESULTS: All three patients recovered without the necessity of further surgical operations. CONCLUSIONS: When using NPWT, management of high-output duodenal fistulas must rely on some degree of customization of the aspiration systems. The aim of the procedure is to put under depression the duodenal hole and surrounding tissues "all in one" and not to separate the complex wound in sectors as usually indicated. We suggest calling this technique Negative Pressure Fistula Therapy.