Showing papers by "Rambam Health Care Campus published in 2011"

Development of the Crohn's disease digestive damage score, the Lémann score†‡§

Abstract: Crohn's disease (CD) is a chronic progressive destructive disease. Currently available instruments measure disease activity at a specific point in time. An instrument to measure cumulative structural damage to the bowel, which may predict long-term disability, is needed. The aim of this article is to outline the methods to develop an instrument that can measure cumulative bowel damage. The project is being conducted by the International Program to develop New Indexes in Crohn's disease (IPNIC) group. This instrument, called the Crohn's Disease Digestive Damage Score (the Lemann score), should take into account damage location, severity, extent, progression, and reversibility, as measured by diagnostic imaging modalities and the history of surgical resection. It should not be "diagnostic modality driven": for each lesion and location, a modality appropriate for the anatomic site (for example: computed tomography or magnetic resonance imaging enterography, and colonoscopy) will be used. A total of 24 centers from 15 countries will be involved in a cross-sectional study, which will include up to 240 patients with stratification according to disease location and duration. At least 120 additional patients will be included in the study to validate the score. The Lemann score is expected to be able to portray a patient's disease course on a double-axis graph, with time as the x-axis, bowel damage severity as the y-axis, and the slope of the line connecting data points as a measure of disease progression. This instrument could be used to assess the effect of various medical therapies on the progression of bowel damage.

Diagnosis of head-and-neck cancer from exhaled breath

Abstract: Head-and-neck cancer (HNC) is the eighth most common malignancy worldwide. It is often diagnosed late due to a lack of screening methods and overall cure is achieved in <50% of patients. Head-and-neck cancer sufferers often develop a second primary tumour that can affect the entire aero-digestive tract, mostly HNC or lung cancer (LC), making lifelong follow-up necessary. Alveolar breath was collected from 87 volunteers (HNC and LC patients and healthy controls) in a cross-sectional clinical trial. The discriminative power of a tailor-made Nanoscale Artificial Nose (NA-NOSE) based on an array of five gold nanoparticle sensors was tested, using 62 breath samples. The NA-NOSE signals were analysed to detect statistically significant differences between the sub-populations using (i) principal component analysis with ANOVA and Student's t-test and (ii) support vector machines and cross-validation. The identification of NA-NOSE patterns was supported by comparative analysis of the chemical composition of the breath through gas chromatography in conjunction with mass spectrometry (GC–MS), using 40 breath samples. The NA-NOSE could clearly distinguish between (i) HNC patients and healthy controls, (ii) LC patients and healthy controls, and (iii) HNC and LC patients. The GC–MS analysis showed statistically significant differences in the chemical composition of the breath of the three groups. The presented results could lead to the development of a cost-effective, fast, and reliable method for the differential diagnosis of HNC that is based on breath testing with an NA-NOSE, with a future potential as screening tool.

ETV6 mutations in early immature human T cell leukemias

Abstract: Early immature T cell acute lymphoblastic leukemias (T-ALLs) account for ∼5–10% of pediatric T-ALLs and are associated with poor prognosis. However, the genetic defects that drive the biology of these tumors remain largely unknown. In this study, analysis of microarray gene expression signatures in adult T-ALL demonstrated a high prevalence of early immature leukemias and revealed a close relationship between these tumors and myeloid leukemias. Many adult immature T-ALLs harbored mutations in myeloid-specific oncogenes and tumor suppressors including IDH1 , IDH2 , DNMT3A , FLT3 , and NRAS . Moreover, we identified ETV6 mutations as a novel genetic lesion uniquely present in immature adult T-ALL. Our results demonstrate that early immature adult T-ALL represents a heterogeneous category of leukemias characterized by the presence of overlapping myeloid and T-ALL characteristics, and highlight the potential role of ETV6 mutations in these tumors.

Population Genetic Structure in Indian Austroasiatic Speakers: The Role of Landscape Barriers and Sex-Specific Admixture

Abstract: The geographic origin and time of dispersal of Austroasiatic (AA) speakers, presently settled in south and southeast Asia, remains disputed. Two rival hypotheses, both assuming a demic component to the language dispersal, have been proposed. The first of these places the origin of Austroasiatic speakers in southeast Asia with a later dispersal to south Asia during the Neolithic, whereas the second hypothesis advocates pre-Neolithic origins and dispersal of this language family from south Asia. To test the two alternative models, this study combines the analysis of uniparentally inherited markers with 610,000 common single nucleotide polymorphism loci from the nuclear genome. Indian AA speakers have high frequencies of Y chromosome haplogroup O2a; our results show that this haplogroup has significantly higher diversity and coalescent time (17-28 thousand years ago) in southeast Asia, strongly supporting the first of the two hypotheses. Nevertheless, the results of principal component and "structure-like" analyses on autosomal loci also show that the population history of AA speakers in India is more complex, being characterized by two ancestral components-one represented in the pattern of Y chromosomal and EDAR results and the other by mitochondrial DNA diversity and genomic structure. We propose that AA speakers in India today are derived from dispersal from southeast Asia, followed by extensive sex-specific admixture with local Indian populations.

Dynamic suspension culture for scalable expansion of undifferentiated human pluripotent stem cells.

Abstract: Human pluripotent (embryonic or induced) stem cells (hPSCs) have many potential applications, not only for research purposes but also for clinical and industrial uses While culturing these cells as undifferentiated lines, an adherent cell culture based on supportive layers or matrices is most often used However, the use of hPSCs for industrial or clinical applications requires a scalable, reproducible and controlled process Here we present a suspension culture system for undifferentiated hPSCs, based on a serum-free medium supplemented with interleukins and basic fibroblast growth factor, suitable for the mass production of these cells The described system supports a suspension culture of hPSC lines, in both static and dynamic cultures Results showed that hPSCs cultured with the described dynamic method maintained all hPSC features after 20 passages, including stable karyotype and pluripotency, and increased in cell numbers by 25-fold in 10 d Thus, the described suspension method is suitable for large-scale culture of undifferentiated hPSCs

Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure

Abstract: Induced pluripotent stem cells (iPSC) are generated from fully differentiated somatic cells that were reprogrammed into a pluripotent state. Human iPSC which can be obtained from various types of somatic cells such as fibroblasts or keratinocytes can differentiate into cardiomyocytes (iPSC-CM), which exhibit cardiac-like transmembrane action potentials, intracellular Ca2+ transients and contractions. While major features of the excitation-contraction coupling of iPSC-CM have been well-described, very little is known on the ultrastructure of these cardiomyocytes. The ultrastructural features of 31-day-old (post-plating) iPSC-CM generated from human hair follicle keratinocytes (HFKT-iPSC-CM) were analysed by electron microscopy, and compared with those of human embryonic stem-cell-derived cardiomyocytes (hESC-CM). The comparison showed that cardiomyocytes from the two sources share similar proprieties. Specifically, HFKT-iPSC-CM and hESC-CM, displayed ultrastructural features of early and immature phenotype: myofibrils with sarcomeric pattern, large glycogen deposits, lipid droplets, long and slender mitochondria, free ribosomes, rough endoplasmic reticulum, sarcoplasmic reticulum and caveolae. Noteworthy, the SR is less developed in HFKT-iPSC-CM. We also found in both cell types: (1) ‘Ca2+-release units’, which connect the peripheral sarcoplasmic reticulum with plasmalemma; and (2) intercellular junctions, which mimic intercalated disks (desmosomes and fascia adherens). In conclusion, iPSC and hESC differentiate into cardiomyocytes of comparable ultrastructure, thus supporting the notion that iPSC offer a viable option for an autologous cell source for cardiac regenerative therapy.

Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia.

Abstract: Introduction Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. While there is much data about risk factors for severe outcome in the general population, there is less focus on younger group of patients. Therefore, we aimed to detect simple prognostic factors for severe morbidity and mortality in young patients with CAP.

Insights into the Demographic History of African Pygmies from Complete Mitochondrial Genomes

Abstract: Pygmy populations are among the few hunter-gatherers currently living in sub-Saharan Africa and are mainly represented by two groups, Eastern and Western, according to their current geographical distribution. They are scattered across the Central African belt and surrounded by Bantu-speaking farmers, with whom they have complex social and economic interactions. To investigate the demographic history of Pygmy groups, a population approach was applied to the analysis of 205 complete mitochondrial DNA (mtDNA) sequences from ten central African populations. No sharing of maternal lineages was observed between the two Pygmy groups, with haplogroup L1c being characteristic of the Western group but most of Eastern Pygmy lineages falling into subclades of L0a, L2a, and L5. Demographic inferences based on Bayesian coalescent simulations point to an early split among the maternal ancestors of Pygmies and those of Bantu-speaking farmers (;70,000 years ago [ya]). Evidence for population growth in the ancestors of Bantu-speaking farmers has been observed, starting ;65,000 ya, well before the diffusion of Bantu languages. Subsequently, the effective population size of the ancestors of Pygmies remained constant over time and ;27,000 ya, coincident with the Last Glacial Maximum, Eastern and Western Pygmies diverged, with evidence of subsequent migration only among the Western group and the Bantuspeaking farmers. Western Pygmies show signs of a recent bottleneck 4,000–650 ya, coincident with the diffusion of Bantu languages, whereas Eastern Pygmies seem to have experienced a more ancient decrease in population size (20,000–4,000 ya). In conclusion, the results of this first attempt at analyzing complete mtDNA sequences at the population level in subSaharan Africa not only support previous findings but also offer new insights into the demographic history of Pygmy populations, shedding new light on the ancient peopling of the African continent.

Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2.

Abstract: Diabetes mellitus type-2 (DM-2) contributes to atherogenesis by inducing endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In DM-2, the circulating EPC count is low and their functionality is impaired. The mechanisms that underlie this reduced count and impaired functionality are poorly understood. Nitric oxide (NO) is a short-lived signalling molecule that is produced by vascular endothelial cells and participates in the maintenance of vascular tone. NO is also known to participate in other physiological processes, such as cell survival, proliferation, and migration. The bioavailability of NO is reduced in EPCs from DM-2 patients. Interestingly, an inverse relationship exists between the reduction in NO bioavailability in EPCs and the patient's plasma glucose and glycated haemoglobin levels. In addition, NO bioavailability in EPCs correlates with plasma oxidized low-density lipoprotein levels in DM-2. Although this reduction in NO bioavailability could be attributed to oxidative stress in DM-2 patients, it also may be due to impairment of one or more members of the protein signalling cascades that are responsible for NO production. The stimulation of NO production or its signalling cascades in EPCs may increase their numbers and improve their function, thus attenuating endothelium damage, independent of the vasodilatory effects of NO. This review summarizes the metabolic alterations that underlie the molecular mechanisms that may be responsible for EPC decrease and dysfunction in DM-2 with emphasis on the involvement of the NO system.

Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

Abstract: For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala.

Periodontal disease as a risk for dental implant failure over time: A long‐term historical cohort study

Abstract: Levin L, Ofec R, Grossmann Y, Anner R. Periodontal disease as a risk for dental implant failure over time: A long-term Historical cohort study. J Clin Periodontol 2011; 38: 732–737. doi: 10.1111/j.1600-051X.2011.01745.x. Abstract Objectives: To evaluate the long-term survival rates of dental implants according to the patient's periodontal status, as well as to estimate if the effect of periodontal status regarding implant failure is constant throughout the long-term follow-up. Materials and Methods: This was a historical prospective cohort study design of all consecutive patients operated from 1996 to 2006 at a periodontal clinic. The cohort consisted of 736 patients, with a total of 2336 dental implants. An extended Cox proportional hazards model, which includes interaction terms between survival time and variables of interest, was used. Results: Patients' mean (SD) age was 51.13 (12.35). The follow-up time was up to 144 months, with a mean (SD) of 54.4 (35.6) months. The overall implant raw survival rate was 95.9%. The Kaplan–Meier estimates for the cumulative survival rate (CSR) at 108 months were 0.96 and 0.95 for implants inserted into healthy and moderate chronic periodontal patients, respectively. The CSR declined to 0.88 at 108 months for the severe periodontitis group. The extended Cox model revealed that severe chronic status turned out to be a significant risk factor for implant failure after 50 months of follow-up [hazard ratio (HR)=8.06; p<0.01]. The extended Cox model for smoking indicates a near-significant effect after 50 months (HR=2.76; p=0.061). Conclusions: Periodontal status and smoking are significant risk factors for late implant failures. The HR for periodontal and smoking status are not constant throughout the follow-up period.

Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres

Abstract: Objective Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. Methods A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). Results Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. Conclusion A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.

Heparanase levels are elevated in the urine and plasma of type 2 diabetes patients and associate with blood glucose levels.

Abstract: Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans. Utilizing an ELISA method capable of detection and quantification of heparanase, we examined heparanase levels in the plasma and urine of a cohort of 29 patients diagnosed with type 2 diabetes mellitus (T2DM), 14 T2DM patients who underwent kidney transplantation, and 47 healthy volunteers. We provide evidence that heparanase levels in the urine of T2DM patients are markedly elevated compared to healthy controls (1162±181 vs. 156±29.6 pg/ml for T2DM and healthy controls, respectively), increase that is statistically highly significant (P<0.0001). Notably, heparanase levels were appreciably decreased in the urine of T2DM patients who underwent kidney transplantation, albeit remained still higher than healthy individuals (P<0.0001). Increased heparanase levels were also found in the plasma of T2DM patients. Importantly, urine heparanase was associated with elevated blood glucose levels, implying that glucose mediates heparanase upregulation and secretion into the urine and blood. Utilizing an in vitro system, we show that insulin stimulates heparanase secretion by kidney 293 cells, and even higher secretion is observed when insulin is added to cells maintained under high glucose conditions. These results provide evidence for a significant involvement of heparanase in diabetic complications.

Classification of breast cancer precursors through exhaled breath.

Abstract: Certain benign breast diseases are considered to be precursors of invasive breast cancer. Currently available techniques for diagnosing benign breast conditions lack accuracy. The purpose of this study was to deliver a proof-of-concept for a novel method that is based on breath testing to identify breast cancer precursors. Within this context, the authors explored the possibility of using exhaled alveolar breath to identify and distinguish between benign breast conditions, malignant lesions, and healthy states, using a small-scale, case-controlled, cross-sectional clinical trial. Breath samples were collected from 36 volunteers and were analyzed using a tailor-made nanoscale artificial NOSE (NA-NOSE). The NA-NOSE signals were analyzed using two independent methods: (i) principal component analysis, ANOVA and Student's t-test and (ii) support vector machine analysis to detect statistically significant differences between the sub-populations. The NA-NOSE could distinguish between all studied test populations. Breath testing with a NA-NOSE holds future potential as a cost-effective, fast, and reliable diagnostic test for breast cancer risk factors and precursors, with possible future potential as screening method.

Relation of Myocardial Mechanics in Severe Aortic Stenosis to Left Ventricular Ejection Fraction and Response to Aortic Valve Replacement

Abstract: Decreased left ventricular (LV) longitudinal strain and increased circumferential LV strain have been demonstrated in patients with severe aortic stenosis (AS) and normal LV ejection fraction (LVEF). Biplane myocardial mechanics normalize after aortic valve replacement (AVR). This study objective was to examine LV mechanics before and soon after AVR in patients with AS and LV systolic dysfunction. Paired echocardiographic studies before and soon (7 ± 3 days) after AVR were analyzed in 64 patients with severe AS: 32 with normal LVEF (≥50%), 16 with mild to moderate LV dysfunction (LVEF

Diabetes blockade of sevoflurane postconditioning is not restored by insulin in the rat heart: phosphorylated signal transducer and activator of transcription 3- and phosphatidylinositol 3-kinase-mediated inhibition.

Abstract: Background: The possibility of restoring sevoflurane postconditioning (sevo-postC) cardioprotection in diabetic animals is uncertain. We hypothesized that attenuation of myocardial injury by sevo-postC might be hindered by inhibition of signal transducer and activator of transcription (STAT) 3-regulated activity of phosphatidylinositol 3-kinase (PI3K) in diabetic animals. To determine whether postC cardioprotection can be restored by normoglycemia, we treated rats with insulin. Methods: Diabetic or nondiabetic rats were randomly subjected to 30-min ischemia/reperfusion, with ischemic postC or sevo-postC, with and without mitochondrial adenosine triphosphate-dependent potassium channel blocker 5-hydroxy decanoate sodium and PI3K antagonist wortmannin. The infarct area, phosphorylated STAT3, and apoptosis were examined. Studies were repeated after insulin treatment. Results: Ischemic postC and sevo-postC significantly reduced infarct size by 50% in the nondiabetic rats (P < 0.002), a phenomenon completely reversed by 5-hydroxy decanoate sodium and wortmannin. Diabetes mellitus blocked the protective effect of postC, and insulin treatment to achieve normoglycemia did not restore cardioprotection. Phosphorylated STAT3 nuclear retention was significantly increased after ischemia-reperfusion and was further enhanced in response to ischemic postC (P < 0.05) but was significantly reduced in diabetic rats (by 43%; P < 0.01). Conclusions: The effective reduction in infarct size and apoptosis in the nondiabetic rat heart by postC was completely abrogated in diabetic rats. This inhibition is not relieved by insulin-induced normoglycemia. The PI3K pathway and mitochondrial adenosine triphosphate-dependent potassium channel activation are involved in the mechanism of postC. In diabetic rats, STAT3 activation was strongly reduced, as was postC cardioprotection, suggesting that the inability of insulin to restore postC may be attributed to diabetes-induced STAT3-mediated inhibition of PI3K signaling.

Gene Expression Differences between Colon and Rectum Tumors

Abstract: Purpose: Colorectal cancer studies typically include both colon and rectum tumors as a common entity, though this assumption is controversial and only minor differences have been reported at the molecular and epidemiologic level. We conducted a molecular study based on gene expression data of tumors from colon and rectum to assess the degree of similarity between these cancer sites at transcriptomic level. Experimental Design: A pooled analysis of 460 colon tumors and 100 rectum tumors from four data sets belonging to three independent studies was conducted. Microsatellite instable tumors were excluded as these are known to have a different expression profile and have a preferential proximal colon location. Expression differences were assessed with linear models, and significant genes were identified using adjustment for multiple comparisons. Results: Minor differences at a gene expression level were found between tumors arising in the proximal colon, distal colon, or rectum. Only several HOX genes were found to be associated with tumor location. More differences were found between proximal and distal colon than between distal colon and rectum. Conclusions: Microsatellite stable colorectal cancers do not show major transcriptomic differences for tumors arising in the colon or rectum. The small but consistent differences observed are largely driven by the HOX genes. These results may have important implications in the design and interpretation of studies in colorectal cancer. Clin Cancer Res; 17(23); 7303–12. ©2011 AACR .

SCT in patients with carbapenem resistant Klebsiella pneumoniae: a single center experience with oral gentamicin for the eradication of carrier state

Abstract: Following an outbreak of carbapenem resistant Klebsiella pneumoniae (CRKP) bacteremia among inpatients in the Hemato-oncology and BMT unit, we studied the course of this infection in patients undergoing intensive chemotherapy and SCT. In addition, we conducted a pilot study aimed to eradicate CRKP colonization in the gastrointestinal tract, using oral gentamicin. Adult patients admitted to the BMT unit, identified as CRKP carriers on surveillance rectal cultures, were included in the study. Oral gentamicin at a dose of 80 mg q.i.d. was administered to all identified carriers until eradication. Among 15 colonized patients included in the study, the eradication rate achieved was 66% (10/15); discontinuation of persistent bacteremia occurred in 62.5% (5/8) and nosocomial spread of CRKP carrier state ceased. Administration of intensive chemotherapy and SCT is feasible, although associated with increased risk. Hematological patients in need of intensive chemotherapy/SCT should not be denied the required treatment on the basis of being CRKP carriers. Oral gentamicin treatment for eradication of CRKP from the gastrointestinal reservoir could serve as additional tool in the combat against the nosocomial spread and severe infections caused by this difficult-to-treat organism.

Absence of APOL1 risk variants protects against HIV-associated nephropathy in the Ethiopian population.

Abstract: Background: Susceptibility to end-stage kidney disease (ESKD) among HIV-infected Americans of African ancestral heritage has been attributed to APOL1 genetic variation. We determine

Air travel and the risk of thromboembolism.

Abstract: Almost two billion people use commercial aircraft annually. Long-haul flights are taken by over 300 million people. A serious complication of long-distance travel (or prolonged time of flight) is thromboembolism. The real incidence of the problem is difficult to evaluate since there is no consensus about the diagnostic tests or limitation of time after landing connected to the VTE complication. A direct relation between VTE incidence and long-distance flights has been documented. The risk for DVT is 3–12% in a long-haul flight. The pathophysiologic changes that increase VTE risk at flight are stasis (sitting in crowded condition), hypoxia in the airplane cabin, and dehydration. Individual risk factors for air travel-related VTE include age over 40 years, gender (female), women who use oral contraceptives, varicose veins in lower limbs, obesity and genetic thrombophilia. Prevention measures include environmental protection such as keeping the pressure inside the airplane cabinet in hypobaric condition, avoiding dehydration and prolonged sitting. For individuals at increased risk, venous blood stasis can be reduced by wearing elastic stockings and prophylactic use of low-molecular-weight heparin.

Home parenteral nutrition (HTPN) for incurable patients with cancer with gastrointestinal obstruction: do the benefits outweigh the risks?

Abstract: Patients with cancer may suffer from malnutrition due to cachexia, this maybe secondary to treatment, psychological factors and/or gastrointestinal (GI) obstruction. GI obstruction indicates a need for TPN. Does this apply to patients with incurable terminal cancer? How does TPN affect longevity and quality of life in this group of patients? What is the course of TPN treatment compared with patients receiving TPN due to nonmalignant GI failure (NMGIF). The aim of this work was to help define the role of TPN in patients with incurable cancer and GI obstruction. Data of all patients treated by home TPN (HTPN) 2003–2009 were collected prospectively and analyzed. Sixty-eight patients were treated with HTPN, 30 of them for NMGIF. Mean age was 52 years (37–87). Primary sites of cancer were ovary (9), stomach (8) and others (11). Median survival of patients with malignant GI failure (MGIF) was 140 days (20–783) with no difference with regard to age, gender, primary diagnosis, BMI, percentage of weight loss and albumin level. Patients with MGIF and a higher performance score had longer survival. Patients with MGIF suffered significantly higher rates of overall and infectious complications per treatment days [P < 0.001]. TPN for MGIF incurable patients with cancer prolongs survival but at the cost of frequent complications. TPN is indicated in a selected group of MGIF. We do not have the tools to predict in which patients the benefits will outweigh the cost, but we found variables which may assist caregivers to make clinical and empathic decisions individually.

Apical and marginal bone alterations around implants in maxillary sinus augmentation grafted with autogenous bone or bovine bone material and simultaneous or delayed dental implant positioning

Abstract: Objective: A re-pneumatization phenomenon was recorded in sinuses grafted with different materials. The specific aims of this paper were to assess the dental implant survival rate and the behavior of marginal and apical bone remodeling around dental implants placed following sinus augmentation. Materials and methods: A retrospective study was conducted on consecutive patients treated in two surgical centers. Different surgical techniques were adopted for sinus augmentation: simultaneous or delayed dental implant insertion with bovine bone-material augmentation or autologous bone grafting (chin and iliac crest). Survival rates were recorded for the overall number of implants (patients of group A). Apical and marginal bone levels (ABL and MBL, respectively) were radiographically measured, and statistical analysis was performed in implants of a subgroup of patients (group B). Results: A total of 282 dental implants were positioned. Recorded cumulative survival rates (CSRs) were 95.6% and 100% for autogenous and bovine bone material, respectively, while CSRs at 2-year follow-up for immediate and delayed procedures were 99.3% and 96.5%. For the subgroup B, 57 sinus augmentation procedures were performed in 39 patients, with the positioning of 154 implants. Generally, the apical- and marginal-bone resorption of the bovine bone-material group was less than that of the autogenous group. The differences between the ABL values of the bovine bone-material and iliac-crest groups were statistically significant at 1 year, whereas this significance disappeared at the 2-year follow-up; tests showed that a statistical difference was recorded in the bovine bone-material group between the 1- and 2-year follow-ups. With regard to MBL comparisons between simultaneous and delayed implantation, the differences maintained their significance at the 2-year follow-up also. Conclusions: Differences regarding apical bone alteration between autogenous bone from the iliac crest and bovine bone material at the 1- and 2-year follow-ups, as well as in the bovine bone-material group between the 1- and 2-year follow-ups, attested to slower but more prolonged physiologic bone remodeling in the bovine-graft-material group than in the autogenous-bone group. The MBL analysis showed that remodeling in the delayed implant group demonstrated a greater resorption in the cervical portion than was seen in the simultaneous implant group. To cite this article: Sbordone L, Levin L, Guidetti F, Sbordone C, Glikman A, Schwartz-Arad D. Apical and marginal bone alterations around implants in maxillary sinus augmentation grafted with autogenous bone or bovine bone material and simultaneous or delayed dental implant positioning. Clin. Oral Impl. Res22, 2011; 485–491 doi: 10.1111/j.1600-0501.2010.02030.x