Atrial fibrillation in cancer patients who develop stroke.

BACKGROUND: Acute ischemic stroke (Stroke) and transient ischemic attacks (TIA) are known complications in cancer patients and those with atrial fibrillation (AF). The role AF plays in Stroke/TIA in the setting of cancer is unclear. The purpose of this study was to assess the relationship between AF and Stroke/TIA in cancer patients. METHODS: We conducted a case-control study comparing all patients who developed Stroke/TIA from 2014 to 2019 following a cancer diagnosis at King Hussein Cancer Center (KHCC), matched to Stroke/TIA-free controls based on age, gender, and cancer site. RESULTS: Two hundred seventy-two patients were included (136 per group). The mean age was 63.95 ± 13.06 and 57% were females. The Stroke/TIA group had more AF at the time of event (14% vs. 4%, OR: 4.25, 95%-CI: 1.39 - 17.36) and had a larger proportion of death on study conclusion (OR: 9.4, 95%-CI: 3.74 - 23.64). On conditional logistic regression, patients in the Stroke/TIA group had higher odds of: AF (OR: 7.93, 95%-CI: 1.6 - 39.18), ischemic stroke before cancer diagnosis (OR: 9.18, 95%-CI: 2.66 - 31.74), being on active cancer treatment (OR: 3.11, 95%-CI: 1.46 - 6.62), dyslipidemia (OR: 3.78, 95%-CI: 1.32 - 10.82), and renal disease (OR: 4.25, 95%-CI: 1.55 - 11.63). On another conditional logistic regression model built to assess the role of the CHA2DS2-VASc score, a score of >=2 in males and >=3 in females significantly increased the risk of developing Stroke/TIA in cancer patients (OR: 2.45, 95%-CI: 1.08 - 5.58). CONCLUSION: AF, previous ischemic stroke, active cancer treatment, dyslipidemia, and renal disease are independent risk factors for Stroke/TIA and a higher CHA2DS2-VASc score significantly increases the risk in cancer patients regardless of AF.

Outcomes, Trends, and Predictors of Gastrointestinal Bleeding in Patients Undergoing Transcatheter Aortic Valve Implantation (from the National Inpatient Sample).

Major bleeding has been identified as one of the most common complications after transcatheter aortic valve implantation (TAVI) with some suffering gastrointestinal bleeding (GIB). This study aimed at assessing the incidence and predictors of GIB after TAVI in the United States. We performed a retrospective analysis of data from the National Inpatient Sample database from 2011 to 2018. A total of 216,023 hospitalizations for TAVI were included. Of the included patients, 2,188 (1%) patients had GIB, whereas 213,835 (99%) patients did not have GIB. The presence of arteriovenous malformation was associated with the highest odds of having a gastrointestinal bleed (odds ratio (OR) 24.8, 95% confidence interval (CI) 17.13 to 35.92). Peptic ulcer disease was associated with an eightfold increased risk of bleeding (OR 8.74, 95% CI, 6.69 to 11.43) followed closely by colorectal cancer (OR 7.89, 95% CI, 5.33 to 11.70). Other comorbidities that were associated with higher propensity-matched rates of GIB were chronic kidney disease (OR 1.27,95% CI, 1.14 to 1.41), congestive heart failure (OR 1.18, 95% CI,1.06 to 1.32), liver disease (OR1.83, 95% CI,1.53 to 2.19), end-stage renal disease (OR 2.08,95% CI, 1.75 to 2.47), atrial fibrillation (OR1.63,95% CI,  1.49 to 1.78), and lung cancer (OR 2.80, 95% CI,1.77 to 4.41). Patients with GIB had higher propensity-matched rates of mortality than those without GIB, (12.1% vs 3.2%, p <0.01). Patients with GIB had a higher median cost of stay ($68,779 vs $46,995, p <0.01) and a longer length of hospital stay (11 vs 3 days, p <0.01). In conclusion, health care use and mortality are higher in hospitalizations of TAVI with a GIB. Baseline comorbidities like peptic ulcer disease, chronic kidney disease, liver disease, atrial fibrillation and, colorectal cancer are significant predictors of this adverse event.

The clinical potential of circulating immune cell counts in primary gastric lymphoma.

BACKGROUND: High neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in gastrointestinal tract cancers. This study explores the clinical value of NLR, in addition to absolute lymphocyte count (ALC) and other hematologic parameters in association with distant metastases and OS in primary gastric lymphoma (PGL) patients. METHODS: Clinical data of 139 PGL patients who received treatment at King Hussein Cancer Center (KHCC), Amman-Jordan were retrospectively evaluated. Using data from complete blood count (CBC) tests, the following hematologic parameters: absolute neutrophil count (ANC), ALC, absolute eosinophil count (AEC), absolute monocyte count (AMC), NLR, platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) were assessed in association with the following clinical outcomes: presence or absence of baseline distant metastases and OS. We conducted univariate and multivariate analyses assessing the various hematologic parameters in association with distant metastases. RESULTS: Univariate and multivariate analyses indicated that patients with an elevated NLR (>3.14) displayed more baseline distant metastases compared to patients with a low NLR (≤3.14), (P value: 0.02 and 0.018, respectively). High baseline ALC (>1,819/µL) was associated with lower baseline distant metastases (P value: 0.04). In the OS analysis, high baseline ANC (>5,100/µL), NLR (>2.75), and PLR (>0.16) were associated with poor OS, (P value: 0.027, 0.016, and 0.011 respectively). CONCLUSIONS: High NLR and ALC were associated with baseline distant metastases. High baseline ANC, NLR, and PLR were associated with poor OS. Hematologic parameters might be potentially helpful in assessing and correlating NLR with the response success to treatment in PGL.

The clinical value of peripheral immune cell counts in pancreatic cancer.

BACKGROUND: Elevated neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in pancreatic cancer. We aim to investigate the association of the various hematologic markers, in particular NLR among others, with distant metastases, a common feature in pancreatic cancer. METHODS: Clinical data from 355 pancreatic cancer patients managed at King Hussein Cancer Center (Amman-Jordan) have been reviewed. We examined the relationship between absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophilic count (AEC), absolute monocytic count (AMC), NLR, monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) with the presence of baseline distant metastases and OS. Receiver Operating Characteristic (ROC) curve analysis was plotted to identify the NLR optimum cutoff value indicative of its association with distant metastases. RESULTS: On univariate and multivariate analyses patients whom on presentation had high NLR (≥3.3) showed more baseline distant metastases compared to patients with low NLR (<3.3), (p-value: <0.0001 and <0.0001, respectively). Patients with high baseline ANC (≥5500/µL), AMC (≥600/µL), MLR (≥0.3) had more baseline distant metastases in comparison to patients with lower values (p-value: 0.02, 0.001, and <0.0001, respectively). High ANC, NLR, MLR, and PLR and low ALC were associated with poorer OS, (p-value: <0.0001, <0.0001, <0.0001, 0.04, and 0.01, respectively). CONCLUSION: This study presents additional evidence of the association of some of the hematologic markers; in particular ANC, NLR, AMC, and MLR, with baseline distant metastases and poor outcome in pancreatic cancer. Whether these immune phenomena can help in identifying patients at higher risk for the subsequent development of distant metastases is unknown.

Hematologic markers of distant metastases in gastric cancer.

BACKGROUND: High neutrophil-lymphocyte ratio (NLR) is associated with poor overall survival (OS) in gastric cancer. This study evaluates whether NLR, in addition to other parameters including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are associated with distant metastases, a common and poor prognostic feature of gastric cancer. METHODS: Clinical data from 502 gastric cancer patients treated at King Hussein Cancer Center (Amman, Jordan) have been retrospectively reviewed. We examined the association between ANC, ALC, AEC, AMC, NLR, MLR and PLR with the baseline distant metastases and OS. Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal NLR cutoff value for association with distant metastases. RESULTS: Univariate and multivariate analyses showed that patients with high baseline NLR (≥3.9) had more distant metastases on presentation than patients with low NLR (<3.9), (P value: 0.0001 and 0.0005, respectively). Furthermore, patients with high baseline ANC (≥6,015/µL), AEC (≥215/µL), PLR (≥0.15) had more distant metastases in comparison to patients with low baseline ANC (<6,015/µL), AEC (<215/µL), PLR (<0.15) (P value: 0.024, 0.001, and 0.001, respectively). High ANC, NLR, MLR and PLR are associated with poor OS (P value: 0.046, 0.0003, 0.027, and <0.0001, respectively). CONCLUSIONS: High ANC, AEC, NLR, and PLR are associated with distant metastases on presentation in gastric cancer. In the era of cancer immunotherapy, whether these immune phenomena predict the response of gastric cancer to immunotherapy is unknown.

MTHFR gene polymorphisms in hypothyroidism and hyperthyroidism among Jordanian females

ABSTRACT Objective Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation that is associated with autoimmune pathology. We investigated the association between MTHFR genetic polymorphisms at g.677C>T and g.1298A>C and their haplotypes, and the risk of thyroid dysfunction among Jordanian females. Subjects and methods A case-control study involving 98 hypothyroidism cases, 66 hyperthyroidism cases and 100 controls was conducted. Polymerase chain reaction/restriction fragment length polymorphism technique was performed to determine genotypes. Statistical analysis using SPSS software was performed. Results Genetic analysis showed a significant difference in genotype frequency of g.1298A>C between cases, and controls [hypothyroidism: AA (45.9%), AC (37.8%), CC (16.3%); hyperthyroidism: AA (9.1%), AC (69.7%), CC (21.2%); controls: AA (37.8%), AC (29.6%), CC (32.7%); CChypo vs. AAhypo: 2.55, 95% CI: (1.18-5.52); OR at least on Chypo: 1.79, 95% CI: (1.07-2.99)]; CChyper vs. AAhyper: 4.01, 95% CI: (1.79-9.01); OR at least on Chyper: 0.18, 95% CI: (0.07-0.48)]. There was no significant difference in genotype frequency of g.677C>T between cases and controls [hypothyroidism: CC (50.0%), CT (32.7%), TT (17.3%); hyperthyroidism: CC (77.3%), CT (15.2%), TT (7.6%); controls: CC (55.6%), CT (32.3%), TT (12.1%)]. There was a significant difference of MTHFR haplotypes among hypothyroidism cases and controls. TA and CC had a lower hypothyroidism risk whereas; TC showed a higher risk. Conclusions g.1298A>C genetic polymorphism of MTHFR may modulate the risk of thyroid disease. CC, TA, and TC haplotypes affect the risk of hypothyroidism. Larger samples should be included in the future to verify the role of MTHFR polymorphisms in thyroid diseases.

MTHFR gene polymorphisms in hypothyroidism and hyperthyroidism among Jordanian females.

OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation that is associated with autoimmune pathology. We investigated the association between MTHFR genetic polymorphisms at g.677C>T and g.1298A>C and their haplotypes, and the risk of thyroid dysfunction among Jordanian females. SUBJECTS AND METHODS: A case-control study involving 98 hypothyroidism cases, 66 hyperthyroidism cases and 100 controls was conducted. Polymerase chain reaction/restriction fragment length polymorphism technique was performed to determine genotypes. Statistical analysis using SPSS software was performed. RESULTS: Genetic analysis showed a significant difference in genotype frequency of g.1298A>C between cases, and controls [hypothyroidism: AA (45.9%), AC (37.8%), CC (16.3%); hyperthyroidism: AA (9.1%), AC (69.7%), CC (21.2%); controls: AA (37.8%), AC (29.6%), CC (32.7%); CChypo vs. AAhypo: 2.55, 95% CI: (1.18-5.52); OR at least on Chypo: 1.79, 95% CI: (1.07-2.99)]; CChyper vs. AAhyper: 4.01, 95% CI: (1.79-9.01); OR at least on Chyper: 0.18, 95% CI: (0.07-0.48)]. There was no significant difference in genotype frequency of g.677C>T between cases and controls [hypothyroidism: CC (50.0%), CT (32.7%), TT (17.3%); hyperthyroidism: CC (77.3%), CT (15.2%), TT (7.6%); controls: CC (55.6%), CT (32.3%), TT (12.1%)]. There was a significant difference of MTHFR haplotypes among hypothyroidism cases and controls. TA and CC had a lower hypothyroidism risk whereas; TC showed a higher risk. CONCLUSIONS: g.1298A>C genetic polymorphism of MTHFR may modulate the risk of thyroid disease. CC, TA, and TC haplotypes affect the risk of hypothyroidism. Larger samples should be included in the future to verify the role of MTHFR polymorphisms in thyroid diseases.

Hematologic Markers of Lung Metastasis in Stage IV Colorectal Cancer.

BACKGROUND: Many studies showed an association between absolute neutrophil count (ANC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) with poor overall survival (OS) in patients with cancer. However, only a few studies were conducted to further investigate this association in colorectal cancer (CRC). METHODS: Clinical data from 299 stage IV CRC patients treated at King Hussein Cancer Center from 2004 to 2012 have been retrospectively reviewed. We examined the association between ANC, AMC, MLR, PLR, and NLR with lung metastasis in stage IV CRC. Receiver Operating Characteristic (ROC) curve analysis was operated to determine the optimal NLR cutoff value. Univariate and multivariate analysis were performed. RESULTS: The ROC value of 3.4 was determined as the cutoff value of NLR to study the association. Univariate and multivariate analysis showed that patients with high baseline NLR (≥ 3.4) had more baseline lung metastasis than patients with low NLR (< 3.4) (p = 0.0001, p = 0.0151, respectively). Also, baseline NLR correlated significantly with the presence of lymphovascular invasion (p = 0.001). In patients with no baseline lung metastasis, high post-treatment NLR was associated with consequent development of lung metastasis (p = 0.0227). Other markers including ANC, AMC, MLR, and PLR were significantly associated with lung metastasis at time of diagnosis (p = 0.0006, p = 0.0006, p = 0.0187, and p = 0.001, respectively). CONCLUSION: Results are suggesting that different hematologic markers obtained from a cheap test (CBC) could potentially be used to predict the likelihood of lung metastasis in stage IV CRC. Prospective studies are needed to further assess the immune cells' role in tumor metastasis promotion.