Phenotypic Variability in PRKCD: a Review of the Literature.

PURPOSE: Protein kinase C δ (PKCδ) deficiency is a rare genetic disorder identified as a monogenic cause of systemic lupus erythematosus in 2013. Since the first cases were described, the phenotype has expanded to include children presenting with autoimmune lymphoproliferative syndrome-related syndromes and infection susceptibility similar to chronic granulomatous disease or combined immunodeficiency. We review the current published data regarding the pathophysiology, clinical presentation, investigation and management of PKCδ deficiency. METHODS: Literature review was performed using MEDLINE. RESULTS: Twenty cases have been described in the literature with significant heterogeneity. CONCLUSION: The variation in clinical presentation delineates the broad and critical role of PKCδ in immune tolerance and effector functions against pathogens.

Tailing growth, neonatal jaundice and anaemia.

At medical school, there is a phrase to help us remember that common things are common: 'If you hear hooves think horses, not zebras'. However, zebras do exist, and from time to time in general paediatric and neonatal practice, we will encounter these rare diagnoses, more of which we can now accurately diagnose through the ever-expanding field of genomics. Our case demonstrates how a rare diagnosis can present with common features of growth restriction, jaundice and anaemia. Paediatricians therefore require a high index of suspicion and increasing knowledge of the logistics of genetic testing.

To prescribe or not to prescribe for paediatric sore throat: a retrospective cohort study comparing clinician-led antibiotic prescriptions to FeverPAIN and Centor scoring in a tertiary paediatric emergency department and a national review of practice.

BACKGROUND: Tonsillopharyngitis is a common presentation to paediatric emergency departments (PEDs). FeverPAIN (FP) and Centor scoring systems are recommended in the UK to help delineate bacterial aetiology, despite being primarily evidenced in adult populations. We investigate how the use of FP or Centor compares to actual clinician practice in guiding antibiotic prescription rates in PED. We establish current national practice in English PEDs. METHODS: We performed a retrospective cohort study of tonsillopharyngitis presentations to a tertiary PED in January-February 2020. Investigators retrospectively assigned each patient FP and Centor scores using documented symptoms. We compared antibiotic prescription rates guided by FP/Centor against the actual rate prescribed by clinicians, and assessed agreement between these strategies using kappa analysis. We contacted 153 English emergency departments to establish national practice. RESULTS: We identified 632 consecutive patients aged 6 months to 15 years. Actual clinician-prescribed antibiotics numbered 116 (18.4%). Prescriptions predicted by FP score numbered 124 (19.6%) and Centor 112 (17.7%). Kappa (K) analysis indicated only moderate agreement between clinician choice versus FP (K=0.434) and clinician choice versus Centor (K=0.476). This was similar for cohorts aged under and over 3 years.National practice was reportedly heterogeneous, with 70 emergency departments (45.8%) not employing a specific system. CONCLUSION: Current guidance is variably interpreted and inconsistently implemented in paediatric populations. FeverPAIN and Centor scoring systems may not rationalise antibiotics as much as previously reported compared with judicious clinician practice. Producing clear paediatric-specific national guidelines, especially for under-5s who are omitted from NICE sore throat guidance, may help further rationalise and standardise antibiotic use in paediatric tonsillopharyngitis.

Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B.

BACKGROUND & AIMS: A better understanding of the immunomodulatory effects of PegIFNα therapy could allow more rational optimisation of future therapeutic approaches in chronic HBV infection. In this study, we evaluated dynamic changes in the innate and adaptive arms of the immune system induced by PegIFNα. METHODS: PBMC were obtained from a cohort of patients with eAg-negative CHB before, during and after PegIFNα treatment. The number, phenotype and function of global and virus-specific T cells and NK cells were analyzed by flow cytometry and serum cytokines by ELISA or CBA. RESULTS: The absolute number of CD8 T cells was strikingly reduced on PegIFNα therapy (p<0.001), with a predominant loss of end-stage effectors, including CMV-specific CD8 T cells. There was no significant recovery of the exhausted HBV-specific CD8 T cell response. By contrast, PegIFNα was able to potently and cumulatively drive the proliferation and expansion in absolute numbers of CD56(bright) NK cell numbers (p<0.001), with induction of the pro-proliferative cytokine IL-15. Expanded CD56(bright) NK cells showed enhanced expression of activation markers and the activating receptor NKp46, accompanied by augmentation of TRAIL and IFN-γ expression (p<0.001). Peak virological response (temporal within individual patients and cross-sectional within the cohort) correlated with the degree of expansion of functional CD56(bright) NK cells. CONCLUSIONS: IFN-α mediates divergent effects on the innate and adaptive arms of the immune system in vivo. The efficacy of PegIFNα may be limited by its depleting effect on CD8 T cells; conversely, it can cumulatively drive proliferation, activation and antiviral potential of CD56(bright) NK cells.

The accuracy of colposcopic biopsy: analyses from the placebo arm of the Gardasil clinical trials.

We evaluated the overall agreement between colposcopically directed biopsies and the definitive excisional specimens within the context of three clinical trials. A total of 737 women aged 16-45 who had a cervical biopsy taken within 6 months before their definitive therapy were included. Per-protocol, colposcopists were to also obtain a representative cervical biopsy immediately before definitive therapy. Using adjudicated histological diagnoses, the initial biopsies and the same day biopsies were correlated with the surgically excised specimens. The overall agreement between the biopsies taken within 6 months of definitive therapy, and the definitive therapy diagnoses was 42% (weighted kappa = 0.34) (95% CI: 0.29-0.39). The overall underestimation of cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ (CIN2-3/AIS) and CIN3/AIS was 26 and 42%, respectively. When allowing for one degree of variance in the correlation, the overall agreement was 92% for CIN2-3/AIS. The overall agreement between the same day biopsy and definitive therapy specimen was 56% (weighted kappa = 0.41) (95% CI: 0.36-0.47), and the underestimation of CIN2-3/AIS was 57%. There were significant associations in the agreement between biopsies and excisional specimen diagnoses when patients were stratified by age, number of biopsies, lesion size, presence of human papillomavirus (HPV)16/18 and region. Of 178 diagnostic endocervical curettages performed, 14 (7.9%) found any HPV disease. Colposcopic accuracy improved when CIN2 and CIN3/AIS were grouped as a single predictive measure of high-grade disease. Colposcopy functioned well when allowed a one-degree difference between the biopsy and the surgical histologic interpretations, as done in clinical practice. Taking more than one biopsy improved colposcopic accuracy and could improve patient management.

Sexualidad en gestantes / Sexuality in gestantes

Con el objeto de aportar al conocimiento de la respuesta sexual de la gestante y siguiendo el instrumento usado en un trabajo realizado con estudiantes de la UNMSM, se realizó un estudio descriptivo de corte transversal en 121 gestantes de 16 años o más, con 36 a 41 semanas gestacionales según FUR, sin trabajo de parto y convivientes durante el embarazo y desde 6 meses antes, con ausencia de patología importante y otros impedimentos para la actividad sexual. Se estudió el interés (deseo), frecuencia (actividad) y respuesta, incluido el orgasmo, así como las razones que pudieron haber influido en los cambios en la actividad sexual con relación al estado pre gestacional. Se encontró una disminución del interés, frecuencia y respuesta incluido el orgasmo en el primer trimestre, una recuperación de magnitud variable en el segundo trimestre y un descenso ostensible en el tercer trimestre en concordancia con los hallazgos del trabajo de uno de los autores y los de la literatura consultada.

Following the protocol used during previous work undertaken at University of San Marcos, and in order to provide further knowledge on the sexual response of pregnant women, a prospective, descriptive study was made on 121 pregnant women aged 16 and more, between 36 and 41 weeks of pregnancy, and before labor. These women had been living with the father of the child to be, for at least six months and during their pregnancy. They did not have any medical complication nor any impediment for a normal sexual life. Desire, frequency and response, including orgasm and any obstacle to normal sexual life, compared with the pre pregnancy state, were studied. We found a diminished desire, frequency and response during first trimester, returning to almost pre pregnancy levels in the second trimester, but with pronounced decrease in the third trimester. These findings are very similar to previous results obtained by one of the authors, and to those reported in the literature.