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BACKGROUND CONTEXT Although autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs. PURPOSE This study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy. STUDY DESIGN/SETTING A prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial. PATIENT SAMPLE A total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4–L5 degenerative spondylolisthesis and/or with L4–L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES Spinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment. METHODS Patients who underwent L4–L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups. RESULTS Seventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups. CONCLUSIONS Compared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study.

Fibrosis is present in an important proportion of myocardial disorders. Injury activates cardiac fibroblasts, which deposit excess extracellular matrix, increasing tissue stiffness, impairing cardiac function, and leading to heart failure. Clinical therapies that directly target excessive fibrosis are limited, and more effective treatments are needed. Immunotherapy based on chimeric antigen receptor (CAR) T cells is a novel technique that redirects T lymphocytes toward specific antigens to eliminate the target cells. It is currently used in haematological cancers but has demonstrated efficacy in mouse models of hypertensive cardiac fibrosis, with activated fibroblasts as the target cells. CAR T cell therapy is associated with significant toxicities, but CAR natural killer cells can overcome efficacy and safety limitations. The use of CAR immunotherapy offers a potential alternative to current therapies for fibrosis reduction and restoration of cardiac function in patients with myocardial fibrosis.

Brain metastases are associated with considerable negative effects on patients' outcome in lung adenocarcinoma (LADC). Here, we investigated the proteomic landscape of primary LADCs and their corresponding brain metastases.Proteomic profiling was conducted on 20 surgically resected primary and brain metastatic LADC samples via label-free shotgun proteomics. After sample processing, peptides were analyzed using an Ultimate 3000 pump coupled to a QExactive HF-X mass spectrometer. Raw data were searched using PD 2.4. Further data analyses were carried out using Perseus, RStudio and GraphPad Prism. Proteomic data were correlated with clinical and histopathological parameters and the timing of brain metastases. Mass spectrometry-based proteomic data are available via ProteomeXchange with identifier PXD027259.Out of the 6821 proteins identified and quantified, 1496 proteins were differentially expressed between primary LADCs and corresponding brain metastases. Pathways associated with the immune system, cell-cell/matrix interactions and migration were predominantly activated in the primary tumors, whereas pathways related to metabolism, translation or vesicle formation were overrepresented in the metastatic tumors. When comparing fast- versus slow-progressing patients, we found 454 and 298 differentially expressed proteins in the primary tumors and brain metastases, respectively. Metabolic reprogramming and ribosomal activity were prominently up-regulated in the fast-progressing patients (versus slow-progressing individuals), whereas expression of cell-cell interaction- and immune system-related pathways was reduced in these patients and in those with multiple brain metastases.This is the first comprehensive proteomic analysis of paired primary tumors and brain metastases of LADC patients. Our data suggest a malfunction of cellular attachment and an increase in ribosomal activity in LADC tissue, promoting brain metastasis. The current study provides insights into the biology of LADC brain metastases and, moreover, might contribute to the development of personalized follow-up strategies in LADC.

Background Context Revision surgery represents a major event for patients undergoing adult spinal deformity (ASD) surgery. Previous reports suggest that ASD surgery has minimal or no impact on health-related-quality of life (HRQOL) outcomes. Purpose The present study aims to investigate the impact of early reoperations within the first year on HRQOL and on the likelihood of reaching the minimally clinically important difference (MCID) after ASD surgery. Design This is a retrospective analysis of prospectively collected data from consecutive surgically treated adult deformity surgery patients included in a multicenter, international database. Patient Sample The present study included 280 patients from a multicenter international prospective database. Outcome Measure Oswestry Disability Index (ODI), Short Form-36 (SF-36), Scoliosis Research Society-22 (SRS-22), MCID were evaluated in this work. Methods Consecutive surgical patients with ASD recruited prospectively in six different centers from four countries with a minimum 2-year follow-up were stratified into two groups: R (revision surgery within the first year) and NR (no revision). Health-related-quality of life (ODI, SF-36, SRS-22) was assessed and compared at 6-month, 1-year, and 2-year follow-up stages. Statistical analysis included chi-square tests, Student t tests, and linear mixed models. Results Forty-three patients (R Group) received 46 revision surgeries. Nineteen patients (41.3%) had implant-related complications, 9 patients (19.6%) had deep surgical site infections, 9 patients (19.6%) had proximal junctional kyphosis, 3 patients (6.5%) had hematoma, and 6 patients (13%) had other complications. Baseline characteristics differed between groups. At 6 months, all HRQOL scores improved in both groups, except in the SF-36 Mental Component Summary and SRS-22 mental health domain in the R Group. At 1 year, ODI and SRS-22 improvement was significantly greater in the NR Group, exceeding the reported MCID. At the 2-year follow-up, ODI, SRS-22, SF-36 MCS, and SF-36 PCS improvement was similar in both groups. However, postoperative change was only above the MCID for SF-36 PCS, ODI, and SRS-22 in the NR Group. Conclusions Early unanticipated revision surgery has a negative impact on mental health at 6 months and reduces the chances of reaching an MCID improvement in SRS-22, SF-36 PCS, and ODI at the 2-year follow-up.

Background Context In 2008, Mirza et al. designed and validated the first and only index capable of quantifying the complexity of spine surgery. However, this index is not fully applicable to adult spinal deformity (ASD) surgery as it does not include the surgical techniques most commonly used and most strongly associated with perioperative complications in patients with ASD. Purpose The objective of this study is to develop an “Adult Deformity Surgery Complexity Index” (ADSCI) to quantify objectively the complexity of the ASD posterior surgery. Study Design/Setting This is an expert consensus (Delphi process) and retrospective analysis of prospectively collected data using multiple regression models. Patient Sample Patients were prospectively enrolled in two comparable multicenter ASD databases sharing the same inclusion criteria. Outcome Measures The ADSCI was internally and externally validated using R2 for intraoperative bleeding and length of surgery. Receiver operating characteristics (ROC) and area under the curve (AUC) analysis was used to assess the sensitivity and specificity of ADSCI. Methods The development and validation of ADSCI was based on the construction and comparison of three different tools: ADSCI score was constructed by three rounds of expert consensus (ADSCI-Delphi) and two multiple regression models (ADSCI-RM-Simple and ADSCI-RM-Mixed). Their predictive capability was compared by means of R2 values in the same subrogated of surgical complexity as in the Mirza index validation: intraoperative bleeding and duration of surgery. Sensitivity and specificity were evaluated using ROC curves and AUC analysis. The external validity was also examined by evaluating its predictive capability in another multicenter ASD database of comparable patients in the United States. Results At the time of the study, the database included 1,325 patients. Four hundred seventy-five patients were eligible for the study, having been treated surgically using a posterior approach only (52.2 years standard deviation 20; 77.7% women; 85.4% American Society of Anesthesiologists I/II). Fifty-one international experts participated in the Delphi consensus process. The surgical variables selected by consensus and included in the equation were divided into actions and factors. Actions selected were number of fused segments, decompressions, interbody fusions, and cemented levels; number and type of posterior osteotomies; and use of pelvic fixation. The factors included were implant density, revision surgery, and team experience. ADSCI-RM-Mixed (regression model with Delphi formula interactions) provided the best estimates and predictive value, well above Mirza's invasiveness index. The ADSCI-RM-Mixed, with greater AUCs (>0.70), was also the most sensitive and specific for both of the dependent variables studied and for complication prediction. ADSCI-RM-Mixed obtained also the highest R2 value in the validation cohort in predicting blood loss (R2=0.34) and surgical time (R2=0.26) with effect sizes similar to those for the derivation cohort. Conclusions The ADSCI is the first tool to be specifically developed for the preoperative assessment of the complexity of ASD surgery. This study confirms its validity, specificity, and sensitivity, and shows that it has greater predictive capability than the more generic Mirza invasiveness index. The ADSCI should be useful for quantitatively estimating the increased risk associated with more invasive surgery and adjusting for surgical case-mix when making safety comparisons in ASDS.

In vitro ischemia models are designed to study various aspects of hypo-perfusion, focusing on the consequences of acute events under body temperature. Cold ischemia is less investigated even though the beneficial effects of cooling is expected. The aim of the present work was to develop a device modeling cold and warm ischemia in vitro. Oxygen-glucose deprivation was applied with continuous nitrogen flow and glucose-free cell culture media to mimic ischemia. The temperature in both chambers were independently set between 4 and 37 °C. Samples were placed inside for the ischemic period, followed by a reperfusion stage under standard cell culture conditions. We tested rat calvaria bone pieces undergoing 1, 7, 12 and 24 h of ischemia at 4 and 37 °C. After 24 h of reperfusion, cell number was measured with a tetrazolium cell viability assay. One hour of warm ischemia paradoxically increased the post-reperfusion cell count, while cold-ischemia had an opposite effect. After 7 h of warm ischemia the cells were already unable to recover, while under cold ischemia 60% of the cells were still functioning. After 12 h of cold ischemia 50% of the cells were still be able to recover, while at 24 h even the low temperature was unable to keep the cells alive. The markedly different effect of warm and cold ischemia suggests that this newly designed system is capable of reliable and reproducible modeling of ischemic conditions. Moreover, it also enables deeper investigations in the pathophysiology of cold ischemia at cellular and tissue level.

Short-segment pedicle screw instrumentation constructs for the treatment of thoracolumbar fractures gained popularity in the 1980s. The load-sharing classification (LSC) is a straightforward way to describe the extent of bony comminution, amount of fracture displacement, and amount of correction of kyphotic deformity in a spinal fracture. There are no studies evaluating the relevance of fracture comminution/traumatic kyphosis on the long-term radiologic outcome of burst fractures treated by short-segment instrumentation with screw insertion in the fractured level.To evaluate the efficacy of the six-screw construct in the treatment of thoracolumbar junction burst fractures and the influence of the LSC score on the 2-year radiologic outcome.Case series of consecutive patients of a single university hospital.Consecutive patients from one university hospital with nonosteoporotic thoracolumbar burst fractures.Being a radiology-based study, the outcome measures are radiologic parameters (regional kyphosis [RK], local kyphosis, and thoracolumbar kyphosis [TLK]) that evaluate the degree and loss of correction.Retrospective analysis of all consecutive patients with nonosteoporotic thoracolumbar burst fractures managed with a six-screw construct in a single university hospital, with more than 2 years' postoperative follow-up.Eighty-six patients met the inclusion criteria, and 72 (83.7%) with available data were ultimately included in the study. The sample included 53 men and 19 women, with a mean (standard deviation [SD]) age of 35.6 years (14.4 years) at the time of surgery. Mean LSC score was 6.3 (SD 1.6, range 3-9). Forty-four of 62 (70.9) fractures had a score greater than 6. Mean (SD) RK and TLK deteriorated significantly during the first 6 months of follow-up: 2.90° (4.54°) p=.005 and 2.78° (6.45°) p=.069, respectively. Surgical correction correlated significantly (r=0.521, p.0001) with the time elapsed until surgery. Loss of surgical correction (postoperative to 6-month RK and TLK increase) correlated significantly with the LSC score (r=0.57, p=.004; r=0.51, p=.022, respectively). Further surgery because of correction loss was not required in any case.The six-screw construct is effective for treating thoracolumbar junction burst fractures. The medium-to-long-term loss of correction is affected by the amount of bony comminution of the fracture, objectified through the LSC score.

Schmallenberg virus (SBV) has emerged in summer-autumn 2011 in north-western Europe. Since then, SBV has been continuously spreading over Europe, including Austria, where antibodies to SBV, as well as SBV genome, were first detected in autumn 2012. This study was performed to demonstrate the dynamics of SBV spread within Austria, after its probable first introduction in summer 2012. True seroprevalence estimates for cattle and small ruminates were calculated to demonstrate temporal and regional differences of infection. Furthermore, the probability of SBV genome detection in foetal tissues of aborted or stillborn cattle and small ruminants as well as in allantoic fluid samples from cows with early foetal losses was retrospectively assessed. SBV first reached Austria most likely in July-August 2012, as indicated by retrospective detection of SBV antibodies and SBV genome in archived samples. From August to October 2012, a rapid increase in seroprevalence to over 98% in cattle and a contemporaneous peak in the detection of SBV genome in foetal tissues and allantoic fluid samples was noted, indicating widespread acute infections. Notably, foetal malformations were absent in RT-qPCR positive foetuses at this time of the epidemic. SBV spread within Austrian cattle reached a plateau phase as early as October 2012, without significant regional differences in SBV seroprevalence (98.4-100%). Estimated true seroprevalences among small ruminates were comparatively lower than in cattle and regionally different (58.3-95.6% in October 2012), potentially indicating an eastward spread of the infection, as well as different infection dynamics between cattle and small ruminants. Additionally, the probability of SBV genome detection over time differed significantly between small ruminant and cattle samples subjected to RT-qPCR testing.

A potential relationship between postoperative urinary tract infection (UTI) and surgical site infection (SSI) following posterior spinal fusion and instrumentation (PSFI) was investigated. A retrospective review was performed of prospectively collected demographic, clinical and microbiological data of 466 consecutive patients (median age, 53.7 years (interquartile range (IQR) 33.8–65.6); 58.6% women) undergoing PSFI to identify those with UTI in the first 4 weeks and SSI in the first 12 weeks after PSFI. Overall, 40.8% had an American Society of Anesthesiologists score of >2, and 49.8% had undergone fusion of more than three segments. Eighty-nine patients had UTI, 54 had SSI, and 22 had both conditions. In nine of the 22 (38%) cases, the two infections were caused by the same microorganism. The urinary tract was the probable source of SSI by Gram-negative bacteria in 38% (8/21) of cases. On multivariate analysis, UTI (OR 3.1, 95% CI 1.6–6.1; P 0.001) and instrumentation of more than three segments (OR 2.7, 95% CI 1.1–6.3; P 0.024) were statistically associated with SSI. Patients receiving ciprofloxacin for UTI had higher microbial resistance rates to fluoroquinolones at SSIs (46.13%) than those without ciprofloxacin (21.9%), although the difference did not reach statistical significance (p 0.1). In our series, UTI was significantly associated with SSI after PSFI. On the basis of our results, we conclude that further efforts to reduce the incidence of postoperative UTI and provide adequate empirical antibiotic therapy that avoids quinolones whenever possible may help to reduce SSI rates and potential microbial resistance.

Resumen Introduccion Mas de un 50% de padres y/o pacientes utilizan Internet para informarse sobre aspectos de la escoliosis idiopatica. Material y metodos En 5 buscadores populares (Google, Yahoo, Bing, Lycos, Ask) se introdujo el termino de busqueda «escoliosis» y los primeros 20 resultados de cada buscador fueron utilizados para el estudio. Tras rechazar las duplicidades, archivos de videos o imagen, se obtuvo una lista de 25 webs, adecuadas para el analisis. La calidad se evaluo segun 3 escalas: DISCERN (calidad de la informacion medica; rango de menor a mayor calidad es de 15 a 80), HONcode (criterios de acreditacion de calidad de paginas web; rango de de menor a mayor es de 15 a 0), y grado de idoneidad de la informacion para padres y pacientes con escoliosis idiopatica (rango de menor a mayor es de 0 a 9). Resultados DISCERN: media 38 (DE = 10,48); el 24% de las paginas superaba el percentil 75 (> 45). HONcode: media 6,9 (DE = 1,8); el 28% de las paginas superaba el percentil 75 ( 5). Conclusiones En terminos generales la calidad de la informacion es aceptable, pero muy pocas paginas pueden considerarse idoneas para padres y pacientes con escoliosis idiopatica.

BACKGROUND CONTEXT Spinal fusion is a widely used surgical technique for a great variety of spine pathologies. Spinal fusion using the patient's iliac crest is the standard surgical technique, although it is associated with a relevant percentage of failures and local morbidity of the bone donor area. PURPOSE The main objective of this clinical trial was to evaluate the feasibility, safety, and efficacy of implantation of a scaffold of heterologous human cancellous bone tissue seeded with autologous bone marrow mesenchymal cells expanded ex vivo (XCEL-MT-OSTEO-ALPHA) and to compare the resulting intervertebral fusion as evaluated by radiography and computed tomography (CT) with that obtained in patients who received autologous iliac crest graft. STUDY DESIGN/SETTING Multicenter, prospective, open-label, randomized, parallel and single-dose phase I-II study (EudraCT No.2010-023999-12; NCT01552707). PATIENT SAMPLE Sixty-five patients from 5 centers (mean age, 61.05 years; 65.6% female) with degenerative spondylolisthesis (79.4%) and/or disc disease at L4-L5. OUTCOME MEASURES Adverse events were recorded and fusion was assessed by radiography (3, 6, and 12 months) and CT (6 and 12 months). Bone fusion status was evaluated according to previously established qualitative criteria by a radiologist who was blind to treatment allocation. METHODS Patients underwent instrumented circumferential fusion at L4-L5; transforaminal lumbar interbody fusion (TLIF) was performed using an intersomatic cage filled with autologous iliac crest graft, and intertransverse fusion consisted of local bone graft on the TLIF side and randomly assigned XCEL-MT-OSTEO-ALPHA (Group A, treatment) or autologous iliac crest graft (Group B, control) on the contralateral side.Patients underwent follow-up for 1 year. RESULTS Groups A and B comprised 31 and 34 patients, respectively. There were no significant differences in preoperative variables between groups, and no serious adverse reactions were associated with the product. Compared with controls the treatment group showed a significantly higher rate of intertransverse fusion as determined by radiography at 3 (85.7% vs 56.3%), 6 (81.5% vs 48.3%), and 12 months (96.3% vs 51.7%) and by CT at 6 months (96.3% vs 54.8%). One year after surgery the intertransverse fusion rate was higher in the treatment than the control group (86.2% vs 66.7%), although this difference was not significant. CONCLUSIONS XCEL-MT-OSTEO-ALPHA is a viable and safe product for use in lumbar fusion surgery. Radiological fusion rates in the area in which the product was applied were significantly higher than those obtained with autologous iliac crest graft. FDA DEVICE/DRUG STATUS XCEL-MT-OSTEO-ALPHA (Not approved for this indication)

Background Approximately 50% of brain metastases originate from non–small-cell lung cancer. The median survival of patients with brain metastases is 1 month without treatment. Novel immunotherapeutic strategies, such as those targeting the programmed death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) axis, are promising in patients with advanced systemic disease but are often preferentially administered to patients with tumors showing PD-L1 positivity. Patients and Methods Surgically resected paired primary lung adenocarcinoma and brain metastasis samples of 61 patients were analyzed. We compared the paired samples regarding the amount of peritumoral and stromal mononuclear infiltration, PD-L1 expression of tumor and immune cells, and PD-1 expression of immune cells. We investigated the effect of radiotherapy, chemotherapy, and steroid therapy on PD-L1 expression in brain metastases. Results There was significant positive correlation regarding the PD-L1 expression of tumor cells between the paired primary lung adenocarcinoma and brain metastatic samples with the use of different cutoff levels (1%, 5%, 50%). We found no impact of chemotherapy or steroid therapy on the changes of PD-L1 expression of tumor cells between the 2 sites. There is no or only limited concordance of the proportion of PD-1– or PD-L1–positive tumor-associated immune cells between the paired tumor samples, which suggests that brain metastases develop their own immune environment. Conclusion We observed a strong correlation of PD-L1 positive tumor cells between primary lung adenocarcinoma cases and their corresponding brain metastases, which is not significantly influenced by chemotherapy or steroid therapy.

Multipotent human adipose tissue mesenchymal stromal cells (hAMSCs) are promising therapy vehicles with tumor-homing capacity that can be easily modified to deliver cytotoxicity activating systems in the proximity of tumors. In a previous work, we observed that hAMSCs are very effective delivering cytotoxicity to glioma tumors. However, these results were difficult to reconcile with the relatively few hAMSCs surviving implantation. We use a bioluminescence imaging (BLI) platform to analyze the behavior of bioluminescent hAMSCs expressing HSV-tTK in a U87 glioma model and gain insight into the therapeutic mechanisms. Tumor-implanted hAMSCs express the endothelial marker PECAM1(CD31), integrate in tumor vessels and associate with CD133-expressing glioma stem cells (GSC). Inhibition of endothelial lineage differentiation in hAMSCs by Notch1 shRNA had no effect on their tumor homing and growth-promoting capacity but abolished the association of hAMSCs with tumor vessels and CD133+ tumor cells and significantly reduced their tumor-killing capacity. The current strategy allowed the study of tumor/stroma interactions, showed that tumor promotion and tumor-killing capacities of hAMSCs are based on different mechanisms. Our data strongly suggest that the therapeutic effectiveness of hAMSCs results from their association with special tumor vascular structures that also contain GSCs.

Aujeszky's disease (AD), caused by Suid herpesvirus type 1 (SuHV-1), is an economically important disease in domestic swine. Thus, rigorous control programmes have been implemented and consecutively AD in domestic swine was successfully eradicated in many countries, including Austria. However, SuHV-1 continues to thrive in wild boar populations, as indicated by high seroprevalences in a number of European countries and by occasional cases of AD in hunting dogs. For the first time, SuHV-1 was detected in Austrian wild boar and a molecular characterization of SuHV-1 isolated from wild boar and hunting dogs was performed. Results of preliminary serological analyses suggest a regional SuHV-1 seroprevalence of over 30% in free-living and almost 70% in fenced wild boar from Eastern Austria. Molecular typing of Austrian SuHV-1 isolates of wild boar origin revealed the presence of two genetically distinct variants of SuHV-1, both capable of infecting dogs that have been exposed to infected wild boar during hunting.

Introduccion El cuestionario de la Scoliosis Research Society (SRS-22) es un instrumento valido para valorar la calidad de vida en la escoliosis idiopatica. No obstante, la correlacion entre las puntuaciones del cuestionario y el valor angular de la curva escoliotica es poco relevante. Otros instrumentos de medida de la salud percibida han mostrado mejores correlaciones con el angulo de Cobb. El objetivo del estudio es medir la relacion del SRS-22 con la magnitud de la escoliosis y valorar si esta relacion puede mejorar al anadir otras dimensiones medidas por otros cuestionarios. Material y metodo Se estudiaron 101 pacientes con escoliosis que completaron los cuestionarios SRS-22 y Walter Reed Visual Assessment Scale (WRVAS), un cuestionario de escalas iconicas que mide la deformidad percibida. El analisis se realizo mediante regresion multiple para calcular el coeficiente de determinacion (r2), con el angulo de Cobb como variable dependiente. Tambien se estudio la consistencia interna del instrumento, basico y modificado. Resultados El cuestionario SRS-22 explico el 17% de la varianza (r2=0,17, p

El objetivo del tratamiento quirurgico para la esco-liosis, cifosis y otro tipo de deformidades del raquis esla fusion de las vertebras para que la columna verte-bral no pueda curvarse. Se colocan implantes metali-cos (barras, tornillos, alambres, placas, etc.), paramantener el raquis mientras las vertebras se fusionan.La artrodesis vertebral se potencia con injerto (autoge-nico y/o alogenico) de hueso. El abordaje quirurgicopuede ser posterior, anterior o combinacion de ambos.La cirugia toracoscopica se puede utilizar en el abor-daje anterior del raquis dorsal.La cirugia correctora del raquis en pediatria y adultoses un procedimiento prolongado (en general mas de 4horas), tiene las complicaciones potenciales de la ciru-gia mayor (hemorragia grave, hipotermia, infeccion,embolismo graso o aereo, hipotension arterial, etc.)

Parathyroid hormone receptor 2 (PTH2R) and its ligand, tuberoinfundibular peptide of 39 residues (TIP39) constitute a neuromodulator system implicated in endocrine and nociceptive regulation. We now describe the presence and distribution of the PTH2R and TIP39 in the brain of primates using a range of tissues and ages from macaque and human brain. In situ hybridization histochemistry of TIP39 mRNA, studied in young macaque brain, due to its possible decline beyond late postnatal ages, was present only in the thalamic subparafascicular area and the pontine medial paralemniscal nucleus. In contrast, in situ hybridization histochemistry in macaque identified high levels of PTH2R expression in the central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular and periventricular nuclei, medial geniculate, and the pontine tegmentum. PTH2R mRNA was also detected in several human brain areas by RT-PCR. The distribution of PTH2R-immunoreactive fibers in human, determined by immunocytochemistry, was similar to that in rodents, including dense fiber networks in the medial preoptic area, hypothalamic paraventricular, periventricular and infundibular (arcuate) nuclei, lateral hypothalamic area, median eminence, thalamic paraventricular nucleus, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, sensory trigeminal nuclei, medullary dorsal reticular nucleus, and dorsal horn of the spinal cord. Co-localization suggested that PTH2R fibers are glutamatergic, and that TIP39 may directly influence hypophysiotropic somatostatin containing and indirectly influence corticotropin releasing-hormone containing neurons. The results demonstrate that TIP39 and the PTH2R are expressed in the brain of primates in locations that suggest involvement in regulation of fear, anxiety, reproductive behaviors, release of pituitary hormones, and nociception.

The pathological findings in nine cases of pneumonia associated with infection by felid herpesvirus-1 (FeHV-1) are presented. The animals affected were five kittens, two subadult cats and two adult cats. The microscopical changes included fibrinonecrotic pneumonia and severe necrosis of the bronchial and bronchiolar epithelium. FeHV-1 antigen was detected immunohistochemically in pneumocytes, alveolar macrophages and necrotic bronchial and bronchiolar epithelial cells. In the youngest kitten viral antigen was also found in the liver. FeHV-1 infection should therefore be considered as a differential diagnosis in cats with fibrinonecrotic pneumonia and demonstration of viral antigen by immunohistochemistry is a useful diagnostic procedure in such cases.

Tuberoinfundibular peptide of 39 residues (TIP39) was identified as the endogenous ligand of parathyroid hormone 2 receptor. We have recently demonstrated that TIP39 expression in adult rat brain is confined to the subparafascicular area of the thalamus with a few cells extending laterally into the posterior intralaminar thalamic nucleus (PIL), and the medial paralemniscal nucleus (MPL) in the lateral pontomesencephalic tegmentum. During postnatal development, TIP39 expression increases until postnatal day 33 (PND-33), then decreases, and almost completely disappears by PND-125. Here, we report the expression of TIP39 during early brain development. TIP39-immunoreactive (TIP39-ir) neurons in the subparafascicular area first appeared at PND-1. In contrast, TIP39-ir neurons were detectable in the MPL at embryonic day 14.5 (ED-14.5), and the intensity of their labeling increased thereafter. We also identified TIP39-ir neurons between ED-16.5 and PND-5 in two additional brain areas, the PIL and the amygdalo-hippocampal transitional zone (AHi). We confirmed the specificity of TIP39 immunolabeling by demonstrating TIP39 mRNA using in situ hybridization histochemistry. In the PIL, TIP39 neurons are located medial to the CGRP group as demonstrated by double immunolabeling. All TIP39-ir neurons in the AHi and most TIP39-ir neurons in the PIL disappear during early postnatal development. The adult pattern of TIP39-ir fibers emerge during postnatal development. However, fibers emanating from PIL can be followed in the supraoptic decussations towards the hypothalamus at ED-18.5. These TIP39-ir fibers disappear by PND-1. The complex pattern of TIP39 expression during early brain development suggests the involvement of TIP39 in transient functions during ontogeny.

Tissue levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been determined in 16 regions and nuclei from human brains, using liquid chromatography/in-line mass spectrometry. Measurements in brain samples stored at -80 degrees C for 2 months to 13 years indicated that endocannabinoids were stable under such conditions. In contrast, the postmortal delay had a strong effect on brain endocannabinoid levels, as documented in brain samples microdissected and frozen 1-6 h postmortem, and in neurosurgical samples 0, 5, 30, 60, 180 and 360 min after their removal from the brain. The tissue levels of AEA increased continuously and in a region-dependent manner from 1 h after death, increasing about sevenfold by 6 h postmortem. In contrast, concentrations of 2-AG, which were 10-100 times higher in human brain regions than those of AEA, rapidly declined: within the first hour, 2-AG levels dropped to 25-35% of the initial ('0 min') value, thereafter they remained relatively stable. As analyzed in samples removed 1-1.5 h postmortem, AEA levels ranged from a high of 96.3 fmol/mg tissue in the nucleus accumbens to a low of 25.0 fmol/mg in the cerebellum. 2-AG levels varied eightfold, from 8.6 pmol/mg in the lateral hypothalamus to 1.1 pmol/mg in the nucleus accumbens. Relative levels of AEA and 2-AG varied from region to region, with the 2-AG:AEA ratio being high in the sensory spinal trigeminal nucleus (140:1), the spinal dorsal horn (136:1) and the lateral hypothalamus (98:1) and low in the nucleus accumbens (16:1) and the striatum (31:1). The results highlight the pitfall of analyzing endocannabinoid content in brain samples of variable postmortal delay, and document differential distribution of the two main endocannabinoids in the human brain.

A combined strategy using bioluminescence imaging, bone densitometry and histology was used to analyze the bone regeneration capacity of human bone marrow (hBMSC) and adipose tissue (hAMSC) mesenchymal stem cells, seeded in an osteoconductive arginine-glycine-aspartate (RGD) crosslinked hydrogel scaffold, implanted in a mouse calvarial bone defect. We show that firefly luciferase labeled stem cells can be monitored in vivo through a prolonged 90 days period, during which hBMSCs survive better than hAMSCs and that the density of scaffold bearing defects increased significantly more than that of defects without scaffolds. (c) 2007 Elsevier Ltd. All rights reserved.

Post-surgical acute cholecystitis has been described mainly as a complication of major abdominal or thoracic surgery sometimes associated with musculoskeletal surgery. In spine surgery it has been related to large-scale procedures such as the correction of deformities in adults. The most frequently mentioned risk factors are hydric restriction, fever, hemolytic phenomena, multiple blood transfusions, nutritional disorders, certain drugs (anesthetics, codeine. atropine, meperidine, morphine) and hemodynamic alterations. The risk is especially high when several of the factors above co-occur in a single patient subjected to a physically stressful situation like surgery. Diagnosis of acute postoperative cholecystitis is often challenging since the condition is often marked by the initial surgical procedure. Symptoms like fever, leucocytosis and abdominal pain after a favorable immediate post-op should put us on guard. Sonographic confirmation and the quick implementation of appropriate treatment are the only way of reducing the high death toll of this complication.

Analytical methods have been developed that allow for the determination of antiphlogistics, lipid regulators, the antiepileptic carbamazepine, cytostatic agents, the psychiatric drug diazepam and iodinated contrast media (ICM) as well as two major polycyclic musk fragrances HHCB (galaxolide) and AHTN (tonalide) in activated and digested sludge. The procedures consist of ultrasonic solvent extraction (USE) using methanol/acetone or pressurized liquid extraction (PLE) using 100% methanol. Clean-up was performed with C18ec material and silica gel followed by LC tandem MS (electrospray or atmospheric pressure chemical ionization) detection for pharmaceuticals and iodinated contrast media as well as GC/MS in the SIM mode for musk fragrances. Absolute recoveries from spiked activated sludge in general ranged from 88+/-4 to 119+/-20% for ICM and were 78+/-15 and 87+/-10% for the AHTN and HHCB, respectively. For the pharmaceuticals, absolute recoveries in activated sludge ranged between 43 and 78%. Subsequently, compensation of losses was carried out by using surrogate standards (acidic pharmaceuticals: fenoprop, neutral pharmaceuticals: dihydro-carbamazepine, musk fragrances: AHTN-D3). With one exception the recoveries were also adequate in digested sludge ranging from 43% to 120%.

Scoliosis is defined as lateral curvature of the spine with vertebral rotation, meaning that it is a 3dimensional deformity. Scoliosis leads to thoracic deformity if the spinal alterations occur in that zone (Figure 1). Scoliosis is classified as either idiopathic or secondary, regardless of what part of the spine is affected. Idiopathic scoliosis is currently thought almost certainly to arise from multiple factors. The most common causes are disordered development of the central nervous system or genetically determined familial disorders.1,2 The prevalence of idiopathic scoliosis in the population at risk (individuals between 10 and 16 years of age) is approximately 2% to 3%. As the magnitude of the curve increases, the incidence decreases, and it is estimated that the percentage of patients who require surgery does not exceed 0.1%.3 The decision of how to treat patients with spinal deformity should be based on an understanding of the natural history of the process. Any decisions taken should have as their objective the modification of that natural history. The main factors influencing therapeutic decisions are the type and magnitude of the curve, age, skeletal maturity, and sex. The most important factors at the time of diagnosis are age and curve magnitude.4,5 Age is especially important because it is related to elasticity3 and on elasticity will depend the possibility of reducing the angle of curvature and the patient’s muscular response to it. Respiratory Function and Deformity