High prevalence of adrenal cortical adenomas in patients with cerebral meningiomas.

PURPOSE: Adrenal cortical adenomas (ACAs) represent one of the most common endocrine neoplasms. Recently, a genetic syndrome, characterized by tumor-suppressor ARMC5-gene mutations and causing primary macronodular bilateral adrenal hyperplasia with concomitant meningiomas of the central nervous system, has been described. Apart from this rare disorder and despite the well-known influence of steroid hormones on meningiomas, no data are available about the association between ACAs and meningiomas. METHODS: We investigated the prevalence of ACAs in a group of patients with cerebral meningioma undergoing unenhanced chest CT scans before attending surgical treatment. Patients with meningioma were age- and sex-matched in a 1:3 ratio with hospitalized patients for COVID-19. RESULTS: Fifty-six patients with meningioma were included and matched with 168 control patients with COVID-19. One-hundred forty-four (66.1%) were female and the median age was 63 years. Twenty ACAs were detected in the overall population (8.9% of the subjects): 10 in patients with meningioma (18%) and the remaining 10 (6%) in the control group (p = 0.007). Multivariate analysis showed that age and presence of meningioma were statistically associated with the presence of ACAs (p = 0.01, p = 0.008). CONCLUSION: We report, for the first time, a higher prevalence of ACAs in patients with meningioma as compared to age- and sex-matched controls. Larger studies are needed to confirm our data and to clarify the characteristics of the ACAs in patients with meningioma. Whether the detection of ACAs should prompt a neuroimaging evaluation to exclude the presence of meningiomas needs also to be considered.

Psychometric properties of burnout measures: a systematic review.

AIMS: Occupational Burnout (OB) is currently measured through several Patient-Reported Outcome Measures (PROMs) and some of them have become widely used in occupational health research and practice. We, therefore, aimed to review and grade the psychometric validity of the five OB PROMs considered as valid for OB measure in mental health professionals (the Maslach Burnout Inventory (MBI), the Pines' Burnout Measure (BM), the Psychologist Burnout Inventory (PBI), the OLdenburg Burnout Inventory (OLBI) and the Copenhagen Burnout Inventory (CBI)). METHODS: We conducted systematic literature searches in MEDLINE, PsycINFO and EMBASE databases. We reviewed studies published between January 1980 and September 2018 following a methodological framework, in which each step of PROM validation, the reference method, analytical technics and result interpretation criteria were assessed. Using the COnsensus-based Standards for the selection of health Measurement Instruments we evaluated the risk of bias in studies assessing content and criterion validity, structural validity, internal consistency, reliability, measurement error, hypotheses testing and responsiveness of each PROM. Finally, we assessed the level of evidence for the validity of each PROM using the GRADE approach. RESULTS: We identified 6541 studies, 19 of which were included for review. Fifteen studies dealt with MBI whereas BM, PBI, OLBI and CBI were each examined in only one study. OLBI had the most complete validation, followed by CBI, MBI, BM and PBI, respectively. When examining the result interpretation correctness, the strongest disagreement was observed for MBI (27% of results), BM (25%) and CBI (17%). There was no disagreement regarding PBI and OLBI. For OLBI and CBI, the quality of evidence for sufficient content validity, the crucial psychometric property, was moderate; for MBI, BM and PBI, it was very low. CONCLUSION: To be validly and reliably used in medical research and practice, PROM should exhibit robust psychometric properties. Among the five PROMs reviewed, CBI and, to a lesser extent, OLBI meet this prerequisite. The cross-cultural validity of these PROMs was beyond the scope of our work and should be addressed in the future. Moreover, the development of a diagnostic standard for OB would be helpful to assess the sensitivity and specificity of the PROMs and further reexamine their validity.The study protocol was registered in PROSPERO (CRD 42019124621).

Hemostatic abnormalities in patients with Ehlers-Danlos syndrome.

Essentials Ehlers-Danlos Syndrome (EDS) is a rare heterogeneous group of inherited collagen disorders. A cohort of EDS patients was investigated for bleeding tendency and hemostatic abnormalities. EDS is associated with an increased risk of bleeding. EDS patients have platelet function abnormalities, whose severity correlates with bleeding risk. SUMMARY: Background Ehlers-Danlos syndrome (EDS) includes a heterogeneous group of connective tissue disorders affecting skin, bones, vessels, and other organs. Patients with EDS have an increased risk of bleeding, but a comprehensive study of hemostasis in EDS patients is lacking. Objective To investigate the bleeding tendency of a cohort of patients with EDS by using the Bleeding Assessment Tool of the ISTH, the bleeding severity score (BSS). Methods The BSS was defined as abnormal when it was ≥ 4 in men and ≥ 6 in women. Patients with a bleeding tendency were compared with those without in terms of type and number of hemostatic abnormalities. Results Fifty-nine of 141 patients with EDS (41.7%) had an abnormal BSS. Prothrombin time and activated partial thromboplastin time were slightly prolonged in 10 patients (7.1%) because of mild coagulation factor deficiencies, which were not responsible for the bleeding diathesis. von Willebrand factor antigen, ristocetin cofactor, endogenous thrombin potential and platelet count were normal in all patients. At least one platelet function abnormality was found in 53 patients (90%) with an abnormal BSS and in 64 (78%) with a normal BSS (adjusted odds ratio [OR] 2.55, 95% confidence interval [CI] 0.87-7.48). The risk of bleeding progressively increased with the number of platelet function abnormalities, reaching an OR of 5.19 (95% CI 1.32-20.45) when more than three abnormalities were detected. Conclusions Our results show that nearly half of patients with EDS have an abnormal BSS, which, in 90% of cases, appear, at least in part, to be attributable to platelet function abnormalities. Abnormalities of primary hemostasis may contribute to the risk of bleeding in patients with EDS.

Inflammation and ventricular-vascular coupling in hypertensive patients with metabolic syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is currently considered to raise the risk for type 2 diabetes and cardiovascular events. It has been suggested that part of this risk excess may be due to a cluster of additional factors associated with MetS. We aimed to investigate the role of inflammation on the ventricular-vascular coupling in patients with MetS. METHODS AND RESULTS: We enrolled a total of 227 hypertensive patients (106 with MetS and 121 without MetS) matched for age and gender. Aortic pulse wave velocity (aPWV), intima-media thickness (IMT) and high sensitivity C-reactive protein (CRP) increased according to the number of MetS components. Patients with MetS showed increased aPWV (11.5 ± 3.7 vs. 10.3 ± 2.5 m/s, P = 0.03) compared with controls. In a model adjusted for age, sex, heart rate and mean blood pressure, aPWV resulted increased in patients with CKD (beta 1.29 m/s, 95%CI 0.61-1.96 m/s, P < 0.001) and MetS (beta 0.89 m/s, 95%CI 0.28-1.51 m/s, P = 0.005). After additional adjustment for CRP and IMT, the slope of aPWV was respectively reduced by 16% and 62%, suggesting that inflammation and intima-media thickening could contribute to aortic stiffening in patients with MetS. In these patients, aPWV was also associated with left-ventricular mass index (beta 0.79 g/m2.7, 95%CI 0.05-1.52 g/m2.7, P = 0.05). CONCLUSION: MetS is characterized by an inflammation-dependent acceleration in cardiovascular ageing. This pattern of pathophysiological abnormalities may contribute to amplify the burden of cardiovascular risk in patients with MetS.

B-type natriuretic peptide may predict prognosis in older adults admitted with a diagnosis other than heart failure.

BACKGROUND AND AIMS: The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF. METHODS AND RESULTS: We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002). CONCLUSIONS: Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF.

Neutrophil-to-Lymphocyte Ratio is a strong predictor of atherosclerotic carotid plaques in older adults.

BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR), an index of systemic inflammation, has been reported to be associated with subclinical atherosclerosis, but its predictive role of the presence of carotid atherosclerotic plaques remains undefined. This study aims to assess this association which gives additional value to this biomarker, with respect to the main risk factors, in the prediction of carotid atherosclerosis in older adults. METHODS AND RESULTS: We recruited 324 patients, aged ≥65 years, without hematopoietic disorders, and/or history of malignancies, evidence of acute infections, chronic inflammatory status, and history of glucocorticoid therapy within the past three months, hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy from January 2014 to December 2016. All patients underwent blood sampling for white blood cell, neutrophil, lymphocyte and platelet counts, and for measurements of inflammatory markers, NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Patients also underwent carotid scan by ultrasonography (US) to evaluate abnormalities of carotid wall. NLR resulted a strong predictor of the presence of carotid plaques. NLR > 2.4 predicted with 80% probability carotid plaques (p < 0.01), while NLR > 3.68 gave 97% probability (p = 0.013). Furthermore, NLR > 2.4 was associated with an average presence of 2.86 carotid plaques (p < 0.001). Fibrinogen and CRP performed well, but with lesser significance, as predictors of the presence of carotid plaques (p = 0.002). CONCLUSION: NLR is a strong predictor of the presence and the number of carotid atherosclerotic plaques. Its use could be useful to identify the risk of harboring carotid plaques.

[Correction of thoraco-mammary deformity of Poland syndrome]. / Correction de la déformation thoracomammaire du syndrome de Poland.

Breast deformity of Poland syndrome is a malformation known to be difficult to treat. Numerous descriptions of surgical corrections have been published but none achieved to correct severe cases before description of lipomodeling technique. The aim of this article is to present thoraco-mammary deformity of Poland syndrome, corrections techniques already available and therapeutical indications in primary and secondary cases. Constant anomaly of Poland syndrome is agenesis of sternocostal part of pectoralis major muscle but other muscular anomalies can be associated. Skin and glandular anomalies present with a fine skin and an absent or hypoplasic subcutaneous fat with a glandular hypoplasia of various degree. Osteo-cartilaginous anomalies can be associated in very severe cases. Clinical sign of Poland syndrome is forced adduction maneuver highlighting pectoralis major agenesis. Functional impact of the deformity is low but psychological and psychosocial implications can be very important, supporting an early surgical correction. Therapeutic means are various and accurate descriptions are given in this article: thoracic bony reconstruction, thoracic implant made of silicone elastomer, breast implant, skin expansion, latissimus dorsi pedicled flap, free flaps, breast lipomodeling, breast-pectoralis flap. Principles of each technique are described and balanced with their actual use in this malformation. Indications have been completely modified these last years due to lipomodeling contribution which represented a huge step in this deformity treatment. In our practice, if autologous reconstruction with lipomodeling is possible, we choose this solution at first. In case of severe thoracic deformity, a silicone elastomer implant made with the help of computed assisted conception can be an important adjunct, mainly by thin young man. In secondary cases, if implant is well tolerated, we found logical to stay in the same reconstruction path and do one or two sessions of lipomodeling in order to improve reconstruction. If implant tolerance is low and skin very thin at risk of exposure, we do recommend a conversion of implant reconstruction to autologous reconstruction. In conclusion, thoraco-mammary deformities of Poland syndrome are rare and hard to treat and should be managed by well trained and experimented surgeons. Breast lipomodeling is a huge step in the treatment of these deformities and should be regarded, in our opinion, as first line treatment if fat deposits are sufficient. In case of low fat provisions or in the thin young man, composite techniques should be used with silicone elastomer implant.

[Fat grafting to improve severe tuberous breast]. / Apport du transfert graisseux dans les formes sévères de seins tubéreux.

INTRODUCTION: Tuberous breast is a rare malformation that has major, negative physical and psychological impacts during puberty. A range of surgical techniques has been used to correct breast shape and volume in this context. Most techniques are based on a combination of skin plasty and mammary gland remodelling, in order to redistribute volumes. Prostheses and local-regional flaps can also be used to correct the missing volume. Fat grafting to the breast has been used in our department since 1998 as a complementary technique in breast reconstruction; it constitutes a natural way of providing volume and modifying the shape of the breast. Since 2000, we have extended this lipomodelling technique to the correction of thorax malformations in general and tuberous breasts in particular. Here, we describe our experience of the correction of severe tuberous breasts by fat grafting. PATIENTS AND METHODS: Over an 11-year period, we performed a retrospective study on tuberous breast patients treated solely with fat grafting (i.e. without using an implant). Each breast deformation was graded according to the Grolleau classification. After aspiration, the fat was centrifuged and then transferred with a specific cannula. Using an 18-G trocar, we sometimes also performed fasioctomies to free up fibrous bridges and mammary gland remodelling. We evaluated the lipofilling for each case (number of sessions and mean fat transfer volume). Technical efficacy was evaluated in terms of patient's satisfaction and the surgeon's opinion. Safety was evaluated by screening for recipient site complications. RESULTS: We performed a retrospective study of 31 cases of tuberous breasts treated between January 2000 and December 2010. The severe tuberous breasts were type 3 in 10 cases. The mean patient age was 21 and the mean body mass index was 21.5. Two session (mean transfer volume: 380 cc) were required in every case. The mean follow-up period after the last fat transfer session was 6 years (range: 1-11). The patients were very satisfied in 90% of cases (n=9) and satisfied in 10% of cases (n=1). No complications were observed. Imaging performed before surgery and one year afterwards did not reveal any anomalies, other than oil cysts. CONCLUSION: The treatment of severe tuberous breast with fat grafting is a reliable technique that produces excellent results and high levels of patient satisfaction. The aesthetic outcome is natural, implant-free and long-lasting. Fat grafting decreases local fibrosis and helps (along with fasciotomies and mammary gland remodelling) modify the shape of the breast. The technique corrects the missing volume in a precise, personalized manner. Lipomodelling efficacy and absence of complications have made it our reference treatment for the correction of severe tuberous breasts (as long as the patient has sufficient adipose reserves).

Predictors of von Willebrand disease diagnosis in individuals with borderline von Willebrand factor plasma levels.

BACKGROUND: In individuals with borderline von Willebrand factor (VWF) plasma levels, second-level tests are required to confirm or exclude von Willebrand disease (VWD). These tests are time-consuming and expensive. OBJECTIVE: To assess which parameters can predict VWD diagnosis in individuals with borderline VWF levels (30-60 IU dL(-1) ). METHODS: Nine hundred and fifty individuals with bleeding episodes or abnormal coagulation test results were investigated with first-level tests (blood count, prothrombin time, activated partial thromboplastin time, blood clotting factor VIII, VWF ristocetin cofactor activity [VWF:RCo], and VWF antigen), and 93 (62 females and 31 males; median age, 28 years; interquartile range 15-44) had borderline VWF:RCo levels. All underwent second-level investigations to confirm or exclude VWD. A multivariable logistic regression model was fitted with sex, age, bleeding score, family history, VWF:RCo and ABO blood group as predictors, and used to predict VWD diagnosis. RESULTS: Forty-five of the 93 individuals (48%) had VWD (84% type 1). A negative linear relationship between VWF:RCo levels and risk of VWD diagnosis was present, and was particularly evident with blood group non-O [adjusted odds ratio 7.00 (95% confidence interval [CI] 1.48-33.11) for every 5 IU dL(-1) decrease in VWF:RCo]. The other variable clearly associated with VWD diagnosis was female sex (adjusted odds ratio 5.76 [95% CI 1.47-22.53]). The area under the receiver operating characteristic curve of the full logistic model was 0.89 (95% CI 0.82-0.95). CONCLUSIONS: In individuals with borderline VWF, the two strongest predictors of VWD diagnosis are low VWF:RCo levels (particularly in those with blood group non-O) and female sex. This predictive model has a promising discriminative ability to identify patients with borderline VWF levels who are likely to have VWD.

[Tolerance and efficacy of lipomodelling as an element of breast symmetry in breast reconstruction]. / Tolérance et efficacité du lipomodelage comme élément de symétrisation en reconstruction mammaire: à propos de 150 patientes.

AIM OF THE STUDY: Fat transfer significantly improved results in breast reconstruction. Final breast symmetry is very important in breast reconstruction, but sometimes, the result is not perfect with usual techniques. The aim of this study is to evaluate the tolerance and efficacy of lipomodelling as a complementary technique for breast symmetrisation. MEANS AND METHODS: In this study, 150 patients had controlateral breast symmetrisation after breast reconstruction, using or completed with fat transfer. Patients were clinically evaluated one year after surgery. Age, BMI, harvested, purified and transferred fat volumes, and postoperatory complications were recorded. Morphological outcomes were evaluated by the surgeon as: very good, good, average or bad. Patients rated their degree of satisfaction as: very satisfying, satisfying, poor or bad. RESULTS: We found out that 98.6 % of morphological results were good or very good, and 86.6 % of the patients were satisfied or very satisfied with the result. Complications were rare (2 % of cytosteatonecrotic lesions). CONCLUSION: Lipomodelling in native breast symmetrisation after reconstruction is a powerful technique because it allows to increase volume of a hypoplastic controlateral breast, to ameliorate its shape, and to finally enhance mammoplasty result by correcting persisting localized volume defects. It definitively is a major therapeutic tool for enhancing breast reconstruction outcomes.

A two-centre comparative evaluation of new automated assays for von Willebrand factor ristocetin cofactor activity and antigen.

von Willebrand disease (VWD) is caused by a quantitative and/or qualitative deficiency of the von Willebrand factor (VWF). The laboratory diagnosis of VWD is dependent on the measurement of VWF antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo). The aim of this study was to undertake a two-centre evaluation of two new automated VWF:Ag and VWF:RCo assays systems from Instrumentation Laboratory (Bedford, USA). Using the two new analytical systems that operated with different detection principles: immunoturbidimetric (TOP500 analyser) and chemiluminescent (AcuStar analyser), VWF:Ag and VWF:RCo levels were determined in samples from 171 healthy normal subjects, 80 VWD patients (16 type 1, 58 type 2 and 6 type 3) and 7 acquired von Willebrand syndrome patients. With commercial lyophilized normal and pathological plasmas VWF: Ag and VWF:RCo assays performed on both analysers exhibited low levels of inter-assay imprecision (AcuStar: CV% range 3.3-6.9; TOP500: CV% range 2.6-6.3). Samples from normal healthy subjects (range: VWF:Ag 44.6-173.9 IU dL(-1) ; VWF:RCo 43.1-191.5 IU dL(-1)) and patients (range: VWF:Ag <0.3-115.1 IU dL(-1) ; VWF:RCo <0.5-57.2 IU dL(-1)) showed a good correlation between the two VWF:Ag and VWF:RCo methods (rs = 0.92 and 0.82 respectively), with only a few inconsistent cases among the patients' samples evaluated. The chemiluminescent assays had a lower limit of detection for both VWF:Ag and VWF:RCo compared to immunoturbidimetric tests (0.3 IU dL(-1) vs. 2.2 IU dL(-1) and 0.5 IU dL(-1) vs. 4.4 IU dL(-1) respectively). The TOP500 and AcuStar VWF:Ag and VWF:RCo assays were precise and compare well between centres, making these systems suitable for the diagnosis of VWD in non-specialized and reference laboratories.

A synonymous (c.3390C>T) or a splice-site (c.3380-2A>G) mutation causes exon 26 skipping in four patients with von Willebrand disease (2A/IIE).

INTRODUCTION: We characterized four unrelated patients with von Willebrand disease type 2A/IIE, sharing the same von Willebrand factor (VWF) in-frame deletion (p.[P1127_G1180delinsR];[=]) resulting from exon 26 skipping (Δ26). OBJECTIVES: To identify the VWF mutations and how they caused the mRNA splicing alteration, to evaluate the deletion by in vitro expression studies, and to assess whether or not the heterogeneity of the patients' phenotype might be related to a different degree of expression of the deleted subunit in patient plasma VWF. METHODS: Sequence analysis was performed with patient genomic DNA and platelet mRNA. Semiquantitative RT-PCR was also carried out to compare the expression of the wild-type (WT) and Δ26 alleles in the four patients. In silico analysis was performed with prediction splicing programs. Expression studies were performed to evaluate mutant recombinant VWF (rVWF) (Δ26 and Δ26/WT) as compared with WT rVWF. RESULTS: Three patients shared the synonymous single-nucleotide substitution (SSS) c.[3390C>T];[=], whereas the novel mutation c.[3380-2A>G];[=] was present in the fourth patient. Semiquantitative RT-PCR of platelet mRNA revealed a different ratio of the WT and Δ26 alleles in the patients, consistent with the different VWF:FVIIIB values present in patient plasma. Expression studies confirmed reduced VWF-FVIII binding of rVWF-Δ26/WT. CONCLUSIONS: SSS can induce alternative splicing, and those like c.3390C>T, which impact on the poorly conserved splicing regulatory elements, are difficult to predict, so that their role can be evaluated only by mRNA analysis. Moreover, these mutations seem to have different effects on the efficiency of alternative splicing, producing heterogeneous VWF variants among the four patients.

[Reconstruction of elbow defect by perforator propeller flap of the brachial region--clinical observation]. / Reconstruction des pertes de substance du coude par lambeau perforant en hélice de la région brachial--observation clinique.

INTRODUCTION: The elbow defects can raise problem to plastic surgeon. Indeed, this region is characterized by thin and mobile tissues; its reconstruction must be long-lasting, resistant to movements, to shear forces and to external support. Perforator propeller flaps beings appear an interesting option in the reconstruction of elbow defects. In this report, we describe a patient having benefited from the excision of a melanoma of the region of the elbow. After multidisciplinary meeting and resection of new margins, a reconstruction by perforator propeller flap was realized. A perforator pedicle of the lateral brachial region was located and used. The postoperative result in term of cover and function was considered very satisfactory. The perforator propeller flaps appear a reliable and interesting solution in the coverage of elbow defect.

[Treatment of Poland syndrome thorax deformity with the lipomodeling technique: about ten cases]. / Correction de la déformation thoraco-mammaire du syndrome de Poland par la technique du lipomodelage : à propos de dix cas.

The correct management, with the classic techniques, of the thoracic deformity in Poland's syndrome is difficult, with often insatisfactory results. The current surgical treatment involves the use of prothetic material and/or different flaps with their own complications and scares. The experience of our team with fat grafting (we named lipomodeling) in breast reconstruction helped us to propose the correction of the thoracic and mammary deformity by repeated fat transfer sessions. Fat grafting is commonly used in our team since 1998 in various indication of breast surgery. We reviewed retrospectively our ten first cases of thoracic deformity in Poland's syndrome treated with only fat grafting. Patients had repeated procedures until obtaining a satisfactory result. The fat was harvested from the thigh, buttocks, and abdomen. There were young patients with a mean age of 16years old (from 12 to 24). The mean follow-up was 51months. An average of 2.9 procedures (1 to 5) with 255cm(3) of fat injection at each procedure was needed to obtain symetry. Hundred percent of the patients were satisfied. No complication was noted. As reported, the reconstruction of the thoracic deformity and the mammary shape can be obtained by fat grafting. The absence of a flap donor site sequelae and the absence an implant allow this technique to be simple, reproductible, and without great complication. These criteria match well the surgical management of this deformity, which is mainly aesthetic. Moreover, the secondary benefit of liposuction of disgracious steatomery helps the acceptance of the procedure. Therefore in our hands, fat grafting to the breast (lipomodeling) is now our first choice treatment in thoracic Poland syndrome deformity. Given the rarity of this syndrome, we recommend a treatment by an operator who makes the learning curve of lipomodeling, and who often deals with Poland syndrome.

Lipomodelling: an important advance in breast surgery.

Based on long-term experiences, the authors consider lipomodelling to be a major advance in plastic, reconstructive and aesthetic surgery of the breast. The technique is now well established and the complication rate is very low. The risk of focal fat necrosis is around 3%. Oncological follow-up (now 14 years for the first patients) shows no increased risk of local recurrence or development of a new cancer. 30-40% of the injected fat is absorbed. Volume of the breast becomes stable in 3 to 4 months and remains definitive if the patient maintains constant weight. Because of very good results obtained and excellent acceptance of the procedure by the patients, this technique has completely modified our indications. In breast reconstruction, lipomodelling with autologous latissimus dorsi flap enables obtaining an entirely autologous breast in the majority of the patients. Analogically, lipomodelling can improve results of implant reconstructions, especially if the expander or the implant is planned to be exchanged. Lipomodelling is an effective tool for correction deformities especially in the décolleté after breast reconstruction with abdominal flap (DIEP, SIEA and TRAM). Lipomodelling is also progressively used in the correction of breast and chest wall deformities. In Poland syndrome, this technique appears to be a major advance that will probably revolutionize the treatment of severe cases. This is mainly due to its ability to achieve previously unachievable quality of reconstruction with minimal scaring. The application of lipomodelling in the treatment of pectus excavatum deformities is promising. Lipomodelling represents an advanced therapeutic alternative for tuberous breasts without the need to use an implant, as well as for breast asymmetry due to unilateral hypoplasia. Lipomodelling is an ideal option for cosmetic breast augmentation in patients who wish to achieve moderate, natural enlargement of breasts and who have considerable fat deposits.

Different bleeding risk in type 2A and 2M von Willebrand disease: a 2-year prospective study in 107 patients.

BACKGROUND: Type 2A and 2M von Willebrand disease (VWD2A and VWD2M) are characterized by the presence of a dysfunctional von Willebrand factor (VWF) and a variable bleeding tendency. So far, a head-to-head comparison of the clinical history and bleeding risk between VWD2A and VWD2M has never been provided in a prospective manner. AIM OF THE STUDY: We assessed the bleeding incidence rate and clinical characteristics in two cohorts of 17 families (46 patients) with VWD2A and 15 families (61 patients) with VWD2M prospectively followed-up for 24 months. VWF gene mutations were characterized in all of them. RESULTS: Mean bleeding score (BS) and VWF antigen at enrollment were significantly higher in VWD2A patients (P = 0.007). No correlation between VWF activity or factor VIII levels and the severity of BS was observed. The incidence rate of spontaneous bleeding requiring treatment was 107/100 patient-years (95% CI, 88.3-131) in VWD2A compared with 40/100 patient-years (95% CI, 30-53) in VWD2M (P < 0.001). The risk of bleeding was significantly higher in patients with BS ≥ 10 at enrollment compared with those with BS 0-2. Furthermore, 54 episodes of gastrointestinal bleeding occurred in 17/46 (36.9%) VWD2A patients and seven in 2/61 (3.3%) VWD2M patients (P < 0.0001). CONCLUSION: Bleeding tendency in VWD2A is greater than that of VWD2M, is not explained by factor VIII or VWF levels and is mainly due to an increased incidence of gastrointestinal bleeding.

Type 2A (IIH) von Willebrand disease is due to mutations that affect von Willebrand factor multimerization.

BACKGROUND: Type IIH von Willebrand disease was reported 20 years ago as a novel variant characterized by the loss of the largest multimers in plasma and platelets and absence of the typical triplet structure. OBJECTIVES AND METHODS: The propositus and his daughter have been reinvestigated and characterized at the molecular level. The identified mutations were expressed in COS-7 cells to evaluate the mechanism of this variant. RESULTS AND DISCUSSION: The propositus had normal von Willebrand factor (VWF):ristocetin cofactor activity (RCo) and high VWF antigen (VWF:Ag) values, with a low VWF:RCo/VWF:Ag ratio (0.51). No abnormalities were found in his daughter, except for the reduced triplet structure in plasma VWF and diminished ultralarge VWF (ULVWF) multimers in platelets. Three mutations were identified in the propositus: 604C>T (R202W), 4748G>A (R1583Q), and 2546G>A (C849Y). The amounts of secreted recombinant VWF (rVWF) were apparently increased for R202W (130%), R202W-R1583Q (131%), and R202W-R1583Q/WT (121%), reduced for C849Y (72%) and C849Y/WT (83%), and normal for R1583Q (107%) and R202W-R1583Q/C849Y (102%). In cell lysates, higher values were found in association with the C849Y mutation. A normal multimeric pattern was found in R1583Q rVWF, mainly dimers in R202W rVWF, and intermediate molecular weight multimers in C849Y rVWF. Hybrid R202W-R1583Q/WT and C849Y/WT rVWFs had a nearly normal multimeric pattern, whereas in hybrid R202W-R1583Q/C849Y rVWF there was a loss of large/intermediate multimers. CONCLUSIONS: The propositus phenotype seems to be due to mutations R202W and C849Y, both affecting the VWF multimerization process and, for C849Y rVWF, intracellular survival. The absent triplet multimeric structure in the propositus and its reduction in his daughter appears to be related to the lack of ULVWF multimers, which mainly contribute to the formation of satellite bands.

Expression studies of missense mutations p.D141Y, p.C275S located in the propeptide of von Willebrand factor in patients with type 3 von Willebrand disease.

Missense mutations are not considered a common cause of type 3 von Willebrand's disease (VWD), the most severe defect of von Willebrand factor (VWF) characterized by undetectable levels of this protein in plasma and platelets. Nevertheless, several missense mutations have been identified in these patients. In this study, we report the cases of two Italian patients with type 3 VWD, both compound heterozygotes for different missense mutations and null alleles, p.D141Y/c.2016_2019del and p.C275S/p.W222X. We performed in vitro expression studies of the candidate missense mutations, both located in the D1 domain of VWF propeptide, to confirm their link with the disease and to understand the mechanisms of type 3 VWD responsible in these patients. Mutant and wild-type (WT) expression vectors were used for transient transfection and co-transfection studies in COS-7 cells. Single construct transfections of both missense mutations showed a strongly reduced but detectable secretion of recombinant (r)VWFs (approximately 15% of WT), with essentially only dimers being visualized on multimeric analysis. As expected, expression of a single construct of either mutation with the WT, showed mildly reduced secretion (approximately 40% of WT) and a full set of multimers. These expression studies indicate that the two amino acids D141 and C275 are key residues in the tertiary structure of the VWF propeptide. Their replacement with a tyrosine and a serine, respectively, might compromise propeptide folding, affecting both its intracellular survival and its capacity to mediate multimerization. Co-expression of hybrid rVWFs confirmed the recessive inheritance pattern of these missense mutations.

Radiotherapy of classic and human immunodeficiency virus-related Kaposi's sarcoma: results in 1482 lesions.

BACKGROUND: The lesions of the various forms of Kaposi's sarcoma (KS), which are relatively radiosensitive, have been treated with different modalities of radiotherapy, with heterogeneous aims and results. OBJECTIVE: To verify the effectiveness and safety of radiotherapy on a large number of lesions endowed (classic KS) with a prolonged follow-up. METHODS: A retrospective study was done on 711 lesions of classic KS and 771 lesions of human immunodeficiency virus (HIV)-related KS, treated with traditional X-ray therapy. RESULTS: In classic KS, a cure rate of 98.7% resulted after 13.5 years from the end of radiotherapy. In three lesions (0.42%) in the same patient, an acute radiodermatitis occurred after traumatic action. In HIV-related KS, a complete remission was obtained in 91.43% of the lesions, partial remission in 6.74% and non-response in 0.51% at 1 to 46 months from the end of radiotherapy. CONCLUSION: Radiotherapy showed to be a safe and effective method, with relevant importance in the therapeutic strategy of KS.