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.

Quiet PROPELLER MRI techniques match the quality of conventional PROPELLER brain imaging techniques.

BACKGROUND AND PURPOSE: Switching of magnetic field gradients is the primary source of acoustic noise in MR imaging. Sound pressure levels can run as high as 120 dB, capable of producing physical discomfort and at least temporary hearing loss, mandating hearing protection. New technology has made quieter techniques feasible, which range from as low as 80 dB to nearly silent. The purpose of this study was to evaluate the image quality of new commercially available quiet T2 and quiet FLAIR fast spin-echo PROPELLER acquisitions in comparison with equivalent conventional PROPELLER techniques in current day-to-day practice in imaging of the brain. MATERIALS AND METHODS: Thirty-four consecutive patients were prospectively scanned with quiet T2 and quiet T2 FLAIR PROPELLER, in addition to spatial resolution-matched conventional T2 and T2 FLAIR PROPELLER imaging sequences on a clinical 1.5T MR imaging scanner. Measurement of sound pressure levels and qualitative evaluation of relative image quality was performed. RESULTS: Quiet T2 and quiet T2 FLAIR were comparable in image quality with conventional acquisitions, with sound levels of approximately 75 dB, a reduction in average sound pressure levels of up to 28.5 dB, with no significant trade-offs aside from longer scan times. CONCLUSIONS: Quiet FSE provides equivalent image quality at comfortable sound pressure levels at the cost of slightly longer scan times. The significant reduction in potentially injurious noise is particularly important in vulnerable populations such as children, the elderly, and the debilitated. Quiet techniques should be considered in these special situations for routine use in clinical practice.

Vacuum Assisted Closure (VAC) therapyTM as a swiss knife multi-tool for enteric fistula closure: tips and tricks: a pilot study.

OBJECTIVE: Enterocutaneous fistulas (ECFs) are an uncommon surgical problem, but they are characterized by a difficult management. Vacuum-assisted closure (VAC) therapy is a method utilized for chronic and traumatic wound healing. At first, VAC therapy had been contraindicated in the treatment of intestinal fistulas, but as time went by, VAC therapy revealed itself to be a "Swiss knife multi-tool". This paper presents some clinical cases of enterocutaneous (ECF) and enteroatmospheric fistulas (EAF) treated with VAC therapy™. MATERIALS AND METHODS: The history of 8 patients treated for complex fistulas was revised. Four of them presented with enterocutaneous and four with enteroatmospheric fistulas. All were treated with VAC therapy with variations elaborated to help in accelerated closure of intestinal wall lesions. RESULTS: Four out of four ECFs closed spontaneously. In the EAF group, in three cases the fistula turned slowly into an entero-cutaneous fistula, and in one out of four it closed spontaneously. The mean length of VAC therapy™ was 35.5 days and that of spontaneous closure was 36.4 days. CONCLUSIONS: The results of our study encourage the use of VAC therapy™ for the treatment of enterocutaneous fistulas. VAC therapy™ use has a double therapeutic value: (1) it promotes the healing of the skin and allows also the management of EAFs; (2) in selected cases, those in which it is possible to create a deep fistula tract ("well") it is possible to assist to a complete healing with closure of the ECFs.

Observational study on preoperative surgical field disinfection: povidone-iodine and chlorhexidine-alcohol.

BACKGROUND AND OBJECTIVES: Surgical site infection (SSI) rate is reported to range around 16%. Preoperative skin disinfection is keystone for SSI reduction. Chlorhexidine-alcohol has been reported to be more effective than Povidone-iodine (PVI). However, in many countries established habits and the inferior costs of PVI restrain the employment of chlorhexidine disinfection kits (ChloraPrep®) for the preparation of the surgical field. MATERIALS AND METHODS: The costs of surgical field preparation in clean-contaminated surgery utilizing PVI (Betadine) and chlorhexidine alcohol and the evaluation of surgeon compliance and satisfaction, were studied by a observational study on 50 surgical operations in which surgical field was prepared with PVI checking established guidelines, and on 50 surgical operations in which chlorhexidine-alcohol (ChloraPrep) was employed. The use of auxiliary material was tabulated as well as the timing of the phases of disinfection and the surgeon's opinions. RESULTS: The use of auxiliary material (gloves, gauzes, paper towels, surgical instruments, small swabs for umbilical cleaning) is associated with the type of disinfectant, with major use of auxiliary materials recorded in PVI disinfection. PVI disinfection does not follow stringent guidelines, in particular waiting for the disinfectant to dry. PVI guidelines are more demanding than those relative to ChloraPrep. The time necessary for the preparation of the field is significantly longer for PVI. Auxiliary material and guideline compliance must be taken into account when calculating costs; the former are direct costs (even though marginal) and the latter can determine major infective risk. CONCLUSIONS: Chlorhexidine in kits is easier and faster to use than PVI, requires less auxiliary material and has been shown previously to reduce SSI in clean contaminated surgery.

The new retained foreign body! Case report and review of the literature on retained foreign bodies in laparoscopic bariatric surgery.

The advent of laparoscopic surgery has created a set of peculiar morbidities. As the laparoscopic devices, also the type of retained foreign bodies has changed. We present a case of unusual, apparently isolated and recurrent lung abscess, pleural effusion and poorly evident subphrenic abscess after laparoscopic gastric bypass, due to a retained Endo-Catch bag. A 27-year-old obese female underwent an uneventful laparoscopic Roux-en-Y gastric bypass. After surgery she developed a left basal lung abscess, that resolved in two weeks with heavy antibiotic therapy, while radiological abdominal imaging was apparently normal. Patient was discharged on p.o. day 30. After two months, she presented with fever and dyspnoea and no gastrointestinal complaints. Chest and abdominal computer tomography showed a left recurrent abscess with effusion but this time a 3 cm subphrenic mass with metallic clips inside was demonstrated on CT scan. Patient was treated with an explorative laparoscopy that identified an Endo-Catch bag with the jejunal blind loop inside. Postoperative left lung abscess can be a warning of a suphrenic surgical complication. Laparoscopic surgery requires even more attention to retained foreign bodies due to the reduced visibility of the surgical field. The recommendation to enforce recording of laparoscopic maneuvers is mandatory.

An economic evaluation of Clostridium difficile infection management in an Italian hospital environment.

BACKGROUND AND OBJECTIVES: Clostridium difficile infection (CDI) accounts for the majority of nosocomial cases of diarrhea, and with recent upsurge of multidrug-resistant strains, morbidity and mortality have increased. Data on clinical impact of CDI come mostly from Anglo-Saxon countries, while in Italy only two studies address the issue and no economic data exist on costs of CDI in the in hospital setting. A retrospective cross-sectional study with pharmacoeconomic analysis was performed on the CDI series of the Policlinico Gemelli of Rome, a major 1400 bed Hospital. PATIENTS AND METHODS: The clinical charts of 133 patients in a 26 month period were reviewed. All costs of the involved resources were calculated and statistical analysis was carried out with means and standard deviations, and categorical variables as number and percentages. RESULTS: The results show the significant sanitary costs of CDI in an Italian hospital setting. The cost analysis of the various elements (exams, imaging studies, therapies, etc.) shows that none independently influences the high cost burden of CDI, but that it is the simple length of hospital stay that represents the most important factor. CONCLUSIONS: Prevention of CDI is the most cost-effective approach. The major break-through in cost reduction of CDI would be a therapeutical intervention or procedure that shortens hospital length of stay.

Intra-abdominal vacuum-assisted closure (VAC) after necrosectomy for acute necrotising pancreatitis: preliminary experience.

Infection of pancreatic necrosis, although present in less than 10% of acute pancreatitis, carries a high risk of mortality; debridment and drainage of necrosis is the treatment of choice, followed by 'open' or 'close' abdomen management. We recently introduced the use of intra-abdominal vacuum sealing after a classic necrosectomy and laparostomy. Two patients admitted to ICU for respiratory insufficiency and a diagnosis of severe acute pancreatitis developed pancreatic necrosis and were treated by necrosectomy, lesser sac marsupialisation and posterior lumbotomic opening. Both of the patients recovered from pancreatitis and a good healing of laparostomic wounds was obtained with the use of the VAC system. Most relevant advantages of this technique seem to be: the prevention of abdominal compartment syndrome, the simplified nursing of patients and the reduction of time to definitive abdominal closure.

Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells.

Thyroid carcinoma cells often do not express thyroid-specific genes including sodium iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin-stimulating hormone receptor (TSHR). Treatment of thyroid carcinoma cells (four papillary and two anaplastic cell lines) with histone deacetylase inhibitors (SAHA or VPA) modestly induced the expression of the NIS gene. The promoter regions of the thyroid-specific genes contained binding sites for hepatocyte nuclear factor 3 beta (HNF3 beta)/forkhead box A2 (FoxA2), thyroid transcription factor 1 (TTF-1), and CCAAT/enhancer binding protein (C/EBP beta). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed decreased expression of HNF3 beta/FoxA2 and TTF-1 mRNA in papillary thyroid carcinoma cell lines, when compared with normal thyroid cells. Forced expression of these genes in papillary thyroid carcinoma cells inhibited their growth. Furthermore, the CpG island in the promoter region of HNF3 beta/FoxA2 was aberrantly methylated; and treatment with 5-aza-2-deoxycytidine (5-Az) induced its expression. Immunohistochemical staining showed that C/EBP beta was localised in the nucleus in normal thyroid cells but was detected in the cytoplasm in papillary thyroid carcinoma cells. Subcellular fractionation of papillary thyroid carcinoma cell lines also demonstrated high levels of expression of C/EBP beta in the cytoplasm, suggesting that a large proportion of C/EBP beta protein is inappropriately localised in the cytoplasm. In summary, these findings reveal novel abnormalities in thyroid carcinoma cells.

[The ATLS Courses in Italy. Twelve years experience]. / I Corsi ATLS (Advanced Trauma Life Support) in Italia. Dodici anni di attività.

ATLS Courses were introduced in the USA in 1980 and have been taught in Italy since 1994. Through theoretical lessons and practical sessions, their scope is to provide proper training for doctors with every kind of speciality who work in Emergency Departments, in order to prepare them to rapidly and effectively intervene on a patient who has suffered a serious trauma. Universities, in fact, do not prepare doctors adequately on this topic, while the application of the ATLS method in the first hours after trauma can effectively improve the prognosis of the patient. This study collects the data of the Italian experience in ATLS training, which has been carried out under the aegis of the Italian Chapter of the American College of Surgeons. The ATLS Courses have become widespread throughout our Country, which today is the fourth in the world for number of courses held every year.

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas.

Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread.