Short-Term Risk of Progression of Patients with Asymptomatic Monoclonal Gammopathies to Active Multiple Myeloma: The Critical Impact of the Tumoral Mass

The identification of risk factors for progression is critical in the clinical management and appropriate follow up of patients with pre-malignant Asymptomatic Monoclonal Gammopathies (AMG) including Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). The development of prognostic score and consequently the early identification of patients with possible short-term progression to Multiple Myeloma (MM) could lead to anticipate the treatment. In this study, we retrospectively evaluated possible risk factors of short-term progression to active MM in a large cohort of MGUS and SMM patients admitted to a single haematological center (Hematology and BMT Unit, University Hospital of Parma) between 2010 and 2018. We analysed a total cohort of 235 patients diagnosed with AMG (81 MGUS and 154 SMM) according to the IMWG recently updated diagnostic criteria. All patients analysed underwent to Bone Marrow (BM) examination; moreover, imaging evaluation was performed in 22 MGUS and 123 SMM patients, in order to exclude the presence of bone disease. In a subgroup of AMG patients (n=50), bone mineral density (BMD) evaluation by Dual-energy X-ray Absorptiometry (DXA) was also available. Median age of the AMG patients analysed was 68 years (range 35-93 years). Median percentage of BM plasma cells (BMPCs) was 12% (range 2-55%) in the entire population, 7% (range 2-9) in MGUS and 15% (range 10-55) in SMM patients. Median serum M-protein was 1.7 g/dL (range: 0.17-4.5), 1.5 g/dL (range 0.17-4.5) in MGUS and 1.8 g/dL (range 0.4-2.7) in SMM patients. An abnormal free light chain (FLC) ratio was found in 70% of AMG patients, among the ones that performed the analysis; regarding SMM patients, FLC ratio value was available in 97 patients: in 72 (76%) the ratio was unbalanced, 37 (39%) had a FLC ratio ≤ 0.125 or ≥ 8 and in 14 (15%) it was > 20; among MGUS patients, value was collected in 41 patients and in 21 (51%) it was <0.26 or >1.65. The presence of immunoparesis in one or two uninvolved immunoglobulins occurred in 59% of the entire population. The median follow up time was 18 months (range 0 - 111 months) for whole population. Overall 44 patients of the entire cohort progressed to MM (41 SMM and 3 MGUS) with a median TTP of 14.5 months. By univariate analysis we found that percentage of BMPCs, entity of M-protein and presence of immunoparesis were significantly correlated with progression to active MM (p<0.001 for each variable). On the other hand, abnormal FLC ratio did not reach a statistical significance, as well as value of the involved FLC (p=0.059). Nevertheless, the presence of a FLC ratio < 0.125 or > 8 (as used in Mayo scoring system for SMM) showed a relationship at the limit of statistical significance in this subgroup of patients (p=0.052). Any significant correlation was not observed with age, sex, Ig isotype, light chain's type and the BMD values (p=NS). Afterwards, we applied Kaplan Meier method on risk factors resulted significant in univariate analysis demonstrating that they also significantly influenced the time to progression to MM. Finally, through a binomial logistic regression, we developed a new prognostic score for whole population. By combining the values of M-protein (< 2, score=0 or ≥ 2 g/dL, score=1) and the percentage of BMPC (<10%, score=0, 10-20%, score=1 and >20%, score=2), we obtained six groups at different probability of progression to active MM (Table 1). Given that result, we stratified patients in 3 groups: low-risk (score=0), intermediate-risk (score=1) and high-risk (score≥2); log-rank test confirmed that high-risk patients had a significantly shorter time to progression to symptomatic MM as compared to intermediate and low-risk patients (p<0.001). In conclusion, our results show that in patients with AMG the clinical factors, which mostly impact on the short-term risk of progression to active MM, are the entity of the PCs infiltrate and the MC related to the tumoral mass. The development of a clinical score based on BMPCs and M-protein will permit to overcome the traditional distinction between MGUS and SMM in the evaluation of the progression of AMG patients to active MM. Disclosures Giuliani: Janssen: Research Funding.

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Immunoglobulin Free Light Chains at Diagnosis: Predictors of Progression and Survival in Solitary Plasmacytoma of Bone.

Blood ◽

10.1182/blood.v106.11.5080.5080 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5080-5080 ◽

Cited By ~ 1

Author(s):

David Dingli ◽

Robert A. Kyle ◽

Vincent S. Rajkumar ◽

Grzegorz S. Nowakowski ◽

Dirk R. Larson ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Cells ◽

Univariate Analysis ◽

Prognostic Indicator ◽

M Protein ◽

Solitary Plasmacytoma ◽

Time To Progression ◽

Number Of Patients ◽

M Proteins ◽

Risk Of Progression

Abstract Background: Solitary plasmacytoma of bone (SBP) is a localized collection of monoclonal plasma cells that is potentially curable with local radiation therapy but associated with a high risk of progression to multiple myeloma. We hypothesized that an abnormal immunoglobulin free light (FLC) ratio at diagnosis may be a prognostic indicator of transformation risk. Methods: We identified a cohort of 133 patients with SBP for whom stored serum taken at the time of diagnosis was available. The diagnosis was ascertained and serum FLC determined in 126 patients. Results: From this cohort, 48 patients have progressed to myeloma and the median time to progression among those who progressed was 1.9 years. On univariate analysis, age (p<0.001), gender (p=0.035), abnormal FLC ratio at diagnosis (p=0.009) and persistence of serum or urine M-protein after therapy (p=0.0070 were all associated with a shorter overall survival (OS) and time to progression to multiple myeloma. Progression by Normal FLC(0.26–1.65) Progression by Normal FLC(0.26–1.65) On multivariate analysis, an abnormal FLC ratio retained its independence in a model that includes age at diagnosis but lost its significance when combined with persistence of the serum or urine M-protein. However, serum or urine M-proteins are not detectable in a significant number of patients with SBP and therefore not informative. Conclusion: The FLC ratio at the time of diagnosis of SBP is a powerful predictor of risk and a useful aid to management of patients with this condition.

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Metastatic Bone Survey in Monoclonal Gammopathy of Undertermined Significance: Useful or Not?

Blood ◽

10.1182/blood.v112.11.2728.2728 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2728-2728

Author(s):

Vrushali s Dabak ◽

Esther Urbaez Duran ◽

Muath Dawod ◽

Amr Hanbali

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Bone Marrow ◽

Serum Calcium ◽

Plasma Cells ◽

Bone Marrow Aspiration ◽

Hemoglobin Concentration ◽

M Protein ◽

Risk Of Progression ◽

Male Sex

Abstract Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of a serum monoclonal protein <3g/dl, with fewer than 10% plasma cells in bone marrow and absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency. Incidence increases with age, especially over 70 and its progression to malignant disease occurs at 1% per year. However, so far there are no studies which can reliably distinguish patients who would progress from those who would remain stable. Based on available literature, it is concluded that MGUS has low risk of progression when M-protein is less than 1.5 g/dl, with no reduction in polyclonal immunoglobulins and bone marrow plasma cells less than 5%. The recommended testing with suspected MGUS is hemoglobin concentration, protein studies, serum calcium, and creatinine. Metastatic bone survey (MBS) and bone marrow aspiration are felt unnecessary if M-protein is less than 1.5 g/dl. However literature to support the use of MBS at diagnosis based on the level of M-protein is limited. Also our observation has been that due to lack of clear guidelines, most physicians obtain a baseline MBS and some follow patients with yearly or every other year MBS irrespective of the level of M-protein. Hence, we decided to review patients diagnosed with MGUS at our institution to determine the importance of MBS and if possible identify risk factors like age, race, M-protein level, hemoglobin concentration, serum calcium or creatinine level, which would identify a subgroup of patients needing a MBS. In doing so we were hoping to separate out those patients in whom we could recommend against unnecessary use of the skeletal survey below a certain defined M protein level. Study: We reviewed charts on 1906 patients at Henry Ford hospital diagnosed with MGUS between 1990 and 2007. All patients with at least one M-protein and one MBS done were included in the analysis. We excluded patients with a level of M-protein >3.0 g/dl, who never had a skeletal survey in our system, had a light chain myeloma, plasmacytoma, chronic lymphocytic lymphoma(CLL), amyloidosis or protein evaluation done for diagnosis other than MGUS. We had 620 such patients. We collected data regarding their age, sex, ethnicity, date of diagnosis, type and level of the M-protein, hemoglobin level, serum calcium and creatinine at baseline, result of the MBS, date of progression to multiple myeloma (MM) if any and the date of last follow up if they did not progress to MM. Positive MBS is defined as x ray findings consistent with myelomatous changes with bone marrow aspiration confirming diagnosis of MM. Results: Of 620 patients, 36 had a positive MBS and applying non parametric Mann Whitney test and a chi-squared test, positive results seemed to correlate with higher level of M-protein, IgG subtype, lower hemoglobin and higher creatinine. Male sex and older age were other risk factors. Using the LOES curve to graph the risk of a positive skeletal event with the level of M-protein, risk was noted to increase significantly with M-protein in the range of 1.8– 3.0 (odds ratio 8.84 compared with 1.31 if level was less than 1.8), which was highly statistically significant as shown in figure 1. Further for 97/620 who progressed to multiple myeloma, the risk of progression was significantly higher for males, younger age at diagnosis of MGUS, lower hemoglobin, higher level of M-protein, IgG subtype and a positive skeletal event. Discussion: Our study is a retrospective chart review with its own limitations. However to our knowledge this is the first study to define the level of M-protein in patients with MGUS above which obtaining a MBS may be of value. Our study identifies 1.8 as a cut off value of M-protein below which doing routine MBS without symptoms of bone pains or other laboratory features suggesting progression to multiple myeloma might be unnecessary. Other risk factors for a positive event and progression to MM like lower hemoglobin, higher creatinine, older age, male sex and IgG subtype in our study are in keeping with what has been described in the literature. Conclusion: Based on our study, obtaining baseline MBS in all patients with suspected MGUS was not beneficial. Hence, we would not recommend obtaining MBS in patients with M-protein <1.8 g/dl in absence of other risk factors for progression to multiple myeloma. Figure 1: LOES curve showing increased likelihood of positive MBS for increasing MPEV level. Figure 1:. LOES curve showing increased likelihood of positive MBS for increasing MPEV level.

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Short-Term Risk for Progression in Patients with Smoldering Multiple Myeloma: The Impact of CD56 Expression

Blood ◽

10.1182/blood-2020-139214 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 11-11

Author(s):

Laura Notarfranchi ◽

Rosanna Vescovini ◽

Roberta Segreto ◽

Sabrina Bonomini ◽

Paola Storti ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Study ◽

Board Of Directors ◽

Research Funding ◽

Prognostic Score ◽

Short Term ◽

Advisory Committees ◽

Risk Of Progression ◽

Cd56 Expression

The identification of risk factors for progression is critical in the clinical management and appropriate follow up of patients with Smoldering Multiple Myeloma (SMM). The early identification of patients with possible short-term progression to Multiple Myeloma (MM) could lead to anticipate the treatment. Several prognostic score identify in SMM patients the main risk factors for progression to MM. The two most used risk stratification models in SMM are the Mayo Clinic model, based on the tumor burden and the free light chains ratio, and the Spanish PETHEMA group model based on the immunophenotyped to identify abnormal plasma cells (PCs) and the reduction of the unevolved immunoglobulins. However, significant discrepancies between these two clinical models currently used in clinical practice has been recently underlined. For this reason, new parameters to identify possible new parameters for progression in SMM need to be defined. The aim of this study was to validate the main prognostic score and to investigate the possible role of the immunphenotype as risk factor for progression in a monocentric cohort of patients with SMM. We retrospectively evaluated a cohort of SMM patients admitted to a single haematological center (Hematology and BMT Unit, University Hospital of Parma) between 2014 and 2018. We analyzed a total cohort of 80 patients diagnosed with SMM according to the IMWG recently updated diagnostic criteria. All patients analysed underwent to Bone Marrow (BM) examination and imaging evaluation was performed in order to exclude the presence of bone disease and/or focal lesions. Both immunophenotypic and FISH analysis were performed of BMPCs. The median age of the SMM patients analysed was 68 years (range 36-93 years). Median percentage of BMPCs was 15% (range 10-40%) in the entire population. Median serum M-protein was 2 g/dL (range: 0.17-4.5). FLC ratio value was available in 66 patients: in 47 (71%) the ratio was unbalanced, 26 (39%) had a FLC ratio ≤ 0.125 or ≥ 8 and in 6 (9%) it was > 20. The presence of a reduction of one or two uninvolved immunoglobulins occurred in 61% of the entire population. The median follow up time was 27 months (range 0 - 76 months) for whole population. Overall 22 patients of the entire cohort progressed to MM with a median the time to progression (TTP) of 22 months. Firstly, we validated the currently score of progression in our cohort of SMM patients. By univariate analysis we found that percentage of BMPCs, abnormal FLC ratio and presence of immunoparesis were significantly correlated with progression to active MM (p<0.005 for each variable). Any significant correlation was not observed with age, sex, Ig isotype and light chain's type (p=NS). Afterwards, we study and confirm the significance of the risk stratification models. "Pethema" (p=0.0002), "20-2-20" Mayo score (p=0.0005) and also the "Danish score" (p= 0.0173) turned out statistically significant. Then, we investigate the possible role of immunophenotype in the risk of progression. Dividing the population-based on CD56 expression, we found that the median TTP in CD56- SMM patients was 21 months as compared to 34 months in CD 56+ SMM patients (p= 0.08). Moreover CD56- patients progressed without a significant increase of the monoclonal component (p=0.48) as compared to those CD56+ SMM patients (p=0.023). Finally, a relationship between CD56 expression and the hyperdiploidy was wound finding that CD56- SMM patients had a significant lower presence of hyperdiploidy as compared to those with CD56+ BMPCs (p=0.024) In conclusion, our data indicate that in SMM patients the factors, which mostly impact on the short-term risk of progression to active MM, are the entity of the PCs infiltrate, the immunoparesis and abnormal FLC ratio. Therefore, we identified the absence of CD56 expression by BMPCs as a possible factor for a more aggressive disease regardless to the tumoral burden. Disclosures Giuliani: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Participation in congresses, Research Funding; Janssen Pharmaceutical: Membership on an entity's Board of Directors or advisory committees, Other: Clinical study sponsorship; participation in congresses, Research Funding; Millennium Pharmaceutical: Other: Clinical study sponsorship, Research Funding; GSK: Other: Clinical study sponsorship, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Other: Participation in congresses.

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Smoldering Multiple Myeloma: Usefulness of Serum Heavy/Light Chain Measurements for the Evaluation of Evolving Pattern

Blood ◽

10.1182/blood-2018-99-117385 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4514-4514

Author(s):

Carlos Fernandez de Larrea ◽

Ignacio Isola ◽

Esther Moga ◽

Maria Teresa Cibeira ◽

Ester Lozano ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Prognostic Factors ◽

Light Chain ◽

Protein Level ◽

Progressive Increase ◽

M Protein ◽

Smoldering Multiple Myeloma ◽

Risk Of Progression

Abstract Introduction: Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous clonal plasma cell disorder. A number of prognostic factors to identify patients at a higher risk of progression have been described, such as the size of the M protein, proportion of abnormal bone marrow plasma cells (BMPCs), immunoparesis and serum free light chain (FLC) k/l ratio. More recently, isotype-specific uninvolved heavy and light chain (HLC) pair suppression measured with the Hevylite assay was also associated with an increased risk of progression. Recent studies have evaluated the key prognostic impact of an increase in M-protein levels during follow-up ("evolving" pattern). However, an important limitation could be the evaluation of M-protein level variations based on serum protein electrophoresis (SPE) in patients with a small size M-spike. The aim of this study was to prospectively analyze the changes in M-protein according to SPE and HLC measurements, as well as other risk factors for progression, in patients with SMM. Methods: Thirty patients newly diagnosed with SMM at a single institution from January 2014 through September 2017 were prospectively included in the study. For each patient, baseline levels of known prognostic factors (serum M-protein, serum and urine immunofixation, clonal BMPCs percentage, total immunoglobulins, involved/uninvolved FLC and involved/uninvolved HLC pairs) were recorded. During the follow up, M-protein level, FLC and isotype specific HLC pairs were also analyzed. Evolving change in M-protein level according to SPE was defined as ³ 10% increase within the first 6 months of diagnosis (if M-protein was ³ 30 g/L) and/or ³ 25% increase within the first 12 months (for any level of M-protein); evolving change according to HLC was defined as a ³ 10% increase in the involved pair. A sequential increase in each of three or more consecutive measurements from diagnosis was considered an evolving change regardless of its magnitude. Results: The clinical characteristics of the total of patients, as well as of the patients with evolving changes in M-protein according to HLC are summarized in Table 1. During the study period, 5/30 (17%) of patients demonstrated an evolving behavior of the M-protein according to SPE. Four of these patients (4/5) also showed a progressive increase in the M-protein in the HLC measurements. One patient showed stable HLC levels even though both the M-protein and the involved FLC progressively increased. This patient was of intermediate and low risk according to Mayo Clinic and PETHEMA scores, respectively. On follow up, no progressive suppression of the isotype-specific uninvolved HLC pair or increase in the FLC ratio was noted, and there have been no signs of progression after a follow up of 3 years. According to involved HLC-pair levels, 12/30 (40%) of patients demonstrated an evolving behavior. Five out of 7 patients that were not classified as evolving by SPE, were IgA isotype. Eight out of 12 patients showed severe isotype-specific suppression of the uninvolved HLC-pair (> 50% below lower level of normal) as well as a highly abnormal FLC ratio (<0.125 or >8). Three out of the 4 remaining patients showed either severe isotype-specific HLC pair suppression or highly abnormal FLC ratio in follow up measurements. Compared to patients with no "HLC-evolving pattern", evolving patients were more likely to have highly abnormal FLC ratios (90 vs. 33%, p=0.009), severe suppression of the other isotypes (64 vs. 19%, p=0,024), highly abnormal isotype-specific HLC ratios (67 vs. 33%, p=NS), severe isotype-specific HLC-pair suppression (75 vs. 50%, p=NS), and immunoparesis (67 vs. 39%p=NS). Five patients progressed to symptomatic multiple myeloma during follow up; 4 of them showed a progressive increase in the involved HLC pair from diagnosis. The remaining patient demonstrated a progressive increase in the involved HLC pair that started 19 months prior to progression, followed 4 months later with an increase in M-protein as measured by SPE. Conclusions: In our series, the Hevylite assay allowed us to identify patients with a progressive increase in M-protein (clonal heavy/light chain pair) that was not evident with SPE measurements. This "HLC evolving pattern" was associated with other risk factors for progression to symptomatic disease and with worsening of other prognostic parameters during follow up. Disclosures Rosinol: Janssen, Celgene, Amgen, Takeda: Honoraria. Bladé:Janssen: Honoraria.

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Prediction of Progression of Smouldering into Therapy Requiring Multiple Myeloma By Easily Accessible Clinical Factors [in 527 Patients]

Blood ◽

10.1182/blood.v124.21.2071.2071 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2071-2071 ◽

Cited By ~ 9

Author(s):

Roman Hajek ◽

Viera Sandecka ◽

Anja Seckinger ◽

Ivan Spicka ◽

Vlastimil Scudla ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Plasma Cells ◽

Risk Model ◽

Validation Cohort ◽

M Protein ◽

Tumour Mass ◽

Clinical Parameters ◽

Clinical Factors ◽

Risk Of Progression

Abstract Background Several models predict the progression from smouldering multiple myeloma (SMM) to therapy requiring multiple myeloma (MM). Three models comprise the assessment of tumour mass by different clinical parameters to stratify in risk groups: 1) the Mayo Clinic model uses bone marrow plasma cells percentage (BMPC) and serum monoclonal protein (M-protein), 2) the PETHEMA model uses immunoparesis and the percentage of abnormal plasma cells by flow cytometry, 3) the Heidelberg group assesses tumour mass by either the percentage of malignant plasma using iFISH or the Mayo assessment depicted above, and the presence of chromosomal aberrations associated with adverse prognosis. Besides tumor mass, they find the number of focal lesions in whole body MRI (>1) as strong prognostic factor. Aim To assess a combination of easily accessible clinical factors identifying patients at ≥ 80% risk of progression to MM requiring treatment within two years from the diagnosis of SMM. Methods Data for this study were obtained from the Registry of Monoclonal Gammopathies (RMG) acquired from hematologic centers of the Czech Republic for 287 SMM patients enrolled from May 2007 to June 2013. A cohort comprising 240 SMM patients from Heidelberg, Germany was used for validation (Neben et al. JCO 2013). Results During the follow up period (median 2.4 years; range 0.6 - 18.0) progression to MM was observed in 51.9% (149/287) patients in the study cohort, representing 16% risk of progression at 1 year, 31.2% at 2 years, 54.8% at 5 years and 73.4% at 10 years. In univariate analysis factors significantly associated with progression were as follows: serum free light chain (iFLC/uFLC) ratio > 30 (HR 2.4 [95% CI: 1.4 - 4.1]; p< 0.001) plasma cell infiltration in bone marrow cytology ≥ 15% (HR 2.1 [1.5-3.0]; p< 0.001), immunoparesis (HR 2.0 [1.3-2.9]; p< 0.001), M - protein concentration ≥ 2.3 g/dL (HR 2.00 [1.4-2.7]; p< 0.001), beta2 microglobulin ≥ 2.0 mg/l (HR 1.8 [1.2-2.7]; p= 0.001), and thrombocyte count ≤ 250 x 109/l (HR 1.7 [1.1-2.4]; p= 0.005). In multivariate analysis, 3 parameters showed independent predictive value (immunoparesis, serum M-protein quantity ≥ 2.3 g/dL and iFLC/uFLC > 30). Combining these factors, we proposed a new risk model for SMM patients (CMG model). The risk of progression from SMM to MM at 2 years was 18.5%, 20.9%, 41.9% and 78.7% if 0 (reference group), 1, 2 or 3 risk factors are present (p< 0.001) (Figure 1) with HR of 1.5 [0.7-2.9]; p=0.283, 2.5 [1.3-5.0]; p= 0.008, 6.8 [3.0-15.2]; p<0.001, n=139), respectively. The CMG model was validated on 240 SMM patients from Heidelberg published in 2013. The risk of progression from SMM to MM at 2 years was 5.3%, 7.5%, 44.8% and 81.3% if 0, 1, 2 or 3 risk factors were present, respectively (p< 0.001) (Figure 1) with HR of 4.2 ([0.5-36.1]; p=0.189), 21.5 ([2.9-159.1]; p= 0.003, HR 38.6 [4.7- 317.7]; p<0.001, n=113). Conclusion We propose and validate a new risk model for SMM patients with prediction of 80% (78.7% on our CMG model; 81.3% on data from Heidelberg) risk of progression to therapy requiring myeloma within two years based on easily accessible clinical parameters (CMG model). The model could especially be used to identify high-risk patients to be included in early treatment clinical trials. Acknowledgments: This work was supported by grants NT13492-4, NT14575-3 and by EU FP7/2007-2013; grant n°278570 and “OverMyR”, as well as the Deutsche Forschungs-Gemeinschaft (DFG) SFB/TRR79. Figure 1: CMG risk model: CMG cohort of patients and validation cohort of Heidelberg patients Figure 1:. CMG risk model: CMG cohort of patients and validation cohort of Heidelberg patients Disclosures Seckinger: Novartis: Research Funding.

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The Prognostic Value of the New Combined Hemo-Eosinophil Inflammation Index (HEI Index): A Multicenter Analysis of Anal Cancer Patients Treated with Concurrent Chemo-Radiation

Cancers ◽

10.3390/cancers13040671 ◽

2021 ◽

Vol 13 (4) ◽

pp. 671

Author(s):

Margherita Rimini ◽

Pierfrancesco Franco ◽

Berardino De Bari ◽

Maria Giulia Zampino ◽

Stefano Vagge ◽

...

Keyword(s):

High Risk ◽

Cancer Patients ◽

Anal Cancer ◽

Prognostic Score ◽

Univariate Analysis ◽

External Validation ◽

Risk Groups ◽

Anal Squamous Cell Carcinoma ◽

Predictors Of Response ◽

Risk Patients

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04–5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

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Which Factors Increase the Risk of Re-Operation after Meniscus Surgery in the Skeletally Immature?

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967118s00064 ◽

2018 ◽

Vol 6 (7_suppl4) ◽

pp. 2325967118S0006

Author(s):

Neeraj M. Patel ◽

Surya Mundluru ◽

Nicholas Beck ◽

Theodore J. Ganley

Keyword(s):

Risk Factors ◽

Cruciate Ligament ◽

Statistical Significance ◽

Univariate Analysis ◽

Multivariate Model ◽

Skeletally Immature ◽

Initial Surgery ◽

Repeat Operation ◽

Operation Rate ◽

Meniscus Surgery

Objectives: The purpose of this study is to determine which factors heighten the risk for subsequent operations in skeletally immature patients undergoing meniscus surgery. Methods: A retrospective institutional database of 1,063 meniscus surgeries performed between 2000 and 2015 was reviewed. All procedures were performed in skeletally immature patients. Demographic and intra-operative information was recorded, as were concurrent injuries or operations and subsequent surgeries. Univariate analysis consisted of chi-square and independent-samples t-tests. Multivariate logistic regression was then performed to control for confounding factors. Results: The mean age at initial surgery was 13.4 years (standard deviation, SD, 2.2 years) and the average follow-up duration was 47 months (SD 54 months). Overall, 314 patients (29.5%) required repeat surgical intervention. 36% of all females required subsequent surgery compared to 26% of males (p<0.01). Discoid menisci underwent repeat operation more frequently than non-discoid menisci (35% vs. 27%, p=0.01). After accounting for confounders in a multivariate model, females had 2.2 times the odds of repeat surgery than males (95% CI 1.4-3.3, p<0.01) and each year of increasing age resulted in 1.3 times higher odds (95% CI 1.1 -1.4, p<0.01). The odds of subsequent surgeries were 4.2 times higher in those with flap tears (95% CI 1.8-9.7, p<0.01) and 2.9 times higher for discoid menisci (95% CI 1.4-6.0, p<0.01). Concomitant anterior cruciate ligament rupture or tibial spine fracture decreased the risk of needing additional surgeries in univariate analysis, but lost statistical significance in the multivariate model. Conclusion: Even when accounting for other factors in a multivariate model, female sex, increasing age, flap tears, and discoid meniscus were risk factors for subsequent procedures after meniscus surgery in skeletally immature patients. The re-operation rate in this population may be higher than previously reported. This study describes, for the first time, risk factors for repeat operations in skeletally immature patients undergoing meniscus surgery. These results can be used to counsel and monitor patients accordingly.

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Intestinal Microsporidiosis Among HIV/AIDS Patients Receiving Antiretroviral Therapy in Sana’a City, Yemen: First Report on Prevalence and Predictors

10.21203/rs.3.rs-684810/v1 ◽

2021 ◽

Author(s):

Kwkab A. R. Al-Barhami ◽

Rashad Abdul-Ghani ◽

Salah A. Al-Qobati

Keyword(s):

Risk Factors ◽

Antiretroviral Therapy ◽

Large Scale ◽

Statistical Significance ◽

Univariate Analysis ◽

Cell Counting ◽

Cd4 Cells ◽

Aids Patients ◽

Intestinal Microsporidiosis ◽

Hiv Aids

Abstract Background: Intestinal microsporidiosis is an opportunistic infection associated with persistent diarrhea among HIV/AIDS patients. In Yemen, however, its epidemiology is unknown. Therefore, this study determined its prevalence and predictors among HIV/AIDS patients receiving antiretroviral therapy (ART) in Sana'a city, Yemen.Methods: This cross-sectional study included 402 patients receiving ART at Al-Jomhori Educational Hospital in Sana'a from November 2019 to December 2020. Data about demographics, clinical characteristics and risk factors were collected using a pre-designed questionnaire. Stool samples were collected and examined for microsporidian spores using the Gram-chromotrope Kinyoun staining. Blood samples were also collected and used for CD4 cell counting by flow cytometry. Univariate analysis was used to test the association of patients’ characteristics and risk factors with intestinal microsporidiosis. Multivariable logistic regression was then used to identify the independent predictors of infection. Statistical significance was considered at P-values <0.05. Results: Intestinal microsporidiosis was prevalent among 14.2% (57/402) of HIV/AIDS patients but was not significantly associated with any of the studied demographics, source of drinking water, bathing and/or swimming outdoors, contact with soil, presence of domestic animals or indiscriminate defecation. However, it was significantly associated with diarrhea (OR=3.4, 95% CI: 1.7–6.6; P=0.001) and <200 CD4 cells/µl (OR=2.7, 95% CI: 1.5–5.0; P=0.001). The significant independent predictors of infection were <200 CD4 cells/µl (AOR=3.2, 95% CI: 1.5–6.9; P=0.003), not washing hands after contacting soil (AOR=2.5, 95% CI: 1.1–5.4; P=0.026) and before eating (AOR=3.1, 95% CI: 1.5–6.4; P=0.003), eating unwashed raw produce (AOR=2.5, 95% CI: 1.2–5.3; P=0.017) and absence of indoor latrines (AOR=6.2, 95% CI: 1.5–25.9; P=0.012).Conclusions: The prevalence of intestinal microsporidiosis among HIV/AIDS patients in Sana'a is high and comparable to that several other countries, being prevalent among approximately 14.0% of patients and significantly associated with diarrhea. It could be predicted among patients who have <200 CD4 cells/µl, poor hand hygiene after contacting soil and before eating, usually eat unwashed raw produce and do not possess indoor latrines. Large-scale studies on its epidemiology and predictors among HIV/AIDS patients across the country are warranted.

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A New Rapid Approach for Predicting Death in Coronavirus Patients: The Development and Validation of the COVID-19 Risk-Score in Fars Province (CRSF)

Iranian Journal of Public Health ◽

10.18502/ijph.v51i1.8310 ◽

2022 ◽

Author(s):

Mehrdad Sharifi ◽

Mohammad Hossein Khademian ◽

Razieh Sadat Mousavi-Roknabadi ◽

Vahid Ebrahimi ◽

Robab Sadegh

Keyword(s):

Risk Factors ◽

Risk Score ◽

Predictive Value ◽

Assessment Tool ◽

Fars Province ◽

Risk Of Mortality ◽

Risk Patients ◽

Independent Risk Factors ◽

Development And Validation ◽

Underlying Diseases

Background:Patients who are identified to be at a higher risk of mortality from COVID-19 should receive better treatment and monitoring. This study aimed to propose a simple yet accurate risk assessment tool to help decision-making in the management of the COVID-19 pandemic. Methods: From Jul to Nov 2020, 5454 patients from Fars Province, Iran, diagnosed with COVID-19 were enrolled. A multiple logistic regression model was trained on one dataset (training set: n=4183) and its prediction performance was assessed on another dataset (testing set: n=1271). This model was utilized to develop the COVID-19 risk-score in Fars (CRSF). Results: Five final independent risk factors including gender (male: OR=1.37), age (60-80: OR=2.67 and >80: OR=3.91), SpO2 (≤85%: OR=7.02), underlying diseases (yes: OR=1.25), and pulse rate (<60: OR=2.01 and >120: OR=1.60) were significantly associated with in-hospital mortality. The CRSF formula was obtained using the estimated regression coefficient values of the aforementioned factors. The point values for the risk factors varied from 2 to 19 and the total CRSF varied from 0 to 45. The ROC analysis showed that the CRSF values of ≥15 (high-risk patients) had a specificity of 73.5%, sensitivity of 76.5%, positive predictive value of 23.2%, and negative predictive value (NPV) of 96.8% for the prediction of death (AUC=0.824, P<0.0001). Conclusion:This simple CRSF system, which has a high NPV,can be useful for predicting the risk of mortality in COVID-19 patients. It can also be used as a disease severity indicator to determine triage level for hospitalization.

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Abstract 78: Risk Factors Associated with Failure of Aggressive Medical Therapy in the SAMMPRIS Trial

Stroke ◽

10.1161/str.45.suppl_1.78 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Michael F Waters ◽

Brian L Hoh ◽

Michael J Lynn ◽

Tanya N Turan ◽

Colin P Derdeyn ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Medical Therapy ◽

Primary Endpoint ◽

Univariate Analysis ◽

Baseline Risk ◽

Medical Group ◽

High Risk Patients ◽

Increased Risk ◽

Risk Patients

Background: The SAMMPRIS trial showed that aggressive medical therapy was more effective than stenting for preventing stroke in high-risk patients with symptomatic intracranial stenosis. However, 15% of patients in the medical group still had a primary endpoint (any stroke or death within 30 days of enrollment or stroke in the territory beyond 30 days) during a median follow-up of 32.7 months. We sought to determine baseline risk factors that were associated with a primary endpoint in the medical arm of SAMMPRIS. Methods: Data on 227 patients randomized to the medical group in SAMMPRIS were analyzed. Baseline demographic features, vascular risk factors, qualifying event, brain imaging and angiographic features were analyzed. The hazard ratio and p-value from a Cox proportional hazard regression model relating time until a primary endpoint to each factor were calculated. Results: Female gender, diabetes, stroke as the qualifying event (especially non-penetrator stroke), old infarct in the territory of the stenotic artery, and > 80% stenosis were associated (p < 0.10) with a higher risk of the primary endpoint on univariate analysis (see accompanying table) (multivariate analysis will be available by the time of ISC). Variables not associated with a higher risk of a primary endpoint in the medical arm included: age, race, antithrombotic therapy at the time of a qualifying event, time from qualifying event to enrollment (< 7 days vs. > 7 days), and location of stenosis. Conclusions: Several features were associated with an increased risk of the primary endpoint in the medical group in SAMMPRIS. On univariate analysis, the most important risk factors were an old infarct in the territory of the stenotic artery and stroke (especially non-penetrator stroke) as the qualifying event. These features will be useful for identifying particularly high-risk patients who should be targeted for future clinical trials testing alternative therapies to aggressive medical management.

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