Normal Screening Results Research Articles

Adaptation and Validation of the Psychological Consequences of Screening Questionnaire (PCQ) for Cognitive Screening in Primary Care.

Context-specific measures with adequate external validity are needed to appropriately determine psychosocial effects related to screening for cognitive impairment. Two-hundred adults aged ≥65 y recently completing routine, standardized cognitive screening as part of their Medicare annual wellness visit were administered an adapted version of the Psychological Consequences of Screening Questionnaire (PCQ), composed of negative (PCQ-Neg) and positive (PCQ-Pos) scales. Measure distribution, acceptability, internal consistency, factor structure, and external validity (construct, discriminative, criterion) were analyzed. Participants had a mean age of 73.3 y and were primarily female and socioeconomically advantaged. Most had a normal cognitive screening result (99.5%, n = 199). Overall PCQ scores were low (PCQ-Neg: = 1.27, possible range 0-36; PCQ-Pos: = 7.63, possible range 0-30). Both scales demonstrated floor effects. Acceptability was satisfactory, although the PCQ-Pos had slightly more item missingness. Both scales had Cronbach alphas >0.80 and a single-factor structure. Spearman correlations between the PCQ-Neg with general measures of psychological distress (Impacts of Events Scale-Revised, Perceived Stress Scale, Kessler Distress Scale) ranged from 0.26 to 0.37 (P's < 0.001); the correlation with the World Health Organization-Five Well-Being Index was -0.19 (P < 0.01). The PCQ-Neg discriminated between those with and without a self-reported subjective cognitive complaint ( = 2.73 v. 0.89, P < 0.001) and was associated with medical visit satisfaction (r = -0.24, P < 0.001) on the Patient Satisfaction Questionnaire. The PCQ-Pos predicted self-reported willingness to engage in future screening ( = 8.00 v. 3.00, P = 0.03). The adapted PCQ-Neg is an overall valid measure of negative psychological consequences of cognitive screening; findings for the PCQ-Pos were more variable. Future studies should address measure performance among diverse samples and those with abnormal screening results. The PCQ scale is an overall valid measure of psychological dysfunction related to cognitive screening in older adults receiving normal screen results.PCQ scale performance should be further validated in diverse populations and those with abnormal cognitive screening results.The adapted PCQ may be useful to both health research and policy stakeholders seeking improved assessment of psychological impacts of cognitive screening.

Hb H disease associated with compound heterozygosity for --SEA deletion and a novel alpha globin chain variant (HBA2:c.175C>A) on the distal histidine in a Chinese family

ABSTRACT Objectives: In clinical practice, the majority of α-thalassaemia cases arise from deletions of the α-globin genes. However, a subset of cases is attributed to rare haemoglobin variants, which can manifest with borderline or normal screening results, potentially leading to missed diagnoses in clinical practice. Methods: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis. Results: The five-month-old proband presented a haematological phenotype consistent with Hb H disease. The mother’s haematology profile was consistent with an α-thalassaemia carrier, while the father exhibited a borderline reduction in MCV and MCH. MALDI-TOF identified an abnormal α-chain in the proband. DNA analysis revealed a novel α-globin variant (HBA2:c.175C>A, α58His>Asn, Hb DG-Nancheng) affecting the distal histidine in the family. The father and the mother had α-genotype of --SEA/αα and αDG-Nanchengα/αα, respectively; while the proband inherited both mutant alleles (--SEA/αDG-Nanchengα). Sequencing of cDNA from HBA2 gene identified an equal ratio of normal and mutant alleles. Conclusion: This rare case highlighted the importance of identifying rare haemoglobin variant during prenatal screening. The clinical and genetic data provides useful information on the pathogenicity of this variant and further insight into the role of distal histidine residue of α-globin.

Эффективность неонатального скрининга на критические врожденные пороки сердца путем двузонного измерения систолического артериального давления и сатурации

Aim. To evaluate screening methods for critical congenital heart defects (CHD), in particular obstructive aortic arch defects (OАADs), using dual-zone systolic blood pressure (SBP) and oxygen saturation measurements in healthy newborns. Design. A prospective observational study. Material and methods. The study included 12 098 healthy newborns aged 48 (36–50) hours of life, who were screened for critical CHDs using dual-zone measurements of SBP and saturation, as well as using physical methods. Screening for critical CHDs was considered normal if the saturation difference was 2% or less, the saturation was more than 95%, the difference in SBP was 9 mm Hg and less. If the screening was abnormal, echocardiography (ECHO-CG) was performed. The end point of the study was to determine the sensitivity and specificity of screening for OPAADs in healthy newborns using dual-zone measurement of SBP and saturation. Results. 12 037 children had normal screening results. In these children, the difference in pre- and postductal SBP was 0 (standard deviation (σ) = 4.26 mm Hg, and the difference (Me) in saturation was 0 (σ = 0.93%). Dual-zone SBP screening was abnormal in 34 newborns. The difference in their SBP was 11 (10–34) mm Hg. In 16 of these children ECHO-CG did not reveal CHD, and in 4 — critical OAADs — coarctation of aorta was diagnosed. A decrease in peripheral pulsation in the femoral arteries was noted only in children with critical OAADs. Pulse oximetry screening was normal in these children with critical OAADs. Dual-zone saturation screening was abnormal in 16 children. The difference in saturation between them was 3 (3–5)%. In 13 of these children, ECHO-CG did not reveal CHDs, and in 1 child critical CHD was diagnosed — transposition of the great arteries. Also, this child (and another who was healthy) had a decrease in saturation of less than 95%. In 11 newborns, screening was abnormal only due to saturation of 95% or less, but ECHO-CG did not reveal CHDs. The sensitivity and specificity of screening for OAADs using dual-zone SBP measurement was 100 and 80%, and using dual-zone pulse oximetry was 0 and 73.6%, respectively. Conclusions. In newborns with OAADs, a difference in SBP of 10 mmHg is recorded after 36 hours of their life. Dual-zone measurement of SBP is the most highly sensitive and specific method for detecting OAADs in comparison with dual-zone pulse oximetry. Dual-zone measurement of SBP and determination of peripheral pulsation are recommended for inclusion in the neonatal screening protocol for critical CHDs. Keywords: congenital heart disease, neonatal screening for congenital heart defects, aortic coarctation, aortic arch interruption, blood pressure.

Prenatal identification of an inverted duplicated 13q marker chromosome with a neocentromere

In this case report, we describe a rare prenatal finding of a small marker chromosome. This marker chromosome corresponds to an inverted duplication of the 13q region 13q31.1q34 (or 13q31.1 → qter) with a neocentromere, detected during genetic analysis of a chorionic villus sample in a fetus with multiple congenital anomalies after a normal prenatal screening result by noninvasive prenatal testing.

Prevalence of high-penetrant copy number variants in 7734 low-risk pregnancies

The rate of clinically significant copy number variants in chromosomal microarray analysis in low-risk pregnancies is approximately 1%. However, these results include copy number variants with low and variable penetrance, although some patients might be interested only in the detection of high-penetrant variants. This study aimed to calculate the prevalence of high-penetrant copy number variants in a large cohort of low-risk pregnancies. This retrospective study was performed using microarray results of pregnancies with normal ultrasound and maternal serum screening. All clinically significant (pathogenic and likely pathogenic) copy number variants were recorded. Of these, only high-penetrant findings were selected. Findings with low and medium penetrance and copy number variants with unknown clinical penetrance, including uniparental disomy of segments not related to known imprinted syndromes, mosaic aneuploidy of <50%, and segmental mosaicism, were excluded. The calculation was performed for the overall cohort, for women aged >35 years and women aged <35 years, and after omission of noninvasive prenatal screening theoretically detectable findings (trisomies 13, 18, and 21). Clinically significant copy number variants were detected in 118 of 7734 cases (1.50% or 1:65), and high-penetrant copy number variants were detected in 33 of 7734 cases (0.43% or 1:234). In women aged ≥35 years, the rates of high-penetrant copy number variants were 29 of 5734 cases (0.51% or 1:198) and 4 of 2000 cases (0.20% or 1:500) in women aged <35 years (P=.0747). Following the omission of 12 theoretically noninvasive prenatal screening-detectable findings, the rates of high-penetrant copy number variants declined to 21 of 7722 cases (0.27% or 1:368) in the whole cohort-18 of 5723 cases (0.31% or 1:318) in woman aged ≥35 years and 3 of 1999 cases (0.15% or 1:666) in younger women (P=.319). The risk of high-penetrant copy number variants in low-risk pregnancies exceeds the risk of miscarriage after invasive testing, even after normal noninvasive prenatal screening results. These results are of importance to genetic counselors and obstetricians, to facilitate maternal informed decision-making when considering invasive prenatal testing in low-risk pregnancies.

Muscle Ultrasound Abnormalities in Individuals with RYR1-Related Malignant Hyperthermia Susceptibility.

Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility. To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients. We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy. Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity.

Multiple Center Research on Relationship Between Screening Quality and Detection of Cervical Cancer - Six Provinces, China, June-December 2021.

The effective implementation of cervical cancer examination programs requires improved cervical cancer screening coverage and quality. The detection rate of ≥high-grade squamous intraepithelial lesions (HSIL) in 6 hospitals was 19.6%. Not having undergone screening in the last 5 years and abnormal screening results had a negative association with detection of ≥HSIL, and abnormal screening results would increase the risk of detection by 75% compared with normal screening results. Additionally, low-grade, high-grade, and cancer of colposcopic impression were associated with a higher risk for detecting ≥HSIL. It is essential to disseminate health knowledge about cervical cancer control to women in order to increase their awareness and screening rates. Additionally, it is necessary to further strengthen the training of professional staff to improve the quality of cervical cancer prevention, including screening, colposcopic examination, and follow-up for target female populations.

Third trimester re-screening for gestational diabetes in morbidly obese women despite earlier negative test can reveal risks for obstetrical complications.

We investigated associations of maternal obesity with late gestational diabetes mellitus (GDM) diagnosis (>34 weeks) in women with previous normal glucose screening, and associations of late GDM with obstetrical outcomes. This retrospective cohort study assessed obstetrical and neonatal outcomes of 238 women with normal (24-28 week) glucose screening results, who underwent late repeat oral glucose tolerance tests (OGTT) (>34 weeks) due to a suspected LGA fetus (54.6%) or polyhydramnios (45.4%). A sub-analysis was performed of outcomes of women with late versus mid-trimester GDM. The GDM rate in repeat OGTT screening was 22.2% for the total sample, and 33% among women with morbid obesity. Among women with late GDM versus without late GDM, rates were higher for macrosomia, large-for-gestational-age fetus induction of labor, neonatal hypoglycemia, jaundice, and the need for phototherapy. Among women with late GDM, a higher pregestational BMI was associated with adverse maternal and perinatal outcomes. Higher risks for macrosomia and CS due to macrosomia were demonstrated in women with late vs. mid-trimester GDM. Late screening in pregnancy may reveal GDM among women with previous normal glucose screening, particularly among those with late third trimester BMI ≥ 35 kg/m2 , GDM in a previous pregnancy or fasting glucose >95 mg/dl. Women diagnosed with GDM at >34 weeks following normal glucose screening at 24-28 weeks are at higher risk for adverse perinatal outcomes. For women with morbid obesity, or suspected macrosomia or polyhydramnios in the late third trimester, and normal glucose screening in the second trimester, retesting should be considered.

A Randomized Trial of Telephone-Based Smoking Cessation Treatment in the Lung Cancer Screening Setting.

Lung cancer mortality is reduced via low-dose computed tomography screening and treatment of early-stage disease. Evidence-based smoking cessation treatment in the lung screening setting can further reduce mortality. We report the results of a cessation trial from the National Cancer Institute's Smoking Cessation at Lung Examination collaboration. Eligible patients (n = 818) aged 50-80 years were randomly assigned (May 2017-January 2021) to the intensive vs minimal arms (8 vs 3 phone sessions plus 8 vs 2 weeks of nicotine patches, respectively). Bio-verified (primary) and self-reported 7-day abstinence rates were assessed at 3, 6, and 12 months post random assignment. Logistic regression analyses evaluated the effects of study arm. All statistical tests were 2-sided. Participants reported 48.0 (SD = 17.2) pack-years, and 51.6% were not ready to quit in less than 30 days. Self-reported 3-month quit rates were statistically significantly higher in the intensive vs minimal arm (14.3% vs 7.9%; odds ratio [OR] = 2.00, 95% confidence interval [CI] = 1.26 to 3.18). Bio-verified abstinence was lower but with similar relative differences between arms (9.1% vs 3.9%; OR = 2.70, 95% CI = 1.44 to 5.08). Compared with the minimal arm, the intensive arm was more effective among those with greater nicotine dependence (OR = 3.47, 95% CI = 1.55 to 7.76), normal screening results (OR = 2.58, 95% CI = 1.32 to 5.03), high engagement in counseling (OR = 3.03, 95% CI = 1.50 to 6.14), and patch use (OR = 2.81, 95% CI = 1.39 to 5.68). Abstinence rates did not differ statistically significantly between arms at 6 months (OR = 1.2, 95% CI = 0.68 to 2.11) or 12 months (OR = 1.4, 95% CI = 0.82 to 2.42). Delivering intensive telephone counseling and nicotine replacement with lung screening is an effective strategy to increase short-term smoking cessation. Methods to maintain short-term effects are needed. Even with modest quit rates, integrating cessation treatment into lung screening programs may have a large impact on tobacco-related mortality.

Whole genome sequencing for newborns—The devil is in the details

Whole genome sequencing for newborns—The devil is in the details

Chromosomal Microarray Analysis Compared With Noninvasive Prenatal Testing in Pregnancies With Abnormal Maternal Serum Screening

OBJECTIVE: To examine the effect of maternal age on the rate of clinically significant chromosomal microarray analysis results in pregnancies with abnormal maternal serum screening and to establish the residual risk for abnormal microarray findings after omitting noninvasive prenatal testing (NIPT)–detectable aberrations in pregnancies with abnormal maternal serum screening. METHODS: This retrospective study included all chromosomal microarray analysis tests performed in pregnancies with abnormal maternal serum screening and normal ultrasonogram results over the years 2013–2021. The rate of clinically significant (pathogenic and likely pathogenic) chromosomal microarray analysis findings was compared with a local control cohort of 7,235 pregnancies with normal maternal serum screening and ultrasonogram results, stratified by maternal age. Calculation of residual risk for clinically significant chromosomal microarray analysis results after normal NIPT was performed by omission of common NIPT-detectable anomalies. Systematic review for studies examining the yield of chromosomal microarray analysis in pregnancies with abnormal maternal serum screening was performed from inception to October 2021, with no time or language restrictions. RESULTS: Of the 559 amniocenteses performed due to abnormal maternal serum screening, 21 (3.8%; 95% CI 2.4–5.7%) clinically significant chromosomal microarray analysis results were found. The residual risk for chromosomal microarray analysis aberrations after theoretically normal NIPT was estimated to be 2.0% (95% CI 1.1–3.6%) (1/50) and was significantly higher for women younger than age 35 years with abnormal maternal serum screening, compared with women with low-risk pregnancies. Systematic review yielded six articles encompassing 4,890 chromosomal microarray analysis results in pregnancies with abnormal maternal serum screening, demonstrating 2.3% residual risk for chromosomal microarray analysis anomalies after theoretically normal NIPT. DISCUSSION: Clinically significant chromosomal microarray analysis findings can be found in 1 of every 50 pregnancies with high-risk maternal serum screening after theoretically normal NIPT, implying that invasive testing and not NIPT should be recommended in such pregnancies. In addition, NIPT use as a first-tier screening modality instead of maternal serum screening would miss pregnancies at increased risk not only for common autosomal trisomies but for additional chromosomal microarray analysis–detectable disorders.

Study Design for an Evaluation of Newborn Screening for SCID in the UK.

Severe combined immunodeficiency is a rare inherited disorder, which, if untreated, invariably proves fatal in late infancy or early childhood. With treatment, the prognosis is much improved. Early treatment of the siblings of cases, before they become symptomatic, has shown considerable improvements in outcomes. Based on this and the development of a test that can be used on the whole population of neonates (measurement of T-cell receptor excision circles—TRECs), many countries have added it to their routine newborn bloodspot screening programmes. The UK National Screening Committee (UKNSC) has considered whether SCID should be added to the UK screening programme and concluded that it was likely to be cost effective, but that there were a number of uncertainties that should be resolved before a national roll-out could be recommended. These include some aspects of the test, such as: cost; the use of different assays and cut-off levels to reduce false positive rates, while maintaining sensitivity; the overall benefits of screening for disease outcome in patients with SCID and other identified disorders; the need for a separate pathway for premature babies; the acceptability of the screening programme to parents of babies who have normal and abnormal (both true and false positive) screening results. To achieve this, screening of two thirds of babies born in England over a two-year period has been planned, beginning in September 2021. The outcomes and costs of care of babies identified by the screening will be compared with those of babies identified with SCID in the rest of the UK. The effect of the screening programme on parents will form part of a separate research project.

Radiographic Follow-up After Normal Ultrasound Screening of the Hip in Breech Infants.

Breech presentation is one of the most important risk factors for developmental dysplasia of the hip, and all breech infants should be screened. The necessity of further follow-up of developmental dysplasia of the hip after normal clinical and sonographic screening is a controversial subject. The purpose of this study to identify the incidence of delayed dysplasia in breech infants after normal ultrasound screening and the necessity of further clinical and radiologic follow-up in these patients. We included the 292 breech babies (128 boys and 164 girls) who showed normal hip ultrasound screening results. To determine the incidence of delayed radiographic dysplasia, anteroposterior hip radiographs were taken between 12 and 24 months of age to measure the acetabular index (AI). The mean AI values were 22.8±3.4 in boys and 24.9±3.1 in girls. Applying the Tönnis criteria, 29 patients (9.9%) were considered to have delayed radiographic dysplasia (16 boys and 13 girls). No significant difference was found in any demographic variables between babies with and without delayed radiographic dysplasia. None of these 29 infants underwent any treatment for radiographic dysplasia. Applying Kuong's criteria to 292 infants, only 2 patients (0.7%) demonstrated radiographic dysplasia on the hip anteroposterior radiographs taken at 14 months. The incidence of radiographic dysplasia significantly varied depending on which criteria were applied. In order to find out more accurate incidence rates of delayed radiographic dysplasia, large-scale studies of the normative AI data for Korean infants are required. Prognostic Level III.

Follow-up study of preterm infants with thyroid dysfunction after medication.

To study the effect of levothyroxine sodium tablets on the growth and development and thyroid function in preterm infants with thyroid dysfunction. A retrospective analysis was performed for 82 preterm infants who were born in the Department of Obstetrics of the First People's Hospital of Yunnan Province, from January 1, 2013 to December 31, 2017, and these infants were hospitalized after birth in the Department of Neonatology of the hospital. They were regularly followed up to observe growth and development and thyroid function at the outpatient service of the Department of Neonatology. According to thyroid function test results, they were divided into an abnormal thyroid function group (observation group; n=31) and a normal thyroid function group (control group; n=51). The infants in the observation group were given oral administration of levothyroxine sodium tablets, while those in the control group were not given any treatment. The two groups were compared in terms of the physical and intelligence development and thyroid function of preterm infants with various gestational ages (28-<32 weeks, 32-<34 weeks, and 34-<37 weeks) after regular follow-up to the corrected age of 12 months. There were no significant differences in physical development indices (body length, body weight, and head circumference) between the observation and control groups at various gestational ages after follow-up to the corrected age of 12 months (P>0.05). There were no significant differences between the two groups in the scores of each functional area of the Gesell Developmental Scale among the preterm infants with a gestational age of 28-<32 weeks and 32-<34 weeks after follow-up to the corrected age of 12 months (P>0.05). For the preterm infants with a gestational age of 34-<37 weeks, compared with the control group, the observation group had a significantly lower score of gross motor ability at the age of 3 and 12 months, significantly lower scores of fine motor ability, language ability, and adaptation ability at the age of 12 months (P<0.05), and a significantly lower score of personal-social ability at the age of 3 months (P<0.05). However, the score of personal-social ability in the observation group was not significantly different from the control group at the age of 12 months (P>0.05). After 2-4 weeks of treatment with levothyroxine sodium tablets, the thyroid function of the 31 preterm infants with thyroid dysfunction returned to normal. Among the 31 infants, 21 (68%) achieved complete drug withdrawal, with normal results of neonatal screening (100%); 10 infants (32%) failed to achieve drug withdrawal, and only 2 (20%) out of the 10 infants had normal neonatal screening results (P<0.05). Early diagnosis and reasonable treatment can reduce the impact on growth and development in preterm infants with thyroid dysfunction. Most preterm infants tend to have transient thyroid dysfunction, while those with positive results of neonatal screening are more likely to develop permanent thyroid dysfunction.

Nationwide Rereview of Normal Cervical Cytologies before High-Grade Cervical Lesions or before Invasive Cervical Cancer

Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001–2016 (p < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer.

Benefit versus risk of chromosomal microarray analysis performed in pregnancies with normal and positive prenatal screening results: A retrospective study.

Most studies on chromosomal microarray analysis (CMA) and amniocentesis risks have not evaluated pregnancies with low risk for genetic diseases; therefore, the efficacy and safety of CMA and amniocentesis in this population are unclear. This study aimed to examine the benefits and risks of prenatal genetic diagnostic tests in pregnancies having low risk for chromosomal diseases. In this retrospective study, we used clinical data from a large database of 30,830 singleton pregnancies at gestational age 16-23 weeks who underwent amniocentesis for karyotyping with or without CMA. We collected socio-demographic, medical and obstetric information, along with prenatal screening, CMA and karyotyping results. Fetal loss events were also analysed. CMA was performed in 5,837 pregnancies with normal karyotype (CMA cohort). In this cohort, 4,174 women had normal prenatal screening results and the risk for identifying genetic abnormalities with >10% risk for intellectual disability by CMA was 1:102, with no significant difference between maternal age groups. The overall post-amniocentesis fetal loss rate was 1:1,401 for the entire cohort (n = 30,830) and 1:1,945 for the CMA cohort (n = 5,837). The main limitation of this study is the relatively short follow-up of 3 weeks, which may not have been sufficient for detecting all fetal loss events. The low risk for post-amniocentesis fetal loss, compared to the rate of severe genetic abnormalities detected by CMA, suggests that even pregnant women with normal prenatal screening results should consider amniocentesis with CMA.

Sarcopenia Screening Allows Identifying High-Risk Patients for Allogenic Stem Cell Transplantation.

Simple SummaryAllogenic stem cell transplantation is a treatment option for various hematological diseases. Due to the intensity of the therapy regimes used, there is a substantial therapy associated mortality and morbidity. Therefore, it is crucial to identify patients with increased risk for treatment associated complications. Sarcopenia, defined as the loss of muscle mass and strength is a risk factor in various diseases. Aim of our study was to implement and evaluate the predictive power of a sarcopenia assessment, based on muscle mass, muscle strength and aerobic capacity (by measuring peak oxygen uptake), on all-cause and non-relapse mortality. A total of 178 patients were screened, with 28% suffering from sarcopenia before transplantation. Our results show a three-fold increase in all-cause and non-relapse mortality in this subpopulation compared to non-sarcopenic patients within a 12-month follow up. The importance of physical performance status demonstrated, raises the question, if exercise interventions might even allow to decrease mortality and morbidity.Allogenic stem cell transplantation (aSCT) is the only potentially curative treatment for high-risk hematological diseases. Despite advancements in supportive measures, aSCT outcome is still affected by considerable transplant-related mortality. We implemented a new sarcopenia assessment prior to aSCT to evaluate its predictive capability for all-cause and non-relapse mortality. Therefore all patients initially scheduled for aSCT within a 25-month period were screened during pre-transplantation-routine for muscle mass, grip strength, and aerobic capacity (AC) by measuring peak oxygen uptake (VO2peak). Patients were assigned to one of five groups adapted according current sarcopenia guidelines. Primary endpoints were all-cause and non-relapse mortality within a follow up time of up to 12 months. A total of 178 patients were included and rated as normal (n = 48), impaired aerobic capacity (n = 56), pre-sarcopenic (n = 26), sarcopenic (n = 27), and severe sarcopenic (n = 22) without significant age-differences between groups. Patients presenting with sarcopenia showed a significant three-fold increase in all-cause and non-relapse mortality compared to patients with normal screening results. AC showed to be the strongest single predictor with a more than two-fold increase of mortality for low AC. We conclude that risk stratification based on combination of muscle mass, grip strength, and AC allowed identifying a subgroup with increased risk for complications in patients undergoing aSCT.

Screening participation after a false positive result in organized cervical cancer screening: a nationwide register-based cohort study

Our aim was to investigate whether receiving a false positive (FP) cervical cytology result affected subsequent cervical cancer screening participation. This Danish nationwide register-based cohort study included 502,380 women aged 22.5–45 attending cervical cancer screening in 2012–2014 with a normal (n = 501,003) or FP (n = 1,377) cytology screening result. A FP result was defined as a cervical cytology showing high grade cytological abnormalities followed by a normal or ‘Cervical Intraepithelial Neoplasia grade 1’ biopsy result. Women were categorized as subsequent participants if they had a cervical cytology within 24–42 months after their last screening or surveillance test. We compared subsequent participation among women with a normal versus a FP result, using odds ratios including 95% confidence intervals. Participation was slightly higher among women with FP results than among women with normal results (71.5% vs. 69.2%, p = 0.058). After adjustment for age and screening history, women with FP results participated significantly more than women with normal results (OR: 1.19, 95% CI 1.06–1.35). Women receiving a FP result did not participate less in subsequent cervical cancer screening than women receiving a normal result. In fact, the use of opportunistic screening seemed to be increased among women receiving a FP result.

Myocardial infarction with non-obstructive coronary arteries in young women presenting with ST-segment elevation myocardial infarction: a case series

Introduction. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an increasingly recognised entity, with comparable mortality to myocardial infarction with obstructive coronary artery disease (CAD). Case presentation. We present the cases of two young females presenting to hospital with ST-segment elevation myocardial infarction without obstructive CAD. Common to both cases was the acute onset of chest pain with no prior cardiac history, minimal cardiac risk factors, and the use of hormone-based contraception. The first patient had an ostially occluded left anterior descending artery (LAD). Flow was restored with balloon inflation and the administration of tirofiban. However, no underlying obstructive CAD was identified, which was confirmed with repeat angiography and optical coherence tomography. The cause was later attributable to plaque erosion, after learning the results of a normal thrombophilia screening. The second patient had ST-segment resolution on arrival to the catheter lab, and on angiography, she had TIMI II flow down the LAD due to significant thrombus burden. Similarly, balloon inflation and tirofiban were administered to improve flow, and non-obstructive CAD was confirmed with repeat angiography and OCT 48 hours later. As with patient 1, this patient too had normal thrombophilia screening results. Both patients were discharged with dual-antiplatelet therapy and secondary prevention, and were advised against hormone-based contraception. Discussion. Patients with MINOCA tend to be younger, with a higher female-to-male preponderance. Multiple causes have been identified, highlighting the importance of following a diagnostic algorithm. This will enable correct treatment, which may differ from that for patients with obstructive coronary disease, thus improving prognosis.

How to perform and interpret the sweat test

Cystic fibrosis (CF) is the most common life-threatening autosomal-recessive disease affecting Caucasians in the western world. The sweat test is the main diagnostic test for CF. It is indicated as...