[Place of 3D custom-made implants after failure of modeling steno-chondro-plasties]. / Place des implants sur mesure 3D après échec des sterno-chondro-plasties modelantes.

Most common congenital malformation of the thorax, Pectus Excavatum affects about one in 500 people. Several surgical or medical techniques have been proposed. Some are followed by complications or insufficient results even though their constant functional value is highly controversial. Secondary surgery with a deep customized 3D elastomer implant, may be an elegant effective and safe solution compared to others; it allows a good aesthetic result expected by patients in the absence of any respiratory or cardio-vascular functional context.

[Breasts and congenital chest-wall deformities: Surgical strategy with 3D implants]. / Le sein et les malformations thoraciques : stratégie chirurgicale et implants.

Computer-aided design and manufacturing of custom-made elastomer implants leads from a CT scan to fill in with precision, a congenital chest wall congenital deformity, both bone (pectus excavatum) and muscle (Poland Syndrome), resulting in a natural repositioning of the breasts. We report our 25 years' experience in 301 women (234 Pectus+64 Poland). Parietal correction must always be done in first intention. It is common to have to carry out a second stage in women with an additional mammaplasty especially in the presence of insufficient glandular volume or a fairly frequently associated tuberous breast.

[Congenital thoracic deformities and 3D custom-made implants. New classification based on a series of 789 treated cases]. / Malformations thoraciques congénitales et implants sur mesure 3D. Nouvelle classification basée sur une série de 789 cas traités.

The authors present a new study on 789 cases of congenital thoracic malformations including 638 pectus excavatum and 151 Poland syndromes, according to a new classification which completes Chin's one. All these malformations were treated with silicone elastomer implants. The contribution of computer-aided design and manufacturing (CAD/CAM) since 2008 is essential. The one-stage surgical protocol is precisely described. The results are impressive, permanent, for life, and complications are rare. The authors evoke a common vascular etiopathogenesis theory at the embryonic stage and question the heavy techniques of invasive remodeling that are most often unjustified.

Male secretory breast cancer: case in a 6-year-old boy with a peculiar gene duplication and review of the literature.

PURPOSE: Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms. METHODS: We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity. RESULTS: To the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6 years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy's genomic profile revealed not only positivity for the typical SBC's translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity. CONCLUSIONS: SBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management.

Dabigatran etexilate and LMWH for the prevention of venous thromboembolism in 532 patients undergoing hip surgery.

OBJECTIVE: Patients undergoing total hip replacement (THR) are at high risk of venous thromboembolism (VTE) and according to guidelines they should receive pharmacological prophylaxis. We would like to compare the efficacy, adherence and safety of dabigatran and low molecular weight heparins (LMWH) for the prevention of VTE in patients who underwent THR. PATIENTS AND METHODS: This study enrolled patients undergoing THR treated with dabigatran (110 mg loading dose then 220 mg/day for 34 days) or the LMWH dalteparin (2500 IU, 6-8 hours before surgery then 5000 IU/day for 35 days). The primary endpoint was adherence to treatment. RESULTS: Of the 532 patients screened and enrolled in the study, 407 (mean age 57.7 ± 12.3 years) completed the study (211 dabigatran, 196 LMWH). Over the 35 days of treatment, adherence was comparable between dabigatran and LMWH: 10.9% and 14.3% of patients receiving dabigatran and LMWH treatment missed > 1 dose of the drug, respectively. There was a lower need for external support in patients who received dabigatran (8.5% vs 58.2%; p < 0.0001) and a lower number of patients receiving dabigatran required support by a professional nurse (1.4% vs 17.3% of patients with LMWH; p < 0.0001). Dabigatran and LMWH were similarly well tolerated; however, fewer patients receiving dabigatran reported bleeding events. CONCLUSIONS: This study demonstrates that dabigatran is associated with high adherence. A lower need for external support in patients who received dabigatran may provide an added benefit compared with other oral treatments for VTE prophylaxis.

Smoking cessation, anxiety, mood and quality of life: reassuring evidences.

A close and complex relationship between smoking and mental health problems was found. Different hypotheses have been proposed to explain these associations: 1) smoking and poor mental health may share common causes (genetic factors or environmental mechanisms); 2) for people with poor mental health smoking is a coping strategy to regulate psychiatric symptoms; 3) smokings worsen mental health. Moreover, smokers with psychiatric disorders may have more difficulty quitting and patients with mental diseases who received mental health treatment within the previous year were more likely to stop smoking than those not receiving treatment. Taylor et al. hypothesized that quitting smoking might improve rather than exacerbate mental health, because it allows to avoid multiple episodes of negative affect induced by withdrawal. With the aim to verify this hypothesis, they conducted a systematic review and meta-analysis on longitudinal studies (randomized controlled trials and cohort studies) in which the difference in change in mental health between subjects who stop smoking and subjects who continue to smoke has been explored. A total of 26 longitudinal studies evaluating anxiety, depression, mixed anxiety and depression, positive effect, psychological quality of life, and stress have been included. The study results provided enough evidence to assure that quitting smoking is associated with a reduction of depression, anxiety, and stress, with an improvement of psychological quality of life and positive affect compared with continuing to smoke. The strength of association was similar for both the general population and study enrolled populations, including those with mental health disorders. The results of this meta-analysis have direct clinical implications: the benefits for mental health could motivate physicians and patients to take into account the possibility of smoking cessation.

Spinal infection multidisciplinary management project (SIMP): from diagnosis to treatment guideline.

Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.

[Calciphylaxis and penile necrosis: a case report and review of the literature ]. / Calcifilassi e necrosi peniena: case report e revisione della letteratura.

INTRODUCTION: Calciphylaxis is a rare clinic condition characterised by skin necrosis due to medial and intimal calcification of small and medium arteries. It's observed in patients affected by end stage renal disease associated to secondary hyperparathyroidism. Penile involvement has been documented in very few cases. We present both a case of penile calciphylaxis and a review of literature, in order to increase comprehension of pathophysiology, diagnosis and therapy of this rare disease. MATERIALS AND METHODS: A retrospective review of literature was performed after treating a case of penile calciphylaxis. We describe patient characteristics, clinical presentation, laboratory and histo-pathologic findings, therapeutic strategy and outcomes of the case. RESULTS: A 65 year-old man, affected by diabetes, chronic ischemic cardiopathy and chronic renal failure in hemodialytic treatment, was referred to our unit for the presence of increased consistency and significative pain of the distal portion of penis evolving in a complete glans necrosis. Blood levels of parathormone (PTH), calcium (Ca) and phosphorous (P) resulted pathologically elevated, promoting tissutal calcium deposition. The patient was treated with partial penectomy and the histologic findings confirm diagnosis of calciphylaxis, showing an ulcerative necrosis of glans with extensive calcium deposition and luminal narrowing of penile small arteries. CONCLUSIONS: The increase of number of patients with chronic renal failure in hemodialytic treatment could make penile calciphylaxis more prevalent in the future. Early diagnosis, lowering of pathologic blood levels of Ca and P associated to surgical treatment of necrotic lesions of the patient could be fundamental for a better prognosis of this aggressive disease.

[Carcinoma of the collecting ducts of Bellini: a case report with cutaneous metastasis as the initial clinical manifestation]. / Carcinoma dei dotti collettori del Bellini: case report con metastasi cutanea come iniziale manifestazione clinica.

INTRODUCTION: Bellini's collecting ducts carcinoma represents a rare tumor with an aggressive behaviour with a poor prognosis and often metastatic at diagnosis. We report the first case documented of Bellini tumor with an initial clinic presentation represented by a cutaneous metastasis of scalp. MATERIALS AND METHODS: All pertinent clinical information were compiled, including patient age, sex, mode of presentation, preoperative laboratory data, radiologic findings, surgery type, macro and microscopic findings, survival data. RESULTS: After reporting an histopathologic finding of cutaneous metastasis of unknown origin adenocarcinoma with poorly differentiation, a voluminous 6 cm left mesorenal mass is diagnosed through uro-CT. Consequently, it is performed a left radical transperitoneal nephrectomy with consensual exeresis of scalp cutaneous lozenge at the level of previous excision. The histopathologic diagnosis reported was Bellini tumor at stage pT3a-N2-M1. It has not reported significative responsiveness to adjuvant chemotherapy and the patient was died seven months after diagnosis of cutaneous metastasis. CONCLUSIONS: Most of Bellini's carcinoma are already metastatic at presentation. Analyzing literature, it is never documented a cutaneous metastasis as first sign at clinical presentation. In this context, radical nephrectomy, differently from others subtypes of advanced renal cell carcinoma, does not seem to improve survival of the patient but rather, it can keep a role in palliation or in the context of new chemotherapeutic protocols.

Clinical and genetic risk factors for moderate hyperbilirubinemia in Brazilian newborn infants.

OBJECTIVE: To identify clinical and genetic risk factors for moderate hyperbilirubinemia during the first week of life. STUDY DESIGN: Using univariate and multivariate multiple regression analyses, the RR for clinical factors, the African variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency (G202A/A376G), and (TA)(n) UGT1A1 polymorphisms were established in a cohort of 608 Brazilian newborn infants. Hyperbilirubinemia was monitored until 134.5 ± 49.8 h of life (IQR, 111.0 to 156.7). The dependent variable was total bilirubinemia (TB) ≥12.9 mg per 100 ml estimated by transcutaneous or plasma bilirubin measurements. RESULT: The African variant of G6PD deficiency and (TA)(7)/(TA)(7) and (TA)(7)/(TA)(8) polymorphisms present in 6.1 and 12.0% of newborns, respectively, were not risk factors for moderate hyperbilirubinemia. Coexpression of G6DP deficiency and UGT1A1 polymorphisms occurred in 0.49% of the subjects. Independent clinical predictors for TB≥ 12.9 mg per 100 ml were gestational age <38 weeks and reference curve percentiles >P40th. CONCLUSION: In this study, G6PD deficiency and UGT1A1 gene promoter polymorphisms were not risk factors for moderate hyperbilirubinemia. Genetic factors may vary considerably in importance among different populations.

[Endometriosis: aetiopathogenetic basis]. / Endometriosi: le basi eziopatogenetiche.

Endometriosis, defined by the presence of endometrial tissue outside the uterine cavity, is a common condition affecting 10% of women in the reproductive age. Menstrual factors reported to increase risk include dysmenorrhea, early menarche, and shorter cycle lengths. The theory of retrograde menstruation with implantation of endometrial fragments, in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted. There is a growing body of evidence that immunological factors and angiogenesis play a key role in the pathogenesis of endometriosis. In women with endometriosis, there appears to be an alteration in the function of peritoneal macrophages, natural killer cells and lymphocytes, with production of growth factors and inflammatory mediators in the peritoneal fluid. Survival, adhesion, proliferation, invasion and vascularization of endometrial tissue in abdominal cavity may be the consequence of retrograde menstruation and referred to as implantation theory.

Pain relief and motor function during continuous interscalene analgesia after open shoulder surgery: a prospective, randomized, double-blind comparison between levobupivacaine 0.25%, and ropivacaine 0.25% or 0.4%.

BACKGROUND AND OBJECTIVES: To compare pain relief and motor impairment of 0.25% levobupivacaine with either an equivalent (0.25%) or equipotent (0.4%) concentration of ropivacaine for continuous interscalene block after open shoulder surgery. METHODS: Seventy-two adult patients scheduled for elective major shoulder surgery received an interscalene injection of mepivacaine 1.5% 30 mL followed by 24 h patient-controlled interscalene analgesia (basal infusion rate: 5 mL h-1; incremental bolus: 2 mL; lockout period: 10 min; maximum boluses per hour: 4) with either 0.25% levobupivacaine (n = 24), 0.25% ropivacaine (n = 24) or 0.4% ropivacaine (n = 24). A blinded observer recorded the evolution of pain relief and recovery of motor block during the first 24 h. Motor function was assessed as the maximum pressure developed while squeezing a sphygmomanometer cuff with the blocked hand. The reduction from preoperative values was considered as an index of motor impairment. RESULTS: No differences were reported among the three groups in the quality of postoperative analgesia. The number of incremental patient-controlled interscalene analgesia doses, total volume of local anaesthetic infused during the 24-h patient-controlled interscalene analgesia, and number of rescue ketoprofen analgesia were higher in the ropivacaine 0.25% group than in the other two groups (P = 0.0005). The hand strength recovered to >or=90% of baseline values within the first 24 h of infusion in all groups, without differences among the three groups. CONCLUSION: When providing patient-controlled interscalene analgesia after open shoulder surgery 0.25% levobupivacaine and 0.4% ropivacaine performed equally in terms of pain relief, motor block and number of patient-controlled boluses required, while patients receiving 0.25% ropivacaine needed significantly more boluses and rescue analgesia to control their pain.

Aspirin induced asthma (AIA) with nasal polyps has the highest basal LTE4 excretion: a study vs AIA without polyps, mild topic asthma, and normal controls.

UNLABELLED: Cysteinil Leukotrienes (LTs) are products of the arachidonic acid cascade which are synthetised by 5-lipoxigenase in inflammatory cells, particularly in eosinophils. Urinary leukotriene E4 concentration (LTE4), that reflects the whole body production of cysteinil-leukotrienes, is particularly increased in patients with aspirin-intolerant asthma (AIA). Aim of the present study was to assess basal urinary LTE4 levels from AIA patients with nasal polyps to those from AIA patients with only rhinitis (without polyps), and those from mild atopic asthmatics and normal controls. SUBJECTS & METHODS: 34 normal subjects (N; 19 - 57y, FEV1 = 102.1% pred. +/- 8.2 sd; negative MCh challenge; negative prick test); 39 mild-persistent atopic asthmatics (A; 18-66y, FEV1 = 92.1 %pred. +/- 14.6 sd; PD20 FEV1 = 380.7mcg +/- 481.2 sd); 24 subjects with AIA with rhinitis (AIA/R; 18 - 56y, FEV1 = 71.6%pred +/- 15.5 sd; reversibility = 15.1% bsln +/- 2.1 sd after salbutamol 200mg), and 10 subjects with AIA and nasal polyposis (AIA/NP; 22-49 y; FEV1 = 70.6%pred. +/- 7.1 sd; reversibility = 13.2% bsln +/- 1.6 sd after salbutamol 200 microg) were studied. After their informed consent, urine were collected in the morning for the LTE4 quantitative immunoenzimatic assay (pg/mg creatinine; Cayman Chemical, Ann Arbour, Mi, USA). STATISTICS: Wilcoxon signed rank test was used, and p<0.05 accepted as the lowest level of statistical significance. RESULTS: AIA/NP subjects had the highest levels of urinary LTE4 (432.3 pg/mg +/- 88.1 sd) compared to AIA/R (330.7 pg/mg +/- 72.3s, p < 0.01), to A (129.1 pg/mg +/- 74.8sd, p < 0.001), and to N controls (66.5 pg/mg +/- 20.6 sd, p < 0.001). Moreover, urinary LTE4 levels measured in AIA/R subjects proved significantly higher than those measured in A (p < 0.001) and in N controls (p<0.001), while LTE4 levels in A proved significantly higher than those in N controls (p<0.001). Furthermore, basal LTE4 levels seem inversely related to those of basal FEV1 (102.1 % pred. +/- 8.2sd in N, 92.1 % pred +/- 14.6 sd in A, 71.6 % pred. +/- 15.5 sd in AIA/R, 70.6 % pred +/- 7.1 sd in AIA/P, respectively). Respiratory function in the two sub-groups of AIA patients proved reduced than in atopic asthmatics (p<0.001) and in normal controls (p < 0.001), even though the difference between these two subgroups of subjects did not reach the statistical significance. CONCLUSIONS: Cys-LTs confirm their relevant pathogenetic role in AIA, but also in early stages of atopic asthma. Urinary LTE4 exexcretion proves directly proportional to the extent of nasal structural changes occurring in ASA-intolerant asthmatics, being subjects with nasal polyps those with the highest LTE4 values, immediately followed by those with hypertrophic rhinitis. Routinary measurements of urinary LTE4 should be regarded as a sensitive indicator in monitoring the clinical evolution of nasal involvement in AIA.

Temperament and character in eating disorders: ten years of studies.

In recent years a number of studies of personality have been performed in subjects with Eating Disorders (EDs) to investigate the clinical differences between controls and ED patients and among EDs subtypes, and its role in the development and course of symptoms. The Tridimensional Personality Questionnaire (TPQ) and the Temperament and Character Inventory (TCI) have been widely used at this purpose, allowing the description of specific temperament and character profiles for EDs. High Harm Avoidance (HA) and low Self-Directedness (SD) are shared by all EDs. Slight differences on some facets have been found among ED subgroups. Nevertheless, HA is influenced by mood and both high HA and low SD are personality traits shared by many mental disorders, whose specificity is rather low. Restrictor anorectics are characterized by high Persistence (P) and a relatively higher SD, and bulimics by higher Novelty Seeking (NS) and the lowest SD, while binge/purging and purging anorectics share some traits with anorexia and some with bulimia. Though current data justify the discrimination among anorexia subtypes, they are not in contrast with the thesis of a continuum in ED personality traits. Since some personality traits display a prognostic value with regard to therapy and clinical outcome, further studies are needed on treatments and prognostic factors in EDs. Moreover, studies attempting to define the neurobiological and genetic correlates of temperament should be supported by clinical pharmacological trials.

Unravelling migrations in the steppe: mitochondrial DNA sequences from ancient central Asians.

This study helps to clarify the debate on the Western and Eastern genetic influences in Central Asia. Thirty-six skeletal remains from Kazakhstan (Central Asia), excavated from different sites dating between the fifteenth century BC to the fifth century AD, have been analysed for the hypervariable control region (HVR-I) and haplogroup diagnostic single nucleotide polymorphisms (SNPs) of the mitochondrial DNA genome. Standard authentication criteria for ancient DNA studies, including multiple extractions, cloning of PCR products and independent replication, have been followed. The distribution of east and west Eurasian lineages through time in the region is concordant with the available archaeological information: prior to the thirteenth-seventh century BC, all Kazakh samples belong to European lineages; while later an arrival of east Eurasian sequences that coexisted with the previous west Eurasian genetic substratum can be detected. The presence of an ancient genetic substratum of European origin in West Asia may be related to the discovery of ancient mummies with European features in Xinjiang and to the existence of an extinct Indo-European language, Tocharian. This study demonstrates the usefulness of the ancient DNA in unravelling complex patterns of past human migrations so as to help decipher the origin of present-day admixed populations.

Cranial trepanation in two skulls of early medieval Italy.

Cranial trepanation is a practice known since prehistory in various, often geographically distant populations. In this work are presented two early medieval trepaned skulls. The first skull comes from Canosa in Apulia (6th-7th c. AD; according to radiocarbon dating), the second is from Ticineto Alessandrino (5th-8th c. AD). The skull of Canosa shows a single perforation on the bregmatic quadrant of the right parietal, whereas the Ticineto skull presents three lesions of different shapes and sizes. Two perforations are on the left parietal and the other is on the right parietal. The lesions of the Ticineto skull can be referred to a therapeutic operation following a trauma, with survival of the individual. In the Canosa skull the absence of a healing reaction suggests a pathological process, without survival of the subject. Moreover, a particular ritual practice cannot be excluded (i.e. a post-mortem trepanation).

Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians.

The efficacy of insulin in stimulating whole-body glucose disposal (insulin sensitivity) was quantified using direct methodology in thirty lacto-ovo vegetarians and in thirty meat-eaters. All subjects were adult, lean (BMI <23 kg/m2), healthy and glucose tolerant. Lacto-ovo vegetarians were more insulin sensitive than meat-eaters, with a steady-state plasma glucose (mmol/l) of 4.1 (95 % CI 3.5, 5.0) v. 6.9 (95 % CI 5.2, 7.5; respectively. In addition, lacto-ovo vegetarians had lower body Fe stores, as indicated by a serum ferritin concentration (microg/l) of 35 (95 % CI 21, 49) compared with 72 (95 % CI 45, 100) for meat-eaters To test whether or not Fe status might modulate insulin sensitivity, body Fe was lowered by phlebotomy in six male meat-eaters to levels similar to that seen in vegetarians, with a resultant approximately 40 % enhancement of insulin-mediated glucose disposal Our results demonstrate that lacto-ovo vegetarians are more insulin sensitive and have lower Fe stores than meat-eaters. In addition, it seems that reduced insulin sensitivity in meat-eaters is amenable to improvement by reducing body Fe. The latter finding is in agreement with results from animal studies where, no matter how induced, Fe depletion consistently enhanced glucose disposal.

Insulin resistance as a predictor of age-related diseases.

The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.