Serum Levels of OPG and MIP-1α in Untreated Multiple Myeloma Patients. Correlations with Staging, Survival and Bone Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5074-5074
Author(s):  
Argyro Papadogiannis ◽  
Marie-Cristine Kyrtsonis ◽  
Theodoros P. Vassilakopoulos ◽  
Tatiana Tzenou ◽  
Antonios G. Antoniadis ◽  
...  
Keyword(s):  
Bone Disease ◽  
Staging System ◽  
Serum Levels ◽  
High Serum ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Bone Lesions ◽  
Disease Biology ◽  
Significant Difference

Abstract Cytokines, such as MIP-1a (macrophage inhibiting factor) and OPG (osteoprotegerin) are assumed to play a role in MM disease biology and bone disease, by mechanisms that are still under investigation. MIP-1a is constitutively secreted by myeloma cells, plays a possible role in the development of MM bone lesions, enhance MM cell adhesion to stromal cells and its serum levels have been recently related to survival in MM. OPG is a soluble decoy receptor which acts as a soluble receptor antagonist that prevents osteoclasts activation and the development of bone disease. Reported findings on serum OPG levels in MM patients are controversial as well as its possible role in the biology of the disease. In order to investigate the possible relationship of MIP-1a and OPG levels in MM patients with prognosis and bone disease, we determined by ELISA serum MIP-1a and OPG levels in 20 MGUS, 82 MM patients and 27 healthy individuals (HI). Both cytokines were determined by ELISA (R&D, Quantikine, USA) in frozen sera collected at dignosis, before treatment. The median age of MM patients was 69 years (44–84) and 50% were males. MM patients’ stage was as follows: 23 stage I, 28 stage II, 31 stage III according to Durie-Salmon staging system and 27 stage I, 17 stage II, 35 stage III according to the International Scoring System (ISS). In HI median MIP-1a was 28 pg/ml (15–54) and median OPG 1600 pg/ml (450–4600). In subjects with MGUS, median MIP-1a was 34 pg/ml (17–58) and median OPG 2300 pg/ml (820–6200). In MM patients, median pretreatment serum MIP-1a was 32 pg/ml (16–100) and OPG 3000 pg/ml (820–25000). No statistical significant difference was observed between HI, MGUS and MM patients with regard to MIP-1a levels but for OPG levels differences between HI and MM patients and between MGUS and MM patients were both significant (0.01 and 0.05 respectively). No relationship was found between MIP-1a or OPG levels and bone disease. However, there was a trend for longer survival in patients with MIP-1a or OPG levels lower than median (5-year overall survival 60 ± 12 vs 38 ± 14, p=0.08 and 66 ± 13 vs 29 ± 13, p=0.07 respectively). In addition MIP-1a levels were correlated with ISS stage: MIP-1a levels were 28.3±11.3 in ISS stage 1, 29.8±11.1 in ISS stage 2, 39±19.2 in ISS stage 3 (p=0.02). In conclusion, in our experience serum OPG levels are higher in MM patients than in MGUS or HI, MIP-1a levels are correlated with the ISS stage and both high serum MIP-1a and OPG levels at diagnosis are related with a shorter survival.

Serum Total-RANKL Is Elevated in Patients with Multiple Myeloma, Increases with ISS Stage and Decreases after Induction Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2511-2511
Author(s):  
Christian Jakob ◽  
Jan Sterz ◽  
Lorenz Kleeberg ◽  
Ivana Zavrski ◽  
Martin Kaiser ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Serum Levels ◽  
Conventional Radiography ◽  
Elisa Test ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Bone Lesions ◽  
Serum Samples

Abstract Enhanced osteolytic bone resorption is a hallmark of multiple myeloma. Several studies demonstrated an elevation of RANKL levels in the bone marrow microenvironment in multiple myeloma, but serum levels of soluble RANKL (sRANKL) revealed controversial results. One study reported elevated sRANKL in serum in myeloma patients, but using the same test, the levels in the majority of the patients were below the detection limit in the hand of other groups. Thus, a novel test was developed which measures both soluble and OPG-bound RANKL (total-RANKL, tRANKL). The objective of the present study was to investigate the clinical significance of circulating levels of tRANKL in monoclonal gammopathies of undetermined significance (MGUS) or multiple myeloma (MM). Serum levels of tRANKL were analyzed by ELISA in 128 individuals: 20 healthy donors, 20 with MGUS and 88 newly diagnosed patients with multiple myeloma. Multiple myeloma patients had significantly (P<0.001) higher serum tRANKL values (median 7.01 μmol/L, range < 2 – 57.6) than healthy controls (median < 2 μmol/L) and individuals with MGUS (median < 2 μmol/L). Serum tRANKL levels increased significantly (P<0.001) from Durie & Salmon stage I to stage III (median values: stage I = 2.98, stage II = 4.61, stage III = 10.45 μmol/L) und from ISS stage I to stage III (median values: stage I = 4.64, stage II = 7.98, stage III = 23.12 μmol/L). Furthermore the serum tRANKL concentrations were significantly elevated in MM Durie & Salmon stage I versus MGUS (P=0.01). Multiple myeloma patients with osteolytic bone lesions in conventional radiography had significantly higher tRANKL levels than those without bone lesions (median 8.34 vs. 4.02 μmol/L, P=0.01). In 32 patients with multiple myeloma in stages II and III, who received chemotherapy and a monthly bisphosphonate treatment with zoledronic acid or pamidronate additional serum samples after 3 months were available. There was a significant (P<0.001) decrease from pre- to post-treatment tRANKL concentrations after three months of treatment. Our study shows that serum tRANKL levels are detectable in the majority of myeloma patients using this novel ELISA test. Advanced disease stages and osteolytic bone lesions in multiple myeloma patients are associated with increased serum tRANKL levels. The decrease of tRANKL after 3 months of induction therapy and bisphosphonates suggest a positive effect of anti-myeloma treatment on RANK ligand expression in multiple myeloma patients.

A Revised International Staging System of Multiple Myeloma in the Era of Novel Agents and Autologous Stem Cell Transplantation in Japan: A Multicenter Retrospective Collaborative Study of the Japanese Society of Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4199-4199
Author(s):  
Shuji Ozaki ◽  
Takayuki Saitoh ◽  
Hiroshi Handa ◽  
Hirokazu Murakami ◽  
Kenshi Suzuki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Novel Agents ◽  
Stage Iii ◽  
Conventional Chemotherapy ◽  
Related Risk ◽  
Significant Difference ◽  
International Staging System

Abstract Survival outcomes of patients with multiple myeloma (MM) vary considerably depending on the presence or absence of disease-related risk factors [i.e., advanced ISS (International Staging System) stage, CAs (cytogenetic abnormalities), etc.], patient-related risk factors, and/or treatment-related risk factors. ISS, developed in 2006 by the IMWG (International Myeloma Working Group), has been considered an important disease-related baseline prognostication model and has been used in routine clinical practice worldwide. However, it is solely determined by the serum biochemistry data without taking account of CAs which are currently identified as the most powerful prognostic indicator for MM. Recently, a Revised ISS (R-ISS) scoring system which is accounting the presence or absence of serum LDH abnormality as well as CAs such as t(4;14), t(14;16), or del(17p) in addition to the ISS stage has been proposed (Oliva S, et al. EHA 2014, #S1289). In the present study, we applied the R-ISS to the Japanese MM patients diagnosed between 2001 and 2012 and compared the clinical relevance of the R-ISS with that of the original ISS in the era of novel agents and autologous stem cell transplantation (ASCT). Clinical data of 3,270 patients were collected from 38 centers; however, ISS and R-ISS were only applicable to 2,998 and 788 patients, respectively. Patient characteristics including age, gender, type of M protein, Durie and Salmon stage, ISS stage, and chromosomal abnormalities were not significantly different between the patients to which ISS and R-ISS were applied. In the 788 patients evaluable for the R-ISS analysis, distribution of the patients according to the ISS stages I, II, and III were 31.4%, 35.8%, and 32.8%, respectively, whereas that of the R-ISS stages were 22.2%, 67.6%, and 10.2%, respectively. Median overall survival (OS) for the ISS stages I, II, and III were 100.7, 65.2, and 50.9 months, respectively, and that of R-ISS stages I, II, and III were 152.8, 62.4, and 40.5 months, respectively. Accordingly, the difference of survival time between the stages seemed more distinct in R-ISS compared with the performance of the original ISS. According to the analysis by the ISS, there were no significant difference in the median OS between the patients whether initially treated with novel agents or with conventional chemotherapy (stage I, 91.2 vs 84.6 months, p=0.054; stage II, 64.1 vs 62.5 months, p=0.18; and stage III, 41.2 vs 37.2 months, p=0.24). In contrast, the analysis by the R-ISS disclosed a beneficial effect of novel therapy than with conventional chemotherapy, particularly in patients with stage I disease (stage I, not reached vs 87.6 months, p=0.018; stage II, 78.8 vs 61.7 months, p=0.075; and stage III, 37.5 vs 45.3 months, p=0.87). As for ASCT, both ISS and R-ISS stages showed a significant difference in the median OS between the patients treated with ASCT and those without ASCT (ISS stages: stage I, 101.3 vs 78.8 months, p=0.40; stage II, 83.8 vs 52.4 months, p=0.0002; stage III, 67.5 vs 31.7 months, p=0.0004; and R-ISS stages: stage I, not reached vs 90.7 months, p=0.21; stage II, 74.2 vs 56.5 months, p<0.00001; stage III, 73.8 vs 37.5 months, p=0.11). Thus, our results have demonstrated that R-ISS is a useful model for the risk assessment of Japanese patients with MM. Notably, the outcome of MM patients with R-ISS stage I showed a dramatic improvement by the initial treatment with novel agents and ASCT. However, the survival benefit remained unmet in patients with advanced stages of R-ISS even in the era of novel agents and ASCT, and further development of therapeutic strategies is needed in high-risk patients with MM. Disclosures Sunami: Takeda pharmaceutical Compani Limited: Research Funding; ONO PHAMACEUTICAL CO.,LTD: Research Funding.

Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  
Keyword(s):  
Natural History ◽  
Median Survival ◽  
Troponin I ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Wild Type ◽  
Staging Systems ◽  
Significant Difference ◽  
History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P&lt;0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P&lt;0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

Clinical Staging for Sleep-Disordered Breathing

2002 ◽  
Vol 127 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Michael Friedman ◽  
Hani Ibrahim ◽  
Lee Bass
Keyword(s):  
Body Mass Index ◽  
Success Rate ◽  
Body Mass ◽  
Sleep Disordered Breathing ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Staging ◽  
Disordered Breathing

OBJECTIVE: The purpose of this study was to identify prognostic indicators that would lead to stratification of patients likely to have successful surgery for sleep-disordered breathing (SDB) versus those destined to fail. STUDY DESIGN: We retrospectively reviewed 134 patients to correlate palate position and tonsil size to the success of the UPPP as based on postoperative polysomnography results. Similar to our previously published data on the Friedman Score as a predictor of the presence and severity of SDB, the palate position was determined on physical examination of the oral cavity and was graded for each patient. This grade combined with tonsil size was used to stage the patients. Stage I was defined as having palate position 1 or 2 combined with tonsil size 3 or 4. Stage II was defined as having palate position 3 or 4 and tonsil size 3 or 4. Stage III patients had palate position 3 or 4 and tonsil size 0, 1, or 2. Any patient with body mass index of greater than 40 was placed in the stage III group. The results of uvulopalatopharyngoplasty (UPPP) were then graded as success or failure and success rates were compared by stage. SETTING: Academically affiliated tertiary care referral center. RESULTS: Stage I patients who underwent UPPP had a success rate of 80.6%, stage II patients had a success rate of 37.9%, and stage III patients had a success rate of 8.1%. CONCLUSION: A clinical staging system for SDB based on palate position, tonsil size, and body mass index is presented. It appears to be a valuable predictor of the success of UPPP. Additional studies and wider use of the staging system will ultimately define its role in the treatment of SDB.

Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

1988 ◽  
Vol 6 (11) ◽  
pp. 1722-1727 ◽  
Author(s):  
W J Curran ◽  
M J Kornstein ◽  
J J Brooks ◽  
A T Turrisi
Keyword(s):  
Relapse Rate ◽  
Salvage Therapy ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Subtotal Resection ◽  
Total Resection ◽  
Mediastinal Irradiation ◽  
Significant Difference

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

Serum Concentrations of DKK-1 Correlate with the Extent of Bone Disease in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3518-3518
Author(s):  
Martin Kaiser ◽  
Maren Mieth ◽  
Peter Liebisch ◽  
Susanne Rötzer ◽  
Christian Jakob ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Serum Levels ◽  
Conventional Radiography ◽  
Bone Lesions ◽  
X Rays ◽  
Myeloma Bone Disease ◽  
Lytic Lesions ◽  
Significant Difference ◽  
First Time

Abstract Objectives: Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells was reported to cause inhibition of osteoblast precursors. DKK-1 is an inhibitor of the Wnt/β-catenin signaling, which is a critical signaling pathway for the differentiation of mesenchymal stem cells into osteoblasts. So far there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions. Methods: DKK-1 serum levels were quantified in 184 previously untreated MM patients and 33 MGUS patients by ELISA, using a monoclonal anti-DKK-1 antibody. For the evaluation of bone disease, skeletal X-rays were performed. Results: Serum DKK-1 was elevated in MM as compared to MGUS (mean 11,963 pg/mL versus 1993 pg/mL, P < 0.05). Serum DKK-1 levels significantly correlated with myeloma stage according to Durie and Salmon (mean 2223 pg/mL versus 15,209 pg/mL in stage I and II/III, respectively; P = 0.005). Importantly, myeloma patients without lytic lesions in conventional radiography had significantly lower DKK-1 levels than patients with lytic bone disease (mean 3114 pg/mL versus 17,915 pg/mL; P = 0.003). Of interest, serum DKK-1 correlated with the number of bone lesions (0 vs. 1–3 vs. >3 lesions: mean 3114 pg/mL vs. 3559 pg/mL vs. 24,068 pg/mL; P = 0.002). Conclusion: This is the largest study of DKK-1 serum levels in multiple myeloma patients and data show for the first time a correlation between DKK-1 serum concentration and the amount of lytic bone disease, suggesting that DKK1 is an important factor for the extent of bone disease and supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

scholarly journals Dynamic Changes in International Staging System As a Predictor of Survival Outcome in Patients with Advanced Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4438-4438
Author(s):  
Jin-Liern Hong ◽  
Victoria Crossland ◽  
Aaron Galaznik ◽  
Paul Dolin
Keyword(s):  
Multiple Myeloma ◽  
Mortality Rate ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Study Cohort ◽  
Dynamic Changes ◽  
Beta 2 Microglobulin ◽  
Line Of Therapy

Abstract Background: The International Staging System (ISS) based on serum beta-2 microglobulin and serum albumin is a useful tool for risk stratification in patients with multiple myeloma. ISS is usually assessed at the time of diagnosis. Recent studies have suggested that risk stratification should be considered dynamic over the disease course. Our study aimed to describe dynamic changes in ISS over time and their impacts on mortality in patients with advanced multiple myeloma. Methods: This study included 417 patients with multiple myeloma from the Flatiron medical records database (Jan 2011- May 2018) who have received at least two lines of therapy and had data on ISS at the time of diagnosis (TDX) and at the time of initiating the second line of therapy (T2L). ISS stage was either abstracted from medical records or derived from the results of laboratory tests of serum beta-2 microglobulin and serum albumin. Patients were followed up from T2L until the earliest event of the last activity in database or death. We calculated mortality rates by TDX and T2L ISS stages, and generated Cox proportional hazard models to estimate the impact of TDX and T2L ISS stages on mortality. Additionally, in the subgroup of patients in ISS stage III at TDX, we used univariate logistic models to identify the predictors for downward shift to ISS stage I or II at T2L. Results: The study cohort had a median age of 70 (interquartile range: 61 to 77), and 59% were male. Based on ISS at TDX, 30%, 37%, and 33% of the study cohort were classified as stage I, II, and III with the mortality rate of 12, 11, and 24 deaths per 100 person-years, respectively. The hazard ratios were 0.95 (95% confidence interval (CI): 0.57-1.61) for patients in stage II and 1.96 (95% CI: 1.22-3.16) for patients in stage III, compared with patients in stage I. Based on ISS at T2L, 47%, 34%, and 20% were classified as stage I, II, and III, with the mortality rate of 7, 19, and 39 deaths per 100 person-years, respectively. The hazard ratios were 2.62 (95% CI: 1.61-4.25) for patients in stage II and 5.18 (95% CI: 3.10-8.64) for patients in stage III, compared with patients in stage I. Dynamic changes in ISS stages over time and mortality rates were depicted in the Table. Among patients in ISS stage I at TDX, about 25% shifted to higher stages at T2L, and had a higher mortality rate (26 per 100 person-years) than did patients remaining in stage I (8 per 100 person-years). For patients in ISS stage II at TDX, 43% stayed in Stage II at T2L, and 46% moved down to Stage I, with a mortality rate of 20 and 5 per 100 person-years, respectively. Among patients in ISS stage III at TDX, 58% moved down to lower stages at T2L. The mortality rate was 10, 21, and 40 per 100 person-years for patients moving down to Stage I and II at T2L and those remaining in Stage III, respectively. In the subgroup of patients in ISS stage III at TDX, strong predictors for shifting down to lower stages were younger age (odds ratio: 2.65; 95% CI:1.20-5.87 for age <65 vs ≥65 years) and serum creatinine ≤ 2 mg/dL at TDX (odds ratio: 2.26; 95% CI:1.03-4.92 for serum creatinine ≤ 2 vs >2 mg/dL), but not gender, race, or cytogenetic abnormality of del17p, t(4;14), and t(14;16). Conclusion: Large changes in ISS stages were observed in multiple myeloma patients when advancing the line of therapy. Changes in ISS stage were also associated with survival outcome. A downward shift to stage I was associated with substantially improved overall survival; in contrast, patients moving up to or remaining in higher stages had poor outcomes, especially for those remaining in ISS stage III. Our results suggest that re-evaluating ISS stage at the time of change in line of therapy can improve prediction of survival outcomes. Disclosures Hong: Takeda Pharmaceuticals International Co.: Employment. Crossland:Takeda Pharmaceuticals International Co.: Employment. Galaznik:Takeda Pharmaceuticals International Co.: Employment. Dolin:Shire: Other: PD holds shares in Shire ; GSK: Other: PD holds shares in GSK; Takeda Pharmaceuticals International Co.: Employment.

scholarly journals OCD-LIKE DISTAL FEMORAL LESIONS IN CHILDREN WITH BLOUNT DISEASE: WHAT IS THE CLINICAL RELEVANCE?

2019 ◽  
Vol 7 (3_suppl) ◽  
pp. 2325967119S0017
Author(s):  
Flo Edobor-Osula ◽  
Tamir Bloom ◽  
Ciaxia Zhao ◽  
Cornelia Wenokor ◽  
Sanjeev Sabharwal
Keyword(s):  
Femoral Condyle ◽  
Medial Femoral Condyle ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Categorical Variables ◽  
Plain Radiographs ◽  
Significant Difference ◽  
Text Figure ◽  
Blount Disease

What was the question? The purpose of this study was to evaluate the prevalence of OCD-like lesions around the knee in children with Blount disease. Additionally, we planned to describe the morphologic features of these OCD-like lesions based on plain radiographs and MRI and evaluate any clinical factors that may be associated with such radiologic findings How did you answer the question? After institutional review board approval, the medical records of all patients with a diagnosis of Blount disease (ICD-9 732.4) treated between January 2005 and March 2016 at a single institution were reviewed. All patients included in this study had an initial standing full-length anteroposterior mechanical axis radiograph and anteroposterior and lateral knee radiographs. MRI information was included when available. All patients noted to have an OCD-like lesion on an imaging study (x-ray and/or MRI) were identified and each such MRI was reviewed by three independent examiners, a musculoskeletal radiologist and two pediatric orthopedic surgeons. Each patient’s OCD-like lesion was graded according to two validated staging systems, as described by DiPaola and Hefti. Student t test for comparison of continuous variables and chi -square for categorical variables. Differences were considered statistically significant at p<0.05. What are the results? A total of 68 patients with Blount disease were identified. Five patients were excluded: two due to inadequate imaging, and three patients were adults at initial presentation. Of the 63 remaining patients (87 affected limbs) all had plain radiographs and 37 of these patients (53 limbs) also had an MRI. A total of 9 OCD-like lesions in 6 patients were identified on plain radiographs, with an overall prevalence of 10% (6/63) of patients and 10% (9/87) limbs. From the 37 patients (53 limbs) who had an MRI, 7/37 (19%) patients 10/53 (19% limbs)had the OCD-like lesion present on their MRI. All lesions were found in the posterior one third of the medial femoral condyle. The mean area of the lesion on plain imaging was 197.2 mm 2 (95%CI = 133.9 mm 2, 260.5 mm 2) and 163.0 mm2 (95%CI = 107.6,218.5) on MRI (p=0.36). Based on the Hefti classification there were 3 stage I, 2 stage II and 5 stage III lesions. Using the Dipaola system there were 4 stage I, 4 stage II and 2 stage III lesions. Comparing patients with an OCD-like lesion versus those without, there was no statistically significant difference between the groups in terms of early-onset versus late-onset disease (p=0.21), gender (p=0.23), mean age at imaging (p=.0.06) and laterality (p=0.07). Additionally, there was also no significant difference between the two groups in terms of mean MAD (63.3 mm vs 71.9 mm, p=0.39), mean mLDFA (91.3 degrees vs 89.7 degrees, p=0.43) and mean MPTA (71.7 degrees vs 71.8 degrees, p=0.95). What is your conclusion? OCD-like lesions in the medial femoral condyle can be seen in children with Blount disease. The overall prevalence of these lesions is around 10% based on plain radiographs and 19% based on MRI scans. Based on the numbers available, we were unable to demonstrate any associations between the presence of such OCD-like lesions and the patient’s age, gender or magnitude of varus deformity. Further research is needed to fully ascertain the etiology and natural history of these lesions in children with Blount disease. [Table: see text][Figure: see text][Figure: see text]

scholarly journals Stage II Differentiated Thyroid Cancer Is a High-Risk Disease in Patients <45/55 Years Old

2019 ◽  
Vol 104 (11) ◽  
pp. 4941-4948 ◽  
Author(s):  
Zeming Liu ◽  
Xiaopei Shen ◽  
Rengyun Liu ◽  
Guangwu Zhu ◽  
Tao Huang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mortality Risk ◽  
Older Patients ◽  
Differentiated Thyroid Cancer ◽  
Staging System ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Ajcc Staging System ◽  
Ajcc Staging

Abstract Purpose The mortality risk of stage II differentiated thyroid cancer (DTC) based on the American Joint Committee on Cancer (AJCC) staging system requires further investigation. Methods Retrospective study of DTC in the US Surveillance, Epidemiology, and End Results program for disease-specific mortality risk in various AJCC stages, with patient age stratification of stage II disease. Results Using AJCC staging system 6.0, hazard ratios (HRs) of mortality for stage II DTC in patients &lt;45 yo and patients ≥45 yo and stages III, IVA, IVB, and IVC compared with stage I were 46.95, 4.95, 9.82, 57.37, 222.10, and 468.68, respectively, showing a robustly higher mortality risk in stage II disease in patients &lt;45 yo than in older patients (P &lt; 0.001), comparable with stage IVA (P = 0.482). Similar results were obtained with AJCC 7.0. With AJCC 8.0, HRs of mortality for stage II in patients &lt;55 yo and patients ≥55 yo and stages III, IVA, and IVB compared with stage I were 75.16, 11.23, 69.45, 134.94, and 235.70, respectively, showing a robustly higher risk in stage II disease in patients &lt;55 yo than in older patients (P &lt; 0.001), comparable with stage III (P = 0.57). Kaplan-Meier survival curves displayed a sharp decline with stage II disease in patients &lt;45/55 yo compared with older patients. Conclusions The mortality risk of stage II DTC was sharply differentiated at patient age 45/55 years, being robustly high in younger patients and comparable with stage III/IVA. This emphasizes the importance of considering age when managing stage II DTC and not treating it as a uniformly low-risk disease.

scholarly journals Stages of ovarian and endometrial cancer detection in women in the postmenapausal period in Baku city

2019 ◽  
Vol 100 (5) ◽  
pp. 746-750
Author(s):  
M A Garashova
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Postmenopausal Women ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Malignant Neoplasms ◽  
Morphological Studies ◽  
Postmenopausal Period ◽  
Significant Difference

Aim. To study the severity (according to the stages at the time of diagnosis) of female genital cancer detected in postmenopausal women in Baku in 20162018. Methods. 306 postmenopausal women with various tumors of the reproductive system were examined. The average age of the examined women was 59.30.4 (4883) years. 166 (54.2%) out of 306 patients had malignant tumors of the genitalia including ovarian cancer (n=97), endometrial cancer (n=50), cervical cancer (n=13), uterine sarcoma (n=6). Clinical, functional, laboratory, radiological, and morphological studies were performed. For the analysis of the obtained digital data, discriminant analysis methods were applied. The rate (Р%) and its 95% confidence intervals (mp%) of ovarian and endometrial cancer of the postmenopausal period among female citizens of Baku were calculated. Statistical significance of the difference between the indicators in the groups was determined by Pearson 2-criterion. All calculations were performed in Excel 2013 and SPSS-20. Results. According to the data of the study, ovarian cancer in the postmenopausal period was diagnosed in 15.53.7% of females at stage I, in 8.22.8% at stage II, in 66.04.8% at stage III, in 10.33.1% at stage IV of the development of the tumor process. In 68.06.6% of patients with endometrial cancer in the postmenopausal period, the tumor was determined at stage I, in 30.06.5% of patients at stage II, and in 2.02.0% of patients at stage III of the development of the tumor process. On comparison of the stages at detection of ovarian and endometrial cancer, a significant difference between these two forms of malignant neoplasms was found for both stages I and III. Conclusion. Detection of genital tumors in postmenopausal women is characterized by the diagnosis of ovarian cancer mainly in the later stages of the disease (compared to endometrial cancer), which indicates the need to develop effective screening methods for earlier detection of this tumor process.

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