The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study.

INTRODUCTION: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. HYPOTHESIS: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). ANIMALS: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7. METHODS: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. RESULTS: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. CONCLUSIONS: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.

Formula feeding and systemic hypoxia synergistically induce intestinal hypoxia in experimental necrotizing enterocolitis.

PURPOSE: Feeding and systemic hypoxia are major stresses inducing necrotizing enterocolitis (NEC). This study aims to investigate the role of systemic hypoxia in NEC and its effect before and after feeding. METHODS: Neonatal mice were studied in three groups. Control (N = 9): breast feeding; NEC A (N = 8), gavage feeding + lipopolysaccharide (LPS) + preprandial hypoxia; and NEC B (N = 9), feeding + LPS + postprandial hypoxia. Pimonidazole, a hypoxia marker, was injected intraperitoneally before ileum was harvested for histology and quantitative RT-PCR studies. Statistical analysis was done using the ANOVA and Chi-square test. RESULTS: NEC incidence was 62.5% in NEC A and 88.9% in NEC B. The mortality in NEC B (55.6%) but not A (25%) is significantly higher than control (0%, p < 0.05). Pimonidazole staining elevated in both NEC A and B with higher pimonidazole grade in NEC B (p < 0.01). Both NEC groups had increased the expression of hypoxia-related genes: HIF-1α, GLUT-1, and PHD-3 with GLUT-1 expressed more in NEC B compared with NEC A (p < 0.01). The inflammation marker, IL6, was similarly raised in both NEC A and B. CONCLUSION: Feeding and postprandial hypoxia synergistically induce intestinal hypoxia in NEC. As feeding increases intestinal oxygen demand, maintaining a balance between intestinal oxygen supply and demand is important to prevent NEC.

Is single incision pediatric endoscopic surgery more painful than standard laparoscopy in children? Personal experience and review of the literature.

AIM: It has been speculated that single incision pediatric endoscopic surgery (SIPES) in children could result in more postoperative pain given the device size for a child umbilicus. Herein, we compare the postoperative pain in children who underwent SIPES or standard laparoscopy (SL). METHODS: Patients who underwent SIPES via Olympus TriPort™ Access system between 2010 and 2011 were prospectively compared with SL controls (similar age, sex and type of operation). Primary endpoint was analgesic requirement (number of doses and dose/kg). A systematic review of the literature included all articles (2008-2012) comparing postoperative pain following transumbilical SIPES and SL in children. Data were analyzed using non-parametric tests. RESULTS: Ten patients (8 males, median age 9 years, range 4-15) underwent 11 SIPES procedures: appendicectomy (N.=6), orchidopexy (N.=2), cholecystectomy (N.=2), and total colectomy (N.=1). There was no difference in paracetamol requirement between SIPES (median 74 mg/kg, range 14-149) and SL (median 59 mg/kg, range 13-108, P=0.76) patients. Morphine was required by only two patients per group (no difference in dosage or frequency). Eight studies (2010-2012) comparing 334 SIPES vs. 343 SL patients were analysed. Three studies showed advantage of SIPES, and four no difference between SIPES and SL. One randomized trial reported greater pain in SIPES appendicectomy, but no difference with SL once patients were discharged home. CONCLUSION: SIPES does not seem to be associated with more postoperative pain than SL in children. In appropriate cases, SIPES is a valid alternative to SL for a good range of pediatric procedures.

Analgesic, antiulcer, antithrombotic drugs and organ damage: a population-based case-control study.

AIM: Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population. METHODS: We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time. RESULTS: We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs. CONCLUSION: NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.

Antegrade continence enema (ACE): predictors of outcome in 111 patients.

PURPOSE: The antegrade continence enema (ACE) is used as a means of managing faecal incontinence and constipation with varying outcomes. We aim to evaluate our outcomes of ACEs and identify predictors of outcome. METHODS: A retrospective case-note review of patients ≤16 years of age undergoing an ACE (March 2000-September 2013) was carried out. Data collected included: patient demographics, functional outcomes and complications. Data are quoted as median (range) and compared using Mann-Whitney and Fisher's exact test. Univariate analysis was performed to identify predictors of successful outcomes. P < 0.05 is significant. Successful outcome = total continence/occasional leakage and failed outcome = regular soiling and/or constipation. RESULTS: 111 patients with complete data sets underwent an ACE [59% male, median age = 9.5 years (3.4-16 years)] and median follow-up = 48 months (4 months-11 years 4 months). Underlying diagnoses were idiopathic constipation (n = 68), anorectal malformation (n = 27), neuropathic bowel (n = 7), Hirschsprung disease (n = 5) and gastrointestinal dysmotility (n = 4). Social continence was achieved in 87/111 (78%). Fifteen percent of patients underwent reversal of ACE due to resolution of symptoms. There was no difference in outcomes related to diagnosis, gender, age or follow-up duration. Complication rate was 20.7% (23/111). CONCLUSIONS: The ACE is safe and effective in the management of intractable constipation and soiling. No predictors of outcome were identified.

Patients' survival after free flap reconstructive surgery of head and neck squamous cell carcinoma: a retrospective multicentre study.

Head and neck squamous cell carcinoma of the (HNSCC) represents approximately 5% of malignant tumours in Italy. HNSCC are commonly treated with surgery or radiotherapy, or a combination of such therapies. The objectives of treatment are maximum cure rate balanced with organ preservation, restoration of form and function, reduction of morbidities and improvement or maintenance of the patient's quality of life. Immediate reconstructive surgery: local, regional or free flaps are now widely advised in the treatment of these patients. Microsurgical transfer requires expertise, is time and resource consuming, and as a whole requires substantial costs. These considerations introduce some concerns about the wide or indiscriminate use of free flap reconstructive surgery. When considering cost-benefit outcomes of such treatment, the main objective is undoubtedly, survival. This data is underreported in the current literature, whereas functional outcomes of free flaps have been largely diffused and accepted. This study collects data from 1178 patients treated with free flap reconstructive surgery following ablation of HNSCC in a group of Italian tertiary hospitals, all members of the Head & Neck Group affiliated with the Italian Society of Microsurgery. According to many authors, free flap surgery for HNSCC seems to be a beneficial option for treatment even in terms of survival.

The colorectal cancer screening program in the local health unit n. 6 of Livorno: evaluation of the screening activity in the period 2000-2011.

INTRODUCTION: The colorectal cancer screening program in the Local Health Unit n. 6 of Livorno is running since July 2000 and is meant to residents, aged between 50 and 70, who are invited to perform the test for faecal occult blood every 2 years. The aim of this work is an evaluation of the screening activity in the period 2000-2011. METHODS: The evaluation is based on the analysis of the main quality indicators formulated by GISCoR (Italian Group for Colorectal screening). RESULTS: The screening activity extension reached 93% in 2006 and 100% in 2009. The compliance level was maintained above the acceptable GISCoR value (> 45%) with a maximum of 54.9%. Values around 80% were recorded for the compliance to colonoscopy. The detection rate (DR) for cancer and advanced adenoma showed, as expected, the highest values in the early years and then move on values consistently lower than the regional average. In 2011, the raw DR for cancer was 0.9 x 1000 and the raw DR for advanced adenoma 5.3 x 1000. The distribution by stage at diagnosis of screen-detected carcinomas shows that 58.1% of these were identified at stage I while the proportion of cases in stage III+ is 19.5%. CONCLUSIONS: The overall analysis shows a good performance of the program. The proportion of colonoscopies performed on the total number of positive subjects remains a critical point of the system. The distribution by stage of screen-detected cancers shows an excellent diagnostic anticipation of the screening program.

Orchidopexy without ligation of the processus vaginalis is not associated with an increased risk of inguinal hernia.

PURPOSE: To report our experience using a modified orchidopexy with division and non-ligation of the processus vaginalis. METHODS: We performed a single-centre retrospective analysis of all patients who underwent orchidopexy between December 2005 and October 2008 at our institution. In the present technique, the processus vaginalis was gently peeled off the spermatic cord structures as high as possible and severed at the level of the internal inguinal ring without its ligation. Postoperative follow-up was routinely offered to all patients. Additionally, we made a special clinical follow-up, ranging from 1 to 69 months (median 34). RESULTS: One hundred and twenty-three patients, aged 1-11 years (median 3), underwent 147 orchidopexies during the study period. Of these, 25 were accomplished using conventional division and ligation of the processus vaginalis, and in the remaining 122 orchidopexies, the processus vaginalis was only divided. Of the 137 testes available at follow-up, 134 were in the scrotum and 3 (2 %) required re-do orchidopexy due to secondary reascent, including 2 treated with division only of the processus vaginalis. None of the patients experienced postoperative hydrocele or inguinal hernia development. CONCLUSIONS: Our findings confirm that division without ligation of a patent processus vaginalis is usually followed by spontaneous peritoneal scarring and complete closure of the internal inguinal ring. Present technique is as effective as traditional orchidopexy and saves extra time spent for meticulous closure of the processus vaginalis or peritoneal tears.

Flexible-tip laparo-endoscopic surgery: a bridge to single port appendicectomy in children.

INTRODUCTION: Single port surgery (SPS) has been demonstrated to have some advantages over conventional laparoscopy. However, currently available port sizes may limit the application in younger children or those with a small umbilicus. Moreover, the consultant learning curve required to master single port surgery may have a negative impact on surgical training. We report the first series of children who were treated with a reduced incision technique for appendicectomy using flexible-tip laparo-endoscopic surgery (FLES). PATIENTS AND METHODS: FLES was set up using one 11-mm and 2 × 5-mm bladeless ports (Ethicon XCEL™) via umbilical and low left iliac fossa incisions. A 10-mm flexible-tip laparo-endoscope was utilized. Tip angulation ensured visibility while minimising instrument clashing. A database of children undergoing FLES was kept prospectively. Demographic and peri-operative information and complications were recorded. Data are presented as medians with ranges. RESULTS: Between March and June 2010, 5 children (4 females) aged 9 (4-13) years underwent FLES for right iliac fossa pain. 2 procedures were performed by the admitting consultant, 3 by a supervised inexperienced laparoscopic trainee. 4 children had acute appendicitis including 1 with an inflammatory mass. Another had a haemorrhagic ovarian cyst. Appendicectomy was performed in all. The duration of surgery was 104 (93-130) min, and postoperative hospital stay was 2 (1-6) days. At 7 (5-8) months' follow-up no complications have been recorded. At follow-up, the cosmetic results were judged to be excellent in all by the children, their parents and the reviewing surgeon. CONCLUSIONS: FLES is an alternative to standard laparoscopy and SPS in children, and be performed effectively and safely by junior trainees. Cosmetic results are excellent. It may represent a bridge technology, particularly for younger children, until single port products and techniques more suitable for appendicectomy in this age group are available. Finally, flexible-tip technology may play a useful role as SPS evolves.

Assessment of a neonatal rat model of necrotizing enterocolitis.

INTRODUCTION: A neonatal rat model of necrotizing enterocolitis (NEC) is useful to investigate this devastating and obscure disease. The aim of this study was to assess a neonatal rat model of NEC to evaluate whether the histological appearance of the damaged intestine could be predicted by the clinical behaviour of the animals and the macroscopic appearance of the gut. MATERIALS AND METHODS: Neonatal rats were delivered at term and assigned either to a control group consisting of breastfeeding and no stress factors, or to a NEC group in which NEC was induced by gavage feeding + hypoxia + oral lipopolysaccharide (4 mg/kg/day once daily for the first 2 days of life). Clinical status was assessed on day 4 using a clinical sickness score (general appearance, response to touch, natural activity, body colour; 0 - 3 for each variable). Neonatal rats were sacrificed at 4 different time points: day 1, day 2, day 3, and day 4. At sacrifice, a macroscopic assessment of the gut was performed using a new scoring system based on: colour (0 - 2), consistency (0 - 2) and degree of dilatation (0 - 2). The resected gut was stained with haematoxylin/eosin, and evaluated microscopically by 2 independent blinded scorers, including a consultant histopathologist. The histology results were used to validate the macroscopic gut assessment. Results were compared by ANOVA and linear regression analysis. Ethics Committee and Home Office approvals were obtained. RESULTS: In the control group NEC was not present either macroscopically or histologically. The clinical sickness score was higher in the NEC group (median = 4.5; range = 2 - 6) compared to controls (median = 0; range = 0 - 1; p < 0.0001). In the NEC group the macroscopic appearance (from day 2) and histological score (from day 1) increased significantly (p < 0.0001) and were strongly correlated (r (2) = 0.74, p < 0.0001). CONCLUSIONS: The clinical behaviour and macroscopic appearance of the intestine are valid tools to assess gut damage in our neonatal rat model of NEC. This allows future studies that are not exclusively based on histology.

Compensatory renal growth in children with unilateral renal tumor treated by nephron-sparing surgery or nephrectomy.

INTRODUCTION: In children with an unilateral renal tumor, nephron-sparing surgery (NSS) results in a more adequate renal function adaptation compared to nephrectomy. In the present study, we investigated whether nephron-sparing surgery is followed by a different renal structure adaptation compared to nephrectomy. METHODS: Sixteen patients with unilateral renal tumor treated by nephrectomy (Group 1) and 10 treated by nephron-sparing surgery (Group 2) were enrolled in the study. Kidney volume was estimated by ultrasonography, using the formula for a prolate ellipsoid. Kidney volume was adjusted to the patient's weight and kidney laterality and expressed as a percentage of the expected volume of two kidneys in a healthy child. Total kidney volume (TKV) corresponded to the volume of the contralateral kidney in Group 1 patients, and to the volume of contralateral kidney + kidney remnant in Group 2 patients. Renal function was evaluated by serum creatinine values adjusted for sex and age and expressed as standard deviation scores (SDS). RESULTS: Group 2 patients presented with a greater indexed TKV compared to Group 1 patients, (97.4 +/- 18.8 % vs. 77.0 +/- 17.7 %; p = 0.005). Indexed TKV below the reference range for healthy controls with two kidneys was found in 4 of 10 Group 2 patients vs. 14 of 16 Group 1 patients (p = 0.017). In both patient groups, correlation analysis of indexed TKV and creatinine SDS showed a negative correlation (r = - 0.47; p = 0.01). CONCLUSION: In children with unilateral renal tumor, NSS is followed by a more adequate compensatory restoration of TKV compared with nephrectomy.

Oromandibular reconstruction using titanium plate and pectoralis major myocutaneous flap.

To assess whether locking-screw titanium plates (UniLOCK) and pedicled pectoralis major myocutaneous flaps are a valid alternative to complex reconstruction with bony free flaps in poor prognosis or poor performance status oncological patients with mandibular defects, a retrospective evaluation has been made of outcomes in 27 consecutive cases. No patient died perioperatively. Mean operating time was 270 minutes. Post-operative course was uneventful in 14. Mean follow-up was 13 months with no loss to follow-up. Twelve patients are alive and well, 12 died from their malignancy, two from non-neoplastic causes, and one from second cancer. Plate exposure - the main problem with bridging plates - occurred in 6 (22%, 4 early, 2 late), 4 with symphyseal and 2 with postero-lateral defects: removal was necessary in 2; 2 died with the plate exposed, and 2 had successful re-coverage, increasing the final success rate from 78% to 85%. Most patients considered the aesthetic outcome acceptable, however all edentulous patients complained of unsatisfactory dental rehabilitation. From the acceptable success rate, it may be concluded that bridging plates represent a useful reconstruction method, provided they are well covered by viable muscular tissue. They should be offered to patients contraindicated for more invasive procedures or with limited functional needs, or poor prognosis.

Unusual extended fibular origin of the human soleus muscle: possible morpho-physiologic significance based on comparative anatomy.

A bilateral anomalous extended origin of the soleus muscle was observed in a 73-year-old female cadaver. It arose from the head, neck, and proximal two-thirds of the medial crest of the fibula and ran through the posterior intermuscular septum of the leg, from the lateral border of the fibula. The soleus muscle formed the vault of a muscular tunnel, overcoming the deep flexor muscles of the leg that was about 15 cm in length and directed inferiorly and laterally. The extended fibular origin delimited a blind recess lateral to the muscular tunnel and parallel to the posterior surface of the fibula. This recess measured 6.5 cm in length and extended 3.5 cm above the inferior opening of the muscular tunnel; the superior portion of the flexor hallucis longus was housed within it between the portions of the extended origin from the medial crest of the fibula and posterior intermuscular septum. The neurovascular bundle of the posterior leg coursed in the muscular tunnel. The tibial origin and calcaneal insertion of the soleus muscle were normal. Phylogenetic studies of the muscles of the lower limbs in mammals indicate that the fibular origin of soleus is more constant than the tibial origin and, in primates, the fibular origin is the only one observed in most monkeys. The case reported might be considered a conspicuous enlargement of the fibular origin observed in primates. This large fibular origin of the soleus muscle may prove to be a difficulty during surgery when accessing the proximal two-thirds of the fibula for ligation of the peroneal artery.