Clonotypic analysis of T cell reconstitution after haematopoietic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency

Haematopoietic stem cell transplantation (HSCT) is performed for treatment of a broad spectrum of illnesses. Reconstitution of an intact immune system is crucial after transplantation to avoid infectious complications, and above all, the establishment of T cell receptor (TCR) diversity is the most important goal in the procedure. Until recently, little has been known of the mechanism of T cell reconstitution in the very early period after HSCT. In this study, we analysed TCR repertoires sequentially in four patients with severe combined immunodeficiency (SCID) before and after HSCT. In all patients, the TCR repertoires were extremely abnormal before HSCT, whereas after transplantation there was progressive improvement in TCR diversity, based on analysis of the TCR Vbeta repertoire and CDR3 size distributions. Somewhat unexpectedly, there was a significant but transient expansion of TCR diversity 1 month after transplantation in all cases. Clonotypic analysis of TCRs performed in one case showed that many T cell clones shared identical CDR3 sequences at 1 month and that the shared fraction decreased progressively. These results indicate that early expansion of TCR diversity may reflect transient expansion of pre-existing mature T cells from the donor blood, independent of de novo T cell maturation through the thymus.     

Anxiety,Depression, and Resilience of Healthcare Workers in Japan During the Coronavirus Disease 2019 Outbreak

Objective Coronavirus disease 2019 (COVID-19) is spreading around the world. The aim of this study was to assess the degree of anxiety, depression, resilience, and other psychiatric symptoms among healthcare workers in Japan during the COVID-19 pandemic. Methods This survey involved medical healthcare workers at the Japanese Red Cross Medical Center (Tokyo, Japan) between April 22 and May 15, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale (GAD-7), Center for Epidemiologic Studies Depression Scale (CES-D), and 10-item Connor-Davidson Resilience Scale. Furthermore, we added original questionnaires comprising three factors: (i) anxiety and fear of infection and death; (ii) isolation and unreasonable treatment; and (iii) motivation and escape behavior at work. Results In total, 848 healthcare workers participated in this survey: 104 doctors, 461 nurses, 184 other co-medical staff, and 99 office workers. Among all participants, 85 (10.0%) developed moderate-to-severe anxiety disorder, and 237 (27.9%) developed depression. Problems with anxiety and fear of infection and death, isolation and unreasonable treatment, and motivation and escape from work were higher in the depression group than in the non-depression group (total CES-D score ≥ 16 points). Being a nurse and high total GAD-7 scores were risk factors of depression. Older workers and those with higher resilience were less likely to develop depression than others. Conclusion During the COVID-19 epidemic, many healthcare workers suffered from psychiatric symptoms. Psychological support and interventions for protecting the mental health of them are needed.     

Gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period

STUDY OBJECTIVE: To determine the presence of impaired gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period. DESIGN: A case series study of 28 patients aged 12 to 19 years with menarche at least 2 years before the study. SETTING: Tertiary care public hospital. PARTICIPANTS: Group I: 14 adolescents previously submitted to chemotherapy during the prepubertal or peripubertal period and with remission of oncologic disease for at least 2 years; Group II: 14 normal adolescents with no previous oncologic disease and with regular menstrual cycles. INTERVENTIONS AND MAIN OUTCOME MEASURES: Pubertal development, menstrual cycles and serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined during the early follicular phase. RESULTS: There were no differences between the two groups in terms of age at appearance of secondary sexual characteristics or age at menarche. Menstrual irregularity was detected in 7 of the 14 patients in Group I, all 8 of whom presented oligomenorrhea. There were no differences in LH levels between the two groups (P = 0.55), although mean FSH levels were higher in Group I than in Group II (6.71 +/- 2.99 mIU/ml vs. 3.83 +/- 2.01 mIU/ml, P = 0.01). CONCLUSION: Although girls submitted to chemotherapy during the prepubertal or peripubertal period presented normal sexual development, the incidence of oligomenorrhea was higher than expected for their age, and FSH levels, although within normal limits, were higher than those seen in normally cycling girls.     

Predictive value of Q waves on the 12-lead electrocardiogram after reperfusion therapy for ST elevation myocardial infarction

Design

The data used for the present study were obtained as part of a clinical trial evaluating the effect of thrombus aspiration after primary percutaneous coronary intervention (PCI).

Setting

The study was conducted at a tertiary referral facility for primary PCI at a University Medical Center Groningen in The Netherlands.

Background

Prognosis after ST elevation myocardial infarction (STEMI) is strongly related to infarct size.

Methods

As part of a randomized clinical trial, the first electrocardiogram (ECG) after primary PCI for STEMI was analyzed for the incidence of Q waves (>0.1 mV) on the 12-lead ECG. Infarct size was measured as area under curve (AUC) of creatine kinase (CK) and CK-myocardial band (CK-MB).

Results and Conclusion

Nine hundred thirty-three patients were included, the median number of Q waves on the postprocedural ECG was 3 (interquartile range, 1-4). The number of Q waves on the postprocedural ECG was an independent predictor of infarct size measured either as AUC of CK (P < .001) or AUC of CK-MB (P < .001) and was a significant predictor of mortality during follow-up of 14 months. In conclusion, the number of Q waves on the postprocedural 12-lead ECG after primary PCI for STEMI is a strong predictor of infarct size and long-term mortality.     

Myocardial Contrast Echocardiography in Assessment of Stable Coronary Artery Disease at Intermediate Dobutamine-Induced Stress Level

Background: Myocardial contrast stress echocardiography (stress MCE) is a novel method for diagnosing coronary artery disease (CAD). Few studies have compared the diagnosis of ischemia by stress MCE to angiographic CAD. Methods: Dobutamine stress MCE and SonoVue contrast infusion were performed before an elective percutaneous coronary intervention in 37 patients (8 women) aged 45–75 years with symptomatic CAD and at least one significant coronary artery stenosis measured by quantitative coronary angiography (QCA). The total and regional perfusion and wall motion (WM) were scored as normal or abnormal and attributed to the three main epicardial coronary arteries using a 17-segment left ventricular model. Results: An intermediate stress level was obtained in 29 (78%) patients, and 2 (5%) patients obtained peak stress. A perfusion defect was detected in 92% and WM abnormality in 57% of the patients at peak stress (P < 0.01). By perfusion, 70% of stenoses were both detected and correctly anatomically located, compared to 42% by WM (P < 0.01). All 21 patients with multivessel disease and/or proximal left anterior descending (LAD) stenosis measured by QCA were identified by stress-induced perfusion defects, while only 11 of them were identified by WM abnormalities (P < 0.01). Conclusion: Perfusion scoring is superior to WM scoring during stress MCE for diagnosing significant CAD in patients obtaining intermediate stress level, in particular, when multivessel disease or proximal LAD stenosis is present.     

Contralateral suppression of otoacoustic emissions in a clinical sample of children with auditory processing disorder

Objective: The suppression of evoked otoacoustic emissions (EOAE) may serve as a clinical tool to evaluate the medial olivocochlear (MOC) reflex, which is thought to aid speech discrimination (particularly in noise) by selectively inhibiting cochlear amplification. The present study aimed to determine if contralateral transient evoked otoacoustic emission (TEOAE) suppression was present in a clinical sample of children with listening difficulties with and without auditory processing disorder (APD).

Design: A three-group, repeated measure design was used.

Study sample: Forty three children aged 8–14?years underwent an auditory processing assessment and were divided into three groups: children with reported listening difficulties with APD, children with reported listening difficulties without APD, and children with normal hearing. APD was defined as per British Society of Audiology.

Results: TEOAE suppression was present in all three participant groups. No significant group, age or ear effects were observed for TEOAE suppression in dB or as a normalised index.

Conclusion: Contralateral TEOAE suppression method could not be used as a clinical tool to identify APD in this study’s participating children and did not support the hypothesised link between reduced MOC function and general listening difficulties in background noise in children with or without APD.     

What characterizes women who want to give birth as naturally as possible without painkillers or intervention?

ObjectiveTo describe the characteristics of pregnant women who wish to have as natural a birth as possible without analgesics and without intervention.Study designNational cohort study.SettingNorwegian Institute of Public Health.Population55,859 pregnant women booked for antenatal care in Norway 1999–2007.MethodsData on women’s interest in natural birth and a set of possible predictors were retrieved from a questionnaire completed at the 30th week of pregnancy and linked to the Medical Birth Registry of Norway.Main outcome measureNatural birth and the characteristics of pregnant women with such preferences.ResultsInterest in natural childbirth was consistently expressed by 72%. Positive experience from previous pregnancies, first birth or third or later birth, no fear of giving birth, and reporting positive intra-psychic phenomena are significantly associated with the wish for natural birth.ConclusionsPositive experiences from previous childbirths and no fear of giving birth are the strongest factors associated with a wish for as natural birth as possible and should be taken into consideration in public health.