Pupillometry measures of autonomic nervous system regulation with advancing age in a healthy pediatric cohort.

PURPOSE: To determine if variables of the pupillary light response mature with age and sex in a healthy pediatric cohort and the utility of pupillometry in assessment among pediatric participants. METHODS: After 1 min in a dark room to establish baseline, pupillometry was performed on 323 healthy, pediatric participants (646 eyes; 2-21 years; 175 females). Variables included initial pupil diameter, pupil diameter after light stimulus, percent pupillary constriction, latency to onset of constriction, average constriction velocity, maximum constriction velocity, average dilation velocity, and time from light stimulus to 75% of the initial pupil diameter. Data analyses employed ANOVAs and non-linear regressions. RESULTS: Analyses of age group differences revealed that participants 12-21 years old had a larger initial pupil diameter and pupil diameter after light stimulus, with males aged 12-18 years demonstrating a larger pupil diameter than all younger participants (ps < 0.05). Participants 12-18 years old had a slower maximum constriction velocity than participants 6-11 years old, with no sex differences (ps < 0.05). Furthermore, males aged 12-18 years old had a smaller percent constriction than males 6-11 years old (ps < 0.05). Regressions revealed that percent constriction and dilation velocity seemed to mature linearly, initial pupil diameter and ending pupil diameter matured quadratically, and the constriction velocity terms matured cubically. CONCLUSIONS: Results revealed maturation of the pupillary light response by age and sex in healthy pediatric participants. Given the value of the pupillary light response as a biomarker, the results provide normative benchmarks for comparison in health and disease, including opiate-exposed and concussion patients.

Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A).

PURPOSE: Advances in preimplantation genetic testing (PGT) have led to practice changes in assisted reproductive technologies (ART), enabling fertility centers to transfer single embryos while maintaining excellent ongoing pregnancy rates, reducing miscarriage rates, and dramatically reducing ART-associated multiple pregnancies. The introduction of next-generation sequencing (NGS) allows PGT laboratories to assess for embryo mosaicism-although the true incidence and reproductive potential of predicted mosaic embryos are controversial. Due to concern for genetic contamination from other spermatozoa, most reference laboratories require use of intracytoplasmic sperm injection (ICSI) for single gene preimplantation genetic diagnosis (PGT-M). However, in PGT for aneuploidy (PGT-A), conventional insemination (IVF) is typically permissible. The purpose of this study was to evaluate rates of euploid, aneuploid, and mosaic in trophectoderm biopsy samples from embryos in IVF versus ICSI PGT-A cycles. Secondary aims were to assess sex ratio, and subtypes of aneuploidy and mosaicism in IVF versus ICSI PGT-A cycles. METHODS: We performed a retrospective review of women undergoing PGT-A at a single academic fertility center from July 1, 2015, to September 1, 2017. In all cycles, PGT-A was performed via trophectoderm biopsy on day 5 or 6 and analyzed using NGS at a single reference lab. We collected and compared patient demographics, fertility testing, cycle characteristics, and PGT-A outcomes between IVF and ICSI cycles. RESULTS: Three hundred two PGT-A cycles were included for analysis: 75 IVF and 227 ICSI cycles, resulting in 251 IVF and 724 ICSI biopsied blastocysts. Mean oocyte age of included cycles was 38.6 years (IVF) and 38.5 years (ICSI), p = 0.85. Baseline characteristics of IVF and ICSI PGT-A cycles were similar with the exception of semen parameters: IVF cycles had higher sperm concentration and total motility compared to ICSI cycles. PGT-A outcomes did not differ between IVF and ICSI cycles: euploid 27.9% (IVF) versus 30% (ICSI); aneuploid 45.4% (IVF) versus 43.1% (ICSI); no result 4.4% (IVF) versus 6.2% (ICSI). Though not significant, we identified a trend toward higher rate of mosaicism in IVF (25.9%) versus ICSI (20.9%). Among mosaic embryos, a lower percentage of simple mosaic embryos resulted from IVF (53.8%) versus ICSI (70.2%). Among aneuploid embryos, a non-significant higher percentage of complex aneuploidy resulted from IVF (16.3%) versus ICSI (9%). IVF resulted in a non-significant higher proportion of cycles with no transferrable embryos (42.7%) versus ICSI (36.6%). Numerical and sex chromosome involvement in mosaicism and aneuploidy were similar between IVF and ICSI cycles. CONCLUSION: IVF and ICSI NGS PGT-A have similar rates of euploid, aneuploid, and no result embryos, though IVF may result in higher rates of mosaicism and demonstrates differences in proportions of mosaic and aneuploid subtypes compared to ICSI. ICSI may be preferable to conventional insemination to minimize the rate of mosaic results in NGS PGT-A cycles.

Determining peripheral skin temperature: subjective versus objective measurements.

AIM: Diseases that affect peripheral vasculature or neurological function can manifest with peripheral skin temperature abnormalities. This pilot study investigates the accuracy of current physical examination techniques and determines whether a hand-held infrared device can be used to estimate peripheral skin temperature and detect temperature disparities. METHODS: Comparison between traditional physical examination of hands/feet by 30 healthcare professionals and a hand-held infrared device was made in 12 individuals (ages 4-25 years; 5 with disorders affecting peripheral skin temperature). Thermal camera measurements served as the reference temperature for comparison. RESULTS: A total of 231 extremity examinations by healthcare professionals were analysed. Healthcare professionals correctly identified subjects with colder or warmer than normal peripheral temperature. Hand-held device measurements were significantly different than reference measurements, with the size of the temperature difference diverging significantly between hands (1.20°C) and feet (0.78°C). When analysing temperature disparities, healthcare professionals identified fewer clinically significant disparities (≥3.0°C) than the hand-held device (76% vs. 99%). CONCLUSION: Although different from reference temperatures, the hand-held infrared device provided a more accurate and objective method than traditional physical exam in identifying peripheral skin temperature asymmetries that may be related to chronic paediatric illness.

An Assessment of Business of Medicine Knowledge in Obstetrics and Gynecology Fellows: A Pilot Study.

STUDY OBJECTIVE: To identify knowledge gaps in business education among obstetrics and gynecology fellows METHODS: An online anonymous survey was distributed to obstetrics and gynecology subspecialty fellows, including pediatric and adolescent gynecology, minimally invasive gynecologic surgery, and reproductive endocrinology and infertility fellows. RESULTS: Of the 483 fellows who received the questionnaire, 159 completed the surveys, resulting in a response rate of 32.9%. A total of 80 reproductive endocrinology and infertility fellows (50.3%), 47 minimally invasive gynecologic surgery fellows (29.6%), and 32 pediatric and adolescent gynecology (20.1%) fellows completed the survey. Over half reported debt from either undergraduate or medical school (52.2%). Over half (58.5%) reported 0 hours of finance education in their residency or fellowship training. In general, fellows reported relatively higher levels of confidence in nonmedical aspects of business, such as purchasing a home (63.9%), life and disability insurance (57.2%), and making financial plans for the future (57.9%). Conversely, a large portion of fellows reported feeling "not at all confident" in business topics related to the field of medicine, including contract negotiation (24.7%), non-competes (27.1%), relative value units system-based pay (32.0%), general office practice management (58.2%), legal aspects of business (71.8%), accounting and billing (54.4%), and marketing (55.7%). CONCLUSION: Our survey demonstrates an unmet demand among obstetrics and gynecology fellows to learn topics related to the business of medicine. Knowledge of these topics is critical for those pursuing private practice or academic medicine. Future initiatives should evaluate other subspecialties and prioritize creating a standardized education tool to better prepare trainees entering medical practice.

Preimplantation genetic diagnosis in early pregnancy loss✰.

Miscarriage is a frequent outcome seen in obstetrics with 1 in 5 pregnancies ending in an early pregnancy loss. Aneuploidy is the most significant single factor affecting early pregnancy failure and miscarriage. The risk of aneuploidy increases significantly with increasing maternal age. There has been tremendous advancement in technology that has made preimplantation genetic testing for aneuploidy reliable and accessible. For women in their mid-to-late 30s there is great utility in the use of PGT-A to facilitate single embryo transfer, reduce the risk of clinical miscarriage and ongoing aneuploidy gestations. The current data supports use of preimplantation genetic testing for aneuploidy and single embryo transfer for this population of women. At this time, more prospective data is needed to determine the effect of preimplantation genetic testing for aneuploidy on rates of miscarriage in the recurrent pregnancy loss population.

A Case Report of Aggressive Angiomyxoma in Pregnancy: Do Hormones Play a Role?

Aggressive angiomyxoma is a rare, locally invasive tumor that generally affects the perineum and pelvis of reproductive age females. Aggressive angiomyxoma is often misdiagnosed, resulting in the delay of the treatment. Case reports show increased growth of the tumor during pregnancy, thus suggesting a hormonal dependency. We report this rare condition in a 29-year-old primigravid female with a growing mass on the right labium majus at 20 weeks' gestation. The patient also developed a smaller mass on the left labium majus at 37 weeks' gestation. The patient underwent a primary cesarean section with resection of the right labial mass, with a final diagnosis of aggressive angiomyxoma. The lesion on her left labium majus resolved spontaneously postpartum. This case report supports a hormonal involvement in this tumor.

Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children.

BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results. METHODS: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. RESULTS: Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P < .001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P = .001; motor, P = .006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P < .05). CONCLUSIONS: These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.

Prevalence of mutations in eyeGENE probands with a diagnosis of autosomal dominant retinitis pigmentosa.

PURPOSE: To screen samples from patients with presumed autosomal dominant retinitis pigmentosa (adRP) for mutations in 12 disease genes as a contribution to the research and treatment goals of the National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE). METHODS: DNA samples were obtained from eyeGENE. A total of 170 probands with an intake diagnosis of adRP were tested through enrollment in eyeGENE. The 10 most common genes causing adRP (IMPDH1, KLHL7, NR2E3, PRPF3/RP18, PRPF31/RP11, PRPF8/RP13, PRPH2/RDS, RHO, RP1, and TOPORS) were chosen for PCR-based dideoxy sequencing, along with the two X-linked RP genes, RPGR and RP2. RHO, PRPH2, PRPF31, RPGR, and RP2 were completely sequenced, while only mutation hotspots in the other genes were analyzed. RESULTS: Disease-causing mutations were identified in 52% of the probands. The frequencies of disease-causing mutations in the 12 genes were consistent with previous studies. CONCLUSIONS: The Laboratory for Molecular Diagnosis of Inherited Eye Disease at the University of Texas in Houston has thus far received DNA samples from 170 families with a diagnosis of adRP from the eyeGENE Network. Disease-causing mutations in autosomal genes were identified in 48% (81/170) of these families while mutations in X-linked genes accounted for an additional 4% (7/170). Of the 55 distinct mutations detected, 19 (33%) have not been previously reported. All diagnostic results were returned by eyeGENE to participating patients via their referring clinician. These genotyped samples along with their corresponding phenotypic information are also available to researchers who may request access to them for further study of these ophthalmic disorders. (ClinicalTrials.gov number, NCT00378742.).