Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.

Inferior subapical osteotomy for dentoalveolar decompensation of class III malocclusion in 'surgery-first' and 'surgery-early' orthognathic treatment.

Increasing experience with alternative timing protocols in orthognathic surgery has given way to new surgical and orthodontic techniques to shorten treatment times, reduce biological costs, and improve the final outcome. A prospective evaluation of class III patients who received an inferior segmental osteotomy (ISO) for decompensation of significantly retroclined lower incisors in the context of 'surgery-first' (SF) or 'surgery-early' (SE) timing protocols was performed. Treatment was planned virtually. A thorough periodontal assessment was performed at baseline and periodically until debonding. A minimally invasive surgical technique including selective interdental corticotomies and elective bone augmentation was used. Patient and orthodontist satisfaction with the treatment was evaluated. Eight patients (mean age 26.3 years) underwent surgery. One had isolated maxillary surgery and seven had bimaxillary surgery in combination or not with additional cosmetic procedures. The periodontal status of all patients remained stable throughout the observation period. The mean duration of orthodontic treatment was 8.7 months in the SF group and 10.5 months in the SE group. Satisfaction with treatment was extremely high. The ISO is a safe, reliable technique for dentoalveolar decompensation in timing protocols with a short or no orthodontic preparatory phase. This methodology may represent a reasonable approach in selected class III patients.

Effectiveness of Fulkerson Osteotomy with Femoral Nerve Stimulation for Patients with Severe Femoral Trochlear Dysplasia.

BACKGROUND: Patients with femoral trochlear dysplasia are at risk for chronic recurrent patellofemoral dislocations, with extreme cases often requiring a surgical procedure. Anteromedialization of the tibial tubercle with intraoperative femoral nerve stimulation and concurrent medial patella-femoral ligament (MPFL) reconstruction is a previously reported method of maximizing patello-femoral congruency. We hypothesize the Fulkerson osteotomy with intraoperative femoral nerve stimulation and concurrent MPFL reconstruction in patients with severe trochlear dysplasia provides equivalent postoperative clinical outcomes to the same procedure in patients with low level trochlear dysplasia. METHODS: 48 knees underwent Fulkerson osteotomy with intraoperative femoral nerve stimulation and concurrent MPFL reconstruction for recurrent lateral patellar dislocations. MRI, surgeon intraoperative assessment, and X-ray were used to assess degrees of trochlear dysplasia; inter-observer and intra-observer error were measured. The knees positive for severe dysplasia on MRI, intraoperative assessment, and X-ray were considered as a comparison cohort to the rest of the study population. We considered postoperative dislocation events and patellar tracking kinematics as outcome measures. Independent student t tests and Fisher exact tests were used to evaluate differences between groups. Significance was set at P<0.05. RESULTS: 11 knees were positive for severe dysplasia (SD) by combined MRI, surgeon intraoperative assessment, and X-ray with the remaining 37 knees categorized as low dysplasia (LD). No patients in either group exhibited apprehension or required re-operation. Mean sulcus angle in the SD group was 175.8 +-2.45 degrees (95% CI 171.0-180.6); the LD group mean sulcus angle was 154.3 +- 0.98 degrees (95% CI 152.4-156.2) (P<.001). Postoperatively there was no significant difference in dislocation events between the SD group (0/11) and the LD group (2/37) (P>0.999). Patellar maltracking decreased in both groups and there were no significant differences in estimates of patellofemoral congruency between the SD (2/11) and LD (8/37) (P>0.999) groups. CONCLUSION: The Fulkerson osteotomy with femoral nerve stimulation aimed at maximizing patellofemoral congruency may be an equally effective procedure for patients with either severe or mild trochlear dysplasia. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Surgical Gown's Cuff Modification to Prevent Surgical Contamination.

The gown-glove interface is the weakest point in the barrier system of gown and glove protection for the surgeon. We are herein presenting an easy modification in the cuff of the gown that increases the security of the gown-glove interface.

Polyetheretherketone custom-made implants for craniofacial defects: Report of 14 cases and review of the literature.

BACKGROUND: Craniofacial defects tend to carry functional and esthetic consequences for the patient. The complex shapes in this region make such reconstructions a challenging procedure and the most suitable material to be used remains controversial. METHODS: We report a series of 14 patients whose craniofacial defects were reconstructed using a computer designed PEEK-PSI (Polyetheretherketone- Patient Specific Implant). We analyzed the complications and outcomes of PEEK custom-made implants and compared our results with those of other case series reported in the current literature. RESULTS: Fourteen patients underwent craniofacial reconstruction using a PEEK-PSI. Three cases involved a one-step primary reconstruction and the rest of cases underwent a delayed reconstruction. Two cases (14.3 %) presented infection and only in one case was the implant definitively removed. Esthetic results were considered to be highly satisfactory. CONCLUSION: With CAD-CAM techniques, it is possible to prefabricate an individual implant. The ideal material for reconstructing maxillofacial defects does not exist, but PEEK has demonstrated good outcomes. When autologous bone is not available or, in selected cases with large or complex defects in the maxillofacial area, PEEK is one of the best options to reconstruct these defects. However, further studies are needed to determine the long-term results.

[Exclusive enteral nutrition continues to be first line therapy for pediatric Crohn's disease in the era of biologics]. / La nutrición enteral exclusiva continua siendo el tratamiento de primera línea en la enfermedad de Crohn pediátrica en la era de los biológicos.

INTRODUCTION: Exclusive enteral nutrition (EEN) has been to be more effective than corticosteroids in achieving mucosal healing without their side effects. OBJECTIVES: To determine the efficacy of EEN in terms of inducing clinical remission in newly diagnosed CD children and to study the efficacy of this therapeutic approach in improving the degree of intestinal mucosa inflammation. MATERIALS AND METHODS: The medical records of patients with newly diagnosed Crohn's disease treated with EEN were reviewed retrospectively. The degree of mucosal inflammation was assessed by fecal calprotectin (FC). Remission was defined as a PCDAI<10. RESULTS: Forty patients (24 males) were included, the age at diagnosis was 11.6 ± 3.6 years. Of the 34 patients who completed the EEN period, 32 (94% per-protocol analysis) achieved clinical remission. This percentage fell to 80% in the intention-to-treat analysis. The compliance rate was 95%. Duration of EEN was 6.42 weeks (IQR 6.0-8.14). FC was significantly higher in patients with moderate and severe disease. Median baseline FC levels (680 µg/g) decreased significantly to 218 µg/g (P<0.0001) after EEN. We found a statistically significant correlation between FC and PCDAI (rho=0.727; P<0.0001). Early use of thiopurines (< 8 weeks) versus subsequent use was not associated with improved outcomes during the follow-up. CONCLUSIONS: EEN administered for 6-8 weeks is effective for inducing clinical remission and decreasing the degree of mucosal inflammation. We did not find differences in terms of maintenance of remission in patients treated early with thiopurines.

Oral tacrolimus for pediatric steroid-resistant ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) occurring during childhood is generally extensive and is associated with severe flares that may require intravenous steroid treatment. In cases of corticosteroid resistance is necessary to introduce a second-line treatment to avoid or delay surgery. AIMS: To describe the efficacy and safety of oral tacrolimus for the treatment of severe steroid-resistant UC. METHODS: We performed a retrospective study that included all patients under age 18 suffering from severe steroid-resistant UC treated with oral tacrolimus during the period January 1998 to October 2012 and with a follow-up period after treatment of 24 months or more. RESULTS: A total of ten patients were included. The age at baseline was 9.4±4.9 years, and the time from diagnosis was 1.3 months (IQR, 1-5.7). Seven of the patients were in their first flare of disease. All of them received an oral dose of 0.12 mg/kg/day of tacrolimus divided in two doses. Trough plasma levels of tacrolimus were maintained between 4 and 13 ng/ml. Response was seen in 5/10 patients at 12 months, colectomy was eventually performed in 60% of patients during the follow-up period. CONCLUSIONS: Tacrolimus is useful in inducing remission in patients with severe steroid-resistant UC, preventing or delaying colectomy, and allowing the patient and family to prepare for a probable surgery. Tacrolimus may also be used as a treatment bridge for corticosteroid-dependent patients until the new maintenance therapy takes effect.

An individualized pre-operative blood saving protocol can increase pre-operative haemoglobin levels and reduce the need for transfusion in elective total hip or knee arthroplasty.

We have prospectively evaluated the efficacy of an individualized pre-operative blood saving protocol in elective total hip arthroplasty (THA) or total knee arthroplasty (TKA). The primary aim was to obtain a pre-operative haemoglobin (Hb) level of > or =14 g dL(-1). A reduction in requirements for allogeneic transfusion was considered the second aim. Several strategies are available for increasing pre-operative Hb levels and reducing red blood cell (RBC) transfusions following THA or TKA, but the success of these programmes depends on selecting the most appropriate treatment for each patient. Three hundred and five patients with an indication of elective THA or TKA were individually assigned to the following strategies according to Hb and ferritin levels and medical conditions: (a) no pre-operative intervention, (b) oral iron therapy, (c) intravenous (i.v.) iron therapy, (d) recombinant human erythropoietin alpha with i.v. iron and (e) pre-operative autologous donation (PAD) plus oral iron. Eighty-two percent of the patients reached a pre-operative Hb level of > or =14 g dL(-1) compared with 62% of patients with Hb levels of > or =14 g dL(-1) at the baseline visit. Treatment with PAD showed a significant reduction in the pre-operative Hb levels. The rate of RBC transfusion was 18.8% compared with 31.5% of matched historic group (P < 0.001). In conclusion, all patients scheduled to undergo THA or TKA should be candidates for an individualized pre-operative blood salvage programme.

Improving the cadmium-induced centriacinar emphysema model in rats by concomitant anti-oxidant treatment.

1. The aim of the present study was to perform an evolutionary analysis of the morphometrical, biochemical and functional parameters of centriacinar emphysema induced by cadmium chloride (CdCl2) in rats and to determine the effects of concomitant N-acetylcysteine (NAC) administration. 2. Male Wistar rats were instilled orotracheally with either CdCl2 (n = 24) or saline (n = 24). One group of rats, consisting of both CdCl2- and saline-treated rats, was fed a normal diet (n = 24), whereas the other group received NAC (n = 24). 3. Changes in inspiratory capacity (IC), lung compliance (CL), expiratory flow at 75% (F75), forced vital capacity (FVC) and hydroxyproline content were assessed 2, 8, 21 and 45 days after instillation. Polymorphonuclear cells were evaluated 2 and 8 days after instillation and the mean linear intercept (Lm) was determined at 21 and 45 days. 4. Over time, CdCl2 instillation causes several changes that are bound up with centriacinar emphysema. The concomitant administration of NAC to CdCl2-treated rats partially reversed Lm at 21 days compared with CdCl2 alone (115 +/- 2 vs 127 +/- 2, respectively; P < 0.05). However, 45 days after instillation, NAC improved lung function in CdCl2-treated rats compared with that in the saline-treated control group (IC 14.64 vs 15.25, respectively (P = 0.054); FVC 16.94 vs 16.28, respectively (P = 0.052), F75 31.41 vs 32.48, respectively (P = 0.062)). In addition, 45 days after instillation, NAC reduced lung collagen content in both the saline-treated control (100 vs 81% alone and in the presence of NAC, respectively) and CdCL2-treated groups (213 vs 161% alone and in the presence of NAC, respectively). In addition, although the results were not significant, NAC tended to reduce Lm and enhance CL in NAC + CdCl2-treated rats. 5. In conclusion, NAC partially improved emphysematous changes and reduced collagen deposition, which diminished the CdCl2-induced fibrotic component of centriacinar emphysema.

Tubes for pretransfusion testing should be collected by blood bank staff and hand labelled until the implementation of new technology for improved sample labelling. Results of a prospective study.

BACKGROUND AND OBJECTIVES: The greatest risk in transfusion medicine is actually human error, resulting in the use of the incorrect blood component. The aim of our study was to identify and evaluate the risk factors involved in the collection and labelling of pretransfusion blood samples. MATERIAL AND METHODS: We prospectively evaluated 6446 samples submitted to the blood bank for pretransfusion testing. Inappropriate samples were classified as 'mislabelled' or 'miscollected'. After 4 months of study, an educational approach was taken. RESULTS: The frequency of inappropriately labelled samples was 6.45%. Such samples were associated with the use of addressograph labels (vs. hand-written labels) [23.4% vs. 1.4%, P < 0.0001], collection by clinical staff (vs. blood bank staff) [8.8% vs. 2.1%, P = 0.001] and emergency situations (vs. routine sampling) [10.1% vs. 6.1%, P = 0.005]. Following educational intervention, the percentage of inappropriately labelled samples decreased from 7.3% (pre-educational) to 5.8% (post-educational), P = 0.005. CONCLUSION: Ongoing monitoring and analysis of labelling and collection should be mandatory in order to improve the safety of transfusion.

Hipoplasia pulmonar en el adulto / Lung hypoplasia in the adult

No disponible

Avances en el manejo del asma bronquial / Advances in the management of bronchial asthma

No disponible

Increased collagen deposition correlated with lung destruction in human emphysema.

BACKGROUND: To study the relationship between collagen amount and degree of emphysema as assessed by mean linear intercept (Lm) and correlating these with lung function test workup in patients with and without COPD. METHODS: Lung function tests were assessed in 16 smokers or ex-smokers and 1 non-smoker in order to separate them into two groups: COPD (FEV1/FVC lower than 70%) and non-COPD. A piece of lung tissue was used to analyse the collagen amount (HYP) by means of a colorimetric method. Morphometry was assessed to divide patients into two groups according to Lm: Lm > 260 micrometers was considered non-emphysema and Lm < 260 mm mild-emphysema. RESULTS: The non-emphysema group had a mean Lm value of 246.08+/-3.12 micrometers and the mild-emphysema group of 276.29+/-4.26 micrometers. The amount of hydroxyproline was significantly higher in the mild-emphysema group than in the non-emphysema group (7.82+/-0.67 vs. 5.50+/-0.54 microgram/g tissue). There was a clear positive correlation between Lm and HYP (r=0.55) and a negative correlation between Lm and DlCO (R=-0.5092). No correlation was found between the functional test and HYP, nor were there significant differences between COPD and non-COPD patients for Lm and HYP. CONCLUSIONS: Emphysema is associated with collagen deposition in the lungs, and air space size correlates with the amount of lung collagen even when there is no emphysema.

Benzenesulfonamide analogs of fluoroquinolones. Antibacterial activity and QSAR studies.

The structure-activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization of N4-piperazinyl of ciprofloxacin (CIP) were studied. The behavior of the new BSFQ series was similar to the previously norfloxacin (NOR) analogs reported, making possible a quantitative structure-activity relationships (QSAR) analysis of the complete set of BSFQs. The presence of the benzenesulfonylamido (BS) groups shifted the activity of classic antimicrobial fluoroquinolones from being more active against Gram-negative to Gram-positive strains. QSAR studies through Hansch analysis showed a linear correlation of the activity with electronic and steric parameters. Small electron-donor groups would increase the in vitro activity against Gram-positive bacteria. Hydrophobic properties played a minor role when activity is measured as minimum inhibitory concentration (MIC). QSAR analysis also reinforces previous biological findings about the presence of new interactions with target topoisomerases.

Effect of pulmonary perfusion on the slopes of single-breath test of CO2.

The objective of this study was to evaluate the effects of lung perfusion on the slopes of phases II (S(II)) and III (S(III)) of a single-breath test of CO(2) (SBT-CO(2)). Fourteen patients submitted to cardiac surgery were studied during weaning from cardiopulmonary bypass (CPB). Pump flow was decreased in 20% steps, from 100% (total CPB = 2.5 l.min(-1).m(-2)) to 0%. This maneuver resulted in a progressive and opposite increase in pulmonary blood flow (PBF) while maintaining ventilator settings constant. SBT-CO(2), respiratory, and hemodynamic variables remained unchanged before and after CPB, reflecting a constant condition at those stages. S(III) was similar before and after CPB (19.6 +/- 2.8 and 18.7 +/- 2.1 mmHg/l, respectively). S(III) was lowest during 20% PBF (8.6 +/- 1.9 mmHg/l) and increased in proportion to PBF until exit from CPB (15.6 +/- 2.2 mmHg/l; P < 0.05). Similarly, S(II) and the CO(2) area under the curve increased from 163 +/- 41 mmHg/l and 4.7 +/- 0.6 ml, respectively, at 20% PBF to 313 +/- 32 mmHg/l and 7.9 +/- 0.6 ml (P < 0.05) at CPB end. When S(II) and S(III) were normalized by the mean percent expired CO(2), they remained unchanged during the protocol. In summary, the changes in PBF affect the slopes of the SBT-CO(2). Normalizing S(II) and S(III) eliminated the effect of changes in the magnitude of PBF on the shape of the SBT-CO(2) curve.

Blakeslea trispora genes for carotene biosynthesis.

We cloned the carB and carRA genes involved in beta-carotene biosynthesis from overproducing and wild-type strains of Blakeslea trispora. The carB gene has a length of 1,955 bp, including two introns of 141 and 68 bp, and encodes a protein of 66.4 kDa with phytoene dehydrogenase activity. The carRA gene contains 1,894 bp, with a single intron of 70 bp, and encodes a protein of 69.6 kDa with separate domains for lycopene cyclase and phytoene synthase. The estimated transcript sizes for carB and carRA were 1.8 and 1.9 kb, respectively. CarB from the beta-carotene-overproducing strain B. trispora F-744 had an S528R mutation and a TAG instead of a TAA stop codon. The overproducing strain also had a P143S mutation in CarRA. Both B. trispora genes could complement mutations in orthologous genes in Mucor circinelloides and could be used to construct transformed strains of M. circinelloides that produced higher levels of beta-carotene than did the nontransformed parent. The results show that these genes are conserved across the zygomycetes and that the B. trispora carB and carRA genes are functional and potentially useable to increase carotenoid production.

Biotechnological lycopene production by mated fermentation of Blakeslea trispora.

A semi-industrial process (800-l fermentor) for lycopene production by mated fermentation of Blakeslea trispora plus (+) and minus (-) strains has been developed. The culture medium was designed at the flask scale, using a program based on a genetic algorithm; and a fermentation process by means of this medium was developed. Fermentation involves separate vegetative phases for (+) and (-) strains and inoculation of the production medium with a mix of both together. Feeding with imidazole or pyridine, molecules known to inhibit lycopene cyclase enzymatic activity, enhanced lycopene accumulation. Different raw materials and physical parameters, including dissolved oxygen, stirring speed, air flow rate, temperature, and pH, were checked in the fermentor to get maximum lycopene production. Typical data for the fermentation process are presented and discussed. This technology can be easily scaled-up to an industrial application for the production of this carotenoid nowadays widely in demand.