Maternal Sex Chromosome Aneuploidy Identified through Noninvasive Prenatal Screening: Clinical Profile and Patient Experience.

OBJECTIVE: Noninvasive prenatal screening (NIPS) may incidentally identify maternal aneuploidies that have health implications. We evaluated patients' experience with counseling and follow-up diagnostic testing after NIPS flags a potential maternal sex chromosome aneuploidy (SCA). STUDY DESIGN: Patients who underwent NIPS at two reference laboratories between 2012 and 2021 and had test results that were consistent with possible or probable maternal SCA were contacted with a link to an anonymous survey. Survey topics included demographics, health history, pregnancy history, counseling, and follow-up testing. RESULTS: A total of 269 patients responded to the anonymous survey, and 83 of these individuals also completed one follow-up survey. Most received pretest counseling. A total of 80% were offered fetal genetic testing during the pregnancy, and 35% of patients completed diagnostic maternal testing. Monosomy X-related phenotypes such as short stature or hearing loss prompted follow-up testing that led to a diagnosis of monosomy X in 14 (6%) cases. CONCLUSION: Follow-up counseling and testing after a high-risk NIPS result suggestive of maternal SCA is heterogenous in this cohort and may be frequently incomplete. Health outcomes may be affected by these results and additional research could improve the provision, delivery, and quality of posttest counseling. KEY POINTS: · NIPS results showing potential SCA could have maternal health implications.. · Variations in counseling and testing after NIPS were observed for women with suspected SCA.. · Comprehensive counseling and diagnostic testing strategies are critical for these patients..

Elucidating clinical phenotypic variability associated with the polyT tract and TG repeats in CFTR.

Biallelic pathogenic variants in CFTR manifest as cystic fibrosis (CF) or other CFTR-related disorders (CFTR-RDs). The 5T allele, causing alternative splicing and reduced protein activity, is modulated by the adjacent TG repeat element, though previous data have been limited to small, selective cohorts. Here, the risk and spectrum of phenotypes associated with the CFTR TG-T5 haplotype variants (TG11T5, TG12T5, and TG13T5) in the absence of the p.Arg117His variant are evaluated. Individuals who received physician-ordered next-generation sequencing of CFTR were included. TG[11-13]T5 variant frequencies (biallelic or with another CF-causing variant [CFvar]) were calculated. Clinical information reported by the ordering provider or the individual was examined. Among 548,300 individuals, the T5 minor allele frequency (MAF) was 4.2% (TG repeat distribution: TG11 = 68.1%, TG12 = 29.5%, TG13 = 2.4%). When present with a CFvar, each TG[11-13]T5 variant was significantly enriched in individuals with a high suspicion of CF or CFTR-RD (personal/family history of CF/CFTR-RD) compared to those with a low suspicion for CF or CFTR-RD (hereditary cancer screening, CFTR not requisitioned). Compared to CFvar/CFvar individuals, those with TG[11-13]T5/CFvar generally had single-organ involvement, milder symptoms, variable expressivity, and reduced penetrance. These data improve our understanding of disease risks associated with TG[11-13]T5 variants and have important implications for reproductive genetic counseling.

Results of carotid endarterectomy in patients with contralateral internal carotid artery occlusion from the Mid-America Vascular Study Group and the Society for Vascular Surgery Vascular Quality Initiative.

OBJECTIVE: Carotid endarterectomy (CEA) is among the most commonly performed vascular procedures. Some have suggested worse outcomes with contralateral internal carotid artery (ICA) occlusion. We compared patients with and patients without contralateral ICA occlusion using the Society for Vascular Surgery Vascular Quality Initiative database. METHODS: Deidentified data were obtained from the Vascular Quality Initiative. Patients with prior ipsilateral or contralateral CEA, carotid stenting, combined CEA and coronary artery bypass graft, or <1-year follow-up were excluded, yielding 1737 patients with and 45,179 patients without contralateral ICA occlusion. Groups were compared with univariate tests, and differences identified in univariate testing were entered into multivariate models to identify independent predictors of outcomes and in particular whether contralateral ICA occlusion is an independent predictor of outcomes. RESULTS: Patients with contralateral ICA occlusion were younger and more likely to be smokers; they were more likely to have chronic obstructive pulmonary disease, preoperative neurologic symptoms (56% vs 47%), nonelective CEA (16% vs 13%), and shunt placement (75% vs 53%; all P < .001). The 30-day ipsilateral stroke risk was 1.3% with vs 0.7% without contralateral ICA occlusion (P = .004). The 30-day and 1-year survival estimates were 99.0% ± 0.5% and 94.1% ± 1.1% with vs 99.6% ± 0.1% and 96.0% ± 0.2% without contralateral ICA occlusion (log-rank, P < .001). Logistic regression analysis identified prior neurologic event (P = .046), nonelective surgery (P = .047), absence of coronary artery disease (P = .035), and preoperative angiotensin-converting enzyme inhibitor use (P = .029) to be associated with 30-day ipsilateral stroke risk, but contralateral ICA occlusion remained an independent predictor in that model (odds ratio, 2.29; P = .026). However, after adjustment for other factors (Cox proportional hazards), risk of ipsilateral stroke (including perioperative) during follow-up was not significantly greater with contralateral ICA occlusion (hazard ratio, 1.21; P = .32). Results comparing propensity score-matched cohorts mirrored those from the larger data set. CONCLUSIONS: This study demonstrates likely clinically insignificant differences in early stroke or death in comparing CEA patients with and those without contralateral ICA occlusion. After adjustment for other factors, contralateral ICA occlusion was not associated with a greater risk of ipsilateral stroke (including perioperative) in longer follow-up. Mortality was greater with contralateral ICA occlusion, and this difference was more pronounced at 1 year despite younger age of the contralateral ICA occlusion group. CEA risk remains low even in the presence of contralateral ICA occlusion and appears to be explained at least in part by other factors. CEA should still be considered appropriate in the face of contralateral ICA occlusion.

A comparison of results of carotid endarterectomy in octogenarians and nonagenarians to younger patients from the Mid-America Vascular Study Group and the Society for Vascular Surgery Vascular Quality Initiative.

OBJECTIVE: Carotid endarterectomy (CEA) reduces stroke risk in selected patients. However, CEA risk profile may be different in older patients. We compared characteristics and outcomes of octogenarians and nonagenarians with those of younger patients. METHODS: Deidentified data from CEA patients were obtained from the Society for Vascular Surgery Vascular Quality Initiative (VQI) database. Prior CEA, carotid artery stent, or combined CEA and coronary artery bypass were excluded, yielding 7390 CEAs in octogenarians and nonagenarians (≥80 years of age) and 35,303 CEAs in younger patients (<80 years of age). We compared post-CEA outcomes, including periprocedural cerebral ischemic events and death, and details such as operative time, bleeding, and return to surgery. RESULTS: Octogenarians and nonagenarians were more likely to have pre-CEA neurologic symptoms (51.4% vs 45.6%; P < .001) and to have never smoked (37.8% vs 22.0%; P < .001), and they were slightly more likely to have required urgent CEA (16.1% vs 13.4%; P < .001). Stenosis ≥70% was similar (octogenarians and nonagenarians, 94.2%; younger patients, 94.4%; P = .45). Perioperative ipsilateral neurologic events and ipsilateral stroke were slightly more common among octogenarians and nonagenarians (1.6% vs 1.1% [P < .001] and 1.2% vs 0.8% [P = .002]). Multivariate modeling (logistic regression) showed that pre-CEA neurologic symptoms (odds ratios, 1.35 [P = .005] and 1.42 [P = .007]), pre-CEA ipsilateral cortical ischemic event (odds ratios, 1.18 [P < .001] and 1.20 [P < .001]), and urgency (odds ratios, 1.75 [P < .001] and 1.67 [P < .001]) remained strong predictors of any ipsilateral neurologic event and any ipsilateral stroke, respectively. However, age ≥80 years remained a significant predictor of these outcomes (odds ratios, 1.37 [P = .003] and 1.44 [P = .004]). Kaplan-Meier estimated survival was lower for octogenarians and nonagenarians at 30 days and 1 year (98.6% vs 99.4% and 93.7% vs 97.0%; log-rank, P < .001). Age ≥80 years was also associated with a greater rate of discharge to other than home after CEA, a difference that was only partially explained by comorbidities in multivariate modeling. CONCLUSIONS: CEA was performed with low rates of perioperative neurologic events and mortality. Multivariate testing showed that the higher rate of neurologic complications in octogenarians and nonagenarians appeared partially related to symptomatic status and urgent surgery; but after adjusting for these factors, age ≥80 years still predicted a slightly higher rate. Periprocedural CEA outcomes appear similar in comparing older and younger patients, although longer term survival is lower for older patients, and older patients are at greater risk of discharge to other than home. CEA was associated with slightly higher risk of neurologic complications in older patients but may be considered appropriate for selected octogenarians and nonagenarians.

Short Communication: changes in gait after 12 wk of shoeing in previously barefoot horses.

Farriery can impact gait symmetry and lameness outcomes, but there is limited scientific data documenting these effects. We hypothesized that shoeing previously barefoot horses with plain stamp shoes on the hind hooves would increase gait symmetry, alter hock angles and increase range of motion, and improve lameness scores more than shoeing with traditional fullered shoes. At the start of the study, gait symmetry via wireless inertial motion sensors (IMS), kinematic gait analysis (hock angle and range of motion), and American Association for Equine Practitioner's (AAEP) lameness scoring were completed for 14 barefoot horses. Horses were then trimmed and hind hooves were shod (wk 0) in three-quarter fullered shoes or plain stamp style shoes. Horses were trimmed and re-shod at week 6. At the end of 12 wk, the IMS analysis, kinematic gait analysis, and lameness scoring were repeated. Differences between shod and barefoot values were calculated for each horse, and impact of shoe type was analyzed via t-test. Significance was determined at P ≤ 0.05. No differences were observed in the IMS scores, hock angles or range of motion, or AAEP lameness scores between horses shod in fullered or plain stamp shoes (P ≥ 0.08). As no variables were determined to be significantly different between the two shoe types, data from all horses were combined to analyze the differences between the barefoot and shod state. Shoeing increased the maximum angle of the right and left hocks (P ≤ 0.03) and the minimum angle of the left (P = 0.02) but not right hock (P = 0.23) relative to barefoot conditions. No differences in hock range of motion were observed in either hock. Lower AAEP lameness scores were observed in horses when shod compared with barefoot (P = 0.001). In conclusion, shoeing previously barefoot horses improved AAEP lameness scores and increased hock angles, regardless of the type of shoe.

Horses are athletic animals whose quality of movement affects their ability to perform. Management of hooves can influence gait symmetry. Shoeing horses is an accepted standard of care for athletic animals. Here, we show that shoeing previously barefoot horses using industry accepted farriery protocols increased maximum hock angles at the trot and reduced lameness scores.

Exogenous and endogenous corticosterone alter feather quality.

We investigated how exogenous and endogenous glucocorticoids affect feather replacement in European starlings (Sturnus vulgaris) after approximately 56% of flight feathers were removed. We hypothesized that corticosterone would retard feather regrowth and decrease feather quality. After feather regrowth began, birds were treated with exogenous corticosterone or sham implants, or endogenous corticosterone by applying psychological or physical (food restriction) stressors. Exogenous corticosterone had no impact on feather length and vane area, but rectrices were lighter than controls. Exogenous corticosterone also decreased inter-barb distance for all feathers and increased barbule number for secondaries and rectrices. Although exogenous corticosterone had no affect on rachis tensile strength and stiffness, barbicel hooking strength was reduced. Finally, exogenous corticosterone did not alter the ability of Bacillus licheniformis to degrade feathers or affect the number of feathers that failed to regrow. In contrast, endogenous corticosterone via food restriction resulted in greater inter-barb distances in primaries and secondaries, and acute and chronic stress resulted in greater inter-barb distances in rectrices. Food-restricted birds had significantly fewer barbules in primaries than chronic stress birds and weaker feathers compared to controls. We conclude that, although exogenous and endogenous corticosterone had slightly different effects, some flight feathers grown in the presence of high circulating corticosterone are lighter, potentially weaker, and with altered feather micro-structure.