Faculty Bibliography

OBJECTIVE:Preeclampsia remains one of the leading causes of perinatal mortality worldwide. Little is known of the modifiable risk factors that can be identified and addressed early in pregnancy to reduce the risk of preeclampsia and its associated adverse outcomes. We sought to determine if there is a synergistic effect of pre-pregnancy body-mass index and obstructive sleep apnea on the risk of preeclampsia. STUDY DESIGN/METHODS:We conducted a retrospective cohort study of singleton pregnancies delivered in Kaiser Permanente Southern California hospitals between January 1, 2010, and December 31, 2020 (n=342,349). Preeclampsia and sleep apnea were ascertained using clinical diagnosis codes. Body-mass index in kg/m2 measured during prenatal care visits was categorized as normal (18.5 to 24.9), overweight (25 to 29.9), and obese (≥30). Multivariable logistic regression was used to estimate adjusted relative risks (adjusted RR) and 95% confidence intervals (CI). RESULTS:Compared to normal weight in a pregnancy, overweight (adjusted RR: 1.6; 95% CI: 1.5, 1.7) and obese body mass index (adjusted RR: 2.5; 95% CI: 2.4, 2.6) were associated with an increased risk of preeclampsia. Independent of pre-pregnancy body-mass index, a pregnancy with obstructive sleep apnea was associated with an increased risk of preeclampsia (adjusted RR: 2.2; 95% CI: 1.8, 2.6). Compared to normal weight without the diagnosis of obstructive sleep apnea in a pregnancy, overweight (adjusted RR: 4.6; 95% CI: 2.9, 7.4) and obese body mass index (adjusted RR: 3.8; 95% CI: 3.2, 4.6) with the diagnosis of obstructive sleep apnea were associated with an increased risk of preeclampsia. CONCLUSIONS:Obstructive sleep apnea and elevated body-mass index have independent and additive relationship with preeclampsia. Overweight women at-risk of preeclampsia should be advised of a higher likelihood of developing preeclampsia when both conditions occur together and may benefit from close monitoring and early interventions for these modifiable risk factors.

BACKGROUND:Guidelines do not recommend routine screening for thyroid nodules when starting a glucagon-like peptide-1 receptor agonist. Patients, however, increasingly present with incidental nodules from imaging ordered at glucagon-like peptide-1 receptor agonist initiation. METHODS:This retrospective case-control study examined patients in a single academic health system from 1 January 2019 to 31 December, 2024 who underwent thyroid ultrasound, fine-needle aspiration biopsy, molecular testing, and/or surgery with glucagon-like peptide-1 receptor agonist initiation compared with patients not prescribed a glucagon-like peptide-1 receptor agonist. Patient, prescription, and intervention data were collected. Chart review was also performed for a subset of patients. RESULTS:From 2019 to 2024, 2,523 patients prescribed a glucagon-like peptide-1 receptor agonist underwent thyroid ultrasound; from 2020 to 2023, there was a higher growth rate of ultrasound scans ordered for them. A random sample of 415 patients prescribed a glucagon-like peptide-1 receptor agonist showed that most ultrasounds were ordered for "thyroid nodules" by the endocrinologist who prescribed glucagon-like peptide-1 receptor agonist. In this subset, 757 nodules were detected on ultrasound; 10.6% (80/757) had fine-needle aspiration biopsy. Cytology showed 3.8% were Bethesda I (3/80), 72.5% Bethesda II (58/80), 15% Bethesda III (12/80), 0% Bethesda IV (0/80), 2.5% Bethesda V (2/80), and 6.6% Bethesda VI (5/80). Of 15 indeterminate nodules, 11 had molecular testing: 5 were positive or suspicious, including fusions, alterations, RAS and BRAF mutations. Sixteen patients had thyroid surgery after glucagon-like peptide-1 receptor agonist initiation (8 total thyroidectomies, 8 hemithyroidectomies, 1 completion). Final pathology demonstrated 6 benign, 10 malignant, 1 NIFTP. The rate of malignancy in the subset was 2.4% (10/415). CONCLUSION/CONCLUSIONS:The malignancy rate in patients prescribed a glucagon-like peptide-1 receptor agonist remains low, but ultrasound screening rates increased for a period. Strong clinical suspicion should govern screening.

Obstructed hemivagina and ipsilateral renal anomaly is a Mullerian anomaly with variable presentations. A patient with this syndrome had a superinfected fluid collection in an obstructed hemivagina after mifepristone and misoprostol administration for an embryonic demise, identifying a potential complication in this population.

OBJECTIVE:Social determinants of health (SDOH) may impact the incidence of Respiratory Syncytial Virus (RSV) infection and the uptake of vaccinations in pregnancy. The objective of this study is to identify contributors to disparities in RSV vaccination in pregnancy. DESIGN/METHODS:This is a retrospective cohort study of patients delivering at term within three hospitals during February and March 2024, comparing pregnant patients identified as receiving vs not receiving RSV vaccinations. This period and gestational age were chosen to include patients who would have qualified for RSV vaccination administration. Vaccination status was extracted from standardized admission templates where these variables were recorded as discrete fields. Patients without RSV vaccination information were excluded. Sociodemographic factors, COVID vaccination status, and delivery campus were evaluated. Outcomes were analyzed using chi-squared, t-test, and McNemar test. RESULT/RESULTS:2181 patients met inclusion criteria and RSV vaccination information was available for 1548 patients (71%) with a 14% vaccination rate. Compared to those not vaccinated (n=1332), RSV vaccinated patients (n=216) were more likely to be older (30.7 vs 34.8, p<0.001), have private insurance (42% vs 85%, p<0.001), speak English (82% vs 95%, p<0.001), and deliver at our regional perinatal center (26% vs 77%, p<0.001). 50% of RSV vaccinated patients had a history of COVID vaccination compared to 33% of those not vaccinated against RSV (p<0.001). CONCLUSIONS:SDOH were associated with differences in RSV vaccination status. In addition, patients without RSV vaccination were less likely to have had COVID vaccination. These findings highlight the need to address SDOH to increase vaccination rates for vulnerable populations.

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell non-Hodgkin lymphoma (NHL) that predominantly affects patients with human immunodeficiency virus infection and is strongly associated with human herpes virus 8 (HHV-8) infection. Due to its rarity, the current understanding of PEL's epidemiology and management is largely derived from case reports and small retrospective studies. Using the SEER-17 database, we conducted a retrospective analysis of adults with pathologically confirmed primary effusion lymphoma diagnosed between 2001-2021. Patients were stratified into two time periods (2001-2010 and 2011-2021) to assess temporal trends. Age-adjusted incidence rates, relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS) were calculated using flexible parametric survival models. Competing risk analysis was performed to evaluate cumulative incidence of lymphoma-specific death. Among 236 patients (median age 51 years, 88% male), 82 were diagnosed in 2001-2010 and 154 in 2011-2021. Age-adjusted incidence rates increased from 1.0 to 1.6 cases per 10,000,000 person-years between periods (p = 0.004). Five-year RS improved from 21% to 37%, with median OS increasing from 4 to 12 months. On multivariable analysis, the more recent period showed significant improvements in OS (HR = 0.65; 95% CI, 0.44-0.97) and LSS (HR = 0.56; 95% CI, 0.36-0.86), with reduced cumulative incidence of lymphoma-specific death (HR = 0.49; 95% CI, 0.33-0.74). In our population-level analysis of PEL, we report a significant improvement in survival outcomes between 2001-2021, likely reflecting advances in both lymphoma treatment and HIV management. However, despite these improvements, OS remains low underscoring the need for prioritizing these patients to clinical trials with novel therapies.

Osteotomies around the knee are an effective procedure that shifts the weight-bearing axis from the pathologic side to the uninvolved side to alleviate pain, unload cartilage transplantations, slow down the progression of arthritis, and protect ligament reconstructions. The advancement in plates from nonlocking to locking have increased the stability of constructs to allow for early mobilization and maintained corrections. Further developments with patient-specific instrumentation have made these techniques more reproducible and accurate. Bone grafting and biologics remain a topic of debate but likely a helpful adjuvant in the context of larger corrections or joint preservation surgeries.

Tibial tuberosity osteotomy (TTO) is a well-described treatment option for a broad range of patellofemoral joint disorders, including patellofemoral instability, focal chondral lesions of the patellofemoral joint, and patellofemoral arthritis. The purpose of this article is to review the indications and highlight the surgical technique for the more commonly performed TTO procedures and discuss outcomes, as well as surgical pearls for this technique.

BACKGROUND/UNASSIGNED:Somapacitan is a once-weekly GH treatment that has shown efficacy and safety profiles equivalent to daily GH in children with GH deficiency (GHD). OBJECTIVE/UNASSIGNED:To investigate long-term safety, efficacy, and treatment burden associated with somapacitan after 7 years (364 weeks) of treatment. METHODS/UNASSIGNED:REAL 3 (NCT02616562) was a phase 2, randomized, open-label trial investigating the efficacy and safety of somapacitan vs daily GH in children with GHD. After 156 weeks, participants entered a 208-week safety extension. Children in cohort I (age 2.5-10.0 years) previously completed 3 years in the trial; cohort II (age <2.5 years) and cohort III (age 9.0-17.0 years) entered the trial at week 156 for safety-only assessment. All participants received somapacitan 0.16 mg/kg/week. Height velocity (HV), HV SD score (SDS), height SDS, IGF-I SDS, incidence of adverse events (AEs), and treatment burden were assessed. RESULTS/UNASSIGNED:Overall, 43 participants (73%) in cohort I, 1 participant (100%) in cohort II, and 11 participants (69%) in cohort III completed the 208-week safety extension. Consistent increments in HV and HV SDS were seen in cohort I, and height SDSs at week 364 were close to 0. The incidence of AEs was aligned with previous investigations across all cohorts; 3 serious AEs in cohort I were considered probably/possibly related to treatment. Treatment burden was reduced in children who switched from daily GH to somapacitan. CONCLUSION/UNASSIGNED:After 7 years of treatment, children with GHD receiving somapacitan experienced consistent increases in height SDS and reduced treatment burden. No new safety concerns were identified.

METHODS:We analyzed the Nuclear Regulatory Commission event notifications related to brachytherapy events that occurred between January 1, 2005, and December 31, 2024. The events were categorized and their distribution and time evolution analyzed. RESULTS:A total of 818 events (227 LDR, 203 HDR, 21 intravascular, 367 microsphere) were identified, excluding events that related purely to shipping. We analyzed the events for the whole period and in consecutive 5-year intervals. The total number of events rose by 27% from the first to the last interval (2005-09:179, 2020-24:227), with the LDR events decreasing by 81% (2005-2009:98, 2020-24: 19) and microsphere events increasing by 588% (2005-09:25, 2020-24:172). HDR events decreased by 15% (2005-09:53, 2020-24:45), while intravascular events increased (2005-09:3, 2020-2024:7) but stayed very rare. . For HDR, the three most frequent categories were treatment planning error (26%), transfer tube issues (13%) and other/unknown issues (13%); the frequency of treatment planning events decreased with time (2005-09: 38%, 2020-24: 18%). For LDR, the three most frequent categories were lost or leaking source (39%), other/unknown issues (24%) and permanent implant sources implanted into wrong tissue (18%). For microspheres, most events were related to the sphere remaining in the delivery apparatus and for intravascular brachytherapy, to the source not retracting. The radioisotopes of LDR events were I-125 (72%), Pd-103 (11%), Cs-137 (8%), Ir-192 (4%), Cs-131 (3%) and Sr-90 (2%); no events relating to Ir-192 or Cs-137 occurred in 2020-24. CONCLUSION/CONCLUSIONS:The reduction in the LDR events is probably explained by the decreased frequency of prostate implants and LDR gynecological procedures. Microspheres now account for most event reports.