Validation of Risk-Adapted Venous Thromboembolism Prediction in Multiple Myeloma Patients

Multiple myeloma (MM) is associated with an increased risk of venous thrombosis (VTE). In the United Kingdom Medical Research Council (MRC) XI study of patients treated with immunomodulatory therapy, the VTE rate was 11.8% despite 87.7% of the patients being on thromboprophylaxis at the time of thrombosis. In order to effectively prevent VTE events in MM patients, a better understanding of patient and disease risk factors that might predict thrombosis is required. We performed a retrospective cohort analysis of over 300 newly diagnosed MM patients at a tertiary referral centre to determine the VTE rate, predictive factors for VTE, value of the Khorana score for MM VTE events and long-term mortality outcomes. Fifty-four percent of the patients were receiving thromboprophylaxis at the time of the VTE event. The mortality odds ratio was 3.3 (95% CI, 2.4–4.5) in patients who developed VTE in comparison to age-matched controls with MM. A younger age at diagnosis and higher white cell count (WCC) were found to be predictive of VTE events. Our data suggest that standard thromboprophylaxis may not be effective in preventing VTE events in myeloma patients, and alternative strategies, which could include higher-intensity thromboprophylaxis in young patients with a high WCC, are necessary.

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Hypocalcemia in Military Casualties From Point of Injury to Surgical Teams in Afghanistan

Military Medicine ◽

10.1093/milmed/usaa267 ◽

2021 ◽

Vol 186 (Supplement_1) ◽

pp. 300-304

Author(s):

Jeffrey R Conner ◽

Linda C Benavides ◽

Stacy A Shackelford ◽

Jennifer M Gurney ◽

Edward F Burke ◽

...

Keyword(s):

Blood Product ◽

Calcium Supplementation ◽

Cohort Analysis ◽

Blood Product Transfusion ◽

Blood Products ◽

Military Trauma ◽

Retrospective Cohort Analysis ◽

Increased Risk ◽

Surgical Teams ◽

Patterns Of Injury

ABSTRACT Introduction Hypocalcemia is a known sequela of citrated blood product transfusion. Civilian data suggest hypocalcemia on hospital admission is associated with worse outcomes. Initial calcium levels in military casualties have not previously been analyzed. The objective of this retrospective review aimed to assess the initial calcium levels in military trauma casualties at different Forward Surgical Teams (FST) locations in Afghanistan and describe the effects of prehospital blood product administration on arrival calcium levels. Materials and Methods This is a retrospective cohort analysis of military casualties arriving from point of injury to one of two FSTs in Afghanistan from August 2018 to February 2019 split into four locations. The primary outcome was incidence of hypocalcemia (ionized calcium < 1.20 mmol/L). Results There were 101 patients included; 55 (54.5%) experienced hypocalcemia on arrival to the FST with a mean calcium of 1.16 mmol/L (95% confidence interval [CI], 1.14 to 1.18). The predominant mechanism of injury consisted of blast patterns, 46 (45.5%), which conferred an increased risk of hypocalcemia compared to all other patterns of injury (odds ratio = 2.42, P = .042). Thirty-eight (37.6%) patients required blood product transfusion. Thirty-three (86.8%) of the patients requiring blood product transfusion were hypocalcemic on arrival. Mean initial calcium of patients receiving blood product was 1.13 mmol/L (95% CI, 1.08 to 1.18), which was significantly lower than those who did not require transfusion (P = .01). Eight (7.9%) of the patients received blood products before arrival, with 6/8 (75%) presenting with hypocalcemia. Conclusions Hypocalcemia develops rapidly in military casualties and is prevalent on admission even before transfusion of citrated blood products. Blast injuries may confer an increased risk of developing hypocalcemia. This data support earlier use of calcium supplementation during resuscitation.

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The Impact of Routine Pulse Oximetry Use on Outcomes in COVID-19-Infected Patients at Increased Risk of Severe Disease: A Retrospective Cohort Analysis

SSRN Electronic Journal ◽

10.2139/ssrn.3804758 ◽

2021 ◽

Author(s):

Noluthando Nematswerani ◽

Shirley Collie ◽

Tommy Chen ◽

Michael Cohen ◽

Jared Champion ◽

...

Keyword(s):

Pulse Oximetry ◽

Retrospective Cohort ◽

Severe Disease ◽

Cohort Analysis ◽

Retrospective Cohort Analysis ◽

Increased Risk ◽

The Impact ◽

Routine Pulse Oximetry

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Correlation of Ki-67 indices from biopsy and resection specimens of neuroendocrine tumours

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2016.0225 ◽

2017 ◽

Vol 99 (3) ◽

pp. 193-197 ◽

Cited By ~ 3

Author(s):

J Barnes ◽

SJ Johnson ◽

JJ French

Keyword(s):

Neuroendocrine Tumours ◽

Tissue Sample ◽

Cohort Analysis ◽

Tumour Grade ◽

Tertiary Referral Centre ◽

Ki 67 ◽

Tissue Samples ◽

Tumour Grading ◽

Retrospective Cohort Analysis ◽

Resection Specimen

INTRODUCTION Neuroendocrine tumours (NETs) are a heterogeneous group of tumours with a highly variable presentation and prognosis. Management decisions are complex. Ki-67 levels in tissue samples are a key indicator used to grade tumours and guide treatment. This study assessed whether the Ki-67 index and tumour grade generated from tissue samples correlated with that assessed in resection specimens. METHODS This was a retrospective cohort analysis of all patients who had both a tissue sample and a resection specimen analysed in our trust, a tertiary referral centre, during 2012 and 2013. RESULTS Data from 36 patients were reviewed. Ki-67 indices from tissue samples and resection specimens showed strong correlation (r=0.95, p<0.001). Tumour grading was the same in the tissue sample and resection specimens for 22 patients (61.1%). In four patients (11.1%), the tissue sample overestimated the grade while in ten (27.8%), the sample underestimated the grade. CONCLUSIONS In most cases, the Ki-67 index and tumour grade from the tissue sample matched that of the resection specimen. However, in nearly 40% of cases, the tissue sample grading did not match the resection tumour grading. In the majority of these, the tissue sample underestimated disease activity. A low Ki-67 index in a tissue sample should therefore be taken as provisional and should not, in isolation, persuade clinicians to choose a more conservative treatment approach if there is clinical, biochemical or radiological evidence suggestive of a more aggressive disease pathology.

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Occupational Exposure and Multiple Myeloma Risk: An Updated Review of Meta-Analyses

Journal of Clinical Medicine ◽

10.3390/jcm10184179 ◽

2021 ◽

Vol 10 (18) ◽

pp. 4179

Author(s):

Rebecca Georgakopoulou ◽

Oraianthi Fiste ◽

Theodoros N. Sergentanis ◽

Angeliki Andrikopoulou ◽

Flora Zagouri ◽

...

Keyword(s):

Multiple Myeloma ◽

Occupational Exposure ◽

Methylene Chloride ◽

Disease Risk ◽

Epidemiological Studies ◽

Preventive Actions ◽

Increased Risk ◽

Hazard Surveillance ◽

Genetic And Environmental Factors ◽

Meta Analyses

The precise etiology of multiple myeloma remains elusive, but both genetic and environmental factors have been suggested to contribute to disease risk. Several occupational categories and toxic agents have been implicated as potentially causative, yet findings from the literature are inconsistent. The aim of this review was to summarize and critically comment on the accumulated epidemiological evidence, across published meta-analyses, about the association between occupational exposure and risk of multiple myeloma. Overall, results from eleven meta-epidemiological studies underscore a significantly increased risk for firefighters, hairdressers, and employees exposed to engine exhaust, whereas farming and methylene chloride exposure have been non-significantly correlated with the disease. Further epidemiological studies are of utmost importance whilst emphasis should be placed on occupational hazard surveillance, as such studies will obtain a more accurate picture of disease occurrence in working populations, and will enable both the implementation of preventive actions and the evaluation of their effectiveness.

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Low ALT values amongst hospitalized patients are associated with increased risk of hypoglycemia and overall mortality: a retrospective, big-data analysis of 51 831 patients

QJM ◽

10.1093/qjmed/hcaa219 ◽

2020 ◽

Cited By ~ 1

Author(s):

E Itelman ◽

A Segev ◽

L Ahmead ◽

E Leibowitz ◽

M Agbaria ◽

...

Keyword(s):

Electronic Medical Records ◽

Medical Records ◽

Cohort Analysis ◽

Surrogate Marker ◽

Tertiary Hospital ◽

Big Data Analysis ◽

Hospitalized Patients ◽

Retrospective Cohort Analysis ◽

Increased Risk ◽

Overall Mortality

Summary Background Sarcopenia and frailty influence clinical patients’ outcomes. Low alanine aminotransferase (ALT) serum activity is a surrogate marker for sarcopenia and frailty. In-hospital hypoglycemia is associated, also with worse clinical outcomes. Aim We evaluated the association between low ALT, risk of in-hospital hypoglycemia and subsequent mortality. Design This was a retrospective cohort analysis. Methods We included patients hospitalized in a tertiary hospital between 2007 and 2019. Patients’ data were retrieved from their electronic medical records. Results The cohort included 51 831 patients (average age 70.88). The rate of hypoglycemia was 10.8% (amongst diabetics 19.4% whereas in non-diabetics 8.3%). The rate of hypoglycemia was higher amongst patients with ALT < 10 IU/l in the whole cohort (14.3% vs. 10.4%, P < 0.001) as well as amongst diabetics (24.6% vs. 18.8%, P < 0.001). Both the overall and in-hospital mortality were higher in the low ALT group (57.7% vs. 39.1% P < 0.001 and 4.3% vs. 3.2%, P < 0.001). A propensity score matching, after which a regression model was performed, showed that patients with ALT levels < 10 IU/l had higher risk of overall mortality (HR = 1.21, CI 1.13–1.29, P < 0.001). Conclusions Low ALT values amongst hospitalized patients are associated with increased risk of in-hospital hypoglycemia and overall mortality.

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Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

Endocrine Related Cancer ◽

10.1530/erc-15-0029 ◽

2015 ◽

Vol 22 (4) ◽

pp. 545-559 ◽

Cited By ~ 6

Author(s):

Rafael Ríos ◽

Carmen Belén Lupiañez ◽

Daniele Campa ◽

Alessandro Martino ◽

Joaquin Martínez-López ◽

...

Keyword(s):

Type 2 Diabetes ◽

Multiple Myeloma ◽

Prediction Models ◽

Disease Risk ◽

Association Studies ◽

Area Under The Curve ◽

Genome Wide Association Studies ◽

Increased Risk ◽

Stratified Analysis

Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10−06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.

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Pregnancy Outcomes among Hispanics Stratified by Country of Origin

American Journal of Perinatology ◽

10.1055/s-0039-1698835 ◽

2019 ◽

Author(s):

Hector Mendez-Figueroa ◽

Suneet P. Chauhan ◽

Haleh Sangi-Haghpeykar ◽

Kjersti Aagaard

Keyword(s):

Cohort Analysis ◽

Perinatal Outcomes ◽

Adverse Outcomes ◽

Foreign Born ◽

Retrospective Cohort Analysis ◽

Increased Risk ◽

The Us ◽

The Usa ◽

Baseline Characteristics ◽

Perinatal Database

Abstract Objective To compare the perinatal outcomes among U.S.-born and foreign-born Hispanics and Caucasians and ascertain if length of time in the US was associated with the rate of adverse outcomes. Study Design Retrospective cohort analysis of gravidae enrolled in our institutional perinatal database. Women delivering a non-anomalous, singleton, at 24 weeks or more and self-identified as Caucasian or Hispanic were included. Women were stratified by country of birth and ethnicity into U.S.-born Caucasian, U.S.-born Hispanic, and U.S. foreign-born Hispanic. Composite maternal (CMM) and neonatal (CNM) morbidity was assessed. Results Of 20,422 women, 21% were Caucasian, 15% were U.S.-born Hispanics, and 64% were U.S. foreign-born Hispanics. Compared to Caucasians, U.S.-born and foreign-born Hispanic were older, more likely to be a grand multiparous, obese and less likely to be married. Compared to Caucasians, foreign-born Hispanics had a 1.42-fold increased risk of CMM (95% CI 1.26–1.30). Paradoxically, the rate of CNM was 40% lower among neonates born to foreign-born Hispanics (95% CI 0.51–0.74). A significant direct relationship was noted between time in the USA and CMM but not CNM among foreign-born Hispanics. Conclusion Despite less favorable baseline characteristics, U.S. foreign-born Hispanics have 40% less CNM compared to both Caucasians and U.S.-born Hispanics.

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A low initial serum sodium level is associated with an increased risk of overcorrection in patients with chronic profound hyponatremia: a retrospective cohort analysis

BMC Nephrology ◽

10.1186/s12882-017-0732-1 ◽

2017 ◽

Vol 18 (1) ◽

Cited By ~ 4

Author(s):

Sae Aratani ◽

Masahiko Hara ◽

Masahiko Nagahama ◽

Fumika Taki ◽

Miyuki Futatsuyama ◽

...

Keyword(s):

Serum Sodium ◽

Retrospective Cohort ◽

Sodium Level ◽

Serum Sodium Level ◽

Cohort Analysis ◽

Retrospective Cohort Analysis ◽

Increased Risk

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Single-cell multiomics reveals increased plasticity, resistant populations and stem-cell-like blasts in KMT2A-rearranged leukemia

Blood ◽

10.1182/blood.2021013442 ◽

2021 ◽

Author(s):

Changya Chen ◽

Wenbao Yu ◽

Fatemeh Alikarami ◽

Qi Qiu ◽

Chia-hui Chen ◽

...

Keyword(s):

Single Cell ◽

Young Patients ◽

Cytotoxic Lymphocytes ◽

Extrinsic Factors ◽

Hematopoietic Stem ◽

Younger Patients ◽

Factors Affecting ◽

Immune Mediated ◽

Younger Age ◽

Increased Risk

KMT2A-rearranged (KMT2A-r) infant ALL is a devastating malignancy with a dismal outcome, and younger age at diagnosis is associated with increased risk of relapse. To discover age-specific differences and critical drivers that mediate poor outcome in KMT2A-r ALL, we subjected KMT2A-r leukemias and normal hematopoietic cells from patients of different ages to single cell multi-omics analyses. We uncovered the following critical new insights: leukemia cells from patients younger than 6 months have significantly increased lineage plasticity. Steroid response pathways are downregulated in the most immature blasts from younger patients. We identify a hematopoietic stem and progenitor-like (HSPC-like) population in the blood of younger patients that contains leukemic blasts and form an immunosuppressive signaling circuit with cytotoxic lymphocytes. These observations offer a compelling explanation for the ability of leukemias in young patients to evade chemotherapy and immune mediated control. Our analysis also revealed pre-existing lymphomyeloid primed progenitors and myeloid blasts at initial diagnosis of B-ALL. Tracking of leukemic clones in two patients whose leukemia underwent a lineage switch documented the evolution of such clones into frank AML. These findings provide critical insights into KMT2A-r ALL and have clinical implications for molecularly targeted and immunotherapy approaches. Beyond infant ALL, our study demonstrates the power of single cell multi-omics to detect tumor intrinsic and extrinsic factors affecting rare but critical subpopulations within a malignant population that ultimately determines patient outcome.

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