Longevity of Resin Composite and Amalgam Posterior Restorations: A Systematic Review.

OBJECTIVES: The objective of this systematic review was to compare the longevity of direct amalgam and composite resin restorations, in posterior teeth, through clinical, prospective or retrospective studies, with at least 5 years of follow-up. MATERIALS AND METHODS: Studies published in the last 15 years (from 2006 to 2021) were collected using the PubMed and Medline databases. RESULTS: The search strategy associated with the established inclusion and exclusion criteria resulted in a total of 17 articles. Factors related to failures in the performance of restorations were analyzed together with the clinical performance results of each material over the years of study, according to the methodology of each article. CONCLUSIONS: Regardless of the restorative material, the successful results over more than 5 years are due much more to the correct application of the technique, the operator's skill/knowledge and factors related to the patient, such as the type of tooth, number of faces involved in the restoration and oral hygiene.

Change in opioid and analgesic use for headaches after aneurysmal subarachnoid hemorrhage over time.

BACKGROUND: Severe headache, a hallmark of aneurysmal subarachnoid hemorrhage (aSAH), affects up to 90% of patients during hospitalization. Opioids remain the guideline recommended mainstay of acute therapy despite their significant side effects and potential for tolerance and addiction. We evaluated time trends in opioid prescriptions, hypothesizing a decline with increasing recognition of the opioid crisis. METHODS: We performed a retrospective review of patients with aSAH admitted to a single tertiary care center between 2012 and 2019 and included patients with Hunt-Hess-Grade≤3 who were able to verbalize pain scores. Collected variables included mean and maximum daily headache scores, aneurysm treatment modality, and daily analgesic medication doses. RESULTS: Of 340 patients with aSAH, 114 (86 from 2012-2016 and 28 from 2017-2019) were included. Of the included patients, 86/114 (75.4%) were female. Patients in the 2012-2016 had a median age of 55 compared to 63 in the 2017-2019 group (P=0.02). Otherwise, there was no significant difference in demographic data including time in hospital, treatment option utilized, or aneurysm characteristics. Maximal daily headache score ranged from 6 to 8 for 2012-2016 and 5 to 8 for 2017-2019 cohorts. Average oral morphine equivalents (in mg) administered during hospitalization were similar between groups (2012-2016: 251±345 95% CI [178,323]; 2017-2019: 207±237 95% CI [119,295]; P=0.319). When prescribed, doses of opioids provided at discharge were less in the more recent group (2012-2016: 84.4±78.9 95% CI [57.5, 111]; 2017-2019: 38.1±20.2 95% CI [33.7, 42.5]; P=0.004) CONCLUSION: Despite recognition of important drawbacks of opioid use for headache control, and efforts to reduce opioid use during hospitalization, we found that utilization during hospitalization for SAH did not decrease over time. Maximal headache scores remained similar in the studied time periods, indicative of insufficient pain relief. This points out a pressing need to further investigate alternative opioid and narcotic sparing strategies for patients with SAH.

Identification of alterations associated with age in the clustering structure of functional brain networks.

Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer.

BACKGROUND: Combination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC. PATIENTS AND METHODS: Patients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations. RESULTS: A total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified. CONCLUSION: The primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported. TRIAL IDENTIFIER: Clinicaltrials.gov NCT01750281.

A Statistical Method to Distinguish Functional Brain Networks.

One major problem in neuroscience is the comparison of functional brain networks of different populations, e.g., distinguishing the networks of controls and patients. Traditional algorithms are based on search for isomorphism between networks, assuming that they are deterministic. However, biological networks present randomness that cannot be well modeled by those algorithms. For instance, functional brain networks of distinct subjects of the same population can be different due to individual characteristics. Moreover, networks of subjects from different populations can be generated through the same stochastic process. Thus, a better hypothesis is that networks are generated by random processes. In this case, subjects from the same group are samples from the same random process, whereas subjects from different groups are generated by distinct processes. Using this idea, we developed a statistical test called ANOGVA to test whether two or more populations of graphs are generated by the same random graph model. Our simulations' results demonstrate that we can precisely control the rate of false positives and that the test is powerful to discriminate random graphs generated by different models and parameters. The method also showed to be robust for unbalanced data. As an example, we applied ANOGVA to an fMRI dataset composed of controls and patients diagnosed with autism or Asperger. ANOGVA identified the cerebellar functional sub-network as statistically different between controls and autism (p < 0.001).

Organ donation protocols.

Organ transplantation improves survival and quality of life in patients with end-organ failure. Waiting lists continue to grow across the world despite remarkable advances in the transplantation process, from the creation of public engagement campaigns to the development of critical pathways for the timely identification, referral, approach, and treatment of the potential organ donor. The pathophysiology of dying triggers systemic changes that are intimately related to organ viability. The intensive care management of the potential organ donor optimizes organ function and improves the donation yield, representing a significant step in reducing the mismatch between organ supply and demand. Different beliefs and cultures reflect diverse legislations and donation practices amongst different countries, creating a challenge to standardized practices. Maintaining public trust is necessary for continued progress in organ donation and transplantation, hence the urge for a joint effort in creating uniform protocols that ensure transparent practices within the medical community.

ANOCVA in R: A Software to Compare Clusters between Groups and Its Application to the Study of Autism Spectrum Disorder.

Understanding how brain activities cluster can help in the diagnosis of neuropsychological disorders. Thus, it is important to be able to identify alterations in the clustering structure of functional brain networks. Here, we provide an R implementation of Analysis of Cluster Variability (ANOCVA), which statistically tests (1) whether a set of brain regions of interest (ROI) are equally clustered between two or more populations and (2) whether the contribution of each ROI to the differences in clustering is significant. To illustrate the usefulness of our method and software, we apply the R package in a large functional magnetic resonance imaging (fMRI) dataset composed of 896 individuals (529 controls and 285 diagnosed with ASD-autism spectrum disorder) collected by the ABIDE (The Autism Brain Imaging Data Exchange) Consortium. Our analysis show that the clustering structure of controls and ASD subjects are different (p < 0.001) and that specific brain regions distributed in the frontotemporal, sensorimotor, visual, cerebellar, and brainstem systems significantly contributed (p < 0.05) to this differential clustering. These findings suggest an atypical organization of domain-specific function brain modules in ASD.

The opinion of children and their parents about four different types of dental restorations in a public health service in Brazil.

AIM: To investigate the opinion of children and their parents of four different types of restoration placed in primary molars. METHODS: A mixed method study in which both children and their parents were involved. In the quantitative study, children and parents gave their opinion using a face scale about four different types of restoration immediately after placement, evaluating how satisfied they were. In the qualitative part, children and their parents were interviewed to report their preference among the four types of restoration using dental models and photos. RESULTS: In the quantitative study, 1045 restorations were placed, being conventional restorations (198 with amalgam and 205 with composite resin) and atraumatic interventions [408 with glass ionomer: ART, atraumatic restorative treatment, and 234 with preformed metal crowns (PMCs): Hall technique]. Almost all participants (children and parents) gave a positive opinion (from 94.9 to 100%) on the four types of restoration placed in the children's teeth. There was no statistical significant difference in opinion in terms of acceptance of the four types of restoration placed (Chi square test, p value > 0.05). In the qualitative approach, 18 children and 11 parents were interviewed. If they could choose, children (16/18) preferred the PMCs, while parents (10/11) preferred aesthetic materials such as composite resin and glass ionomer cement. CONCLUSIONS: A high degree of satisfaction was observed with children and their parents in the four types of restoration after placement. However, if it could be chosen in advance, children prefer the PMCs and parents a tooth-coloured material.

Morphological and molecular characterization of Cladosporium cladosporioides species complex causing pecan tree leaf spot.

The objective of this study was to characterize species of the Cladosporium cladosporioides complex isolated from pecan trees (Carya illinoinensis) with symptoms of leaf spot, based on morphological and molecular approaches. Morphological attributes were assessed using monosporic cultures on potato dextrose agar medium, which were examined for mycelial growth, sporulation, color, and conidia and ramoconidia size. Molecular characterization comprised isolation of DNA and subsequent amplification of the translation elongation factor 1α (TEF-1α) region. Three species of the C. cladosporioides complex were identified: C. cladosporioides, Cladosporium pseudocladosporioides, and Cladosporium subuliforme. Sporulation was the most important characteristic differentiating species of this genus. However, morphological features must be considered together with molecular analysis, as certain characters are indistinguishable between species. TEF-1αcan be effectively used to identify and group isolates belonging to the C. cladosporioides complex. The present study provides an important example of a methodology to ascertain similarity between isolates of this complex causing leaf spot in pecan trees, which should facilitate future pathogenicity studies.

Imaging of rare medullary adrenal tumours in adults.

Although adrenal medullary tumours are rare, they have important clinical implications. They form a heterogeneous group of tumours, ranging from benign, non-secretory, incidental masses to hormonally active tumours presenting acutely, or malignant tumours with disseminated disease and a poor prognosis. Increasingly, benign masses are incidentally detected due to the widespread use of imaging and routine medical check-ups. This review aims to illustrate the multimodality imaging appearances of rare adrenal medullary tumours, excluding the more common phaeochromocytomas, with clues to the diagnosis and to summarise relevant epidemiological and clinical data. Careful correlation of clinical presentation, hormone profile, and various imaging techniques narrow the differential diagnosis. Image-guided percutaneous adrenal biopsy can provide a definitive diagnosis, allowing for conservative management in selected cases. A close collaboration between the radiologist, endocrinologist, and surgeon is of the utmost importance in the management of these tumours.

The Effects of Forefoot Striking, Increasing Step Rate, and Forward Trunk Lean Running on Trunk and Lower Limb Kinematics and Comfort.

This study aimed to compare the immediate effects of 3 running technique modifications on the ankle, knee, hip and trunk kinematics and on the perceived comfort in healthy runners. The modifications were: forefoot striking pattern (FFOOT); increasing 10% of step rate (10% SR); and increasing forward trunk lean (FTL). 31 healthy runners participated. 3-dimensional lower limb and trunk kinematics were quantified while performing each condition on a treadmill. At initial contact, the FFOOT showed an increase in plantar flexion and knee external rotation, and reduction in knee flexion and adduction. During the stance phase, this condition showed greater peak knee external rotation and less mean and peak dorsiflexion and knee flexion. The 10% SR resulted in less hip flexion at initial contact. During the stance phase this technique showed less mean and peak knee flexion, peak reduction for dorsiflexion, knee abduction, hip flexion and hip adduction. At initial contact and during the stance phase, the FTL caused greater knee adduction and hip flexion. The usual running was the most comfortable technique. The techniques showed different lower limb kinematic modifications; which could potentially reduce knee injury risk. This knowledge is clinically relevant as it can be used to better prescribe techniques in prevention and rehabilitation programs.

First Report of Ilyonectria macrodidyma Associated with Black Foot Disease of Grapevine in Brazil.

Cultivated grapevine (Vitis labrusca and V. vinifera) is of considerable economic importance to the Brazilian fruit industry for both fresh market consumption and for the production of wines, sparkling beverages, and juices. Black foot disease is caused by fungi of the genera Ilyonectria P. Chaverri & C. Salgado (anamorph: Cylindrocarpon Wollew.), Campylocarpon Halleen, Schroers & Crous, and Cylindrocladiella Boesew. In 2012, 4- to 40-year-old grapevines (Vitis spp.) showing reduced vigor, vascular lesions, necrotic root lesions, delayed budding, vine decline, and death were collected from seven locations at Rio Grande do Sul state, Brazil. Fungal isolations were made from root fragments and crown lesions (at least 2 cm above the bottom) on potato dextrose agar (PDA) medium added with 0.5 g L-1 streptomycin sulfate. Eight isolates were obtained and identified on the basis of morphological features and multi-gene analysis (rDNA-ITS, ß-tubulin, and histone H3) as Ilyonectria macrodidyma (Halleen, Schroers & Crous) P. Chaverri & C. Salgado. One representative isolate (Cy5UFSM) was used for more detailed morphological and molecular characterization, and pathogenicity confirmation. When incubated in the dark at 20°C for 7 to 10 days, colonies of felty straw-colored mycelium (3) 4.79 cm diameter on average were observed. No sporodochia or other fruiting bodies were produced on carnation leaf agar (CLA) medium after 30 days. Microconidia that were produced after 5 weeks on spezieller nährstoffarmer agar (SNA) medium with addition of two pieces of 1 cm2 filter paper showed ovoid and ellipsoid shape (6.4 × 3.6 µm) and one-septate macroconidia (17.3 × 4.1 µm). To confirm the species, primer pairs ITS1 and ITS4 (4); Bt2a and Bt2b; and H3-1a and H3-1b (2) were used to amplify the ITS1-5.8S rRNA-ITS2, part of the ß-tubulin and histone H3 genes, respectively. Sequences of these three regions showed 99, 100, and 100% of homology with I. macrodidyma, respectively. To confirm pathogenicity, 4-month-old rooted cuttings of V. labrusca cv. Bordô were inoculated by immersing them in a conidial suspension of the isolate (106 conidia ml-1) for 60 min (1). Thirty days later, inoculation was performed again by drenching the crown with 40 ml of 106 conidia ml-1 suspension to ensure infection of the roots. In the control treatment, plants were inoculated with sterile distilled water. Plants inoculated with I. macrodidyma showed necrosis of the leaf ribs, reduction in root mass, root and crown necrosis, browning of vessels, drying of shoots, and death. I. macrodidyma was re-isolated from the crown necrosis and vascular lesions, confirming Koch's postulates. To our knowledge, this is the first report of I. macrodidyma associated with black foot disease of grapevine in Brazil, which poses considerable threat to the industry unless management options are realized. References: (1) A. Cabral et al. Phytopathol. Mediterr. 51:340, 2012. (2) N. L. Glass et al. Appl. Environ. Microbiol. 61:1323, 1995. (3) R. W. Rayner. A Mycological Colour Chart. Commonwealth Mycological Institute and British Mycological Society, 1970. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.

Hip and knee kinematics are associated with pain and self-reported functional status in males and females with patellofemoral pain.

Altered hip and knee kinematics in the frontal and transverse planes may increase patellofemoral joint stress and contribute to the development of patellofemoral pain. The purpose of this cross-sectional study was to evaluate the association among hip and knee kinematics, pain, and self-reported functional status in males and females with patellofemoral pain. 20 males and 20 females with patellofemoral pain participated in this study. 3-dimensional hip and knee kinematics were quantified while performing a step-down task. A visual analogue scale was used to evaluate usual knee pain. The anterior knee pain scale was used to evaluate the knee functional score. For both groups combined, greater usual pain was associated with greater peak hip adduction, hip internal rotation and knee abduction (r=0.54-0.57, P<0.001). Also, modest to low correlations (r=-0.48 to - 0.37, P=0.03-0.08) were found among hip and knee kinematics and functional score. Stepwise regression revealed that peak hip internal rotation and hip adduction were significant predictors of pain, while peak hip adduction was the only predictor of function. Greater hip adduction, hip internal rotation and knee abduction are associated with higher levels of pain and reduced function in males and females with patellofemoral pain.

First Report of Fusarium sambucinum Associated on Pinus elliottii Seeds in Brazil.

An elevated incidence of the fungal genus Fusarium was ascertained during a health quality analysis of a batch of Pinus elliottii Englm. seeds obtained from the Florestas Institute for Agricultural and Forest Research (Fundação Estadual de Pesquisa Agropecuária [FEPAGRO] Florestas) in Santa Maria (29° 39' 55″ S and 53° 54' 45″ W), state of Rio Grande do Sul, Brazil. This genus comprised about 75% of all fungal genera observed in a blotter test. The fungus was then isolated and purified to perform pathogenicity tests. Healthy seeds of P. elliottii were inoculated by contact with fungal mycelium for 48 h (3). Forty-two days after inoculation, a reduction was observed in the germination potential of the seeds; however, those seeds that germinated developed normally until, as seedlings, they suffered damping-off. Fusarium was isolated from the affected vegetal material by transferring mycelium tips to potato dextrose agar (PDA) medium in petri dishes in order to morphologically identify the species. After 72 h, a tan mycelial pad 5.5 cm in diameter had formed. After transfer to carnation leaf agar (CLA), pale orange sporodochia that formed macroconidia could be observed. The macronidia were relatively short and narrow (40.2 × 4.7 µm), each containing a mean of 5 septa; the apical cell was pointed, while the basal one was foot-shaped (2,4). The chlamydospores formed in clusters, while the conidiogenous cells could be seen on top of monophialides. Primer pairs ITS1 and ITS4, EF1-T and EF1-567R, and ßtub-F and ßtub were employed to amplify the three regions ITS1.8S ITS2, elongation factor - 1α (TEF 1-α), and ß-tubulin, respectively. The sequences of these three regions showed 97, 95, and 99% of similarity with Fusarium sambucinum Fückel, respectively. The pathogen was reinoculated on P. elliottii seeds in order to complete Koch's postulates. The pathogenicity test was repeated with the same conditions described before and the results were confirmed. No occurrence of damping-off was observed in the control seedlings. The inoculated seedlings showed, besides damping-off, a visible reduction in root system expansion as well as reductions in fresh and dry tissue weight. F. sambucinum has already been reported on P. radiata D. Don in New Zealand, causing root rot and dieback (1); however, in Brazil, the present study is, to the best of our knowledge, the first to report the association of this pathogen with P. elliottii. References: (1) M. A. Dick and K. Dobbie. N. Z. Plant Prot. 55:58, 2002. (2) W. Gerlach and H. Nirenberg. The Genus Fusarium - A Pictorial Atlas. Biologische Bundesanstalt für Land - und. Forstwirtschaft, Berlin, 1982. (3) M. Lazarotto et al. Summa Phytopathol. 36:134, 2010. (4) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual, 1st ed. Wiley-Blackwell, Hoboken, NJ, 2006.

Desenvolvimento e Teste Preliminar da Estabilidade de formulações cosméticas acrescidas de extrato comercial de Trichilia catigua Adr. Juss (e) Ptychopetalum olacoides Bentham / Development and Preliminary Stability Testing of cosmetic formulations containing the commercial extract of Trichilia catigua Adr. Juss and Ptychopetalum olacoides Bentham

O presente estdo apresenta etapas de desenvolvimento de emulsões cosméticas, contendo 5% do extrato comercial de Trichilia catigua Adr. Juss (e) Ptychopetalum olacoides Bentham. Desenvolveram-se 14 formulações-teste e avaliou-se a obtenção de emulsões macroscopicamente estáveis, com valores de viscosidade aparente variados, pH compatível com o da pele e características organolépticas adequadas, por meio dos Testes de Estabilidade Preliminar e Acelerada. Estas formulações foram divididas em dois grupos: um com emulsões fluidas e outro com emulsões mais viscosas. Após análise, oito formulações-teste foram consideradas aptas para serem submetidas ao Teste de Estabilidade Preliminar. Após os ensaios, cinco formulações-teste foram selecionadas para o Teste de Estabilidade Acelerada. Os ensaios foram conduzidos em condições de armazenamento, de luminosidade e de temperatura extremas. Ao final do estudo, duas formulações-teste foram consideradas aprovadas por apresentarem os perfis mais estáveis durante o estudo, sendo ambas, emulsões fluidas constituídas de ceras auto-emulsionantes e 0,3% p/p de um polímero natural,e uma delas adicionada também de 2,0% lecitina de soja.

Regional Brazilian diet-induced low birth weight is correlated with changes in renal hemodynamics and glomerular morphometry in adult age.

Number of nephrons, renal hemodynamics, and glomerular morphometry were assessed in rats submitted to a multideficient diet which was developed from a basic regional diet consumed in a Brazilian region of sugarcane cultivation. We evaluated three groups of male Wistar rat offspring: (1) from dams fed a standard diet throughout mating, pregnancy and lactation (control group) and (2) from dams fed the multideficient diet during mating and pregnancy (MalN1 group) or (3) throughout mating, pregnancy, and lactation (MalN2 group). At adult age, the animals were anesthetized to measure mean arterial blood pressure and renal hemodynamics. The MalN1 group, as compared with the control group, showed unaltered body and kidney weights, nephron deficiency, a high mean arterial blood pressure, glomerular hypertrophy, and renal vasoconstriction. The MalN2 group showed the same nephron deficiency and mean arterial blood pressure levels as the MalN1 group. These animals exhibited lower body and kidney weights and no glomerular hypertrophy. In conclusion, the alterations induced by intrauterine malnutrition are compatible with the development of chronic renal failure.

Performance of ultrasound echo decomposition using singular spectrum analysis.

Diagnostic ultrasonography has its well-established role in medicine. Nevertheless, the quantitative characterisation of biological tissues by ultrasound (US) is still a main topic of research. Several parameters have been explored with this purpose, (e.g. attenuation, backscatter coefficient, US speed). More recently, mean scatterer space (MSS) has been proposed as a characterisation parameter. The objective of this work was to investigate the potential of the singular spectrum analysis (SSA) to estimate MSS. This method proposes the reconstruction of the periodic part of the original US signal from where the MSS of the medium can be estimated. SSA is applied to simulated and real backscattered echoes from a phantom and a bovine liver sample. Consistent results were obtained from both Monte-Carlo simulation and real data. They were compared with literature. Presently, precision, accuracy and sensibility of SSA are being investigated.

Molecular analysis of CDKN2 (p16) in gliomas associated with clinical data.

We analyzed alterations in CDKN2 in gliomas from an ethically mixed population and correlated the results with patients clinical data. We screened for methylation at CDKN2 and for microsatellite instability (MSI) and loss of heterozygosity (LOH) in the region 9p21-22 using 4 markers. We found: 3/30 (10%) cases with CDKN2-methylated gliomas; an average of 4% of MSI; and 24.5% of LOH in the region 9p21-22. Methylation of CDKN2 was only detected in patients showing high-grade gliomas with short survival. MSI and LOH in the region 9p21-22 were detected in patients showing high-grade gliomas with short survival and in one patient with a recurrent low-grade astrocytoma grade II who died from the disease after 3 years, indicating that such alterations represent poor prognosis.

Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease.

We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 x 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3), acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear.