While clinical outcomes from colorectal cancer (CRC) are influenced by stage at diagnosis and treatment, mounting evidence suggests that an enhanced lymphocytic reaction to a tumor may also be an ...informative prognostic indicator.
The roles of intratumoral T lymphocyte infiltration (TIL), peritumoral Crohn's-like lymphoid reaction (CLR), microsatellite instability (MSI), and clinicopathological characteristics in survival from CRC were examined using 2369 incident CRCs from a population-based case-control study in northern Israel. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in multivariable models adjusted for age, sex, ethnicity, grade, stage, and MSI. All statistical tests were two-sided.
Tumors with TIL/high-powered field (HPF) of 2 or greater were associated with a statistically significant increase in CRC-specific (P < .001) and overall survival (P < .001) compared with tumors with TIL/HPF of less than 2. Similarly, tumors with a prominent CLR experienced better CRC-specific (P < .001) and overall survival (P < .001) as compared with those with no response. High TILs (HR = 0.76, 95% CI = 0.64 to 0.89, P < .001) and a prominent CLR (HR = 0.71, 95% CI = 0.62 to 0.80, P < .001), but not MSI, were associated with a statistically significant reduction in all-cause mortality after adjustment for established prognostic factors.
TILs and CLR are both prognostic indicators for CRC after adjusting for traditional prognostic indicators.
Abstract
Background
Approximately one in six women in the USA takes antidepressants and a third use selective serotonin reuptake inhibitors (SSRIs) after breast cancer diagnosis. Recent investigation ...demonstrated serotonin receptor (5-HTR2B) expression in the breast and serotonin production as an indicator of poor breast cancer prognosis. This study investigates the association between SSRI use at different time intervals relative to breast cancer diagnosis on survival.
Methods
A population-based sample of 6959 consecutive, newly diagnosed breast cancer cases in Northern Israel was included. Patients were recruited from January 2000 and followed up through March 2020. Participants completed risk factor questionnaires regarding medical, reproductive and family history, medication use and health habits. Full prescription data were available through the Israeli national Clalit medical database. Multivariate Cox proportional hazard models were used to determine survival based on time of SSRI use.
Results
Use of SSRIs in the 5 years prior to breast cancer diagnosis was associated with a 66% increase in overall mortality (HRadj = 1.66; CI: 1.05–2.63). SSRI use that initiated after breast cancer diagnosis was associated with an 81% increase in mortality (HRadj = 1.81; CI: 1.58–2.06). Use of SSRIs in the 5 years post-diagnosis was associated with a dose–response increase (P < 0.001) in long-term mortality (>5 years). Heavy SSRI use (≥24 prescription fills) after diagnosis was associated with nearly doubling in mortality (HR = 1.99; CI: 1.39–2.83).
Conclusion
SSRI use prior to and after breast cancer diagnosis is associated with increased mortality in breast cancer patients. Additional research is needed to better understand mechanisms mediating this association.
Bisphosphonates are commonly used for the treatment of osteoporosis and for prevention and treatment of skeletal lesions due to malignancy. However, the association between the use of bisphosphonates ...and the risk of developing breast cancer has not been reported.
The Breast Cancer in Northern Israel Study is a population-based case-control study in northern Israel of patients with breast cancer and age-, clinic-, and ethnic-group matched controls. Use of bisphosphonates was assessed in 4,039 postmenopausal patients and controls, members of Clalit Health Services, using pharmacy records.
The use of bisphosphonates for longer than 1 year before diagnosis, but not for shorter than 1 year, was associated with a significantly reduced relative risk of breast cancer (odds ratio OR, 0.61; 95% CI, 0.50 to 0.76). This association remained significant after adjustment for age, fruit, and vegetable consumption, sports activity, family history of breast cancer, ethnic group, body mass index, use of calcium supplements, hormone replacement therapy use, number of pregnancies, months of breast feeding, and age at first pregnancy (OR, 0.72; 95% CI, 0.57 to 0.90). Breast cancer risk did not change further if bisphosphonates were used for more years. Breast tumors identified in bisphosphonates users were more often estrogen receptor positive and less often poorly differentiated.
The use of bisphosphonates for longer than 1 year was associated with a 28% relative reduction in the risk of postmenopausal breast cancer. Tumors developing under bisphosphonates treatment tended to have a favorable prognostic factors profile.
An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this ...association remain unclear.
Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF.
AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases.
Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Purpose The use of statins has been associated with reduced risk of malignancies in a variety of organ sites. This study was aimed at studying the effects of statins on gynecological ...cancers. Methods The Cancer in The Ovary and Uterus Study (CITOUS) is a case–control study of newly diagnosed cases of gynecological malignancies and age/sex/clinic/ethnic-group matched population controls. Use of statins prior to and following diagnosis was assessed in a subset of 424 cases of ovarian and endometrial cancers and 341 controls, enrolled in Clalit Health Services (CHS), using pharmacy records. Results The use of statins for more than one year prior to diagnosis was associated with a significantly reduced risk of ovarian cancer (OR = 0.56, 95% CI: 0.33–0.94) and of endometrial cancer (OR = 0.59, 95% CI: 0.40–0.87). The association with endometrial cancer, but not with ovarian cancer (OR = 0.54, 0.26–1.13), remained statistically significant after adjustment for fruit and vegetable consumption, sports activity, family history of endometrial and colorectal cancer, ethnicity, BMI, duration of breast feeding, age at 1st pregnancy and use of menopausal hormones (RR = 0.48, 0.26–0.89). Women who used statins only after diagnosis of cancer had a significantly better survival of both ovarian cancer (Log rank test, p = 0.021, age adjusted HR = 0.47, 0.26–0.85) and endometrial cancer ( p = 0.06, age adjusted HR = 0.45, 0.23–0.87). Conclusion The use of statins for more than one year before diagnosis was associated with a reduction in the risk of endometrial cancer and possibly ovarian cancer. A significantly improved survival of cases of both malignancies was noticed when statins were taken only after diagnosis.
Abstract Objective Low 25(OH)D levels are associated with increased parathyroid hormone levels leading to progressive bone loss. The serum levels of 25(OH)D sufficient to keep the parathyroid hormone ...level at a range that will prevent bone loss are still unclear. The current study was aimed at evaluating the relationship between 25(OH)D levels and concomitant parathyroid hormone levels. Methods The computerized laboratory database of Clalit Health Services, a not-for-profit health maintenance organization covering more than half of the Israeli population, was searched for all 25(OH)D and parathyroid hormone tests performed in 2009. Concomitant tests of parathyroid hormone and 25(OH)D were identified in 19,172 people. Results Serum parathyroid hormone levels were inversely correlated with 25(OH)D levels ( r = −0.176, P < .001); 25(OH)D levels less than 50 nmol/L were associated with a steep increase in parathyroid hormone levels and hyperparathyroidism, which decreased with increasing 25(OH)D levels and reached a plateau at 25(OH)D levels of 75 to 85 nmol/L. The quadratic fit with plateau model showed that parathyroid hormone stabilizes at 25(OH)D level of 78.9 nmol/L. However, after excluding 5449 people with hypercalcemia or renal failure, the parathyroid hormone plateau was attained at a significantly lower 25(OH)D cut point of 46.2 nmol/L. Conclusion Our data suggest that a 25(OH)D threshold of 50 nmol/L is sufficient for parathyroid hormone suppression and prevention of secondary hyperparathyroidism in persons with normal renal function. 25(OH)D levels greater than 75 nmol/L do not seem to be associated with additional change in parathyroid hormone levels.
Bisphosphonates are commonly used for the treatment of osteoporosis and bone metastases caused by breast cancer and were recently reported to be associated with a reduced risk of breast cancer, ...possibly acting through the mevalonate pathway, but their association with risk of other cancers is unknown.
The Molecular Epidemiology of Colorectal Cancer study is a population-based, case-control study in northern Israel of patients with colorectal cancer and age-, sex-, clinic-, and ethnic group-matched controls. Long-term use of bisphosphonates before diagnosis was assessed in a subset of 933 pairs of postmenopausal female patients and controls, enrolled in Clalit Health Services, using computerized pharmacy records.
The use of bisphosphonates for more than 1 year before diagnosis, but not for less than 1 year, was associated with a significantly reduced relative risk (RR) of colorectal cancer (RR, 0.50; 95% CI, 0.35 to 0.71). This association remained statistically significant after adjustment in a model for vegetable consumption, sports activity, family history of colorectal cancer, body mass index, and use of low-dose aspirin, statins, vitamin D, and postmenopausal hormones (RR, 0.41; 95% CI, 0.25 to 0.67). Concomitant use of bisphosphonates and statins did not further reduce the risk.
The use of oral bisphosphonates for more than 1 year was associated with a 59% relative reduction in the risk of colorectal cancer, similar to the recently reported association of this drug class with reduction in breast cancer risk.
OBJECTIVETo examine the association between statin exposure in a dose-dependent manner and intracerebral hemorrhage (ICH) in a large nationwide study.
METHODSThe computerized database of the largest ...health care provider in Israel was used to identify diagnosed ICH among new users of statins, who started statin treatment between 2005 and 2010. We assessed a dose–response relationship between ICH and statins, using the average atorvastatin equivalent daily dose (AAEDD). Multivariable Cox proportional hazard regression models, adjusted for baseline disease risk score, were applied to estimate the hazard ratio of ICH.
RESULTSOf the 345,531 included patients, 1,304 were diagnosed with ICH during a median follow-up of 9.5 years (interquartile range 7.6–11.0). Overall, 75.3% of patients had AAEDD <10 mg/d, 19.0% had AAEDD 0–19.9 mg/d, and 5.7% had AAEDD ≥20 mg/d. The corresponding proportions were 81.0%, 15.0%, 4.0% among ICH cases, and 75.3%, 19.0%, 5.7% among non-ICH cases. Compared to those with AAEDD <10 mg/d (reference), the adjusted hazard ratio (HR) for ICH was 0.68 (95% confidence interval CI 0.58–0.79) in those with AAEDD 10–19.9 mg/d, and 0.62 (0.47–0.81) in those with AAEDD ≥20 mg/d. Compared to the lowest baseline total cholesterol quartile, the adjusted HR for ICH was 0.71 (95% CI 0.62–0.82), 0.55 (0.47–0.64), and 0.57 (0.49–0.67) in those in the second, third, and highest quartiles, respectively. The results were similar and robust among highly persistent statin users and after controlling for the change in cholesterol level.
CONCLUSIONSThis study confirms that the risk of ICH decreases with increasing cholesterol levels, but suggests that statin use might be associated with decreased risk of ICH.
Aim
We investigated the prevalence of elevated liver aminotransferases (ALT) and additional comorbidities in a large cohort of Israeli children and adolescents with overweight and obesity.
Methods
...This study included data from medical records of 2‐ to 18‐year‐old children and adolescents, with body mass index (BMI) in the overweight or obesity range (WHO definitions), for whom ALT testing was performed.
Results
Overweight was present in 50 418 (10.7%) and obesity in 70 515 (15.0%). Elevated ALT, above 30 IU/L (0.51 μkat/L), was reported in 2245 (7.2%) of children with overweight and 5475 (16.8%) of children with obesity (P < .0001). Compared to children with overweight and obesity and ALT within normal range, children with elevated ALT were older (11.9 ± 4.2 vs 10.9 ± 4.2, P < .001), mostly male (68.0% vs 49.4%, P < .001) and had higher BMI (27.3 ± 6.1vs 24.0 ± 4.8, P < .001). They also had a more unfavourable cardiometabolic profile with significantly higher either systolic or diastolic blood pressure, total cholesterol and triglycerides, and had more than three criteria defining metabolic syndrome.
Conclusion
In this large cohort, abnormally elevated ALT was present in a high number of individuals with overweight or obesity. The children and adolescents with abnormal ALT had higher BMI, were older, male and had more cardiometabolic risk factors.
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