David Pereg

Are platelet volume indices of clinical use? A multidisciplinary review

Abstract Platelet size correlates with platelet activity and can be assessed by platelet volume indices (PVI). The PVI, mean platelet volume (MPV), is universally available with routine blood counts by automated hemograms and therefore is an attractive index to study in clinical scenarios. PVI are useful in assessing the etiology of thrombocytopenia. In addition, a normal platelet distribution width in the setting of thrombocytosis is highly suggestive of a reactive etiology. Higher MPV is also associated with the presence of cardiovascular risk factors, chest pain due to acute coronary syndrome, and adverse outcome after acute coronary syndrome. Results from studies evaluating MPV in patients with peripheral artery disease, unprovoked deep vein thrombosis, and pulmonary embolism further advocate a potential role for MPV in identifying patients at high risk of thrombosis. Nevertheless, most of these data come from retrospective studies some of which have small study populations and confounding factors influencing platelet volume. Moreover, the cut-off values derived from these retrospective studies have not been validated prospectively. Despite the potential for clinical utility evident from these studies, the above-mentioned flaws together with technical problems in measuring MPV currently limit its clinical usefulness. Our review provides a perspective on PVIs potential clinical use.

Hair cortisol and the risk for acute myocardial infarction in adult men.

Acute stress is increasingly recognized as a precipitant of acute myocardial infarction (AMI). However, the role of chronic stress in developing AMI is less clear. We have developed a method to measure cortisol in hair, which allows longitudinal assessment of cortisol levels prior to an acute event. We aimed to evaluate the hypothesis that chronic stress, as assessed by hair cortisol content, is associated with the development of AMI. A prospective case–control study included 56 patients admitted to hospital with AMI and 56 control patients, admitted to internal medicine wards for other indications. An enzyme immunoassay technique was used to measure cortisol in the most proximal 3 cm of hair, considered to represent the most recent 3 months of exposure. Median hair cortisol contents (range) were 295.3 (105.4–809.3)ng/g in AMI patients and 224.9 (76.58–949.9)ng/g in controls (p = 0.006, Mann–Whitney U-test). After controlling for other risk factors for AMI using multiple logistic regression, log-transformed hair cortisol content remained the strongest predictor (OR 17.4, 95% CI 2.15–140.5; p = 0.007). We demonstrated elevated hair cortisol concentrations in patients with AMI. This suggests that chronic stress, as assessed by increased hair cortisol in the 3 months prior to the event, may be a contributing factor for AMI.

Cancer in pregnancy: Gaps, challenges and solutions

Cancer is the second leading cause of death during the reproductive years complicating between 0.02% and 0.1% of pregnancies. This incidence is expected to rise with the increase in age of childbearing. The relatively rare occurrence of pregnancy-associated cancer precludes conducting large, prospective studies to examine diagnostic, management and outcome issues. This article reviews the available data regarding the different aspects of the diagnosis and treatment of cancer during pregnancy as well as the effect of pregnancy on cancer prognosis. In pregnant patients diagnosed with cancer during the first trimester, treatment with multi-drug anti-cancer chemotherapy or radiotherapy (with fetal exposure >0.1-0.2 Gy) is associated with an increased risk of congenital malformations and therefore should follow a strong recommendation for pregnancy termination. The risk for malformation diminishes as pregnancy advances and when cancer is diagnosed during the second or third trimesters there is usually no clear indication for abortion. Treatment postponement, until achieving fetal maturity, while closely monitoring tumor growth may be considered in selected cases. According to the available experience it seems that non-obstetrical surgery may be performed during pregnancy without an increased risk for adverse outcomes. In most types of cancer, pregnancy has no effect on maternal prognosis when compared to non-pregnant patients matched by age, cancer stage and treatment.

The treatment of Hodgkin's and non-Hodgkin's lymphoma in pregnancy

Lymphoma is the fourth most frequent malignancy diagnosed during pregnancy, occurring in approximately 1:6000 of deliveries. Its occurrence may increase due to the current trend to postpone pregnancy until later in life and the suggested high incidence of AIDS-related non-Hodgkins lymphoma in developing countries. The relatively rare occurrence of pregnancy-associated lymphoma precludes the conduction of large, prospective studies to examine diagnostic, management and outcome issues. Chemotherapy and radiotherapy during the first trimester are associated with increased risk of congenital malformations and this risk diminishes as pregnancy advances. In the vast majority of cases, when lymphoma is diagnosed during the first trimester, treatment with a standard chemotherapy regimen, following pregnancy termination should be recommended. In the rare patients at low risk, such as those with stage 1 Hodgkins lymphoma or indolent non-Hodgkins lymphoma, therapy can be delayed until the end of the first trimester and of embryogenesis while keeping the patients under close observation. When lymphoma is diagnosed during the second and third trimesters, evidence exists suggesting that full-dose chemotherapy can be administered safely without apparent increased risk of severe adverse fetal outcome.

How I treat acute and chronic leukemia in pregnancy

The prevalence of pregnancy associated leukemia is approximately 1 case out of 10,000 pregnancies. This rare occurrence precludes the conducting of large, prospective studies to examine diagnostic, management and outcome issues. The treatment of a pregnant woman with leukemia may be associated with severe adverse fetal outcome including death and malformations, and therefore poses a difficult challenge for both the patient and the attending physician. Chemotherapy during the 1st trimester is associated with an increased risk for congenital malformations. However, this risk diminishes as pregnancy advances. When acute leukemia is diagnosed during the 1st trimester, patients should be treated promptly similar to non-pregnant patients. However, the aggressive induction therapy should follow pregnancy termination. When the diagnosis is made later in pregnancy standard chemotherapy regimen should be considered and usually pregnancy termination is not mandatory. However, both the mother and the fetus should be under close observation and delivery should be postponed to a non-cytopenic period. Pregnancy associated chronic myelogenous leukemia (CML) can be treated with interferon throughout pregnancy with no apparent increase in adverse fetal outcome. In the very rare case of chronic lymphocytic leukemia (CLL) during pregnancy treatment can usually be delayed until after delivery.

Probiotics for patients with compensated liver cirrhosis: a double-blind placebo-controlled study.

BACKGROUND Gut flora is related to the major complications of liver cirrhosis including hepatic encephalopathy, spontaneous bacterial peritonitis, and variceal bleeding. Prior studies have reported a beneficial effect of gut flora modification with probiotic bacteria in patients with minimal hepatic encephalopathy. We aimed to study the effect of probiotics on clinical and laboratory parameters of patients with compensated cirrhosis. METHODS A double-blind placebo-controlled study that included patients with liver cirrhosis and at least one major complication of cirrhosis in the past, clinical evidence of portal hypertension, or decreased hepatic synthetic function. Participants were randomly assigned to receive probiotic capsules containing Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium lactis, and Streptococcus thermophiles or placebo for a period of 6 mo. RESULTS A total of 36 patients were available for final analysis (distributed equally between the probiotic and placebo groups). The administration of probiotics was not associated with significant differences in either clinical or laboratory parameters between the two groups. Because the lack of a beneficial effect may be related to the compensated liver disease of patients, we conducted a subanalysis of patients with baseline ammonia levels > 50 mmol/L. In this subgroup, the administration of probiotics appeared to significantly reduce the ammonia levels starting after 1 mo of treatment. However, this effect diminished and lost its significance following comparison to the placebo group. CONCLUSIONS Our study did not show a significant beneficial effect of probiotic supplementation in patients with compensated liver cirrhosis. Nevertheless, it points toward a possible positive effect of probiotics in patients with above normal baseline ammonia levels. This issue requires further investigation in larger cohorts.

Mean platelet volume on admission correlates with impaired response to thrombolysis in patients with ST-elevation myocardial infarction

Mean platelets volume (MPV) has been shown to correlate with impaired reperfusion and increased mortality in patients with ST-elevation myocardial infarction (STEMI) treated with primary precutaneous coronary intervention (PCI). We aimed to study whether the same association exists in STEMI patients treated with thrombolysis. Included in the study were STEMI patients receiving thrombolysis. Thrombolysis failure was defined as a need for rescue precutaneous coronary intervention (PCI), in-hospital mortality, unplanned PCI during hospitalization or complete occlusion of the culprit coronary artery in a follow-up angiography. MPV levels were compared between patients with failed or successful thrombolysis. Of the 122 patients, 30 had failed thrombolysis while the other 92 fulfilled the criteria for successful treatment. There were no significant differences in demographic or clinical baseline characteristics of the two groups. Mean MPV was significantly higher in patients with failed thrombolysis compared to patients with successful treatment (9.2 ± 1.1fl and 8.7 ± 1.0fl respectively, p = 0.019 in multivariate analysis). The prevalence of thrombolysis failure was significantly higher in patients with MPV > 8.6 fl compared to those with MPV ≤ 8.6 fl (31.8% and 16% respectively, p = 0.048 in multivariate analysis). It appears that higher MPV correlates with thrombolysis failure in patients presenting with STEMI. MPV may be used as an adjunctive readily available factor for assessing thrombolysis outcome upon admission.

Cortisol and Testosterone in Hair as Biological Markers of Systolic Heart Failure

BACKGROUND Congestive heart failure (CHF) is associated with increased stress and alterations in metabolism, favoring catabolism over anabolism. Hormonal profiles of patients with heart failure have been assessed using serum and saliva as matrices, which are only point measurements and do not provide long-term information. Scalp hair is a novel matrix that allows for measurement of hormones over a period of several months. PATIENTS AND METHODS We aimed to evaluate whether levels of cortisol and testosterone and their ratio (C/T) in hair correlate with severity of heart failure. We conducted a prospective study in ambulatory male patients with a left ventricular ejection fraction (LVEF)≤40%. Hormone levels were measured using immunoassays in the proximal 2 cm of hair (representing approximately two months of systemic hormone exposure). Primary endpoints included the correlation of hair cortisol, testosterone, and C/T levels with the New York Heart Association (NYHA) class, LVEF, exercise capacity and NT-proBNP. RESULTS The 44 CHF patients had a median hair level (range) of cortisol of 207 (117.7-1277.3)ng/g. Hair cortisol levels correlated positively with NYHA class (r=0.48, p=0.001) and negatively with treadmill stress test performance, (r=-0.37, p<0.05). The hair testosterone was 5.17 (2.39-24.64)ng/g and the C/T ratio was 39.89 (12.98-173.73). No associations were found between hair testosterone and C/T ratio and heart failure severity; however, the C/T ratio was higher in patients who required a CHF-related hospitalization than in patients who did not require this in the year following the inclusion in the study. CONCLUSIONS Hair cortisol levels correlate with heart failure severity as assessed by the NYHA class and exercise capacity, while hair testosterone and C/T levels do not correlate with heart failure severity.

Prevalence of asthma in a large group of Israeli adolescents: influence of country of birth and age at migration.

Background:  The occurrence of asthma has geographic variations and is lower in developing compared with industrialized countries. Both environmental and genetic factors may influence its prevalence. We aimed to evaluate the importance and effect of immigration (country of birth and age at immigration to Israel) on the prevalence of asthma in a large group of Israeli adolescents.

Maternal and Fetal Effects of Systemic Therapy in the Pregnant Woman with Cancer

The diagnosis of cancer and the need to administer chemotherapy during pregnancy pose challenges to the woman, her family, and the medical team. The great challenge is to treat the mother without adversely affecting fetal outcome. The relative rarity of pregnancy-associated cancer precludes conducting large prospective studies to examine the safety of the different chemotherapeutic drugs, and the literature is largely composed of small retrospective studies and case reports. In this chapter we critically review available data, controversies, and unresolved issues regarding the administration of chemotherapy during pregnancy and lactation.