Post-operative Complication Rate Comparison Between Airway Surgery and Upper Airway Stimulation Using NSQIP and ADHERE.

OBJECTIVE: Postoperative complication rates were compared between obstructive sleep apnea surgery (OSAS) and hypoglossal nerve upper airway stimulation (UAS). STUDY DESIGN: Cohort. SETTING: Multi-institutional international databases. METHODS: OSAS data were collected from the NSQIP database (2014; American College of Surgeons National Surgery Quality Improvement Program). UAS data were obtained from the ADHERE registry (Adherence and Outcome of Upper Airway Stimulation for OSA International Registry; 2016-December 2019). ADHERE comorbidities and complications were categorized to match NSQIP definitions. A chi-square test was used for proportion P values. RESULTS: There were 1623 UAS procedures in ADHERE and 310 in NSQIP. The UAS group was older than the OSAS group (mean ± SD, 60 ± 11 vs 42 ± 13 years) but similarly male (75% vs 77%) and overweight (body mass index, 29 ± 4 vs 29 ± 3 kg/m2). There was a higher proportion of hypertension, diabetes, and heart disease in the UAS cohort. Palatopharyngoplasty was the most common surgical procedure (71%), followed by tonsillectomy (25%). UAS operative time was longer (132 ± 47 vs 54 ± 33 minutes). Postoperative length of stay was not normally distributed, as 71% of UAS stays were <1 day as opposed to 40% of OSA stays (P < .0001). Thirty-day return to the operating room related to the procedure was 0.1% for UAS and 4.8% for OSAS (P < .0001). Surgical site infections were 0.13% for UAS and 0.9% for OSAS (P = .046). CONCLUSION: The UAS cohort was older and more likely to have comorbid hypertension, diabetes, and heart disease. Despite baseline differences, the postoperative complication rate was lower with UAS than with OSAS.

Referral Center Experience With Nonpalpable Contraceptive Implant Removals.

OBJECTIVE: To describe our experience with office removal of nonpalpable contraceptive implants at our referral center. METHODS: We performed a retrospective cohort study by reviewing the charts of patients referred to our family planning specialty center for nonpalpable or complex contraceptive implant removal from January 2015 through December 2018. We localized nonpalpable implants using high-frequency ultrasonography and skin mapping in radiology, followed by attempted removal in the office using local anesthesia and a modified vasectomy clamp. We abstracted information on demographics, implant location, and outcomes. RESULTS: Of 61 referrals, 55 patients attended their scheduled appointments. Seven patients had palpable implants; six elected removal. The other 48 patients had ultrasound localization, which identified 47 (98%) of the implants; the remaining patient had successful localization with computed tomography imaging. Nonpalpable implants were suprafascial (n=22), subfascial (n=25) and intrafascial (n=1); four of these patients opted to delay removal. Of 50 attempted office removals, all palpable (n=6), all nonpalpable suprafascial (n=21 [100%, 95% CI 83-100%]), and 19 out of 23 (83%, 95% CI 67-98%) subfascial implants were successful. Three of the four patients with failed subfascial implant office removal had successful operating room removal with a collaborative orthopedic surgeon; the other patient sought removal elsewhere. Transient postprocedure neuropathic complaints were noted in 7 out of 23 (30%, 95% CI 12-49%) subfascial and 1 out of 21 (5%, 95% CI 0-13%) suprafascial removals (P=.048). Nonpalpable implants were more likely to be subfascial in nonobese patients (24/34, 71%) as compared with obese (1/13, 8%) patients (P<.001). Seven (28%) of the 25 subfascially located implants had been inserted during a removal-reinsertion procedure through the same incision. CONCLUSION: Most nonpalpable contraceptive implants can be removed in the office by an experienced subspecialty health care provider after ultrasound localization. Some patients may experience transient postprocedure neuropathic pain. Nonpalpable implants in thinner women are more likely to be in a subfascial location.

Medical abortion with mifepristone and vaginal misoprostol between 64 and 70 days' gestation.

OBJECTIVE: To evaluate outcomes with mifepristone 200 mg orally followed 24-48 h later by misoprostol 800 mcg vaginally for medical abortion at 64-70 days of gestation. STUDY DESIGN: We reviewed electronic databases and medical records for medical abortion cases at 64-70 days' gestation at British Pregnancy Advisory Service clinics in England and Wales from May 2015 through October 2016. Women selected in-office follow-up or self-evaluation of abortion outcome using a checklist along with low-sensitivity urine pregnancy testing. We excluded cases in which we could not locate records and when women did not proceed with medical abortion, did not use misoprostol following mifepristone if abortion had not occurred and did not attend a scheduled follow-up assessment. We analyzed demographic characteristics, treatment outcomes and significant adverse events. We defined treatment success as complete abortion without surgical evacuation and without continuing pregnancy. RESULTS: Of 2743 cases identified, we could not locate 40 charts and excluded 30 cases, leaving a final sample of 2673. Overall, 2538 (94.9%, 95% CI 94.1-95.8) women had a successful medical abortion. Reasons for failure included continuing pregnancy (n=90, 3.4%, 95% CI 2.7-4.1), retained nonviable pregnancy (n=2, 0.1%, 95% CI 0-0.2) and incomplete abortion (n=43, 1.6%, 95% CI 1.1-2.1). Of those with continuing pregnancies, 81 underwent a uterine aspiration and 9 opted to continue the pregnancy. Thirty-five (1.3%, 95% CI 0.9-1.7) women had significant adverse events; 16 (0.6%, 95% CI 0.3-0.9) underwent an in-hospital aspiration. Pelvic infection (n=4, 0.2%) and transfusion (n=1, 0.03%) occurred rarely. CONCLUSION: Medical abortion from 64 to 70 days with mifepristone and vaginal misoprostol is effective with a low rate of serious adverse events. IMPLICATIONS: Medical abortion between 64 and 70 days of gestation may be offered on an outpatient basis using mifepristone and vaginal misoprostol. Service provision without an in-person follow-up is feasible. Not all women with a continuing pregnancy after medical abortion treatment opt to have an aspiration procedure.

Prospective quantification of fetomaternal hemorrhage with dilation and evacuation procedures.

OBJECTIVE: To describe fetomaternal hemorrhage (FMH) during second-trimester dilation and evacuation (D&E) to evaluate if Rhesus-immune globulin (RhIG) 100 mcg (used in the United Kingdom) and 300 mcg (used in the United States) provide adequate prophylaxis. STUDY DESIGN: We conducted an exploratory prospective descriptive study of women undergoing D&E between 15 weeks 0 days and 23 weeks 6 days of gestation. Enrolled participants had Kleihauer-Betke testing on specimens obtained before and after D&E. We assessed the main outcome measures of FMH in mL suggesting need for more than 100 mcg and 300 mcg RhIG (FMH of 10 mL and 30 mL fetal whole blood, respectively) and association of postprocedure FMH with demographic characteristics and procedure-related variables. RESULTS: The 300 participants had a mean gestational age of 19 weeks 6 days±2 weeks 2 days. The median preprocedure FMH was 0 mL (range 0-50 mL) with 2 (0.67%) women exceeding 10 mL (19 mL and 50 mL). The median postprocedure FMH was 1 mL (range 0-60 mL). Almost all participants had postprocedure FMH <10 mL (n=295, 98.3%) and <30 mL (n=298, 99.3%). All participants under 18 weeks had FMH <10 mL. We found no demographic or procedure-related factors to be predictive of FMH quantity. CONCLUSIONS: FMH occurring with routine second-trimester D&E procedures is minimal. Adequate prophylaxis with RhIG 100 mcg and 300 mcg occurred in >98% of women and in all cases <18 weeks of gestation. This study is the first step to potentially reducing the dose and costs of RhIG administration with D&E. IMPLICATIONS: This study is a first step in quantifying fetomaternal hemorrhage with routine dilation and evacuation procedures; larger trials are needed, especially to understand why some women have recognizable hemorrhage preprocedure. If dosing requirements are too high with current guidelines, lower doses will result in resource and cost savings.

Comparing Postpartum Visit Attendance with a Scheduled 2- to 3-Week or 6-Week Visit after Delivery.

OBJECTIVE: To evaluate whether scheduling a 2- to 3-week versus 6-week postpartum visit results in higher visit attendance. STUDY DESIGN: We conducted a secondary analysis of a quasi-experimental before-after study to compare postpartum visit attendance after changing routine scheduling of visits from 6 weeks to 2 to 3 weeks after delivery. Secondary outcomes include patient satisfaction and breastfeeding continuation at 3 and 6 months postpartum. We collected postpartum visit information through a chart review and conducted telephonic interviews at 3 and 6 months postpartum to assess satisfaction with visit timing and breastfeeding status. We performed multivariable analyses to assess predictors of visit attendance. RESULTS: Women scheduled at 2 to 3 weeks postpartum demonstrated higher visit attendance (90.2%; 95% confidence interval [CI]: 86.6-93.9%) compared with 6 weeks (81.6%; 95% CI: 76.3-86.2%; p < 0.01). Predictors for visit attendance include postpartum visit timing, age, education, parity, prior miscarriage, and high-risk index pregnancy in multivariate analysis. Scheduling at 2 to 3 weeks postpartum increased visit completion in women who were younger and had lower educational attainment, high-risk index pregnancy, and no prior miscarriages. We found no differences in patient satisfaction or breastfeeding continuation at 3 and 6 months postpartum related to postpartum visit timing. CONCLUSION: Scheduling a 2- to 3-week postpartum visit is associated with higher attendance.

Etonogestrel implant use in women primarily choosing a combined oral contraceptive pill: A proof-of-concept trial.

OBJECTIVE: We evaluated a novel concept of initiating the etonogestrel implant as a "back-up" method in women who desire using combined oral contraceptives (COC) but want to decrease their risk of unintended pregnancy with a more effective method. STUDY DESIGN: In this prospective cohort study, we planned to include 20 women as a proof-of-concept. We enrolled both new COC starters and continuing COC users and placed an etonogestrel implant. Participants completed daily bleeding diaries and attended follow-up visits at 1, 3, and 6 months. We assessed implant continuation through six months of study participation and side effects with dual hormonal contraceptive use. RESULTS: Between September and December 2016, we enrolled 10 new starters and 10 current COC users. All participants completed 1-month follow-up, and 18 (90%) subjects completed the 3- and 6-month follow-up assessments. Two current COC users had the implant removed for mood changes before 6 months. At the 6-month follow-up visit, 10 women were using both pills and implant, seven relied on the implant only, and one was using a COC only. Three new starters chose implant removal at end of study participation; one for weight gain and acne, another for mood changes, and one for decreased libido. No subjects discontinued the implant for bleeding complaints. CONCLUSION: In this proof-of-concept study, women using COCs were willing to initiate the implant as a "back-up" method to improve pregnancy prevention. Most women continued the implant through 6 months and after completing study participation. IMPLICATIONS: Initiating the etonogestrel implant as a "back-up" method may be an option for women who desire more effective pregnancy prevention while using combined oral contraceptive pills for its bleeding profile or non-contraceptive benefits.

Long-Acting Reversible Contraception Initiation With a 2- to 3-Week Compared With a 6-Week Postpartum Visit.

OBJECTIVE: To evaluate whether a department policy changing the scheduling of the postpartum visit from 6 weeks to 2-3 weeks after delivery is associated with higher long-acting reversible contraception initiation at the postpartum visit. METHODS: We conducted a quasiexperimental before-after study to evaluate long-acting reversible contraception initiation, specifically an intrauterine device or contraceptive implant, at the postpartum visit between women scheduled for follow-up at 6 weeks (before policy change) and 2-3 weeks after delivery (after policy change). Secondary outcomes included postpartum visit completion, overall contraception initiation at the postpartum visit, overall contraceptive use at 6 months after delivery, and repeat pregnancies by 6 months postpartum. We obtained delivery and postpartum information using the electronic medical record and contacted participants 3 and 6 months after delivery to assess contraception use and repeat pregnancies. RESULTS: We enrolled 586 participants between December 2014 and November 2015, of whom 512 women (256 in each cohort) continued to meet eligibility criteria after delivery. Long-acting reversible contraception initiation rates at the postpartum visit were lower in the 2- to 3-week (16.5%, 95% CI 12.2-21.8) compared with the 6-week group (31.1%, 95% CI 25.2-37.7, P<.01), primarily as a result of patient and health care provider preferences for delaying intrauterine device insertion to a later visit. More women completed a scheduled 2- to 3-week postpartum visit (90.2%, 95% CI 86.0-93.3) compared with a 6-week visit (81.6%, 95% CI 76.4-85.9, P<.01). Deferral of any contraception initiation was higher in the 2- to 3-week group (27.3%, 95% CI 21.9-33.4) compared with the 6-week group (15.8%, 95% CI 11.5-21.4, P<.01), but there were no differences in overall contraceptive use patterns at 6 months postpartum. No intrauterine device perforations or expulsions were observed in women who underwent insertion at 2-3 weeks postpartum. Five pregnancies were reported in each cohort by 6 months after delivery. CONCLUSION: Scheduling a visit at 2-3 weeks after delivery was not associated with increased long-acting reversible contraception initiation at this visit despite higher postpartum visit attendance.

Intrauterine Contraception.

Currently, there are only two basic types of intrauterine devices (IUDs): copper and hormonal. However, other types of IUDs are under development, some of which are in clinical trials around the world. Continued development has focused on increasing efficacy, longer duration of use, and noncontraceptive benefits. This review discusses currently available intrauterine contraceptives, such as the Cu380A IUD and levonorgestrel-releasing intrauterine systems; novel intrauterine contraceptives that are available in select parts of the world including the intrauterine ball, low-dose copper products, frameless devices, and intrauterine delivery systems impregnated with noncontraceptive medication; and novel products currently in development.

Presence of soil-dwelling clostridia in commercial powdered infant formulas.

OBJECTIVE: Because Clostridium botulinum was isolated from powdered infant formula (PIF) fed to an infant in the United Kingdom who subsequently developed infant botulism and from unopened PIF from the same manufacturer, we tested PIF manufactured in the United States for the presence of clostridial spores. STUDY DESIGN: Thirty PIF ingested by 19 California infants with botulism within 4 weeks of onset of illness (48% of all patients fed PIF during study) in 2006-2007 were cultured anaerobically to isolate clostridia. All isolated clostridia were identified to the species level and enumerated with standard microbiologic and molecular methods. RESULTS: Five of 30 (17%) PIF samples ingested by patients contained clostridial spores. Spores were also found in 7 of 9 (78%) market-purchased PIF samples. Clostridium sporogenes was isolated most frequently, followed by Clostridium butyricum and at least 10 other soil-dwelling clostridial species. No neurotoxigenic clostridia were isolated. The most probable number of clostridial spores in PIF ranged between 1.1 to >23 per 100 g. CONCLUSIONS: With the notable exception of production of botulinum neurotoxin, C sporogenes is physiologically comparable with proteolytic strains of C botulinum, and both share the same natural reservoir (soils and dust worldwide). The isolation of C sporogenes and potentially pathogenic clostridia from U.S.-manufactured PIF suggests that neurotoxigenic clostridial spores have the potential to be present in these products.

Effects of long-term flutamide treatment during development in zebra finches.

The molecular mechanisms responsible for the sexual differentiation of the zebra finch song system remain mysterious. Androgen receptors are expressed in a sexually dimorphic fashion in the zebra finch song system: males have more cells expressing androgen receptors, and this sex difference appears very early in development (day 9 posthatch). Estrogen administration to hatchling females up-regulates androgen receptor expression in their song system and profoundly masculinizes their song system's morphology. Co-administering flutamide, an androgen receptor blocker, with estrogen impedes estrogen's masculinizing effects on the song system, suggesting that androgens are required for masculine development. Accordingly, to investigate further the role of androgens in the sexual differentiation of the zebra finch song system, we sought to block androgen activity in males by administering large, sustained doses of flutamide from just before androgen receptors are expressed in the song system (day 7) through to the day of sacrifice (days 61-63). Flutamide profoundly reduced the size of the testes, demonstrating that this drug and mode of administration could have a large impact on tissues. In contrast, flutamide had only a minor impact on the song system: the number of RA neurons was slightly reduced, and the corrected HVC volume showed a trend toward demasculinization. Other brain measures (uncorrected HVC, and corrected and uncorrected volumes of Area X, lMAN, RA, and Rotundus; neuron size in lMAN, HVC, and RA; and number of HVC and LMAN neurons) were not significantly affected. The present results do not support an important role for androgen in masculinizing the song circuit after posthatch day 7.

Genomic Ly49A transgenes: basis of variegated Ly49A gene expression and identification of a critical regulatory element.

Several gene families are known in which member genes are expressed in variegated patterns in differentiated cell types. Mechanisms responsible for imposition of a variegated pattern of gene expression are unknown. Members of the closely linked Ly49 inhibitory receptor gene family are expressed in a variegated fashion by NK cells. Variegated expression of these genes results in subsets of NK cells that differ in specificity for MHC class I molecules. To address the mechanisms underlying variegation, a 30-kb genomic fragment containing a single Ly49 gene was used to generate a panel of murine transgenic lines. The results demonstrated that, in almost all of the lines, the isolated Ly49A gene was expressed in a variegated pattern, remarkably similar in nearly all respects to the expression pattern of the endogenous Ly49A gene. Furthermore, the developmental timing of gene expression and regulation by host MHC molecules closely mirrored that of the endogenous Ly49A gene. Therefore, Ly49 variegation does not require competition in cis between different Ly49 genes, and the sequences imposing variegation are located proximally to Ly49 genes. Efforts to define regulatory elements of the Ly49A gene led to the identification of a DNase I hypersensitive site 4.5 kb upstream of the Ly49A gene transcription initiation site, which was shown to be essential for transgene expression. Highly related sequence elements were found upstream of other Ly49 genes, suggesting that a similar regulatory element controls each Ly49 gene.

A novel ligand for the NKG2D receptor activates NK cells and macrophages and induces tumor immunity.

NK cells are involved in the immune response against viral and microbial infections and tumors. In contrast to B and T cells, NK cells employ various modes of immune recognition. An important mode of immune recognition employed by NK cells is "induced self recognition" exemplified by the NKG2D receptor-ligand system. The NKG2D immunoreceptor, expressed by NK cells, and by activated CD8+ T cells and macrophages, recognizes one of several cell surface ligands that are distantly related to MHC class I molecules (i.e. H60 and Rae1 proteins in mice, and MHC class I chain-related proteins and UL-16-binding proteins in humans). These ligands are not expressed abundantly by most normal cells but are up-regulated on cells exposed to various forms of cellular insults. Here we report the cloning of another ligand for NKG2D; transcripts of this ligand are found in a wide variety of tissues and in various tumor cells. Cross-linking of NKG2D with the novel ligand potently activated NK cells and macrophages. Tumor cells ectopically expressing the molecule were efficiently rejected by naive mice, and induced strong protective immunity to the parental, ligand-negative tumor cells.

Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D.

Optimal lymphocyte activation requires the simultaneous engagement of stimulatory and costimulatory receptors. Stimulatory immunoreceptors are usually composed of a ligand-binding transmembrane protein and noncovalently associated signal-transducing subunits. Here, we report that alternative splicing leads to two distinct NKG2D polypeptides that associate differentially with the DAP10 and KARAP (also known as DAP12) signaling subunits. We found that differential expression of these isoforms and of signaling proteins determined whether NKG2D functioned as a costimulatory receptor in the adaptive immune system (CD8+ T cells) or as both a primary recognition structure and a costimulatory receptor in the innate immune system (natural killer cells and macrophages). This strategy suggests a rationale for the multisubunit structure of stimulatory immunoreceptors.