Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia-Any Link with Known Prognostic Factors?

Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; p = 0.027) and CD86 on CD19+ cells (r = 0.6950; p < 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling (p < 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.

Coping with Stress in Complicated Pregnancy and Gestational Weight Gain.

Maternal obesity is one of the leading health problems in the world. Excessive gestational weight gain (GWG) can lead to many complications during pregnancy, especially when it is accompanied by diabetes. Moreover, the risk of excessive GWG in pregnant women is significant, irrespective of prenatal counseling. Studies on this subject concerning coping with stress are lacking in the literature. The present work is aimed at evaluating the styles of coping with stress and their relation to GWG in pregnant women with gestational diabetes (GDM) for whom sudden adaptation to dietary management during this period can be challenging. It was indicated that women with GDM reported high stress related to potential maternal-fetal complications and worries about compliance with dietary management. The overall weight gain of participants in pregnancy was determined in connection to their prepregnancy body mass index (BMI) and classified based on the Institute of Medicine guidelines. A standardized psychological scale was used to assess coping styles. The results showed that almost half of the participants did not meet the Institute of Medicine recommendations for weight gain during pregnancy. There were significant correlations between the styles of coping with stress and the GWG. Additionally, low correlations were indicated between emotional, avoidant, task-oriented coping styles and the age of pregnant women with GDM. Regression analysis showed that the stress-coping style that focused on emotions was the most predictive of overall weight gain. There is a need for a better understanding of psychological barriers in achieving the recommended GWG and potential limitations in providers' interventions, particularly for GDM.

Wanda Blenska and the program of leprosy treatment in Uganda.

Wanda Blenska (1911-2014), a Polish physician, established a leprosy treatment center in the village of Buluba in Uganda in 1951, which lasted until 1993. Through her efforts, the village for lepers in Buluba, established in 1934, which had previously been a place of isolation conducted by the Little Sisters of St. Francis in Uganda, became such an important leprosy treatment and research center that eventually the facility was able to cooperate with similar centers in India and South Africa. It then became affiliated with research institutes in London and Amsterdam; the Borstel Research Institute near Hamburg, Germany; and the World Health Organization. Blenska developed a working relationship with the government of Uganda and contributed to changes in the government provision of health care for lepers by creating a network of leprosy treatment stations throughout the country. Through her efforts, public health education and leprosy prophylaxis became available for thousands of people, effectively changing the national attitude toward this disease. In 1994, one of the buildings of the St. Francis hospital complex in Buluba was named in her honor (The Wanda Blenska Training Centre).

Interstitial HDR Brachytherapy in the Treatment of Non-Melanocytic Skin Cancers around the Eye.

BACKGROUND: Eyelid tumors are rare skin cancers, the most common of which is basal cell carcinoma characterized primarily by local growth. In addition to surgery, radiotherapy is among the basic methods of treatment. External beam radiotherapy is associated with the risk of complications within ocular structures, especially the lens. In the case of interstitial brachytherapy, it is possible to administer a high dose to the clinical target volume (CTV), while reducing it in the most sensitive structures. METHODS: This paper presents the results of an analysis of 28 patients treated with interstitial high dose rate (HDR) brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral canthus; and the cheek, nose and temples with the infiltration of ocular structures. The patients were treated according to two irradiation schedules: 49 Gy in 14 fractions of 3.5 Gy twice a day for 7 days of treatment, and 45 Gy in 5 Gy fractions twice a day for 5 days. The mean follow-up was 22 months (3-49 months). RESULTS: two patients (6%) had a relapse: a local recurrence within the irradiated area in one of them, and metastases to lymph nodes in the other. The most common early complication was conjunctivitis (74%), and the most common late complication was dry eye syndrome (59%). CONCLUSIONS: Interstitial HDR brachytherapy for skin cancers of the upper and lower eyelid; medial and lateral cants; and the cheek, nose and temples with infiltration of ocular structures is a highly effective, short and relatively low burden type of treatment.

Programmed cell death 1 expression and Epstein-Barr virus infection in chronic lymphocytic leukaemia: a prospective cohort study.

PURPOSE: Infection with Epstein-Bar virus (EBV) is associated with an unfavourable prognosis in chronic lymphocytic leukaemia (CLL), but the underlying mechanisms remain unknown. We aimed to establish whether EBV worsens the course of CLL by up-regulating the programmed cell death 1 expression. PATIENTS AND METHODS: Using polymerase chain reaction, we measured EBV DNA in the blood of 110 newly diagnosed, treatment-naïve patients with CLL. We used flow cytometry to measure the expression of programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand (PD-L1) on CD4+, CD8+, and CD19+ cells. Additionally, PD-1 and PD-L1 serum concentrations were measured using enzyme-linked immunosorbent assays. We related the expressions of PD-1 and PD-L1 to EBV DNA load and clinical outcomes. RESULTS: Fifty-nine (54%) patients had detectable EBV DNA [EBV(+)], and these patients had more advanced disease at baseline than the rest. PD-1 and PD-L1 serum concentrations and their expressions on all cell populations were higher in EBV(+) than EBV(-) patients. EBV load correlated positively with unfavourable clinical markers of CLL and the expression of PD-1 and PD-L1 on CD4+ and CD8+ cells (rho =0.42-0.75; p<0.001). EBV(+) patients had increased risks of treatment initiation and lymphocyte doubling during a median follow-up period of 32 months (p<0.001). Among EBV(+), but not EBV(-), patients, higher expressions of PD-1 and PD-L1 on CD4+ and CD8+ cells were associated with higher risks of treatment initiation and lymphocyte doubling (p≤0.020). CONCLUSION: EBV-induced up-regulation of PD-1-PD-L1 expression is associated with worse outcomes in CLL.

Searching for Medical Substances Safe for Mother and Child, Facilitating the Delivery of Pain Management and Decreasing Exhaustion--Evaluation of Obstetric Gel by Pregnant Women.

The aim of the present study was to determine whether applying obstetric gel, a noninvasive method of pain management that is safe both for the mother and the child, during labor influences delivery satisfaction by facilitating pain management and decreasing exhaustion. Forty-seven primiparous women were included in the study: 23 on whom during the delivery gel was used and 24 whose delivery proceeded without the use of a gel (control group). The following research tools were used for the evaluation of satisfaction with the course of the delivery: Visual Analogue Scale (VAS), self-authorship survey, and the State-Trait Anxiety Inventory. There were no significant differences in intensification of pain in the first and second periods of delivery, exhaustion after delivery and intensification of pain in the second period of delivery, and increased anxiety between the study group and the control group. Our results suggest that application of obstetric gel during the first and second period of delivery does not significantly influence women's satisfaction with the course of delivery.