Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia

Objective: The aim of the present study was to evaluate changes in maternal serum neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin (PCT) concentrations in preeclampsia.

Material and method: This case–control study consisted of 40 preeclamptic and 40 healthy singleton pregnancies matched for age and body mass index. Serum NGAL and PCT levels were compared between the groups. Diagnostic performance and clinical association of these markers were evaluated.

Results: NGAL and PCT concentrations were significantly higher in preeclamptic group (p?p?=?0.001, respectively) and their levels were correlated with the severity of the preeclampsia. There were significant positive correlation between these markers and mean arterial pressure (MAP) and spot urine protein excretion. There was negative correlation between NGAL and apgar scores and fetal birth weight. Pregnancies with higher NGAL (OR: 4.89; 95% CI: 1.81–13.21) and higher PCT (OR: 6.67; 95% CI: 2.44–18.21) concentrations had higher risk for preeclampsia.

Conclusion: NGAL and PCT may be potential biomarkers for preeclampsia. Their levels increase significantly in preeclampsia and they are related to the severity of the disease. These results are in agreement with the generalized endothelial damage and persistant inflammatory status in preeclampsia. NGAL may also be an indicator for adverse neonatal outcomes with decreased placental hypoperfusion.     

CARMIL2-related immunodeficiency manifesting with photosensitivity

We report a case of a newly recognized primary immunodeficiency due to biallelic mutations in CARMIL2 manifesting as an actinic prurigo-like photodermatitis, allergic diathesis and recurrent infections in a child. We present this case to highlight a rare phenotype seen in this T-cell immunodeficiency and provide an overview of other dermatologic manifestations among published reports of this condition.     

Cognition of the mothers of patients with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) has been found to be associated with cognitive impairment. However, few studies have addressed cognitive impairment among mothers of children with DMD. In the present study, the neuropsychological profiles of both carrier mothers (C-Ms) and noncarrier mothers (NC-Ms) were examined, and the findings were compared with healthy control mothers (HC-Ms). There were 90 participants, consisting of 31 C-Ms, 24 NC-Ms, and 35 HC-Ms, each of whom completed a neuropsychological test battery. C-Ms had poorer cognition performance in attention, working memory, immediate verbal memory, visuospatial skills, and executive functions than NC-Ms, and HC-Ms. This study provides evidence that there may be cognitive impairment in mothers of patients with DMD. The cognitive impairment of C-Ms has similarities to that seen in children with DMD.     

Telaprevir Experience From Turkey

Background:

In patients with chronic hepatitis C, triple drug regimens containing a protease inhibitor, peginterferon and ribavirin were found to significantly increase sustained virologic response rates compared to dual drug regimen containing pegylated interferon and ribavirin, especially in genotype 1.

Objectives:

In Turkey, telaprevir has been used since March 2013. We aimed to evaluate results of patients with chronic hepatitis C treated with telaprevir, peginterferon and ribavirin.

Patients and Methods:

We evaluated 28 patients with genotype 1 chronic hepatitis C infection treated with triple drug regimen containing telaprevir, in three medical centers in Turkey, retrospectively. Demographic data of patients, treatment indications, adverse events and outcomes were recorded.

Results:

Of 28 patients intended to treat, 25 (89.2%) patients completed the treatment. Overall, 21 (82.1%) patients had relapse and five patients were non-responder. Regarding the treatment outcomes of Telaprevir based regimen, 20/26 patients achieved sustained virological response. Pruritus, rash, dysgeusia, anorectal discomfort and anemia were main adverse effects. Blood transfusion and ribavirin dose reduction required for 7 and 11 patients, respectively. Due to several adverse effects, 10 patients were hospitalized.

Conclusions:

Although more frequent and severe adverse effects, telaprevir has been promising for patients with treatment-experienced hepatitis C.     

Time interval from the initiation of the electrocardiographic P wave to the start of left atrial appendage ejection flow: A novel method for predicting atrial fibrillation recurrence

OBJECTIVE: The incidence of paroxysmal and persistent atrial fibrillation (AF) recurrence is high and unpredictable. In this study, a novel noninvasive method that was thought to reflect the interatrial conduction time was investigated to predict AF recurrence. This method was on the basis of the measurement of time interval from initiation of the electrocardiographic P wave to the start of left atrial (LA) appendage (LAA) ejection flow (P-LAA). Methods and Results: Forty-five consecutive patients (age, 61 +/- 11 years; 20 male) with newly diagnosed AF (mean duration, 132 hours; range: 6 hours-3 months) who converted to in sinus rhythm spontaneously or with cardioversion were studied prospectively. Transthoracic and transesophageal echocardiography were performed to measure LA size, mechanical functions, LAA ejection velocity, and P-LAA. Transesophageal echocardiography was performed for the measurement of P-LAA 1 to 2 days after conversion to in sinus rhythm. The patients were followed up for a period of 163 +/- 72 days for the recurrence of AF. AF recurred in 17 (38%) patients after a mean time of 81 +/- 67 days. P-LAA was significantly higher in patients with AF recurrence (123 +/- 36 vs 92 +/- 24 milliseconds, P =.0047) and multiple regression analysis indicated that P-LAA was an independent predictor of AF recurrence. Multiple regression analysis revealed no significant differences in LA size parameters, or in clinical and LA mechanical function parameters recorded after restoration of in sinus rhythm between patients with and without AF recurrence. CONCLUSION: P-LAA may be considered to be an independent predictor of recurrent AF.     

The effect of parity on pelvic floor muscle strength and quality of life in women with urinary incontinence: a cross sectional study

[Purpose] The purpose of this study was to analyze the pelvic floor muscle (PFM) activity after vaginal birth, and the effect of parity on PFM strength and quality of life (QoL) in women with urinary incontinence. [Subjects and Methods] Patients (n=241) who gave birth vaginally and experienced urinary incontinence were divided into three groups: group 1 consisted of women having 1–3 children, group 2 consisted of women having 4–6 children, and group 3 consisted of women having more than 6 children. All patients underwent detailed examination of the PFM. The Turkish version of the self-administered Incontinence Quality of Life Instrument (I-QoL) questionnaire was used to evaluate the effects of stress urinary incontinence on participants’ QoL. [Results] Comparison of PFM strengths showed a significant intergroup difference. Group 1 showed significantly higher PFM strength scores than those of groups 2 and 3. I-QoL scores related to stress incontinence showed a significant intergroup difference. As number of deliveries increased, quality of life decreased. Comparison of PFM strengths and I-QoL scores related to stress incontinence showed a significant intergroup difference. [Conclusion] Increasing the awareness of PFM training in women will reduce potential postpartum incontinence due to a weak PFM strength; and will increase quality of life.Key words: Parity, Pelvic floor muscle strength, Urinary incontinence     

Internalized Stigma in Pediatric Psoriasis: A Comparative Multicenter Study

BackgroundInternalized stigma, adoption of negative attitudes and stereotypes of the society regarding persons'' illness, has not been studied previously in pediatric psoriasis patients.ObjectiveWe aimed to investigate the internalized stigma in pediatric psoriasis patients and to determine differences according to factors affecting internalized stigma compared to adult psoriasis patients.MethodsThis multicenter, cross-sectional, comparative study included 125 pediatric (55 female, 70 male; mean age±standard deviation [SD], 14.59±2.87 years) and 1,235 adult psoriasis patients (577 female, 658 male; mean age±SD, 43.3±13.7 years). Psoriasis Internalized Stigma Scale (PISS), Dermatology Life Quality Index (DLQI), Perceived Health Status (PHS), and the General Health Questionnaire (GHQ)-12 were the scales used in the study.ResultsThe mean PISS was 58.48±14.9 in pediatric group. When PISS subscales of groups were compared, the pediatric group had significantly higher stigma resistance (p=0.01) whereas adult group had higher scores of alienation (p=0.01) and stereotype endorsement (p=0.04). There was a strong correlation between mean values of PISS and DLQI (r=0.423, p=0.001). High internalized stigma scores had no relation to either the severity or localization of disease in pediatric group. However, poor PHS (p=0.007) and low-income levels (p=0.03) in both groups, and body mass index (r=0.181, p=0.04) in the pediatric group were related to high PISS scores.ConclusionInternalized stigma in pediatric patients is as high as adults and is related to poor quality of life, general health, and psychological illnesses. Unlike adults, internalized stigma was mainly determined by psoriasis per se, rather than disease severity or involvement of visible body parts, genitalia or folds.