Proteomic Profiling of Smad Proteins Expression in AML: Pan Expression with High Phosphorylation Is Prognostically Adverse

Abstract Abstract 891 The Transforming growth factor β (TGF-β) signaling pathway has been previously known to play a tumor suppressor role in hematologic malignancies. Smad proteins and their phosphorylation play a vital role in TGF-β signaling pathway. There are three class of Smads; Receptor-regulated Smads (1, 2, 3, 5, 8), Common mediator Smad (4) and Inhibitory Smads (6, 7). However, little is known about the expression and activation of Smad proteins in AML and nothing has been reported about correlation with clinical features or outcomes. Interestingly, Tabe et.al, (ASH 2012) recently identified pro-survival effect of TGF-β in leukemia cells via upregulation of MMP-1 and that the anti-apoptotic effect of TGF-β was associated with G0/G1 cell cycle arrest We performed proteomic profiling of Smad expression, measuring the level of total Smad 1, 2, 3, 4, 5, 6, and phosphorylated Smad 2 (p245, p465) and 5 (p463) using reverse phase protein array (RPPA) technology. All antibodies were strictly validated. Analysis was performed on a cohort of 511 newly diagnosed AML (non APL) cases randomly divided into training and test sets. Normal bone marrow derived CD34+ cells (n=11) served as expression controls. Hierarchical clustering with Wald linkage rules and Euclidean distance matrix were used to define signatures. Cox model and long rank test were used to assess the survival outcome with different sample signatures. When comparing expression of individual Smad proteins with control CD34+ cells, most cases had expression within the normal CD34+ cell range, but levels of Smad 2, 2p465 and 4 had higher percentages of cases with expression below normal, while levels of Smad 3, 5, 5 (p463) and 6 were more frequently expressed at levels above normal. There were no major differences in expression between bone marrow and blood, and diagnosis and relapse samples. When unbiased hierarchical clustering was performed on the training set, four distinct Smad protein expression signatures were identified (Figure 1). Group 1 is characterized by pan-low Smad expression; Group 2 by high expression in Smad 2, 5, 5 (p463); Group 3 by high expression of phosphorylated Smad 2 (p245, p465) and 5 (p463); and Group 4, by pan-high Smad expression. Group 2 was associated with Ras mutation (28% vs. 9% for the other 3, p=0.03) and FLT3 ITD (p=0.009) mutation frequency was significantly lower in group 1. Smad group was not associated with FAB classification, demographics, prior treatment history, cytogenetics, and other molecular mutations. Higher Smad expression was statistically significantly correlated with higher counts of WBC (p=0.04), bone marrow and peripheral blast % (p=0.009, 0.004), CD33 and 34 counts (p=0.006, 0.002). Intriguingly, among 210 other proteins assayed in RPPA, expression of Integrin/Adhesion proteins IGFBP2, CD49B, CD11A and Fibronectin were inversely correlated with Smad expression consistent with the above observation. Pan Smad expression was strongly correlated with AKT pathway activation and high expression of several proliferation promoting proteins. Pan-high Smad expression (group 4) was associated with inferior overall survival (OS) (Figure 2) and event free survival (EFS) whereas the OS and EFS of Group 1, 2, and 3 were similar (log-rank test OS p=0.017; EFS p=0.03). Median OS, EFS were 36.3 and 19.3 weeks in Group 4 versus 56.1 and 26.9 weeks in other groups, respectively. Patients in group 4 had a lower remission rate (51% vs. 66%). When validated with the test set, similar results were observed and group 4 again had inferior survival (median 26.7 vs. 58 weeks, p = 0.0047) compared to the other groups. In conclusion, we observed that Smad expression in AML segregates into four distinct heterogeneous expression and activation patterns. Pan-high Smad expression was linked with significantly worse OS, EFS, and trends for inferior CR rates. The clinical features (high WBC and % PB and BM blasts) and inferior clinical outcome associated with pan-high Smad expression suggest that dominant TGF-β signaling is adverse in AML and that these patients may benefit from TGF-β blockade. Our finding suggest a tumor promoting, rather than tumor suppressing role, for TGF- β in AML, possibly mediated via MMP-1 activation. Further studies are required to investigate the mechanism of TGF-β pathway activation possibly inducing chemotherapy resistance leading to poor survival. Disclosures: No relevant conflicts of interest to declare.

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Serum Transferrin Receptor Value as a Universal Indicator of Erythropoietic Activity.

Blood ◽

10.1182/blood.v104.11.3682.3682 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3682-3682

Author(s):

Young Soo Lee ◽

Chul Soo Kim ◽

Jong Weon Choi

Keyword(s):

Bone Marrow ◽

Transferrin Receptor ◽

Bone Marrow Cells ◽

Reticulocyte Count ◽

Serum Transferrin Receptor ◽

Group 4 ◽

Universal Indicator ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract The serum transferrin receptor (sTfR) is thought a sensitive and quantitative parameter of tissue iron deficiency as well as an indicator of erythropoietic activity. This study was aimed at the verification of a hypothesis that sTfR is a general indicator of erythropoiesis regardless whatever the cause is. A total of 173 patients in heterogeneous diseases who underwent bone marrow study as a workup for anemia were measured for sTfR, reticulocyte maturity index (RMI), erythroid element proportion of bone marrow cells, and other hematologic parameters (hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, red cell distribution width, absolute reticulocyte count). By immunoenzymometric method sTfR was measured using IDeATMcTfR kids (Orion Diagnostica, Orion, Finland). Reticulocyte count and proportion was measured manually by one expert examiner after standard blood smear and stain. Reticulocyte subpopulation was automatically analyzed by flow cytometry using R-3000 TM (Sysmex, TOA, Japan). RMI was calculated from the equation of (medium fluorescent reticulocyte fraction + high fluorescent reticulocyte fraction) X 100 / low fluorescent reticulocyte fraction. Correlation analysis was done among the variables including sTfR, RMI, erythroid element proportion of bone marrow cells, and other hematologic parameters using SAS 6.12 soft ware. The analysis was carried out for the whole 173 patients to see the general trends and repeated for 4 groups of disease category, arbitrarily divided to group 1 (n=33, iron deficiency or or disease with no predisposition to anemia of chronic disease), group 2 (n=53, hematologic malignancies), group 3 (n=44, solid tumors), and group 4 (n=43, chronic or infectious disease) to see if the trends may be affected by specific diseases. The results showed a solid correlation of sTfR with RMI as well as erythroid precursors in bone marrow, not only in the whole patient population (e.g. sTfR vs RMI, R=0.587, p=0.0001) but also in individual groups (e.g. sTfR vs RMI, R=0.48, p=0.005 in group 1, R=0.69, p=0.0001 in group 2, R=0.58, p=0.0001 in group 3, R=0.81, p=0.0001 in group 4). These findings indicated the significance of sTfR is valid under any clinical setting as a universal indicator of hematopoietic activity. The sTfR can be used as a useful parameter for monitoring of erythropoiesis in a variety disease.

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Leukemic and Hematopoietic Stem Cells Compete for the Same Functional Marrow Niche in a MLL-AF9 Murine Leukemia Model

Blood ◽

10.1182/blood.v120.21.4897.4897 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4897-4897

Author(s):

Ronan G. Desmond ◽

Taha Bat ◽

Olena Kamenyeva ◽

Benjamin Mizukawa ◽

James C. Mulloy ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Murine Model ◽

Leukemic Cells ◽

Hematopoietic Stem ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Abstract 4897 Much is known regarding the location, cellular composition, signaling pathways, and functional role of the normal hematopoietic stem cell (HSC) niche in the bone marrow microenvironment. Microenvironmental cells including osteoblasts, other specialized mesenchymal cells, and vascular endothelial cells exert control over HSC self-renewal, differentiation, and engraftment. Niche occupancy appears to be competitive and limiting in terms of controlling the number of HSCs per organism. Leukemia stem cells (LSCs), through their inherent properties of quiescence and resistance to chemotherapeutic agents, are thought to be one of the principal mechanisms underlying disease relapse in patients. Much less is known regarding the interaction of LSCs and the marrow microenvironment. It is not clear whether LSCs localize to the same niches as HSCs, compete with HSCs for niche occupancy, or share dependence on niche signals, and whether those signals affect tumor responses to chemotherapy. Using a human pre-B ALL xenograft mouse model, Colmone et al (Science 2008) recently showed that leukemic cells may alter the normal microenvironment, resulting in initial homing of transplanted normal HSPCs in distinct atypical niches. Shiozawa et al (JCI 2011) showed that metastatic prostate cancer cells, a tumor type known to target bone, impeded HSC engraftment in a murine model, suggesting competition for the same niche. To investigate the relationship between HSC and LSC niche localization and functional occupancy, we used murine progenitor cells transduced with an MLL-AF9 vector expressing GFP in a murine syngeneic competitive transplantation model. MLL-AF9 cells are highly enriched for LSCs, particularly the c-kit+ compartment (Somervaille Cancer Cell 2006). We found that between approximately 21% and 24% of cells were c-kit+ by FACS in 2 separate experiments. In our model, mice transplanted with unsorted MLL-AF9 cells (1×107) died of AML with a latency of 11–14 days. We cotransplanted a fixed number of MLL-AF9-GFP cells (1×106) with increasing numbers of normal mouse whole bone marrow (WBM) cells, derived from dsRed transgenic mice to facilitate distinction from the GFP+ MLL-AF9 cells, into mice irradiated with 1000 rads: 1×105 [group 1], 1×106 [group 2], 1×107 [group 3], 5×107 [group 4]. Control groups received 1×105 and 1×106 normal WBM cells only. Survival was monitored daily. The control group receiving 1×105 cells only all died with median time to death of 16.5 days from lack of count recovery, those receiving 1×106 cells are still alive 35 days after transplant, indicating that 1×106 cells is adequate to rescue from irradiation. Mice were bled weekly until death and samples were analyzed by flow cytometry. Complete blood counts, blood smears, and splenic sections were obtained from these mice. As expected, there were no circulating blasts detected 7 days post transplant and all mice were healthy. However, 14 days after transplant the percentages of GFP+ leukemic cells detected in the blood were inversely proportional to the number of normal dsRed WBM cells transplanted (group 1 vs. group 2 vs. group 3 vs. group 4 mean percentage of GFP+ cells, 83.97 v 66.53 v 18.73 v 9.275 p< 0.0001). At day 15, mice from group 1, but not from groups 2 to 4, became moribund and were sacrificed. Spleens in this group were heavier than in those mice transplanted with 1×105 normal WBM cells alone and 2 out of 3 showed leucocytosis compared to leucopenia in all mice in the group transplanted with normal cells alone. When mice in the other groups had blood samples taken for analysis while moribund, GFP+ cells were greater than 80% suggesting that mice in group 1 died from complications relating to leukemic infiltration. Confocal microscopy confirmed the colocalization of normal HSPCs and MLL-AF9-GFP LSCs in the niche. Most interestingly, survival was proportional to the numbers of normal WBM cells transplanted, with a continuous delay in leukemic death proportional to the number of normal WBM cells cotransplanted with the same dose of MLL-AF9 cells (Figure 1). Hence, this murine model of leukemia suggests that normal and leukemic cells compete for the same functional niche, that manipulation of the niche could impact on response to anti-leukemic therapies, and that cell dose in the context of stem cell transplantation for leukemia may have an impact on outcome via niche competition. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

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Imaging the Differential Engraftment of GFP-Expressing Spleen and Bone Marrow Cells in Various Organs after Reduced-Intensity Stem Cell Transplantation in Mice Model.

Blood ◽

10.1182/blood.v108.11.3228.3228 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3228-3228

Author(s):

Yuji Heike ◽

Zhijian Yang ◽

Huaiyu Ma ◽

Robert Hoffmann ◽

Yuriko Morita ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Pelvic Bone ◽

Donor Cells ◽

Cd34 Cells ◽

Group 2 ◽

Reduced Intensity ◽

Group 1

Abstract [Background] Reduced-intensity allogeneic stem cell transplantation is of critical importance in the treatment of hematological malignancies. The object of this experiment is to establish fludrabine-based reduced-intensity allogeneic stem cell transplantation model using donor cells labeled with GFP and image the engraftment process of donor cells in various organs. [Materials and Methods] GFP transgenic C57/BL6 mice (GFP-Tgm) were used as donors and C57/BL6 × DBA F1 mice (BDF1) were used as recipients. Recipient mice were pretreated with fludarabine (Flu) 150 mg/kg/day × 6 days i.p. and cyclophosphamide (CPA) 150 mg/kg/day × 2 days i.p. On day 0, 107 GFP splenocytes (Group 1) and GFP bone marrow cells (Group 2) were injected in the tail vein. Whole body and intravital imaging were used to visualize the migration of GFP-Tgm cells into various organs including the brain, femur, intestine, liver, lung, ovary, pelvic bone, ribs, skin, skull, spine, spleen and uterus on days-7 and -14. The macro images were obtained with the Olympus OV100 Small Animal Imaging System. GFP-Tgm cell migration, particularly CD34+ cells in the various organs was also analyzed by flow cytometry (FACS) using APC-labeled anti-CD34 monoclonal antibodies. [Results and Discussion] On day-7, the migration of donor GFP-Tgm cells in peripheral lymph nodes, intestine, lung, ovary, skin and uterus were detected in both groups. Migration of GFP-Tgm cells in the femur, pelvic bone, ribs and skull were clearly detected in Group 2, but not in Group 1. On day-14 GFP donor cells were imaged in the lung, ovary, skin and uterus both groups. However, GFP-Tgm cells were no longer imaged in the intestine in Group 2 except in Payer patches. In both groups the GFP-Tgm cells were strongly detected in the femur, pelvic bone, skull and spine on day-14. We also analyzed the migration of CD34+ GFP-Tgm cells by FACS analysis. On day-14, the percentage of GFP-Tgm cells in the bone marrow and spleen was, respectively, 14% and 53% in Group 1, and 10% and 13% in Group 2. The percentage of CD34+ GFP-Tgm cells among total CD34+ cells in the bone marrow was 10% in Group 1 and 14% in Group 2, and in the spleen was 24% and 19%, respectively. Those results suggested that in this model, donor bone marrow and spleen cells, but not purified CD34+ cells, have different engraftment kinetics in various organs including the intestine, which is a target organ for graft-versus host disease. These results clearly suggest that caution should be paid to evaluate engraftment kinetics of infused cells, at least in mice model.

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Guava leaf juice effect towards number of megakaryocytes in bone marrow of thrombocytopenic mice

Zinc supplementation improves heme biosynthesis in rats exposed to lead ◽

10.18051/univmed.2018.v37.19-24 ◽

2018 ◽

Vol 37 (1) ◽

pp. 19

Author(s):

Nur Atik ◽

Al Hadi Amrullah ◽

Andri Reza Rahmadi

Keyword(s):

Bone Marrow ◽

Thrombocyte Count ◽

Anova Test ◽

Group 4 ◽

Group 3 ◽

The Mean ◽

Group 2 ◽

Guava Leaf ◽

Leaf Juice ◽

Group 1

Background Dengue virus infection that most frequently occur in tropical and subtropical regions can cause many symptoms, one of which is a decrease in thrombocyte count. Recent studies showed that guava leaf extract can increase the thrombocyte count in rats. The present study aimed to determine the effect of guava leaf juice in increasing the number of megakaryocytes in the bone marrow of thrombocytopenic mice. Methods This study was of experimental design. The study subjects were 24 mice (Mus musculus). The mice were randomly divided into four groups that were subjected to intervention for 14 days. Group 1 was given guava leaf juice (56 mg/kg) and quinine (14 mg/kg), group 2 guava leaf juice (56 mg/kg) only, group 3 was given quinine (14 mg/kg) and group 4 distilled water. After 14 days, from the bone marrow of the femoral bones of each of the mice, hematoxylin eosin stained histologic preparations were made. Anova test was used to analyze the data. Results The mean megakaryocyte count per field of view in group 1 (2.83), group 2 (3.30), group 3 (2.24) and group 4 (2.93). Anova test results for all groups showed significant differences between groups (p<0.05). The mean megakaryocyte count was increased in group 1 compared to group 3, but the difference was statistically not significant (p=0.206). Conclusion Guava leaf juice can increase the megakaryocyte count in the bone marrow of thrombocytopenic mice. This suggests a potential role of guava leaf juice in improving the platelet count in thrombocytopenic disorders.

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Small medullary thyroid carcinoma: post-operative calcitonin rather than tumour size predicts disease persistence and progression

Acta Endocrinologica ◽

10.1530/eje-14-0076 ◽

2014 ◽

Vol 171 (1) ◽

pp. 117-126 ◽

Cited By ~ 14

Author(s):

Katerina Saltiki ◽

Gianna Rentziou ◽

Kimon Stamatelopoulos ◽

Georgios Georgiopoulos ◽

Charalambos Stavrianos ◽

...

Keyword(s):

Disease Progression ◽

Tumour Size ◽

Characteristic Curve ◽

Rank Test ◽

Medullary Thyroid ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Disease Persistence ◽

Group 1

ObjectiveRecently, small medullary thyroid carcinomas (smallMTCs; ≤1.5 cm) are frequently diagnosed, occasionally as incidental findings in surgical specimens. Their clinical course varies. We examined tumour size as a predictor of clinical behaviour.DesignA retrospective study.MethodsA total of 128 smallMTC patients (35.2% males and 45% familial) were followed up for 0.9–30.9 years. According to tumour size (cm), patients were classified into four groups: group 1, 0.1–0.5 (n=33); group 2, 0.6–0.8 (n=33); group 3, 0.8–1.0 (n=29) and group 4, 1.1–1.5 (n=33).ResultsPre- and post-operative calcitonin levels were positively associated with the tumour size (P<0.001). Capsular and lymph node invasion were more frequent in groups 3 and 4 (P<0.03); the stage was more advanced and the outcome was less favourable with an increasing tumour size (P<0.001). Groups 1 and 2 patients were more frequently cured (group 1, 87.8%; group 2, 72.7%; group 3, 68.9%; and group 4, 48.5%; P=0.002). The 10-year probability of lack of disease progression according to the tumour size differed between patients with tumour sizes of 0.1–1.0 and 1.1–1.5 cm (96.6%, 81.3%, x2=4.03, P=0.045 for log-rank test). Post-operative calcitonin was the only predictor significantly associated with the 10-year progression of disease. Post-operative calcitonin levels ≥4.65 pg/ml predicted disease persistence (sensitivity 93.8% and specificity 90%) and ≥14.5 pg/ml predicted disease progression (sensitivity 100%, specificity 82%, receiver operating characteristic curve analysis).ConclusionsTumour size may be of clinical importance only in patients with MTCs >1 cm in size. Post-operative calcitonin is a more important predictor than size for disease progression.

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Histomorphometric Analysis of Bone Regeneration Using a Dual Layer of Membranes (dPTFE Placed Over Collagen) in Fresh Extraction Sites: A Canine Model

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-13-00027 ◽

2015 ◽

Vol 41 (2) ◽

pp. 188-195 ◽

Cited By ~ 1

Author(s):

Khalid Al-Hezaimi ◽

Giovanna Iezzi ◽

Ivan Rudek ◽

Abdullah Al-Daafas ◽

Khalid Al-Hamdan ◽

...

Keyword(s):

Bone Marrow ◽

Canine Model ◽

Control Group ◽

Ridge Preservation ◽

Alveolar Ridge ◽

Group 4 ◽

Significant Difference ◽

Group 2 ◽

Bone Particles ◽

Group 1

In untreated extraction sockets, buccal bone remodeling compromises the alveolar ridge width. The aim of this study was to histologically assess the efficacy of using a dual layer of membranes (high-density polytetrafluoroethylene [dPTFE] placed over collagen) for ridge preservation in fresh extraction sites. Eight beagle dogs were used. After endodontic treatment of mandibular bilateral second (P2), third (P3), and fourth (P4) premolars, mandibular bilateral first premolars and distal roots of P2, P3, and P4 were extracted atraumatically. Animals were randomly divided into 4 treatment groups. group 1, the control group, received no treatment; in group 2, allograft was placed in the alveolum and the socket covered with dPTFE membrane; in group 3, allograft was placed in the alveolum, the buccal plate was overbuilt with allograft, and the socket was covered with dPTFE membrane; in group 4, allograft was placed in the alveolum and covered with dual layer of membranes (dPTFE placed over collagen). No intent of primary closure was performed for all groups. After 16 weeks, the animals were sacrificed and mandibular blocks were assessed histologically for buccolingual width of alveolar ridge, percentage of bone formation and bone marrow spaces, and the remaining bone particles. The buccolingual width of the alveolar ridge was significantly higher among sockets in group 4 than in group 1 (P < .05). the amount of newly formed bone in each socket was higher in extraction sockets in group 4 than in groups 1, 2, and 3 (P < .001). A significant difference was found in the percentage of bone marrow spaces among all groups (P < .001). No significant difference was found in the number of nonresorbed bone particles among the groups. Using a dual layer of membrane was more effective in ridge preservation than conventional socket augmentation protocols.

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In-vivo evaluation of the effect of cyanoacrylate on prosthetic vascular graft infection – does cyanoacrylate increase the severity of infection?

VASA ◽

10.1024/0301-1526/a000867 ◽

2020 ◽

Vol 49 (4) ◽

pp. 281-284

Author(s):

Atıf Yolgosteren ◽

Gencehan Kumtepe ◽

Melda Payaslioglu ◽

Cuneyt Ozakin

Keyword(s):

Vascular Graft ◽

Graft Infection ◽

Vascular Graft Infection ◽

Group 4 ◽

Significant Difference ◽

Group 3 ◽

Group 2 ◽

Prosthetic Vascular Graft Infection ◽

Group 1

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.

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Does Perioperative Hemoglobin A1c Level Affect the Incidence, Pattern and Mortality of Lower Extremity Amputation?

Current Vascular Pharmacology ◽

10.2174/1570161116666180123112529 ◽

2019 ◽

Vol 17 (4) ◽

pp. 354-364

Author(s):

Hassan Al-Thani ◽

Moamena El-Matbouly ◽

Maryam Al-Sulaiti ◽

Noora Al-Thani ◽

Mohammad Asim ◽

...

Keyword(s):

Glycemic Control ◽

Lower Extremity ◽

Hazard Ratio ◽

Lower Extremity Amputation ◽

Group 4 ◽

Group 3 ◽

Group 5 ◽

Group 2 ◽

Extremity Amputation ◽

Group 1

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.

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Association between cervical disc disease and lesions of multiple sclerosis

The Neuroradiology Journal ◽

10.1177/1971400920983565 ◽

2021 ◽

pp. 197140092098356

Author(s):

Marwan Alkrenawi ◽

Michael Osherov ◽

Azaria Simonovich ◽

Jonathan Droujin ◽

Ron Milo ◽

...

Keyword(s):

Spinal Cord ◽

Cervical Disc ◽

Cervical Disc Disease ◽

Disc Disease ◽

Group 4 ◽

Demyelinating Lesions ◽

Grade Ii ◽

Group 3 ◽

Group 2 ◽

Group 1

Background Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. Methods Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1–C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher’s exact test was used to test the association between demyelinating lesions and disc pathology. Results Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease ( p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). Conclusion Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.

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The Relationship between Serum Ferritin Levels and 5-Year All-Cause Mortality in Hemodialysis Patients

Blood Purification ◽

10.1159/000515639 ◽

2021 ◽

pp. 1-7

Author(s):

Emre Erdem ◽

Ahmet Karatas ◽

Tevfik Ecder

Keyword(s):

Serum Ferritin ◽

Hemodialysis Patients ◽

Rank Test ◽

Significant Difference ◽

All Cause Mortality ◽

Group 3 ◽

Group 2 ◽

The Relationship ◽

Group 1

Introduction: The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. Methods: A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin <800 ng/mL, group 2: serum ferritin 800–1,500 ng/mL, and group 3: serum ferritin >1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. Results: Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5–60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, p = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05–0.49]; p = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12–0.88]; p = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23–1.04]; p = 0.063). Conclusion: Time-averaged serum ferritin levels >1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.

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