SPECC1L regulates palate development downstream of IRF6.

SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.

Caprini Model Integration into an Electronic Medical Record to Improve Perioperative Venous Thromboembolism Prophylaxis.

This quality-improvement retrospective cohort study of patients undergoing major elective nononcologic gynecologic surgery compares the proportion of patients receiving appropriate perioperative venous thromboembolism (VTE) chemoprophylaxis before and after a novel integration of the Caprini risk-assessment model (RAM) into the electronic medical record (EMR). A sample size of 83 patients in each group (166 total) was calculated to provide 80% power and show a 20% increase in appropriate administration of VTE prophylaxis, with an alpha of 0.05. Heparin was appropriately used in 24 patients (28.9%) in the pre-Caprini-RAM group and 39 patients (47.0%) in the post-Caprini-RAM group ( P =.016). There were no differences in bleeding events, transfusions, or other secondary outcomes. Integrating the Caprini-RAM into an EMR for patients undergoing nononcologic gynecologic surgery significantly improved appropriate use of VTE chemoprophylaxis.

Postoperative Lower Extremity Neuropathy With Boot Stirrups Compared With Candy Cane Stirrups.

OBJECTIVE: To assess whether candy cane stirrup use is associated with an increased risk of lower extremity peripheral neuropathy compared with boot stirrups in women undergoing surgery requiring dorsal lithotomy positioning. METHODS: This retrospective cohort study (June 2008-August 2015) included patients who underwent gynecologic surgery for benign indication lasting 60 minutes or longer in the lithotomy position. Patients with preexisting neurologic disease were excluded. Stirrup type, demographics, medical history, surgical factors, and relevant outcomes were collected from the medical record. Postoperative neuropathy was identified in clinical diagnoses or in physician documentation through the 6-week postoperative visit. Patient characteristics and outcomes were compared using Student's t test, χ2 test, or Fisher exact test. Logistic regression analysis was used to adjust for other clinical characteristics associated with the outcome at P≤.1. RESULTS: The study included 2,449 patients, 1,838 (75.1%) with boot and 611 (24.9%) with candy cane stirrups. Women positioned in boot stirrups were younger (mean age 45.6 years [SD 13.5] vs 55.9 [SD 15.7] years; P<.001), heavier (mean body mass index [BMI] 31.5 [SD 8.7] vs 29.6 [SD 7.0]; P<.001), more likely to smoke (n=396 [21.5%] vs n=105 [17.2%]; P=.021), and had longer surgical duration (mean 176.5 minutes [SD 90.0] vs 145.3 [SD 63.9] minutes; P<.001), respectively. Diabetes (8.3%) did not differ between the groups (P=.122. Neuropathy occurred less often in the boot cohort (n=29, 1.6%, 95% CI 1.1-2.3%) than in the candy cane cohort (n=21, 3.4%, 95% CI 2.1-5.2%) (P=.008). After adjusting for age, BMI, smoking, anesthesia type and surgical time, only candy cane stirrup type (adjusted odds ratio [aOR] 2.87, 95% CI 1.59-5.19) and surgical time (per hour) (aOR 1.40, 95% CI 1.20-1.63) were independently associated with postoperative neuropathy. CONCLUSION: Candy cane stirrups are associated with a significantly increased risk of lower extremity postoperative neuropathy compared with boot stirrups for women undergoing gynecologic surgery for benign indication.