Health technology assessment through the six sigma approach in abdominoplasty: Scalpel vs electrosurgery.

Abdominoplasty is a surgical procedure conducted to reduce excess abdominal skin and fat and improve body contouring. Despite being commonly performed, it is associated with a risk of complications such as infection, seroma, haematoma and wound dehiscence. To reduce the incidence of complications, different methods are used to create the abdominal flap, i.e., incision with a scalpel or electrosurgery. In this study, health technology assessment (HTA) using the Six Sigma methodology was conducted to compare these incision techniques in patients undergoing abdominoplasty. Two consecutively enroled groups of patients (33 in the scalpel group and 35 in the electrosurgery group) who underwent surgery at a single institution, the University of Campania "Luigi Vanvitelli", were analysed using the drain output as the main outcome for comparison of the incision techniques. While no difference was found regarding haematoma or seroma formation (no cases in either group), the main results also indicate a greater drain output (p-value<0.001) and a greater incidence of dehiscence (p-value=0.056) in patients whose incisions were made through electrosurgery. The combination of HTA and the Six Sigma methodology was useful to prove the possible advantages of creating skin incisions with a scalpel in full abdominoplasty, particularly a significant reduction in the total drain output and a reduction in wound healing problems, namely, wound dehiscence, when compared with electrosurgery, despite considering two limited and heterogeneous groups.

Opioids switching with transdermal systems in chronic cancer pain.

BACKGROUND: Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy OBJECTIVE: To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. METHODS: A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks RESULTS: Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 +/- 20.5 (mean +/- SD) to 3.75 +/- 8.06, and 33.8 +/- 18.9 to 3.75 +/- 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment. CONCLUSION: Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

Signalling profile and antitumour activity of the novel Hsp90 inhibitor NVP-AUY922 in multiple myeloma.

We as well as others have recently shown that Hsp90 is overexpressed in multiple myeloma (MM) and critically contributes to tumour cell survival. Pharmacologic blockade of Hsp90 has consistently been found to induce MM cell death. However, most data have been obtained with MM cell lines whereas knowledge about the molecular effects of pharmacologic Hsp90 blockade in primary tumour cells is limited. Furthermore, these investigations have so far focused on geldanamycin derivatives. We analysed the biochemical effects of a novel diarylisoxazole-based Hsp90 inhibitor (NVP-AUY922) on signalling pathways and cell death in a large set of primary MM tumour samples and in MM cell lines. Treated cells displayed the molecular signature and pharmacodynamic properties for abrogation of Hsp90 function, such as downregulation of multiple survival pathways and strong upregulation of Hsp70. NVP-AUY922 treatment efficiently induced MM cell apoptosis and revealed both sensitive and resistant subgroups. Sensitivity was not correlated with TP53 mutation or Hsp70 induction levels and stromal cells from the bone marrow microenvironment were unable to abrogate NVP-AUY922-induced apoptosis of MM cells. Thus, NVP-AUY922 may be a promising drug for treatment of MM and clinical studies are warranted.

The usefulness of transesophageal echocardiography in the staging of locally advanced lung cancer.

BACKGROUND: The pre-operative staging of locally advanced non-small cell lung cancer (NSCLC) is an important clinical and radiological issue. Computed tomography (CT) scan cannot always provide sufficient information about resectability and some patients may undergo unnecessary thoracotomy. The purpose of this study was to evaluate the utility of transesophageal echocardiography (TEE) in distinguishing T3 from T4 lesions in patients with lung cancer possibly involving cardiovascular structures and to compare its findings with those of computed tomography and, whenever possible, of surgical samples. METHODS: Between January 1998 and December 2001, sixteen patients were referred to our pulmonology unit for evaluation of locally advanced NSCLC possibly involving the heart or great vessels. All patients underwent mediastinal staging with both contrast enhancement CT scan and TEE. RESULTS: The mediastinal staging by CT scan classified eleven patients as T4N0M0 and five patients as T3N0M0. TEE suggested mediastinal extension of the tumour in nine out of sixteen patients, who were eventually classified as T4; the remaining seven patients had no mediastinal involvement according to TEE and were therefore classified as T3. The pathologic staging confirmed clinical TEE staging in all of the ten patients who subsequently underwent surgery. The remaining six patients were excluded from surgery either because of major coexistent illnesses or because refused to be operated on. CONCLUSION: TEE is a useful diagnostic tool in the staging of patients with locally advanced NSCLC which suspect involvement of heart and/or great vessels.

Pain and sensory dysfunction after breast cancer surgery: neurometer CPT evaluation.

The purpose of our study was to evaluate the presence of anatomical and functional damage to the afferent and sensorial fibres using the Neurometer CPT test. A questionnaire regarding pain was sent to 300 women who had undergone surgery six months earlier. Out of 300 patients 67 did not respond; 105 experienced no pain; while 128 felt pain. One hundred and twenty-eight women were divided into two groups: mastectomy with reconstruction and simple mastectomy. The intensity of pain at T0 in women with reconstruction was significantly higher; at T4, on the other hand, was lesser and there was no significant difference between the two groups. In both groups at T4, the daily diary revealed that interference with sleep and normal daily activities were more evident in patients who had undergone reconstruction (p > 0.001). The final results at T4 demonstrated that among patients with reconstruction, 47% showed slight hypoesthesia-paraesthesia in the breast, armpit and arm zones, 39% slight hypoesthesia in the same locations and 18% severe hypoesthesia. Patients with reconstruction, instead, showed different percentages: 75% showed slight hypoesthesia-paraesthesia, 16% a slight hypoesthesia and 9% severe hypoesthesia. Our results support the utilization of the Neurometer CPT test as a device for monitoring post-mastectomy pain.

Is dermolipectomy effective in improving insulin action and lowering inflammatory markers in obese women?

OBJECTIVE: Obesity is a major risk factor for coronary heart disease, and surgical treatment of obese patients as part of a multidisciplinary approach seems to provide faster results than diet therapy. The aim of this study was to evaluate the effect of dermolipectomy on insulin action and inflammatory markers in 20 obese women. PATIENTS: At baseline and 40 days after dermolipectomy, 20 obese women underwent indirect calorimetry and hyperinsulinaemic glucose clamp. Twenty obese nonsmoking females (age range 25--40 years) volunteered for the study. All subjects had a stable body weight for 2 months before the study. No patient was affected by cardiovascular and/or pulmonary disease, type 2 diabetes, thyroid dysfunction, acute or chronic hepatitis, renal insufficiency or cancer. No patients was receiving any drug therapy and all measurements were made during the follicular phase of the menstrual cycle. RESULTS: At baseline, fat mass (FM) correlated with plasma triglycerides (r=.58, P<0.009), free fatty acids (FFA) (r=0.73, P<0.001), insulin (r=0.70, P<0.002), leptin (r=0.55, P<0.01), adiponectin (r=-0.32, P<0.02) and resistin (r=0.31, P<0.01), insulin sensitivity (IS) (r=-0.59, P<0.005) and respiratory quotient (Rq) (r=0.62, P<0.002). With regard to inflammatory markers, FM was significantly correlated with plasma interleukin (IL)-6 (r=0.71, P<0.001), IL-10 (r=-0.67, P<0.002), tumour necrosis factor-alpha (TNF-alpha) (r=0.78, P<0.001) and soluble IL-6 receptor (sIL-6r) (r=-0.65, P<0.003). Dermolipectomy resulted in a significant decline in total FM of 2.3+/- 0.2 kg. A significant decline in BMI was also observed (30.0+/- 0.08 vs. 31.1+/- 0.7 kg/m(2)). After 40 days a significant decline in plasma resistin (P<0.001) and inflammatory markers and an increase in plasma adiponectin (P<0.03) were observed. Those metabolic changes were accompanied by a significant improvement in insulin-mediated glucose uptake (P<0.001), substrate oxidation and degree of inflammation. Changes in FM following dermolipectomy correlated with the changes in IS (P<0.01), substrate oxidation and FFA (P<0.001). CONCLUSIONS: In obese patients, dermolipectomy is associated with weight lost, improved glucose handling and lower inflammatory markers.

Effect of liposuction on insulin resistance and vascular inflammatory markers in obese women.

Liposuction is one of the more common elective surgical procedures in the US and is supposed to be on the increase. There are no reported studies specifically addressing the metabolic sequelae of liposuction in obesity. The aim of the present study was to investigate the role of large-volume liposuction on insulin resistance and circulating inflammatory markers in obese people. Thirty healthy premenopausal obese (body mass index (BMI) from 30 to 45) and 30 age-matched normal weight (BMI<25) women were studied. In obese women, insulin sensitivity, as measured by the Homeostasis Model Assessment (HOMA=fasting plasma glucose x fasting serum insulin divided by 25), as well as serum adiponectin, the novel adipocytokine with insulin sensitising properties, were significantly lower, as compared with nonobese women (p<0.01), indicating insulin resistance; on the contrary, serum concentrations of the proinflammatory cytokines IL-6, IL-18 and TNF-alpha, as well as the sensitive marker of inflammation C-reactive protein, were significantly higher (p<0.01). All obese women were submitted to a single large volume liposuction (superwet technique): the mean aspirate volume was 3540 ml (range 2550-4670), corresponding to a net lipid loss of 2.7+/-0.7 kg (mean+/-SD). After six months of stable body weight after liposuction, women were less insulin resistant (p<0.05), had reduced concentrations of IL-6, IL-18, TNF-alpha and CRP (p<0.05-0.02), and increased serum levels of adiponectin (p<0.02) and HDL-cholesterol (p<0.05). There was a significant correlation between the amount of fat aspirate and changes in HOMA (r=0.28, p<0.05), TNF-alpha (r=0.31, p<0.02), and adiponectin (r=-0.34, p<0.02), as well as between the decrease in TNF-alpha and the increase in adiponectin after the surgical procedure (r=-0.45, p<0.01). Our study demonstrates that liposuction is safe and free of metabolic sequelae in obese women, pending a careful screening of the patient. Moreover, it is associated with amelioration of insulin resistance and reduced circulating markers of vascular inflammation which may help obese subjects to reduce their cardiovascular risk.

T lymphocyte phenotypic profile in lung segments affected by cavitary and non-cavitary tuberculosis.

Clinical manifestations of pulmonary tuberculosis (TB) may depend on a complex interaction between the host and the pathogen. Clinical outcomes of pulmonary tuberculosis are variable, ranging from asymptomatic lifelong infection to parenchymal lung destruction, resulting in cavitary lesions. To investigate the hypothesis that local cellular immune response may affect presentation and outcome in tuberculosis, we performed bronchoalveolar lavage (BAL) in lung segments affected by cavitary and non-cavitary tuberculosis. We then correlated the type of cellular response at the level of the involved lung segments with clinical evolution in terms of cavity formation. We found alveolar lymphocytosis in patients with both cavitary and non-cavitary pulmonary tuberculosis, with increased CD4+ lymphocytes in patients with non-cavitary pulmonary tuberculosis. A predominant Th1 immune response has been observed in non-cavitary patients, while cavitary involved segments exhibit the presence of Th2 lymphocyte subsets. These data, while confirming the importance of Th1-type CD4+ cells and IFN-gamma in effective cellular immunity in active pulmonary tuberculosis, also suggest that the presence of Th2 lymphocytes may contribute to tissue necrosis phenomena associated with cavitary evolution of pulmonary tuberculosis. Our observations indicate the importance of the type of local immune response at the site of disease in the development of different clinical characteristics and outcome in pulmonary tuberculosis.

[Use of dermo-adipose grafts in facial morphology restoration in cases of progressive partial lipodystrophy]. / Utilizzazione degli innesti dermoadiposi nel ripristino della morfologia del viso in casi di lipodistrofia parziale progressiva.

Two cases of partial progressive lipodystrophy syndrome with extensive soft tissue atrophy of the face and of the upper part of the trunk, with kidney and blood alteration, are presented. On the basis of the psysical examination and pathological history of the patients, blood and instrumental tests have been performed in both cases. The diagnosis of partial progressive lipodystrophy syndrome has been made and a surgical treatment with dermal fat graft from the inguinal region was proposed to the patients after several information and was performed to improve the facial contour. After a follow up of 18 months a resorption of 50% of dermal fat graft was found according to surgeons' expectations with a good esthetic improvement of the face.

Elevated plasma free fatty acid concentrations do not modify cardiac repolarization in patients treated by electrolyte-glucose-insulin infusion.

Fat emulsion infusion is routinely used as a source of calories and essential fatty acids for critically ill patients who may be at risk for acquired ventricular repolarization alterations due either to drugs or electrolyte disturbances. The aim of this study was to evaluate whether acute elevations of plasma free fatty acid concentrations influence the corrected Q-T interval (Q-Tc), Q-Tc dispersion and sympathetic nervous system activity in patients requiring parenteral nutrition. Thirty hospitalized patients (mean +/- SD: 62 +/- 17 yr of age) requiring total parenteral nutrition received an infusion of 10% (500 ml) triacylglycerol emulsion as a source of calories (450 Kcal); on another occasion, and in random order, the same patients received an infusion of 20% (500 ml) triacylglycerol emulsion (900 Kcal). The infusion lasted 8 h and was preceded by a sc injection of heparin (5,000 U). Infusions of both 10% and 20% triacylglycerol emulsion increased plasma free fatty acid (p<0.00 1) and triacylglycerol (p<0.01) concentrations, and was associated with no significant change in mean BP, heart rate, and plasma catecholamines. At baseline, Q-Tc and Q-Tc dispersion were within the normal range (<440 milliseconds for QTc and <40 ms for QTc-d) and did not show any significant change at any time during infusion of triacylglycerol emulsion at both concentrations. In the setting of a balanced parenteral nutrition, acute elevation of plasma free fatty acid concentrations in critically ill patients do not modify ventricular repolarization.

Onset of action following formoterol Turbuhaler and salbutamol pMDI in reversible chronic airway obstruction.

Short-acting beta(2)-agonists are currently recommended for symptom relief in asthma and the treatment of mild, acute exacerbations in COPD. However, formoterol has as fast an onset of action as salbutamol with the additional benefit of longer-lasting bronchodilation (approximately 12 h). Furthermore, systemic side effects observed with formoterol are of a similar duration but less pronounced than with short-acting beta(2)-agonists. In this double-blind, randomized, cross-over study, 20 adult patients with reversible chronic airway obstruction (intrinsic asthma or COPD) inhaled single doses of formoterol 9 microg or salbutamol 100 microg (group A) or formoterol 18 microg or salbutamol 200 microg (group B). FEV(1) was measured prior to and 5, 10, 15, 20, 25 and 30 min following inhalation of study drug. No significant differences in FEV(1) values were observed between group A (P=0.704) or group B (P=0.270) at baseline, or at 5 (Group A: P=0.340; Group B: P=0.559) and 15 min (Group A: P=0.526; Group B: P=0.818) post dose. No adverse events were reported during the study. Formoterol Turbuhaler has as rapid an onset of action as salbutamol pMDI when given at the recommended doses.

Respiratory function and atmospheric pollution.

The effects of environmental pollutants on human health and, in particular, on the respiratory apparatus, can be studied fundamentally by means of epidemiological and controlled exposure studies. One epidemiological study has reported the results of research which compared pulmonary function in adults with the average annual concentration of major pollutants in 8 geographical areas of Switzerland; the results demonstrated a direct relationship between atmospheric pollution and a worsening of pulmonary function. Controlled exposure studies, on the other hand, document the effects of specific air pollutants. Ozone (O3) is a secondary pollutant produced in the atmosphere by photochemical reactions which exerts a potent antioxidant and peroxidant action on biomolecules, whether intra or extracellular, with the production of free radicals. Nitrogen dioxide (NO2) is found mainly indoors due to its being a product of combustion of kitchen gas--it possesses low reactivity and low solubility that allows its penetration to the periphery of the lungs; the harmful mechanisms induced by NO2 are not well understood and could differ from those of O3. Sulphur dioxide (SO2) is found above all outdoors and is documented to affect the respiratory function of asthmatic subjects at concentrations above 1 part per million (ppm) while it has a doubtful effect on healthy subjects. Suspended particulate matter (SPM) is one of the major pollutants present in the air that comes mainly from vehicle exhausts, especially diesel models. Although the epidemiological data indicates a close relationship with both cardiac and respiratory pathology, the biological mechanisms by which it exerts its toxicity are still not well established. The great variability in individual response to pollutants suggests the need for further sensitivity tests to be carried out: it is of importance to identify specific genes with a stabilising role in cellular protection against oxidative stress, that influence the production of chemical mediators of inflammation.

[The nitric oxide metabolism in the hypoxic, ischemic and reperfused human skeletal muscle cell: clinical and therapeutical observations]. / L'ossido nitrico nella cellula muscolare umana ischemica e riperfusa: connessioni cliniche e terapeutiche.

BACKGROUND: The biochemical and metabolic role played by nitric oxide (NO) in course of oxidative stress due to cell hypoxia, ischemia and reperfusion has a determinant relevance in the mitochondrial adaptive changes which antagonize the irreversible morpho-functional damage. In particular conditions, such as in prolonged ischemia and/or exogenous NO supplementation, this element is present in the radical form (NOO*) concurring to peroxidative cell injury. Aim of this study was to investigate these opposite NO aspects in hypoxic, ischemic and reperfused human skeletal muscle tissue. METHODS: Skeletal muscle samples were taken during elective knee orthopedic surgery in 10 consecutive patients. The biopsies were obtained before, after 5+/-1 min and 58+/-2 min from tourniquet application and then after 18+/-3 min following muscle reperfusion. The samples, immediately frozen in liquid nitrogen, were assayed for endocellular free NO following the gas-amperometric method described by Palmerini C. RESULTS: When compared with normoxic tissues, a significant decrease in free NO content was observed in hypoxic samples. After about 60 min of prolonged ischemia the NO levels show an evident increase, while the tissue reperfusion leads to a progressive restoration of physiological content in the cellular free nitric oxide. CONCLUSIONS: The obtained data in hypoxic muscle cell seem to underline the pivotal role played by NO in adapting the cytochrome c oxidase oxidative activity to lower O2 bio-availability. On the other hand the prolonged ischemia leads to a consistent NOO* generation triggered by oxyradical generation and Ca2+ intracellular over load. Even if the tissue reoxygenation restores the normal NO levels it is arguable that the pre-treatment of ischemic cell with antioxidants, Ca-antagonist and Dexamethasone supplementation could represent a crucial and specific therapeutic approach to critically ill patient.

Phenotypic features of alveolar monocytes/macrophages and IL-8 gene activation by IL-1 and TNF-alpha in asthmatic patients.

The alveolar macrophage (AM), a major defense cell in the lung, participates in immune and inflammatory reactions through the release of several regulatory and chemotactic cytokines. In particular, macrophages are considered to play a pivotal proinflammatory role in the production and maintenance of airway inflammation and bronchial hyperreactivity. To assess the phenotypic pattern of AM from asthmatic subjects, we performed the following experiments: 1) cytofluorometric analysis of specific phenotypic features (CD11b, CD14, CD16, CD45, HLA-DR, CD71, CD95, and CD44) 2) assessment of the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and the chemotactic regulatory cytokine IL-8 by unstimulated and lipopolysaccharide-stimulated AM. In these patients, we phenotypically characterized the AM, showing their strong proinflammatory activity also in patients with mild asthma. Their activity has been clarified by our biomolecular data that showed a constitutive basal IL-8 production by AM, and also indicated that IL-1 and TNF-alpha were able to upregulate the ability of activated human AM to produce IL-8 at the protein and messenger ribonucleic acid (mRNA) levels.

[Biochemical and metabolic aspects of oxyradical pathology in the hypoxic-ischemic reperfused human skeletal muscle tissue. Clinical markers and therapeutic approach]. / Aspetti biochimici e metabolici della patologia ossiradicalica nel muscolo scheletrico umano ipossico-ischemico-riperfuso. Parametri valutativi nella clinica e nella terapia del paziente critico.

BACKGROUND: Following our previous studies on the biomolecular and biochemical aspects of the human tissue oxidative damage due to hypoxia, ischemia and reperfusion, aim of the present work is to evaluate the role played by oxyradical generation in the morphofunctional cellular injury. We evaluated the tissue levels of some metabolic markers (MDA, Catalase, Uric Acid) to obtain a pathogenic picture and then a therapeutic approach closely related to the cellular biodynamics. METHODS: A skeletal muscle samples were taken during elective knee orthopedic surgery in 20 consecutive patients. The biopsies were taken in normoxic conditions and after 5 +/- 1 and 62 +/- 3 min form tourniquet application and finally 21 +/- 2 min following muscle reperfusion. The samples were assayed for tissue Malondialdeyade (MDA), uric acid and catalase (CAT) contents with HPLC and fluorimetric procedures. All data were evaluated in terms of computerized statistical analysis. RESULTS: When compared to normoxic tissue (1.24 +/- 0.26 nmoli.mg-1 protein), the MDA levels show a moderate increase in hypoxic (1.66 +/- 0.12) and ischemic tissue (1.78 +/- 0.13), while highly significant is the rise in reperfused muscle MDA content (5.94 +/- 0.15). The uric acid as far as CAT shows no appreciable alterations in hypoxia and ischemia. Following reoxygenation an increase in uric acid contents with a concomitant CAT tissue consumption appear evident. CONCLUSIONS: The obtained data seem to underline the cytoprotective role played by adaptive changes in the hypoxic and ischemic human cells. On the contrary, the rapid reoxygenation of the ischemic tissue appears to start oxyradical neo-generation. In clinical and therapeutic terms these observations underline a peculiar and different approach to the critically ill patient.