Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer.

BACKGROUND: α-Selective phosphatidylinositol 3-kinase (PI3K) inhibitors improve outcome in patients with PIK3CA-mutated, hormone receptor-positive (HR+)/Her2- metastatic breast cancer (mBC). Nevertheless, it is still unclear how to integrate this new drug family in the treatment landscape. PATIENTS AND METHODS: A total of 649 patients with mBC from the SAFIR02 trial (NCT02299999), with available mutational profiles were selected for outcome analysis. PIK3CA mutations were prospectively determined by next-generation sequencing on metastatic samples. The mutational landscape of PIK3CA-mutated mBC was assessed by whole-exome sequencing (n = 617). Finally, the prognostic value of PIK3CA mutations during chemotherapy was assessed in plasma samples (n = 44) by next-generation sequencing and digital PCR. RESULTS: Some 28% (104/364) of HR+/Her2- tumors and 10% (27/255) of triple-negative breast cancer (TNBC) presented a PIK3CA mutation (P < 0.001). PIK3CA-mutated HR+/Her2- mBC was less sensitive to chemotherapy [adjusted odds ratio: 0.40; 95% confidence interval (0.22-0.71); P = 0.002], and presented a worse overall survival (OS) compared with PIK3CA wild-type [adjusted hazard ratio: 1.44; 95% confidence interval (1.02-2.03); P = 0.04]. PIK3CA-mutated HR+/Her2- mBC was enriched in MAP3K1 mutations (15% versus 5%, P = 0.0005). In metastatic TNBC (mTNBC), the median OS in patients with PIK3CA mutation was 24 versus 14 months for PIK3CA wild-type (P = 0.03). We further looked at the distribution of PIK3CA mutation in mTNBC according to HR expression on the primary tumor. Some 6% (9/138) of patients without HR expression on the primary and 36% (14/39) of patients with HR+ on the primary presented PIK3CA mutation (P < 0.001). The level of residual PIK3CA mutations in plasma after one to three cycles of chemotherapy was associated with a poor OS [continuous variable, hazard ratio: 1.03, 95% confidence interval (1.01-1.05), P = 0.007]. CONCLUSION: PIK3CA-mutated HR+/Her2- mBC patients present a poor outcome and resistance to chemotherapy. Patients with PIK3CA-mutated TNBC present a better OS. This could be explained by an enrichment of PIK3CA mutations in luminal BC which lost HR expression in the metastatic setting. TRIAL REGISTRATION: SAFIR02 trial: NCT02299999.

The Blomia tropicalis allergen Blo t 7 stimulates innate immune signalling pathways through TLR2.

BACKGROUND: Although the house dust mite species Blomia tropicalis is a leading cause of allergic diseases in tropical and subtropical regions, the identification and characterization of the allergenic proteins remain incomplete. OBJECTIVE: We aimed to characterize a recombinant form of Blo t 7 (rBlo t 7) in terms of IgE reactivity, lipid-binding activity and ability to stimulate innate immunity. METHODS: The mature Blo t 7 cDNA was cloned by PCR methods for the expression of a secreted form of the allergen in P. pastoris. The IgE reactivity to purified rBlo t 7 as well as the potential cross-reactivity with Der p 7 was determined by ELISA. The lipid-binding capacity of rBlo t 7 was assayed using fluorescent lipid probes. The stimulation of TLR2 signalling pathway by rBlo t 7 was examined in cell activation and reporter assays. RESULTS: The amplified mature Blo t 7 cDNA revealed the presence of a 60 base pair insertion compared with the reference sequence registered in the GenBank database. Multiple protein sequence alignments of group 7 mite allergens confirmed that this longer deduced amino acid sequence was the authentic Blo t 7 polypeptide chain. Analysis of IgE reactivity can classify rBlo t 7 as an intermediate B. tropicalis allergen which displayed weak cross-reactivity with Der p 7. Purified rBlo t 7 was shown to bind selectively the naturally fluorescent lipid probe cis-parinaric (cPNA) with a dissociation constant of 2 µmol/L. The group 7 Blomia allergen stimulated the TLR2-, NF-kB- and MAPK-dependent production of IL-8 and GM-CSF in respiratory epithelial cells. CONCLUSIONS & CLINICAL RELEVANCE: Through its propensity to transport fatty acids/lipids and to stimulate TLR2 signalling pathways in airway epithelial cells, Blo t 7 can represent a key allergen for the initiation of the B. tropicalis-induced airway inflammation.

The minor house dust mite allergen Der p 13 is a fatty acid-binding protein and an activator of a TLR2-mediated innate immune response.

BACKGROUND: The house dust mite (HDM) allergen Der p 13 could be a lipid-binding protein able to activate key innate signaling pathways in the initiation of the allergic response. We investigated the IgE reactivity of recombinant Der p 13 (rDer p 13), its lipid-binding activities, and its capacity to stimulate airway epithelium cells. METHODS: Purified rDer p 13 was characterized by mass spectrometry, circular dichroism, fluorescence-based lipid-binding assays, and in silico structural prediction. IgE-binding activity and allergenic potential of Der p 13 were examined by ELISA, basophil degranulation assays, and in vitro airway epithelial cell activation assays. RESULTS: Protein modeling and biophysical analysis indicated that Der p 13 adopts a ß-barrel structure with a predominately apolar pocket representing a potential binding site for hydrophobic ligands. Fluorescent lipid-binding assays confirmed that the protein is highly selective for ligands and that it binds a fatty acid with a dissociation constant typical of lipid transporter proteins. The low IgE-binding frequency (7%, n = 224) in Thai HDM-allergic patients as well as the limited propensity to activate basophil degranulation classifies Der p 13 as a minor HDM allergen. Nevertheless, the protein with its presumptively associated lipid(s) triggered the production of IL-8 and GM-CSF in respiratory epithelial cells through a TLR2-, MyD88-, NF-kB-, and MAPK-dependent signaling pathway. CONCLUSIONS: Although a minor allergen, Der p 13 may, through its lipid-binding capacity, play a role in the initiation of the HDM-allergic response through TLR2 activation.

Patterns of IgE sensitization in house dust mite-allergic patients: implications for allergen immunotherapy.

BACKGROUND: Understanding patterns of IgE sensitization in Dermatophagoides-allergic patients living in various geographical areas is necessary to design a product suitable for worldwide allergen immunotherapy (AIT). METHODS: Using a HIFI Allergy customized microarray assay, IgEs specific for 12 purified allergens from Dermatophagoides pteronyssinus or D. farinae were assessed in sera from 1302 house dust mite (HDM)-allergic patients living in various areas. Comprehensive mass spectrometric (MS) analyses were conducted to characterize HDM extracts, as well as purified bodies and feces. RESULTS: Patterns of IgE reactivity to HDM allergens are comparable in all cohorts of patients analyzed, encompassing adults and 5- to 17-year-old children, as well as American, Canadian, European, and Japanese patients. Overall, >70% and >80% of HDM-allergic patients are sensitized to group 1 and group 2 allergens, respectively, from D. pteronyssinus and/or D. farinae species. Furthermore, 20-47% of patients also have IgEs to allergens from groups 4, 5, 7, 13, 15, 21, and 23. All patients have IgEs to allergens present in mite bodies and feces. MS-based analyses confirmed the presence of mite allergens recorded by IUIS in D. pteronyssinus and D. farinae extracts, with groups 2, 8, 10, 11, 14, and 20 prominent in bodies and groups 1, 6, 18, and 23 well represented in feces. CONCLUSIONS: Mite-specific AIT should rely upon a mixture of D. pteronyssinus and D. farinae extracts, manufactured from both feces and bodies. Such a combination is appropriate to treat children and adult Dermatophagoides-allergic patients from Asia, Europe, and North America.

Development of recombinant stable house dust mite allergen Der p 3 molecules for component-resolved diagnosis and specific immunotherapy.

BACKGROUND: The allergen Der p 3 is underrepresented in house dust mite (HDM) extracts probably due to autolysis. Recombinant stable molecule of the allergen is thus needed to improve the diagnosis of allergy and the safety and efficacy of immunotherapy. OBJECTIVE: The current study reports the immunological characterization of two recombinant molecules of the HDM allergen Der p 3 as useful tools for diagnosis and immunotherapy. METHODS: Recombinant mature (rDer p 3) and immature (proDer p 3) Der p 3 and their corresponding S196A mutants were produced in Pichia pastoris and purified. The stability, IgE-binding capacity and allergenicity of the different proteins were analysed and compared with those of the major mite allergen Der p 1 used as a reference. Additionally, the immunogenicity of the different allergens was evaluated in a murine model of Der p 3 sensitization. RESULTS: Compared to the IgE reactivity to recombinant and natural Der p 3 (nDer p 3), the mean IgE binding of patient's sera to rDer p 3-S196A (50%) was higher. The poorly binding to nDer p 3 or rDer p 3 was due to autolysis of the allergen. Contrary to Der p 3, proDer p 3 displayed very weak IgE reactivity, as measured by sandwich ELISA and competitive inhibition, rat basophil leukaemia degranulation and human basophil activation assays. Moreover, proDer p 3 induced a TH 1-biased immune response that prevented allergic response in mice but retained Der p 3-specific T-cell reactivity. CONCLUSION: rDer p 3-S196A should be used for the diagnosis of HDM allergy elicited by Der p 3, and proDer p 3 may represent a hypoallergen of Der p 3.

The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.

Astrocyte dysfunction has previously been linked to multiple neurodegenerative disorders including Parkinson's disease (PD). Among their many roles, astrocytes are mediators of the brain immune response, and astrocyte reactivity is a pathological feature of PD. They are also involved in the formation and maintenance of the blood-brain barrier (BBB), but barrier integrity is compromised in people with PD. This study focuses on an unexplored area of PD pathogenesis by characterizing the interplay between astrocytes, inflammation and BBB integrity, and by combining patient-derived induced pluripotent stem cells with microfluidic technologies to generate a 3D human BBB chip. Here we report that astrocytes derived from female donors harboring the PD-related LRRK2 G2019S mutation are pro-inflammatory and fail to support the formation of a functional capillary in vitro. We show that inhibition of MEK1/2 signaling attenuates the inflammatory profile of mutant astrocytes and rescues BBB formation, providing insights into mechanisms regulating barrier integrity in PD. Lastly, we confirm that vascular changes are also observed in the human postmortem substantia nigra of both males and females with PD.

Preliminary results on a proposed histopathological assessment of predictive factors for basal cell carcinoma recurrence after primary free margin excision.

Background: Basal cell carcinoma (BCC) incidence is steadily increasing but therapeutic solutions remain limited and present a public health challenge. Aims: To identify predictive factors of BCC recurrence after primary free margin excision, with automated methods, by evaluating cell proliferation, the Hedgehog pathway activation and primary cilia. Materials and Methods: This case-control study included 32 patients (16 with recurrence occurring at least 6 months after complete resection, and 16 without recurrence) who underwent surgery for BCC. Formalin-fixed paraffin-embedded cutaneous resections were processed for immunohistochemistry or immunostaining with the following primary antibodies: mouse anti-MCM6, rabbit anti-ARL13B and rabbit anti-GLI1. Results: BCC recurrence after free margin excision was significantly linked to a higher proliferative index (p < 0.001) and a lower cilia count (p = 0.041) in the primary lesion. No significant differences were observed regarding cilia length (p = 0.39) or GLI1-positive nuclei. Discussion: The complex interplay between essential signaling pathways, cell proliferation and cilia requires further experimental investigations in the context of BCC recurrence. Conclusion: A higher proliferative index evaluated with MCM6 antibody could be a useful prognosis marker of BCC risk of recurrence. The lower cilia count in the primary lesion unveiled novel perspectives to understand BCC recurrence molecular mechanisms.

Interactions of airway epithelium with protease allergens in the allergic response.

Among the apparently innocuous environmental proteins routinely inhaled by human subjects, only a small proportion of these antigens triggers allergy in susceptible individuals. Although the molecular basis of the allergenicity of these airborne proteins remains to be fully characterized, numerous studies suggest that the ability of such proteins to promote allergic responses is at least due to their proteolytic activity. This review will summarize insights into the interactions of protease allergens with the respiratory epithelium. In addition to their capacity to facilitate their antigen presentation through epithelial barrier degradation, protease allergens can directly activate airway mucosal surfaces to recruit inflammatory cells and to initiate the airway remodelling process. A greater understanding of the effects of protease allergens in the airways inflammation as well as on the relevant targets could define novel therapeutic strategies for the treatment allergic asthma.

Evaluation of therapeutic sublingual vaccines in a murine model of chronic house dust mite allergic airway inflammation.

BACKGROUND: Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes. OBJECTIVE: To develop a chronic house dust mite (HDM) allergy model to evaluate sublingual therapeutic vaccine candidates. METHODS: The BABL/c mice that were used were sensitized with Dermatophagoides pteronyssinus (Dpte) and Dermatophagoides farinae (Dfar) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy (SLIT) with either Dpte, Dfar or Dpte/Dfar extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho-alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively. RESULTS: Mice sensitized to Dpte and Dfar allergens exhibited strong airway hyperresponsiveness (AHR) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted Th2-biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts-based vaccines. In this model, SLIT decreased AHR and Th2 responses and induced HDM-specific IgAs in saliva. The Dpte/Dfar mix proved the most efficacious when compared to Dpte or Dfar extracts alone. CONCLUSIONS AND CLINICAL RELEVANCE: The efficacy of a sublingual vaccine based on a Dpte/Dfar allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation animal model is a useful tool to design and select candidate vaccines to be tested in humans.

Goal-directed arm movements in children with fetal alcohol syndrome: a kinematic approach.

BACKGROUND: Although many studies have documented deficits in general motor functioning in children with fetal alcohol syndrome (FAS), few have employed detailed measurements to explore the specific nature of such disabilities. This pilot study explores whether three-dimensional (3D) kinematic analysis may generate increased knowledge of the effect of intrauterine alcohol exposure on motor control processes by detecting atypical upper-limb movement pattern specificity in children with FAS relative to typically developing (TD) children. METHODS: Left and right arm and head movements during a sequential unimanual goal-directed precision task in a sample of children with FAS and in TD children were registered by an optoelectronic tracking system (ProReflex, Qualisys Inc.). RESULTS: Children with FAS demonstrated evidently poorer task performance compared with TD children. Additionally, analyses of arm movement kinematics revealed atypical spatio-temporal organization in the children with FAS. In general, they exhibited longer arm movement trajectories at both the proximal and distal level, faster velocities at the proximal level but slower at the distal level, and more segmented distal movements. Children with FAS also showed atypically augmented and fast head movements during the task performance. CONCLUSIONS: Findings indicate neuromotor deficits and developmental delay in goal-directed arm movements because of prenatal alcohol exposure. It is suggested that 3D kinematic analysis is a valid technique for furthering the understanding of motor control processes in children with FAS/fetal alcohol spectrum disorders. A combination with relevant neuroimaging techniques in future studies would enable a more clear-cut interpretation of how atypical movement patterns relate to underlying brain abnormalities.

Production and immunogenicity of hypoallergenic codon-optimized DNA vaccine encoding mature Der p 1 allergen.

BACKGROUND: Genetic vaccination with plasmid DNA encoding allergens is a promising potential approach for the treatment or prevention of allergy. Nonetheless, because the allergens expressed can display immunoglobulin (Ig) E reactivity, methods to deliver hypoallergenic variants can minimize the risk of type 2 helper (T(H)2) cell priming after DNA immunization. METHODS: A humanized synthetic gene encoding mature Dermatophagoides pteronyssinus group 1 (Der p 1) allergen was cloned into the pHIS expression vector carrying unmethylated CpG 2006 (CpG 2006) motif but devoid of signal sequence. The immunogenicity of this DNA construct was compared in naïve mice with that of recombinant ProDer p 1 protein adjuvanted with alum. RESULTS: Codon optimization of the cDNA encoding mature Der p 1 markedly improved allergen expression. Mature Der p 1, expressed intracellularly in Human Embryonic Kidney 293 cells (HEK 293 cells) transfected with codon-optimized Der p 1 cDNA (pHIS-mHuDer p 1), was shown to be hypoallergenic as it displayed no IgE reactivity. Intradermal vaccinations of naïve Balb/C mice with pHIS-mHuDer p 1 elicited an allergen-specific T(H)1 response characterized by the production of specific IgG2a, a very low amount of specific IgG1, and no specific IgE. Lipoplex formulation with cationic liposome composed of lecithin, N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) and cholesterol not only accelerated the induction of T(H)1 response but also increased its intensity. CONCLUSION: A codon-optimized DNA vaccine encoding mature Der p 1 in a lipoplex formulation could represent a promising hypoallergenic vaccine candidate for safer immunotherapy against house dust mite allergy.

Immunomodulatory properties of Lactobacillus plantarum and its use as a recombinant vaccine against mite allergy.

BACKGROUND: Selected lactic acid bacteria were reported to prevent atopic dermatitis and experimental asthma but the mechanisms of their immunomodulatory effects are not fully elucidated. In this study, the signaling pathways triggered by Lactobacillus plantarum NCIMB8826 were investigated and the potential use of this strain producing a variant of the mite allergen Der p 1 as live vaccine vehicle was evaluated. METHODS: Mouse bone marrow-derived dendritic cells were stimulated with wild-type or a L. plantarum teichoic acid mutant to evaluate the secretion of cytokines. A recombinant L. plantarum expressing Der p 1 was engineered, its in vitro immunomodulatory properties were characterized and its prophylactic potential was evaluated in a Der p 1-sensitization murine model. RESULTS: Mouse dendritic cells stimulated by L. plantarum triggered the release of interleukin-10 (IL-10), IL-12 p40, IL-12 p70 and tumor necrosis factor-alpha (TNF-alpha). IL-12 p40 secretion was dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases, Toll-like receptor 2 (TLR2), TLR9 and on the bacterial teichoic acid composition. Recombinant L. plantarum producing Der p 1 exhibited similar immunostimulatory properties as wild-type. Prophylactic intranasal pretreatment of mice with this recombinant strain prevented the development of the typical Th2-biased allergic response by a drastic reduction of specific IgE and the induction of protective allergen-specific IgG2a antibodies. Moreover, both wild-type or recombinant L. plantarum reduced airway eosinophilia following aerosolized allergen exposure and IL-5 secretion upon allergen restimulation. CONCLUSION: By combining both Th1-type immunostimulatory properties and an efficient allergen delivery capacity, recombinant L. plantarum producing Der p 1 represents a promising vaccine against house dust mite allergy.

The challenge of preserving renal function after liver transplantation.

Thanks to new surgical techniques and the use of calcineurin inhibitors for the prevention of allograft rejection, the long-term outcome of liver transplantation has recently improved. In case of liver transplantation, the occurrence of renal failure can impair the outcome. Renal function preservation is, therefore, necessary to improve transplantation outcome.

Prevention of calcineurin inhibitor nephrotoxicity in renal transplantation.

Calcineurin inhibitors (CNI) cyclosporine (Csa) and tacrolimus (Tac) are now first intention immunosuppressive drugs in renal transplantation. However, although these treatments are effective for preventing allograft rejection, they are nephrotoxic: they can cause chronic renal dysfunction and degradation of renal graft function [Nankivell BJ, et al. The natural history of chronic allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33]. In view of these undesirable effects, several strategies have been developed to minimize or even avoid their use. These strategies are reviewed and discussed in this paper.

[Sexual assault: medicolegal findings and legal outcomes (analysis of 756 cases)]. / Les victimes d'abus sexuels: éléments médicolégaux et suites judiciaires (analyse de 756 cas).

OBJECTIVES: We describe the medico-legal findings in a population of sexual assault cases assessed in an urban referral center, analyse the legal outcomes in each case and determine whether the medico-legal findings were associated with conviction of the assailant. MATERIALS AND METHODS: We performed a retrospective study of medico-legal reports in all the sexual assault cases reported in Tours during a 7-year period. Legal outcomes were obtained from courtroom proceedings. The relationship between the outcomes and the circumstances of the case was analyzed by logistic regression. RESULTS: 756 cases were enrolled. 68.3% of the cases involved children under 15 years old. Genital trauma occurred in 6.8% of the girls and 6% of the boys in this group. 31.7% of all the victims were aged 15 years or more. Genital injury was documented in 11.3% of the women. 36.3% of the assailants were convicted. Examination at the request of the police authorities and previous acquaintance of the assailant by the victim were significantly associated with conviction. The presence of general body and/or genital trauma was not associated with conviction. CONCLUSION: Non-medical variables must be thoroughly collected by the medical examiner. Physical evidence of trauma was neither predictive nor essential for conviction.

Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP.

Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.

Fast and effective treatment of malignant hypercalcemia. Combination of suppositories of calcitonin and a single infusion of 3-amino 1-hydroxypropylidene-1-bisphosphonate.

Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed.

[Quilting suture after mastectomy in prevention of postoperative seroma: a prospective observational study]. / Intérêt du capitonnage de la loge de mastectomie dans la prévention des séromes post-opératoires : étude prospective.

OBJECTIVES: The occurrence of a postoperative seroma is the main complication of mastectomy. In 2011, Ouldamer et al. adapted a quilting technique used in reconstructive surgery in mastectomy closure. The aim of this study is to evaluate the impact of quilting in the prevention of postoperative seroma. PATIENTS AND METHODS: This is an observational prospective study to the Centre Hospital-University of Tours. Hundred and forty-four patients who underwent a mastectomy between January 1st, 2011 and October 1st, 2012 were included. Patients were divided into 2 groups, one with a classic wound closure with drainage and the second with quilting suture of skin flaps to the underlying musculature after mastectomy without drainage. RESULTS: Quilting suture significantly reduces the postoperative seroma appearance (OR=0.15; CI95% [0.06-0.39]; P<0.001). Operative time is increased by 20minutes in the quilted group (P<0.001). Postoperative pain is not changed by quilting. The duration of hospitalization is significantly shorter (5.09±1.46 days versus 6.49±2.77 days; P<0.001). Quality of the healing and appearance of the scar, rated by patients, are identical in both groups. CONCLUSION: Quilting is an effective method not only for prevention of seroma, but also for reducing of hospitalization duration, without increasing of postoperative pain and complications.

A single-day treatment of tumor-induced hypercalcemia by intravenous amino-hydroxypropylidene bisphosphonate.

Twenty patients with malignant hypercalcemia were treated with amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of a single-day treatment and determine the optimal dose of this compound, all patients received AHPrBP intravenously over 24 h, but they were divided into two subsequent groups of 10 patients: Group A received a single dose of 60 mg AHPrBP and group B received a single dose of 30 mg. In both groups all patients responded to AHPrBP with a decrease in plasma calcium concentration after a mean time lag of 1 day. Within 6 days, plasma calcium (corrected for serum proteins) fell from 3.24 +/- 0.14 to 2.24 +/- 0.06 mmol/liter in group A (p less than .001), but only from 3.22 +/- 0.15 to 2.49 +/- 0.10 mmol/liter in group B (p less than .005). Whereas in all patients from group A plasma calcium was within the normal range at days 9 and 14, in 4 patients of group B it was still above the normal range at day 9, and in 5 patients at day 14. There was a significant difference in plasma calcium between group A and group B from days 5 to 14 (p less than .005). In both groups, urinary calcium excretion fell dramatically and similarly, and plasma phosphate concentration decreased significantly (p less than .01) to values slightly below the normal range from days 4 to 6.(ABSTRACT TRUNCATED AT 250 WORDS)