The core components of cardio-oncology rehabilitation.

The increased efficacy of cancer therapy has resulted in greater cancer survival and increasing number of people with cancer and cardiovascular diseases. The sharing of risk factors, the bidirectional relationship between cancer and cardiovascular diseases and the cardiotoxic effect of chemotherapy and radiotherapy, are the cause of the rapid expansion of cardio-oncology. All strategies to preserve cardiovascular health and mitigate the negative effect of cancer therapy, by reducing the cardiovascular risk, must be pursued to enable the timely and complete delivery of anticancer therapy and to achieve the longest remission of the disease. Comprehensive cardiac rehabilitation is an easy-to-use model, even in cancer care, and is the basis of Cardio-Oncology REhabilitation (CORE), an exercise-based multi-component intervention. In addition, CORE, besides using the rationale and knowledge of cardiac rehabilitation, can leverage the network of cardiac rehabilitation services to offer to cancer patients exercise programs, control of risk factors, psychological support, and nutrition counseling. The core components of CORE will be discussed, describing the beneficial effect on cardiorespiratory fitness, quality of life, psychological and physical well-being, and weight management. Furthermore, particular attention will be paid to how CORE can counterbalance the negative effect of therapies in those at heightened cardiovascular risk after a cancer diagnosis. Barriers for implementation, including personal, family, social and of the health care system barriers for a widespread diffusion of the CORE will also be discussed. Finally, there will be a call-to-action, for randomized clinical trials that can test the impact of CORE, on morbidity and mortality.

Exercise for slowing the progression of atherosclerotic process: effects on inflammatory markers.

Atherosclerosis is a dynamic process driven by all cardiovascular risk factors that can be briefly divided into an early and a late phase. Inflammation is one of the fundamental substrates that initiates the atherosclerotic process in the early stages and promotes and maintains it in the final stages. In the last decades, clinical and experimental data have shown that inflammation is supported by mediators that respond to physical activity. The present review aimed at investigating the effect of physical exercise on inflammatory mediators, both the positive ones that have a proinflammatory effect (interleukin 6, c-reactive protein and tumor necrosis factor α, interferon γ, high-mobility group box-1), and the negative ones which have an anti-inflammatory effect (interleukin 10). Pooled data support the evidence that physical exercise can directly modulate the activity of inflammatory cytokines slowing down or preventing the formation of the atherosclerotic stage.

Histological and Histomorphometric Evaluation of New Bone Formation after Maxillary Sinus Augmentation with Two Different Osteoconductive Materials: A Randomized, Parallel, Double-Blind Clinical Trial.

This study aimed to investigate the histological features of deproteinized equine bone mineral (DEBM) and anorganic bovine bone (ABB) after human sinus augmentation with the lateral approach. Twenty-three sinus augmentations were performed in 16 patients (male: 10/female: 6) using DEBM or ABB in a randomized fashion. Healing took place over the next 6 months. Bone core biopsies (N = 23) were obtained for each subject prior to placing the dental implants. The biopsies were processed for both histological descriptions and histomorphometric analysis. Statistical analyses were applied as appropriate, defining statistical significance as p < 0.05. Core bone biopsies revealed no differences in terms of newly formed bone between groups, or differences in terms of tissue inflammation. Both DEBM and ABB appear to be suitable biomaterials for bone augmentation in sinus lift surgery in the short term. However, dedicated studies are required to confirm these results and their stability in the long term.

Sacubitril/Valsartan Improves Autonomic Function and Cardiopulmonary Parameters in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. METHODS: Patients with HFrEF admitted to outpatients' services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. RESULTS: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = -0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = -0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = -0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = -2.065, SE = 0.354, p < 0.001). CONCLUSIONS: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.

Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement.

Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.

Secondary prevention advices after cardiovascular index event: From drug prescription to risk factors control in real world practice.

The present study aims at evaluating the achievement of blood pressure, lipid and blood glucose targets, healthy lifestyle changes and appropriate drug prescription/adherence in patients attending secondary prevention/CR ambulatory visit after index cardiovascular event in a time period ranging 1 to 5 year. At ambulatory visit, a predetermined set of data collection was used, including demographic data, cardiovascular risk factors and lifestyle habits, type and time of index event, current symptoms, physical sign, biochemistry and current medical treatment (including type and dosage). Cardiovascular risk profile (smoking habits, physical activity and body weight), secondary prevention goals (LDL-cholesterol, blood pressure, resting heart rate, glycated haemoglobin level) and the use of recommended drugs were also evaluated and categorized. Study population consisted of 800 patients [644 men (84.5%), aged 69±10.9 years)]. Cardiovascular index events were coronary artery bypass graft (CABG) (20%) ST segment elevation myocardial infarction (STEMI) (28%), non-ST segment elevation myocardial infarction (NSTEMI) (21%) and stable angina (13%) by unstable angina (13%) and stroke (5%). About 30% of patients was symptomatic (angina or dyspnoea) at the time of ambulatory visit. Major comorbidities were hypertension (73%), dyslipidaemia (64%) and diabetes (40%). More than 80% of patients achieved target levels for blood pressure. Patients that have participated to cardiac rehabilitation programmes after cardiovascular index event showed best achievement in blood pressure target (83.8% vs 76.8%, p=0.02). LDL-cholesterol target (<70 mg/dl) was achieved in about 2/3 of patients; HbA1c target (<7%) was achieved in 56.4% of diabetic population. About 75% of study cohort was treated with RAAS inhibitors, 85% with beta-blockers, 92% with statins and 87% with acetylsalicylic acid. All drugs were increasingly adopted from index event. Implementing secondary prevention guidelines into the 'real world' clinical practice in "late" interval from 1 to 5 years after a cardiovascular event improved risk factors control and appropriate drug prescription. Whether these improvements translated into prognostic advantages remains to be elucidated.

Immediate loading of three (fixed-on-3) vs four (fixed-on-4) implants supporting cross-arch fixed prostheses: 1-year results from a multicentre randomised controlled trial.

PURPOSE: To evaluate the outcome of three (fixed-on-3 = Fo3) vs four (fixed-on-4 = Fo4) implants immediately restored with metal-resin screw-retained cross-arch prostheses in fully edentulous jaws. MATERIALS AND METHODS: Forty-eight edentulous or to be rendered edentulous patients were randomised in six centres (eight patients per centre) to the Fo3 group (24 patients: 12 maxillae and 12 mandibles) and to the Fo4 group (24 patients: 12 maxillae and 12 mandibles) according to a parallel group design. To be immediately loaded, implants had to be inserted with a minimum torque of 40 Ncm. Outcome measures were prosthesis and implant failures, complications and peri-implant marginal bone level changes evaluated up to 1 year post-loading. RESULTS: One maxillary prosthesis per group was delayed loaded because implants could not be placed with a torque of at least 40 Ncm. Ten patients in the Fo3 group and four in the Fo4 group had implants placed flapless. One year after loading no drop out occurred. One patient of the Fo3 group lost three implants vs three patients of the Fo4 group who lost four implants, the difference being no statistically significant (risk difference = -0.08; 95% CI: -0.27 to 0.10; Fisher's exact test P = 0.609). One mandibular Fo3 and one maxillary Fo4 prosthesis failed. Six Fo3 patients were affected by complications vs three Fo4 patients (risk difference = 0.12; 95% CI: -0.10 to 0.34; Fisher's exact test; P = 0.461). Both groups lost marginal bone in a statistically significant way (0.22 ± 0.20 mm for Fo3 patients and 0.40 ± 0.21 mm for Fo4 patients), with Fo3 group showing less marginal peri-implant bone loss than Fo4 group (estimate of the difference = -0.18 (standard error: 0.06) mm; 95% CI: -0.30 to -0.06; P = 0.005). There were no differences in clinical outcomes between the six operators. CONCLUSIONS: These preliminary results suggest that immediately loaded cross-arch prostheses of both jaws can be supported by only three dental implants at least up to 1 year post-loading, though longer follow-ups are definitively needed.

Pancreaticoduodenectomy for malignancies in children.

PURPOSE: Malignant tumors of the common bile duct or of the pancreas head are uncommon in childhood [Perez EA, Gutierrez JC, Koniaris LG, Neville HL, Thompson WR, Sola JE. Malignant pancreatic tumors: incidence and outcome in 58 pediatric patients. J Pediatr Surg. 2009; Jan; 44 (1): 197-203]. With radical surgery being the standard cure for nonmetastatic diseases, pancreaticoduodenectomy (PD) is the best choice when the tumor is localized in the head of the pancreas, or in the lower portion of the common bile duct. The purpose of the present study is to describe five consecutive children managed by PD, and reviewing the particular aspects and results of this rare procedure in children. METHODS: Between 2007 and 2010, five patients (median age: 7 years) underwent PD for nonmetastatic malignant tumors. In two cases, PD was performed en bloc with a right hepatectomy in order to achieve the radical resection of a recurrent biliary sarcoma. Four patients benefited from a "pylorus-preserving" PD procedure. In two patients, resection of the portal vein and vascular reconstruction was performed, and in one case, an extended resection of the biliary ductal system was necessary. RESULTS: All resection margins were clear. The postoperative course was uneventful, with no pancreatic or biliary leakage in all of the patients. Oral refeeding was achieved by the eighth postoperative day. In two cases, a late revision of pancreatic-jejunal anastomosis was performed because of mild steatorrea and a suspected anastomotic stricture. Two of the patients, who were subsequently operated on second hand, for biliary sarcoma, died from the recurrence; while three of the others, with pancreatic malignancies, are alive and well, with a good functional outcome. CONCLUSIONS: Surgical resection is the treatment of choice for tumors of the pancreatic head area. In the absence of regional or metastatic extension, the radicality of primary intervention is associated with favorable outcomes. Good functionality results were observed after the PD was limited to the head of the pancreas and subject to pylorus-preserving techniques.

Prehepatic portal hypertension with aneurysm of the portal vein: unusual but treatable malformative pattern.

INTRODUCTION: Portal vein aneurysms (PVAs) are usually located at the vein trunk or at its bifurcation, rarely intra-hepatic, or at the umbilical portion. Etiology remains unclear. METHODS: Three children with PVA were identified over a 5-year period. PVA anatomy was assessed by Doppler Ultrasound, Angio CT/MRI, and trans-jugular retrograde portography. RESULTS: Three children with intrahepatic PVA (including the umbilical portion) were identified during assessment for pre-hepatic portal hypertension: all had splenomegaly and hypersplenism. One presented with massive variceal bleeding. In two cases, a portal vein cavernoma was found, and in the third a severe stricture at the portal bifurcation was observed. Restoration of portal venous flow was achieved by a meso-Rex bypass in two cases and transposing the PV into the Rex in one. High hepatopetal portal flow was restored immediately, with follow-up confirming long-term patency and resolution of signs of portal hypertension with time. CONCLUSIONS: These original observations suggest a common initial malformative pattern consisting of a portal venous stricture/web causing a post-stenotic aneurysmal dilatation of the intrahepatic portal branches complicated by thrombosis and cavernomatous transformation of the portal vein trunk. Importantly, the Meso-Rex bypass allows restoring a normal portal flow and cures the portal hypertension.

Meso-Rex bypass as an alternative technique for portal vein reconstruction at or after liver transplantation in children: review and perspectives.

Direct portal revascularization can be achieved by interposing a vascular graft between the SMV and the Rex recessus (left portal vein system): the MRB. To review indications and results of the procedure in the setting of pediatric liver transplantation, reports were selected from the English literature. Previously reported series were updated to analyze long-term outcome. A new series was added and analyzed as a complementary set of cases. A total of 51 cases were analyzed. With a 96% overall patient survival rate and a 100% long-term patency rate when the IJV is used for the bypass, MRB achieves a very successful physiologic cure of chronic portal hypertension and restores the portal flow into and through the liver graft. It also has been used successfully for primary revascularization of liver grafts, as well as for managing early acute portal vein thrombosis episodes. The use of this procedure in conjunction with other strategies and techniques might be of interest for transplant surgeons, particularly those caring for children.

Surgical management of portal hypertension in children.

The management of children with portal hypertension has dramatically changed during the past decade, with an improvement in outcome. This has been achieved by improved efficiency of endoscopic variceal control and the success of liver transplantation. Emergency surgical shunt procedures are rarely required, with acute bleeding episodes generally controlled endoscopically or, occasionally in adults, by interventional radiological procedures. Portosystemic shunts may be considered as a bridge to transplant in adults but are rarely used in this context in children. Nontransplant surgery or radiological interventions may still be indicated for noncirrhotic portal hypertension when the primary cause can be cured and to allow normalization of portal pressure before liver parenchyma is damaged by chronic secondary changes in some specific diseases. The meso-Rex bypass shunt is used widely but is limited to those with a favorable anatomy and can even be performed preemptively. Elective portosystemic shunt surgery is reserved for failure to respond to conservative management in the absence of alternative therapies.

Creatine phosphate: pharmacological and clinical perspectives.

Since the 1970s, extensive experimental and clinical research has demonstrated that relevant reductions of creatine phosphate (CrP) or phosphocreatine availability occur in a wide spectrum of pathophysiological situations. A decrease in intracellular concentrations of creatine (Cr) and CrP results in a hypodynamic state of cardiac and skeletal muscle pathology. Many experimental and clinical studies have evaluated the possibility to improve cardiac and skeletal muscle performance by exogenous administration of CrP. Furthermore, many experimental studies have shown that CrP may play two important roles in the regulation of muscle energetics and work. First, CrP maintains local adenosine triphosphate pools and stabilizes cellular membranes due to electrostatic interactions with phospholipids. The second mechanism decreases the production of lysophosphoglycerides in hypoxic hearts, protects the sarcolemma of cardiac cells against ischemic damage, decreases the frequency of arrhythmias, and increases post-ischemic recovery of contractile function. Recent research on CrP has demonstrated positive therapeutic results in various clinical applications. These benefits have been applied in several pathological conditions, such as heart failure, acute myocardial ischemia, chronic ischemic heart disease, cardiac surgery, skeletal muscle hypotonotrophy, and cerebral ischemia. This review describes the CrP shuttle, pathophysiological basis of the supplementation of CrP, and its therapeutic effects in multiple clinical conditions. The major aim is to summarize results of the intense research carried out over 40 years to provide evidence to support the adjunctive use of CrP in many pathological conditions that may target cellular energy impairment; thus, increasing energy metabolism.

Congenital intrahepatic portohepatic shunt managed by interventional radiologic occlusion: a case report and literature review.

Congenital intrahepatic portosystemic shunts are rare hepatic vascular anomalies that often lead to severe secondary conditions. A 6-year-old boy was referred for assessment of severe hypoxia, and a large liver mass was diagnosed with such a malformation and was managed by direct closure of the venous fistula by interventional radiology. Follow-up assessment shows normalization of the respiratory condition and a progressive reduction of the vascular liver lesion. Review of literature suggests that radiologic interventions are currently the criterion standard for managing these conditions, with surgery reserved for patients who are not eligible for radiologic procedure and those requiring liver transplantation.

Giant pilomatricoma mimicking a malignant parotid mass.

Pilomatricomas are benign neoplasms of the hair follicle occurring relatively often in the pediatric population. However, lesions attaining massive proportions are very rarely encountered. We describe such a case presenting in the parotid region and initially misdiagnosed as malignancy. Preoperative biopsy provided accurate diagnosis and allowed definitive surgical excision using a parotid-sparing approach. In children, giant pilomatricoma should be included into the differential diagnosis of noninflammatory masses of the salivary gland region.

Conservative management of cervicomediastinal chyloma in an infant.

The accumulation of chyle into the mediastinum after surgical intervention is considered an extremely rare event, which has been previously described only in adulthood. We report on a 9-month-old boy who developed a cervicomediastinal chyloma after excision of a large left-sided supraclavicular cystic hygroma. Notwithstanding considerable tracheal deviation, the infant remained asymptomatic and was successfully treated by nonoperative treatment. Professionals should be aware of such an unusual condition, which may benefit from expectant management when evaluation establishes a high likelihood of clinical diagnosis, and patient's general condition remains stable. This approach may avoid, with little risk, unnecessary early surgical intervention in some of these patients.

Infantile abdominoscrotal hydrocele: a not so benign condition.

PURPOSE: Infantile abdominoscrotal hydrocele is a rarely described condition. We report the outcome of the largest single institution experience managing these lesions. MATERIALS AND METHODS: We retrospectively reviewed descriptive case series of all infants treated between January 1998 and December 2007. Postoperative followup ranged from 3 to 107 months (median 48). RESULTS: A total of 18 consecutive patients underwent abdominoscrotal hydrocele repair at age 3 to 21 months (median 8). The first 13 patients underwent inguinal hydrocelectomy, which consisted of high ligation of the processus vaginalis and complete excision of the abdominal component of the lesion. The remaining 5 patients underwent plication of the tunica vaginalis accomplished through the scrotum. Included in this group were 2 patients initially treated expectantly because the lesion was without undue tension at diagnosis. Both cases demonstrated spontaneous resolution of the abdominal component of the lesion but ultimately required surgery for scrotal hydrocele. Overall 23 testes (5 bilateral lesions) were operated on, of which 18 had some degree of testicular dysmorphism detected by ultrasonography or during surgery and 15 fully recovered postoperatively. A total of 11 patients experienced 1 or more postoperative complications, including persistent scrotal swelling (7), hypoplastic testis (3), scrotal hematoma (2), inguinal hernia (1) and cryptorchidism (1). Morbidity related to scrotal hydrocelectomy was negligible. There were no recurrences of abdominoscrotal hydrocele in the series. CONCLUSIONS: Tense infantile abdominoscrotal hydroceles are associated with a high rate of testicular dysmorphism, which is often reversed by early intervention. Simple transscrotal plication of the tunica vaginalis represents an effective procedure with decreased postoperative complications.

The eyelid crease approach to angular dermoid cysts in pediatric general surgery.

PURPOSE: We recently adopted an approach described by eyelid surgeons for angular dermoid cyst excision. The aim of this study was to compare the outcome of this technique with that accomplished through a conventional trans-eyebrow incision. METHODS: Prospective nonrandomized study of 34 consecutive children treated between January 2000 and December 2006. Twenty-six patients (group I) were operated on through a trans-eyebrow incision, whereas 8 (group II) received an upper eyelid crease incision. Performance measures included cosmesis, operative time, and complications. Cosmesis was assessed blindly with comparative photographs, using a 100-mm visual analog scale. RESULTS: No significant differences were found between groups I and II with regard to age at surgery (22 +/- 17 vs 24 +/- 4 months; P = .07) and operative time (42 +/- 21 vs 40 +/- 16 minutes; P = .9). In group II, the scar resulted invisible when the affected side was assessed with the eye open and still significantly better than group I, when evaluated with the eye closed (96 +/- 7 vs 81 +/- 18 mm; P = .0001). All patients and their families reported great satisfaction and an excellent scar. There were neither major postoperative complications nor recurrence of the lesion. CONCLUSIONS: Angular dermoid cyst excision using an eyelid crease approach yields excellent cosmesis and represents a safe, simple, and easily reproducible procedure in pediatric general surgical practice.

One-stage excision of massive cervicomediastinal lymphangioma in the newborn.

We report the first neonate successfully treated with one-stage complete excision of massive cervicomediastinal lymphangioma producing alarming respiratory distress. Early postoperative course was complicated by refractory bilateral chylothorax, which effectively responded to insertion of external pleuroperitoneal shunts. At the 6-year follow-up, the child remains symptom free and recurrence free. One-stage resection for cervicomediastinal lymphangioma is curative and well tolerated even shortly after birth.