Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Correlation of polyp grading scales with patient symptom scores and olfaction in chronic rhinosinusitis: a systematic review and meta-analysis.

BACKGROUND: Various nasal polyp (NP) scoring systems have been proposed and used in the literature. However, no single system has been identified as superior. Correlations between NP scoring systems and patient symptoms, quality of life (QOL) or olfaction vary widely. METHODS: A systematic search of PubMed, CINAHL, Scopus, and Cochrane Library was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Any study examining endoscopy scores and symptom, QOL or olfaction measures in cross sectional manner or after therapeutic intervention were included. RESULTS: This review identified 55 studies for a pooled meta-analysis of Lund-Kennedy (LK-NP) polyp scores (N = 6), Meltzer scores (N = 6), Nasal polyp scores (NPS; N = 19), Total polyp score (TPS; N=8) Lilholdt scores (N = 8), Olfactory cleft endoscopy score (OCES; N =4), Discharge, inflammation, polyp/edema score (DIP; N = 2), and Perioperative sinus endoscopy score (POSE; N = 2). Meta-regression assessed correlations between NP grading systems and SNOT-22, nasal congestion scores, total nasal symptom scores (TNSS), and Smell Identification Test-40 (SIT40). None of the NP grading systems correlated significantly with any symptom, QOL or olfactory metric. In intervention studies of surgery or monoclonal antibody treatment, changes in NPS scores did not correlate with any patient reported outcome measure (PROM) or olfactory outcomes. CONCLUSION: Current NP endoscopic scoring systems are not associated with PROMs such as SNOT-22, nasal congestion scores, and TNSS as well as objective measures of olfaction. NP grading systems with improved clinical utility are needed.

Identification and enjoyment of food items is reduced in dysosmic subjects: a pilot study.

BACKGROUND: Although dysosmia affects a significant proportion of the adult population, there are a paucity of studies addressing its impact on flavor perception and food enjoyment. This study aimed to assess flavor perception and food enjoyment in subjects with and without dysosmia, comparing performance of items considered olfactory-dominant or trigeminal-dominant. METHODS: Adult subjects prospectively underwent Sniffin' Sticks olfactory testing from which threshold, discrimination, and identification (TDI) scores were used to identify dysosmic (TDI over 31) and normosmic subjects (TDI under 31). Forced-choice, blinded flavor identification testing was performed using 8 flavor extracts and 8 real-food purees of either trigeminal- or olfactory-dominant flavor profile. Food enjoyment was quantified using visual analog scales. RESULTS: Forty-one subjects were enrolled, including 20 dysosmics and 21 normosmics, with no difference in age or gender. Compared with normosmics, dysosmic subjects had significantly lower identification of extracts and purees. Among dysosmics, overall identification of trigeminal-dominant extracts and foods was higher than olfactory-dominant extracts and foods. Compared with normosmics, dysosmic subjects reported significantly reduced enjoyment of olfactory-dominant extracts and foods; however, there was no significant difference in enjoyment of trigeminal-dominant extracts or foods. CONCLUSIONS: Identification and enjoyment of food items is reduced in dysosmic subjects, with the greatest impact in olfactory items. These findings suggest that diet modification might lead to greater enjoyment in those with dysosmia.

Correlation of polyp grading scales with patient symptom scores and olfaction in chronic rhinosinusitis: a systematic review and meta-analysis.

BACKGROUND: Various nasal polyp (NP) scoring systems have been proposed and used in the literature. However, no single system has been identified as superior. Correlations between NP scoring systems and patient symptoms, quality of life (QOL) or olfaction vary widely. METHODS: A systematic search of PubMed, CINAHL, Scopus, and Cochrane Library was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Any study examining endoscopy scores and symptom, QOL or olfaction measures in cross sectional manner or after therapeutic intervention were included. RESULTS: This review identified 55 studies for a pooled meta-analysis of Lund-Kennedy (LK-NP) polyp scores (N = 6), Meltzer scores (N = 6), Nasal polyp scores (NPS; N = 19), Total polyp score (TPS; N=8) Lilholdt scores (N = 8), Olfactory cleft endoscopy score (OCES; N =4), Discharge, inflammation, polyp/edema score (DIP; N = 2), and Perioperative sinus endoscopy score (POSE; N = 2). Meta-regression assessed correlations between NP grading systems and SNOT-22, nasal congestion scores, total nasal symptom scores (TNSS), and Smell Identification Test-40 (SIT40). None of the NP grading systems correlated significantly with any symptom, QOL or olfactory metric. In intervention studies of surgery or monoclonal antibody treatment, changes in NPS scores did not correlate with any patient reported outcome measure (PROM) or olfactory outcomes. CONCLUSION: Current NP endoscopic scoring systems are not associated with PROMs such as SNOT-22, nasal congestion scores, and TNSS as well as objective measures of olfaction. NP grading systems with improved clinical utility are needed.

Nonpharmacological interventions to reduce respiratory viral transmission: an evidence-based review with recommendations.

BACKGROUND: Viral respiratory infections are a leading cause of worldwide mortality and exert the potential to cause global socioeconomic crises. However, inexpensive, efficacious, and rapidly deployable strategies to reduce viral transmission are increasingly important in the setting of an ongoing pandemic, though not entirely understood. This article provides a comprehensive review of commonly employed nonpharmacological interventions to interrupt viral spread and provides evidence-based recommendations for their use. METHODOLOGY: A systematic review of three databases was performed. Studies with defined endpoints of subjects receiving one of five interventions (nasal washing, gargling, personal protective equipment (PPE), social distancing, and hand hygiene) were included. An evidence-based review of the highest level of evidence, with recommendations, was created in accordance with a previously described, rigorous, iterative process. RESULTS: Fifty-four primary studies were included. The most commonly studied intervention was hand hygiene, followed by PPE, gargling, saline nasal washing, and social distancing. CONCLUSIONS: Mask use and hand hygiene are strong recommendations for prevention of viral transmission. Donning gloves, gowns, and eye protection are a recommendation in healthcare settings. Saline nasal washing and gargling are options in selected populations. Although an aggregate level of evidence is not provided, the authors recommend social distancing.

The Olfactory Cleft Endoscopy Scale: a multi-institutional validation study in chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction (OD) associated with chronic rhinosinusitis (CRS) remains quite challenging. Instruments to precisely assess olfactory cleft anatomy and their association with olfaction are needed. METHODS: The olfactory cleft endoscopy scale (OCES) was used to assess the olfactory cleft in healthy control subjects and a cohort of patients with CRS. Psychophysical and psychosocial olfactory function were assessed and correlations with OCES scores were measured. RESULTS: Control subjects and subjects with CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) were enrol- led. OCES correlated with both psychophysical and psychosocial olfaction, as measured by threshold, discrimination and identi- fication (TDI) scores and Questionnaire on Olfactory Disorders (QOD-NS) scores for all case and control subjects combined. OCES improved in both CRS groups postoperatively with the highest correlation seen in postoperative olfaction in CRSwNP patients. CRS patients who achieve near perfect OCES and sinus endoscopy scores after surgery have olfactory metrics that are indistin- guishable from controls regardless of polyp status. CONCLUSIONS: The OCES is a valid olfactory-specific measure that demonstrates strong validity and provides complimentary infor- mation to traditional sinus endoscopy to aid in our understanding of OD associated with CRS.

Lack of impact of radiologic septal measurements upon patient symptoms and performance of septoplasty during endoscopic sinus surgery.

BACKGROUND: Recent literature suggests that concurrent septoplasty during endoscopic sinus surgery (ESS) improves patient outcomes, however, the underlying indications for performing concurrent septoplasty are unknown. The objective of this study was to investigate the relationship between objective radiologic measures of nasal septal deviation with preoperative patient symptomatology and measures of CRS disease severity. We also sought to understand the association of objective radiologic measurements with surgeon performance of concurrent septoplasty during ESS. METHODOLOGY: Seventy-four patients with CRS undergoing ESS were prospectively enrolled. Angles of septal deviation, intranasal areas and volumes were assessed on preoperative computed tomography (CT) scans and correlated with a robust battery of patient reported outcomes measures (PROMs), objective measures of CRS severity including olfaction scores, radiologic and endoscopic staging, and performance of septoplasty. RESULTS: Intranasal areas and volumes demonstrated only weak linear associations with patient-reported nasal congestion, however, angles of septal deviation alone did not correlate with congestion or any other PROM measure. Meanwhile, radiologic septal-related measurements did not correlate with objective measures of CRS disease severity or the performance of a concurrent septoplasty. CONCLUSIONS: Though prior studies demonstrate improved patient outcomes in the setting of concurrent septoplasty during ESS, this study failed to establish an association between preoperative radiologic septal-related measurements and patient symptomatology or surgeon decision to perform septoplasty. Although objective factors to identify patients most likely to benefit from concurrent septoplasty remain unidentified, the potential improvement of surgical recommendations and patient outcomes makes this an important area of continued investigation.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

Mode of birth in twins: data and reflections.

Our primary objective was to compare neonatal and maternal outcomes in women with twin pregnancies, beyond 32 weeks, having a planned vaginal birth or a planned caesarean section (CS). This was a retrospective cohort study from a single tertiary centre over nine years. 534 sets of twins ≥32 + 0 weeks of gestation were included. 401 sets were planned vaginally and 133 sets were planned by CS. We compared a composite adverse perinatal outcome (perinatal mortality or serious neonatal morbidity; five minute APGAR score ≤4, neurological abnormality and need for intubation) and a composite maternal adverse outcome (major haemorrhage, trauma or infection) between the groups. There were no significant differences. Given the similarity of these results with several other larger studies of twin birth, we sought to look at reasons why there is still a rising rate of CS for twin births. We further make suggestions for keeping this rate to a sensible minimum. Impact statement What is already known on this subject? The largest randomised controlled study comparing planned vaginal birth with planned CSs for lower risk twins between 32 and 39 weeks of gestation, showed no added safety from planned CS. However, in most of the Western countries this conclusion has failed to increase the number of planned vaginal births for lower risk twins. What do the results of this study add? This observational study from a single tertiary centre provides external validation of the twin trial results in a practical day-to-day setting. It also provides insights as to how planned vaginal birth can be developed and maintained, with a key focus on safety and maternal participation in decision making. It does focus on consent and providing accurate data. What are the implications of these findings for clinical practice and/or further research? There are good grounds to encourage vaginal birth for low-risk twin pregnancies. The trend of rising caesarean rates in low-risk twin pregnancies worldwide will erode important skills for the conduct of vaginal births without any clear benefit for mothers or babies. The current situation demands careful thought about implementing innovative training opportunities for younger obstetricians. Finally, we need intelligent responses to many non-evidence-based factors which can drive clinical practice.

Asthma quality of life and control after sinus surgery in patients with chronic rhinosinusitis.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) often have comorbid asthma. Prior studies have not examined the impact of CRS or endoscopic sinus surgery (ESS) upon asthma quality of life (QOL) and asthma control using validated outcome metrics. METHODS: Patients with CRS, both with and without polyps, and comorbid asthma completed the Mini Asthma QOL Questionnaire (miniAQLQ) and Asthma Control Test (ACT) at baseline and 6 months postoperatively as part of a multi-institutional, prospective study. RESULTS: Baseline metrics were available on 86 patients. Patients undergoing ESS reported improved miniAQLQ [0.5 (SD ±1.1), 95% CI: 0.2-0.7; P = 0.002] and ACT scores [1.3 (±4.1), 95% CI: 0.2-2.4; P = 0.025]. Uncontrolled baseline asthma (ACT < 20) was present in 51% of patients undergoing ESS. In uncontrolled patients, ESS resulted in a minimal clinically important difference 57% of the time for miniAQLQ scores (≥0.5 points) and 50% of the time for ACT scores (≥3.0 points). After adjustment with linear regression, baseline miniAQLQ scores were worse in patients with comorbid allergy (P = 0.045) and chronic obstructive pulmonary disease (COPD; P = 0.015). Adjusted baseline ACT scores were worse in patients with COPD (P = 0.004). Covariates associated with changes in miniAQLQ scores after ESS were pre-operative corticosteroid dependency (P = 0.011) and change in total SNOT-22 score (P = 0.010). Covariate associated with significantly less improvement in ACT scores was obstructive sleep apnea (P = 0.016). CONCLUSIONS: Patients with CRS often present with uncontrolled asthma, and ESS improves both miniAQLQ and ACT. Approximately half of patients with uncontrolled asthma improve after ESS, yet there are few CRS-specific factors associated with asthma QOL or control or ESS outcomes.

Responsiveness and reliability of the Sinus Control Test in chronic rhinosinusitis.

BACKGROUND: The Sinus Control Test (SCT) is a patient-reported questionnaire designed to help physicians identify sub-optimally controlled chronic rhinosinusitis (CRS). This study measures responsiveness to surgery and reliability of the SCT. METHODOLOGY: Adults meeting diagnostic criteria for CRS were recruited from rhinology clinics at a tertiary academic institution. To measure responsiveness, the SCT was administered at baseline and at least 3 months after surgery to 62 CRS patients. To measure reliability, the SCT was administered at two clinical encounters a maximum of 14 days apart to 22 CRS patients. RESULTS: Total SCT scores significantly improved from baseline to post-operative follow-up, and the distribution of patients with total SCT scores falling into the uncontrolled, partially controlled, and controlled categories before and after surgery were significantly different in the direction of improvement. The SCT met minimum standards for reliability and internal consistency as measured by: test-retest reliability coefficient, intra-class correlation coefficients, and item-total correlations. Cronbach alpha; values with each item deleted were lower than the overall Cronbach alpha. The SCT captures the full range of disease control as measured by floor and ceiling effects. CONCLUSION: The SCT is responsive to surgical intervention and a reliable tool to monitor changes in CRS control levels.

Position paper on olfactory dysfunction.

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Maternal CD4+ microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section.

BACKGROUND: Maternal CD4+ cell microchimerism may be greater after caesarean section compared to spontaneous vaginal delivery and could cause mother-to-child transmission (MTCT) in HIV-exposed newborns. AIMS: To evaluate maternal CD4+ cell microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section. STUDY DESIGN AND SUBJECTS: In this prospective single-centre study, neonates whose mothers were infected with HIV and had normal MTCT risk according to the German Austrian Guidelines were considered for study enrolment. Maternal CD4+ cell microchimerism in the newborns' umbilical cord blood was measured and compared by mode of delivery. RESULTS: Thirty-seven HIV-infected mothers and their 39 newborns were included in the study. None of the 17 (0.0%) newborns delivered vaginally had quantifiable maternal CD4+ cells (95% confidence interval (CI): 0.00-0.00) in their circulation at birth compared with four of 16 (25.0%) newborns delivered via planned caesarean section, who showed 0.01-0.66% maternal cells (95% CI: -0.06-0.16; P=0.02) in their circulation. The intention to treat analysis, which included six additional newborns delivered by unplanned caesarean section, showed quantifiable maternal CD4+ cells in one (0.05%; 95% CI: -0.02-0.04) of 23 (4.3%) newborn at birth compared to four of 16 (25.0%) born via planned caesarean section (95% CI: -0.06-0.16; P=0.04). There was no MTCT in any of the newborns. CONCLUSION: In this small cohort, spontaneous vaginal delivery in HIV-infected women with normal MTCT risk was associated with lower maternal CD4+ cell transfer to newborns compared to planned caesarean section.

Position paper on olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study.

Co-infection with CMV in HIV-positive pregnant women is associated with perinatal mother-to-child transmission (MTCT) of both viruses. This retrospective study reports on the incidence of maternal and neonatal CMV (presence of anti-CMV IgG and IgM, CMV DNA PCR and/or CMV virus isolation) in high-risk pregnancies due to maternal HIV infection, MTCT of HIV and/or CMV. One hundred and eleven maternal samples and 75 matched neonatal samples were available for HIV and subsequent CMV testing. In this cohort of HIV-positive pregnant women, 96 (86.5 %) serum samples were anti-CMV IgG positive. In nine (9.4 %) of these, anti-CMV IgM was detected, and in none of them a maternal primary CMV infection was suspected. Fifty-seven (51.8 %) maternal serum samples were tested retrospectively by CMV DNA PCR; one sample was positive (0.9 %). All matched neonates were tested for HIV by PCR in the first month of life; HIV transmission was detected in one case. In 74 (67.2 %) of neonates, CMV testing was performed. Sixty-six of these serum samples were tested retrospectively by CMV DNA PCR. Two newborns (2.7 %) showed laboratory markers for CMV infection (one by detection of CMV DNA in plasma, and one by isolation of CMV from a urine sample). In the follow-up, neither of these two showed clinical signs for active CMV disease. We discussed these findings in the light of the national official guidelines. All CMV transmissions occurred due to maternal reinfection or endogenous reactivation. This suggests the success of highly active antiretroviral therapy in preventing MTCT of HIV and CMV disease and highlights the importance of adequate care and follow-up.

ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects.

BACKGROUND: Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, has been shown to affect brain functional endophenotypes of the disorder, while studies of white matter structure have been inconclusive. METHOD: We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey and white matter using voxel-based morphometry (VBM) in high-resolution T1-weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54 matched healthy controls. RESULTS: We found a significant (p < 0.05, family-wise error corrected for multiple comparisons) interaction effect of diagnostic group x genotype for local grey matter in the left orbitofrontal and right and left lateral temporal cortices, where patients and controls showed diverging effects of genotype. Analysing the groups separately (at p < 0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas. We did not find effects of genotype of regional white matter in either of the two cohorts. CONCLUSIONS: Our findings demonstrate effects of ZNF804A genetic variation on brain structure, with diverging regional effects in schizophrenia patients and healthy controls in frontal and temporal brain areas. These effects, however, might be dependent on the impact of other (genetic or non-genetic) disease factors.

[Mortality of very low birth weight infants during a 24 year period in Hesse a province of Germany - impact of variation in registration]. / Mortalität von Frühgeborenen über einen Zeitraum von 24 Jahren in Hessen - Einfluss veränderter Datensammlung auf die Ergebnisse.

AIM: To study mortality in very low birth weight infants (VLBW) and the impact variation how to register that. METHODS: Data from the Hessian neonatal register from a 24 years period were analyzed. The only outcome criterion was mortality. The whole study time was divided into 6 parts for a period of 4 years. The death rate of preterm infants of 24 weeks of gestation, of those below 24 weeks, and of preterms of 27 weeks was analyzed separately. RESULTS: During 24 years the absolute number of deaths in the group of VLBW increased from an average of 37 patients per year to 60 (p>0.05). The relative mortality decreased from 13.5% to 10.1%. There was an increasing registration of extreme preterm babies of 24 weeks or less. In the last period 13.3% of all VLBW were <25 weeks. These patients represented 54.7% of all deaths in VLBW during 2009-2012. Mortality of preterms of 24 weeks of gestation decreased significantly from 83.3% at the start of the registry to 20.8% in the last period (p=0.007) whereas death rate of preterm infants of 27 weeks dropped from 24.4% to 13.6% (p>0.05). There were also more admissions of extreme preterm infants to neonatal intensive care units. CONCLUSION: Infant death rates are influenced by variation in registration of extreme preterm infants. On the other hand increased registration of these patients seems to encourage doctors to treat them.