Utility of microbial cell free DNA next-generation sequencing for diagnosis and management of infectious diseases.

Microbial cell-free DNA (mcfDNA) sequencing is a promising tool to identify infectious pathogens when traditional methods fail to identify the causative agent. We performed a retrospective observational cohort study to evaluate clinical outcomes among pediatric and adult patients who underwent mcfDNA testing. 127 mcfDNA tests were reviewed from 112 patients. Baseline characteristics included 61 (54.5 %) adults, 52 (40.9 %) tests were from female patients, and 67 (52.8 %) tests were obtained from patients designated as immunocompromised. Of all tests obtained, 59 (46.4 %) were deemed clinically relevant. 41 (32.3 %) of tests also led to a change in antimicrobial management for the corresponding patient. No statistically significant association was ascertained between patient-specific factors and clinically relevant test results. Testing in certain clinical scenarios or high-risk settings may be useful, however further studies are needed to assess the cost-benefit of this approach.

Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis.

Coccidioides is an endemic fungus that causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016 and 2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months, and 9 months post-transplant, patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (P = 0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.

Solid organ transplant recipients can be highly immune suppressed, and infection with Coccidioides (valley fever) after transplant can lead to severe infections in these patients. Our study showed that fluconazole was safe and effective for preventing Coccidioides in kidney transplant recipients.

Performance of CT With Adrenal-Washout Protocol in Heterogeneous Adrenal Nodules: A Multiinstitutional Study.

BACKGROUND. CT with adrenal-washout protocol (hereafter, adrenal-protocol CT) is commonly performed to distinguish adrenal adenomas from other adrenal tumors. However, the technique's utility among heterogeneous nodules is not well established, and the optimal method for placing ROIs in heterogeneous nodules is not clearly defined. OBJECTIVE. The purpose of our study was to determine the diagnostic performance of adrenal-protocol CT to distinguish adenomas from nonadenomas among heterogeneous adrenal nodules and to compare this performance among different methods for ROI placement. METHODS. This retrospective study included 164 patients (mean age, 59.1 years; 61 men, 103 women) with a total of 164 heterogeneous adrenal nodules evaluated using adrenal-protocol CT at seven institutions. All nodules had an available pathologic reference standard. A single investigator at each institution evaluated the CT images. ROIs were placed on portal venous phase images using four ROI methods: standard ROI, which refers to a single large ROI in the nodule's center; high ROI, a single ROI on the nodule's highest-attenuation area; low ROI, a single ROI the on nodule's lowest-attenuation area; and average ROI, the mean of the three ROIs on the nodule's superior, middle, and inferior thirds using the approach for the standard ROI. ROIs were then placed in identical locations on unenhanced and delayed phase images. Absolute washout was determined for all methods. RESULTS. The nodules comprised 82 adenomas and 82 nonadenomas (36 pheochromocytomas, 20 metastases, 12 adrenocortical carcinomas, and 14 nodules with other pathologies). The mean nodule size was 4.5 ± 2.8 (SD) cm (range, 1.6-23.0 cm). Unenhanced CT attenuation of 10 HU or less exhibited sensitivity and specificity for adenoma of 22.0% and 96.3% for standard-ROI, 11.0% and 98.8% for high-ROI, 58.5% and 84.1% for low-ROI, and 30.5% and 97.6% for average-ROI methods. Adrenal-protocol CT overall (unenhanced attenuation ≤ 10 HU or absolute washout of ≥ 60%) exhibited sensitivity and specificity for adenoma of 57.3% and 84.1% for the standard-ROI method, 63.4% and 51.2% for the high-ROI method, 68.3% and 62.2% for the low-ROI method, and 59.8% and 85.4% for the average-ROI method. CONCLUSION. Adrenal-protocol CT has poor diagnostic performance for distinguishing adenomas from nonadenomas among heterogeneous adrenal nodules regardless of the method used for ROI placement. CLINICAL IMPACT. Adrenal-protocol CT has limited utility in the evaluation of heterogeneous adrenal nodules.

Correlation between epidural space depth measured with ultrasound and MRI compared to clinical loss of resistance when performing lumbar epidural steroid injection.

BACKGROUND: This prospective study assessed the accuracy of MRI and ultrasound (US) measurements as a preprocedural assessment tool for predicting clinical loss of resistance depth (CLORD) during fluoroscopy-guided lumbar epidural steroid injections (ESIs). MATERIALS AND METHODS: Sixty patients enrolled received lumbar ESIs at an academic chronic pain clinic. The MRI measurement calculated the distance between the skin and the posterior epidural space, while US measurements included transverse and parasagittal oblique views of the interlaminar space. The epidural space measurements were compared with the CLORD during the performance of the prone epidural injections. The differences in measurements were analyzed using two one-sided tests for equivalency with a 0.5 equivalency margin. The intraclass correlation coefficients between CLORD and the imaging modalities were estimated using mixed effects models. RESULTS: MRI was equivalent to CLORD with a mean difference of -0.2 cm (95% CI -0.39 to -0.11). US transverse and US parasagittal oblique measurements were not equivalent to and underestimated CLORD with mean differences of -0.98 cm (90% CI -1.8 to -0.77) and -0.79 cm (90% CI -1.0 to -5.9), respectively. The intraclass correlation coefficients between MRI and CLORD were the highest at 0.85, compared with 0.65 and 0.73 for transverse and parasagittal oblique US views, respectively. CONCLUSIONS: MRI measurements are preferable over US for preprocedural assessment of patients receiving lumbar ESIs for predicting CLORD.

Comparison of coccidioidal complement fixation and quantitative immunodiffusion serology at a reference laboratory.

The incidence of coccidioidomycosis continues to increase. The diagnosis frequently relies on non-invasive diagnostic testing with immunodiffusion and complement fixation (CF) testing the current gold standard. A direct comparison of quantitative immunodiffusion and CF for IgG antibodies has not been previously reported. In a comparison of 368 samples, there was close concordance observed (360/368 = 97.8%) (P-value < .001). These tests can be considerably interchangeable in the reference laboratory setting.

There are several diagnostic methodologies available in coccidioidomycosis. Direct comparisons of these methods are limited. Prior studies have not compared quantitative immunodiffusion to complement fixation testing. Our results show these tests are highly concordant.

Association of Parity and Previous Birth Outcome With Brachial Plexus Birth Injury Risk.

OBJECTIVE: To evaluate the association of maternal delivery history with a brachial plexus birth injury risk in subsequent deliveries and to estimate the effect of subsequent delivery method on brachial plexus birth injury risk. METHODS: We conducted a retrospective cohort study of all live-birth deliveries occurring in California-licensed hospitals from 1996 to 2012. The primary outcome was recurrent brachial plexus birth injury in a subsequent pregnancy. The exposure was delivery history (parity, shoulder dystocia in a previous delivery, or previously delivering a neonate with brachial plexus birth injury). Multiple logistic regression was used to model adjusted associations of delivery history with brachial plexus birth injury in a subsequent pregnancy. The adjusted risk and adjusted risk difference for brachial plexus birth injury between vaginal and cesarean deliveries in subsequent pregnancies were determined, stratified by delivery history, and the number of cesarean deliveries needed to prevent one brachial plexus birth injury was determined. RESULTS: Of 6,286,324 neonates delivered by 4,104,825 individuals, 7,762 (0.12%) were diagnosed with a brachial plexus birth injury. Higher parity was associated with a 5.7% decrease in brachial plexus birth injury risk with each subsequent delivery (adjusted odds ratio [aOR] 0.94, 95% CI 0.92-0.97). Shoulder dystocia or brachial plexus birth injury in a previous delivery was associated with fivefold (0.58% vs 0.11%, aOR 5.39, 95% CI 4.10-7.08) and 17-fold (1.58% vs 0.11%, aOR 17.22, 95% CI 13.31-22.27) increases in brachial plexus birth injury risk, respectively. Among individuals with a history of delivering a neonate with a brachial plexus birth injury, cesarean delivery was associated with a 73.0% decrease in brachial plexus birth injury risk (0.60% vs 2.21%, aOR 0.27, 95% CI 0.13-0.55) compared with an 87.9% decrease in brachial plexus birth injury risk (0.02% vs 0.15%, aOR 0.12, 95% CI 0.10-0.15) in individuals without this history. Among individuals with a history of brachial plexus birth injury, 48.1 cesarean deliveries are needed to prevent one brachial plexus birth injury. CONCLUSIONS: Parity, previous shoulder dystocia, and previously delivering a neonate with brachial plexus birth injury are associated with future brachial plexus birth injury risk. These factors are identifiable prenatally and can inform discussions with pregnant individuals regarding brachial plexus birth injury risk and planned mode of delivery.

Treatment Outcomes With Conservative Management of Frontal Sinus Outflow Tract Fractures.

OBJECTIVE: Historically, early surgical management of frontal sinus outflow tract (FSOT) fractures has been standard practice. There has been a paradigm shift toward nonsurgical or delayed management. Unfortunately, clinical indications and treatment outcomes for this approach are poorly understood. This study evaluates radiologic indicators, as well as sinus reaeration and complication rates for FSOT injuries treated nonsurgically. STUDY DESIGN: A retrospective cohort study of FSOT injuries between 2005 and 2019. SETTING: Academic, tertiary care medical center. METHODS: Radiographic fracture patterns of the frontal ostia (FO) and frontal recess (FR) were recorded as either patent, disrupted, or obstructed. Sinus reaeration, surgical rescue, and complication rates were documented. Patients with follow-up imaging >42 days were included. Patients undergoing immediate surgical intervention were excluded. RESULTS: One hundred patients were identified and 44 met the criteria (88 sinuses). Among nonobstructed FSOT injuries (ie, patent or disrupted), reaeration occurred in 91% of the FO and 98% of FR injuries. Two sinuses required surgical rescue including 1 Draf IIB (1%), and 1 obliteration (1%). Two sinuses had complications including 1 mucocele (1%) and 1 cerebrospinal fluid leak (1%). FO and FR fracture patterns had no identifiable correlation with long-term reaeration rates or the need for surgical intervention. CONCLUSION: Among nonobstructive injuries to the FSOT, average reaeration rates in observed patients were high (91%-98%). Rescue surgery (2%) and complication rates (2%) were low, suggesting that nonsurgical management of nonobstructed FSOT is a viable strategy. No radiographic features were clearly identified to be predictive of sinus reaeration.

Characteristics and outcomes of patients undergoing second-trimester dilation and evacuation for intrauterine fetal demise vs induced abortion.

OBJECTIVES: Patients with intrauterine fetal demise (IUFD) are at higher risk of complications when undergoing dilation and evacuation (D&E) compared to patients undergoing abortion for other indications. We aimed to compare baseline characteristics and describe outcomes, including frequencies of complications such as disseminated intravascular coagulation (DIC) and hemorrhage, in patients undergoing D&E for IUFD vs induced abortion, with a goal of identifying associated risk factors for complications. STUDY DESIGN: We conducted a retrospective matched cohort study of patients undergoing nonemergent D&Es for singleton ≥14-0/7-week IUFD January 1, 2019 to May 31, 2021, matched with two patients undergoing induced second-trimester D&Es by cesarean delivery history, patient age, and gestational age (GA). We collected demographics, history, GA, coagulation studies, quantitative blood loss (QBL), and complications. We calculated descriptive statistics and tested for association using chi-square, Fisher's exact, t, and Wilcoxon's rank sum tests. RESULTS: Of 1390 procedures, 64 patients with IUFD met inclusion criteria and were matched with 128 patients undergoing induced D&E. Eight (12.5%) patients with IUFD and six (4.7%) undergoing induced D&E had hemorrhage (odds ratio [OR] = 2.90, 95% confidence interval [0.96, 8.77]). Six (9.4%) patients with IUFD and none undergoing induced D&E had DIC (OR = 28.56 [1.58, 515.38]). Median QBL was 75.0 mL (50, 162.5) for patients with IUFD vs 110.0 mL (50, 200) for those undergoing induced D&E (p = 0.083). Twelve (18.8%) patients with IUFD vs seven (5.5%) undergoing induced D&E received at least one intervention due to bleeding complications (p = 0.004). CONCLUSIONS: We found a higher DIC frequency but no significant difference in hemorrhage or QBL in IUFD D&E compared to induced abortion. Our IUFD D&E complication frequency is higher than those previously published. IMPLICATIONS: Our results affirm current standards of care for D&E in patients with IUFD. Large referral centers may have higher proportions of complications compared to other sites.

Comparison of Time Within Therapeutic Range Using Anti-Factor Xa Versus Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin in Children.

OBJECTIVE: To compare unfractionated heparin (UFH) monitoring using time in therapeutic range of activated partial thromboplastin time (aPTT) versus anti-factor Xa activity (anti-Xa) in children. METHODS: This retrospective chart review, with data between October 2015 and October 2019, included pediatric patients younger than 18 years on therapeutic UFH infusion with aPTT or anti-Xa monitoring. Patients receiving extracorporeal membrane oxygenation, dialysis, concomitant anticoagulants, prophylactic UFH, no stated goal, and UFH administered for less than 12 hours were excluded. The primary outcome compared the percentage of time in therapeutic range between aPTT and anti-Xa. Secondary outcomes included time to first therapeutic value, UFH infusion rates, mean rate adjustments, and adverse events. RESULTS: A total of 65 patients were included, with 33 aPTT patients and 32 anti-Xa patients, representing 39 UFH orders in each group. Baseline characteristics were similar between groups, with an overall mean age of 1.4 years and mean weight of 6.7 kg. The anti-Xa cohort demonstrated a statistically significantly higher percentage of time in therapeutic range compared with the aPTT group (50.3% vs 26.9%, p = 0.002). The anti-Xa group also demonstrated a trend toward decreased time to first therapeutic value compared with aPTT (14 vs 23.2 hours, p = 0.12). Two patients in each group experienced new or worsening thrombosis. Six patients in the aPTT cohort experienced bleeding. CONCLUSIONS: This study demonstrated greater time was spent within therapeutic range for children receiving UFH monitored with anti-Xa compared with aPTT. Future studies should assess clinical outcomes in a larger population.

Maternal Epidemiology of Brachial Plexus Birth Injuries in California: 1996 to 2012.

OBJECTIVE: This study aimed to evaluate the incidence of brachial plexus birth injury (BPBI) and its associations with maternal demographic factors. Additionally, we sought to determine whether longitudinal changes in BPBI incidence differed by maternal demographics. STUDY DESIGN: We conducted a retrospective cohort study of over 8 million maternal-infant pairs using California's Office of Statewide Health Planning and Development Linked Birth Files from 1991 to 2012. Descriptive statistics were used to determine BPBI incidence and the prevalence of maternal demographic factors (race, ethnicity, age). Multivariable logistic regression was used to determine associations of year, maternal race, ethnicity, and age with BPBI. Excess population-level risk associated with these characteristics was determined by calculating population attributable fractions. RESULTS: The incidence of BPBI between 1991 and 2012 was 1.28 per 1,000 live births, with peak incidence of 1.84 per 1,000 in 1998 and low of 0.9 per 1,000 in 2008. Incidence varied by demographic group, with infants of Black (1.78 per 1,000) and Hispanic (1.34 per 1,000) mothers having higher incidences compared with White (1.25 per 1,000), Asian (0.8 per 1,000), Native American (1.29 per 1,000), other race (1.35 per 1,000), and non-Hispanic (1.15 per 1,000) mothers. After controlling for delivery method, macrosomia, shoulder dystocia, and year, infants of Black (adjusted odds ratio [AOR] = 1.88, 95% confidence interval [CI] = 1.70, 2.08), Hispanic (AOR = 1.25, 95% CI = 1.18, 1.32), and advanced-age mothers (AOR = 1.16, 95% CI = 1.09, 1.25) were at increased risk. Disparities in risk experienced by Black, Hispanic, and advanced-age mothers contributed to a 5, 10, and 2% excess risk at the population level, respectively. Longitudinal trends in incidence did not vary among demographic groups. Population-level changes in maternal demographics did not explain changes in incidence over time. CONCLUSION: Although BPBI incidence has decreased in California, demographic disparities exist. Infants of Black, Hispanic, and advanced-age mothers are at increased BPBI risk compared with White, non-Hispanic, and younger mothers. KEY POINTS: · The incidence of BPBI has decreased over time.. · Demographic disparities in BPBI incidence and risk exist.. · Infants of Black, Hispanic, and advanced age mothers are at greatest risk of BPBI..

Are There Ultrasound Features to Distinguish Small (<3 cm) Peripheral Renal Angiomyolipomas From Renal Cell Carcinomas?

BACKGROUND: Small echogenic renal masses are usually angiomyolipomas (AMLs), but some renal cell carcinomas (RCCs) can be echogenic and confused with an AML. OBJECTIVES: This is a study to evaluate any distinguishing demographic and sonographic features of small (<3 cm) peripheral AMLs versus peripheral RCCs. METHODS: This is a HIPAA-compliant retrospective review of the demographics and ultrasound features of peripheral renal AMLs compared with a group of peripheral RCCs. All AMLs had confirmation of macroscopic fat as noted on thin-cut CT or fat-saturation MRI sequence images. All RCCs were pathologically proven. Statistical analysis was used to compare findings in the two groups. RESULTS: There were a total of 52 patients with 56 AMLs, compared with 42 patients with 42 RCCs. There were 42 females in the AML group versus 10 females in the RCC group (P < .0001). The AML diameters (15.7 mm × 12.0 mm) were statistically significantly smaller (Plargest = .0085, Psmallest < .001) than the diameters of the RCCs (19.9 mm × 18.5 mm). Ultrasound features found to be statistically different between the two groups were the ratio of the largest dimension to the smallest dimension (P < .001), a lobulated versus smooth margin of the AML (26 vs 30) compared with the RCC group (3 vs 39) (P = .0012), and an "unusual" versus a round shape (P < .001) of the AML group (45 vs 11) compared with the RCC group (9 vs 33). In the multivariable model, the patient sex, margin, and mass shape were predictive of AML, with an area under the receiver operating characteristic curve of 0.92. CONCLUSION: For a small (<3 cm) peripheral echogenic mass in a female patient, a lobulated lesion with an unusual shape is highly predictive of being an AML.

The classical and alternative circulating renin-angiotensin system in normal dogs and dogs with stage B1 and B2 myxomatous mitral valve disease.

BACKGROUND: The behavior of the comprehensive circulating renin-angiotensin system (RAS) in dogs with myxomatous mitral valve disease (MMVD) before to the onset of congestive heart failure remains largely unexplored. HYPOTHESIS/OBJECTIVES: The classical and alternative RAS activity and aldosterone concentrations will be significantly higher in dogs with American College of Veterinary Internal Medicine (ACVIM) stage B2 MMVD compared to normal dogs and dogs with ACVIM stage B1 MMVD. ANIMALS: One-hundred seventeen client-owned dogs (normal = 60; B1 = 31; B2 = 26). METHODS: Prospective observational study. Angiotensin peptides (AP) and aldosterone concentrations were measured using liquid chromatography and mass spectrometry. Angiotensin converting enzymes 1 and 2 (ACE, ACE2) and renin activity surrogates were calculated from AP concentrations. Equilibrium dialysis (ED) and immediate protease inhibition (PI) methods of AP quantification were compared in 14 healthy dogs. RESULTS: Core RAS activity and aldosterone concentrations did not differ among the 3 groups. However, the balance between the alternative and classical RAS differed, with dogs with stage B2 MMVD having significantly higher ACE2 activity surrogate (ACE2surr ) when compared to normal dogs (adjusted P = .02; ratio of medians for ACE2surr [B2:normal], 1.89; 95% confidence interval [CI]: 1.4-2.6). The ED and PI methods of AP quantification were highly correlated (AngI, r = .9, P < .0001; AngII, r = .8, P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Circulating alternative RAS activity, specifically the surrogate measure of ACE2 activity, was increased in dogs with stage B2 MMVD as compared to normal dogs. Equilibrium dialysis results are analogous to immediate protease inhibition in dogs.

Complex Family Planning fellowship graduates' intended practice plans and barriers to practicing in areas of unmet need.

OBJECTIVES: To describe practice patterns and challenges encountered by Complex Family Planning (CFP) fellowship graduates. STUDY DESIGN: We invited all 110 obstetrics and gynecology physicians who graduated from the CFP fellowship from 2017-2020 via email to complete an anonymous online survey. We inquired about demographics, intended and obtained postfellowship positions, and successes and challenges in obtaining jobs. We used Fisher's exact test to assess if the proportion of graduates who grew up, attended residency, and completed fellowship in a US region (Northeast, Midwest, South, and West) and practiced in that same region differed. RESULTS: Ninety-nine (90.0%) graduates completed the survey. When entering fellowship, most (n = 92 [92.9%]) expected to practice in an academic environment. About half (n = 49 [49.5%]) pursued fellowship with the intent to practice in a location with an unmet need for abortion providers, of which 22 (44.9%) did so. Forty-nine (49.5%) respondents did not practice after fellowship where they initially intended, citing common challenges of job availability, family-related concerns, safety concerns, and relationship status changes. We found associations between regions where graduates completed residency and currently practice (p = 0.004), driven primarily by higher associations in the South (76.9%) and West (70.6%) and a lower association in the Midwest (22.7%). We found no association between current practice region and where graduates grew up (p = 0.15) or completed fellowship (p = 0.23). CONCLUSIONS: CFP fellowship graduates from 2017-2020 primarily intended to practice in academic environments with half planning to practice in underserved locations. However, more than half of those who entered fellowship hoping to fill an unmet need for abortion providers did not do so. IMPLICATIONS: About half of CFP fellowship graduates from 2017-2020 intended to obtain positions in areas they defined as having an unmet need for abortion provision. Personal life and job barriers prevented many from serving in such positions after fellowship. Practice location intentions and outcomes may be different in a post-Dobbs environment.

Impact of Vaccination on Cost and Course of Hospitalization Associated with COVID-19 Infection.

Objective: Examine the impact of vaccination status on hospital cost and course for patients admitted with COVID-19 infection. Design: Retrospective cohort study characterizing vaccinated and unvaccinated individuals hospitalized for COVID-19 between April 2021 to January 2022. Setting: Large academic medical center. Methods: Patients were included if they were greater than 18 years old, fully vaccinated or unvaccinated against COVID-19, and admitted for COVID-19 infection. Patients: 437 consecutively admitted patients for COVID-19 infection met inclusion criteria. Of these, 79 were excluded for unknown or partial vaccination status, transfer from an outside hospital, or multiple COVID-19 related admissions. Results: Overall, 279 (77.9%) unvaccinated patients compared to 79 (22.1%) vaccinated patients were hospitalized with a diagnosis of COVID-19. Average length of stay was significantly lower in the vaccinated group (6.47 days versus 8.92 days, P = 0.03). Vaccinated patients experienced a 70.6% lower risk of ICU admission (OR = 0.29, 95% CI 0.12-0.71, P = 0.006). The unadjusted cost of hospitalization was not found to be statistically significant ($119,630 versus $191,146, P = 0.06). After adjusting for age and comorbidities, vaccinated patients experienced a 26% lower cost of hospitalization compared to unvaccinated patients (P = 0.004). Unvaccinated patients incurred a significantly higher cost of hospitalization per day ($29,425 vs $13,845 P < 0.0001). Unvaccinated patients (n = 118, 42.9%) were more likely than vaccinated patients (n = 16, 20.3%) to require high-flow oxygen or mechanical ventilation (OR = 2.95, 95% CI 1.62-5.38, P = 0.0004). Conclusion: Vaccinated patients experienced a lower cost of hospitalization after adjusting for age and comorbidities and shorter length of stay compared to unvaccinated patients admitted for COVID-19.

Chronic Exposure to Low Levels of Parabens Increases Mammary Cancer Growth and Metastasis in Mice.

Methylparaben (MP) and propylparaben (PP) are commonly used as food, cosmetic, and drug preservatives. These parabens are detected in the majority of US women and children, bind and activate estrogen receptors (ER), and stimulate mammary tumor cell growth and invasion in vitro. Hemizygous B6.FVB-Tg (MMTV-PyVT)634Mul/LellJ female mice (n = 20/treatment) were exposed to MP or PP at levels within the US Food and Drug Administration's "human acceptable daily intake." These paraben-exposed mice had increased mammary tumor volume compared with control mice (P < 0.001) and a 28% and 91% increase in the number of pulmonary metastases per week compared with the control mice, respectively (P < 0.0001). MP and PP caused differential expression of 288 and 412 mammary tumor genes, respectively (false discovery rate < 0.05), a subset of which has been associated with human breast cancer metastasis. Molecular docking and luciferase reporter studies affirmed that MP and PP bound and activated human ER, and RNA-sequencing revealed increased ER expression in mammary tumors among paraben-exposed mice. However, ER signaling was not enriched in mammary tumors. Instead, both parabens strongly impaired tumor RNA metabolism (eg, ribosome, spliceosome), as evident from enriched KEGG pathway analysis of differential mammary tumor gene expression common to both paraben treatments (MP, P < 0.001; PP, P < 0.01). Indeed, mammary tumors from PP-exposed mice had an increased retention of introns (P < 0.05). Our data suggest that parabens cause substantial mammary cancer metastasis in mice as a function of their increasing alkyl chain length and highlight the emerging role of aberrant spliceosome activity in breast cancer metastasis.

The Impact of Surgical Posterior Nasal Nerve Cryoablation on Symptoms and Disease-Specific Quality of Life in Patients With Chronic Rhinitis.

OBJECTIVE: Preliminary data have demonstrated long-term efficacy of posterior nasal nerve (PNN) cryoablation in reducing rhinitis symptoms for patients with allergic rhinitis (AR) and nonallergic rhinitis (NAR). We sought to evaluate the impact of procedural cryoablation of the PNN on quality of life (QOL) in patients with AR and NAR. METHODS: Adult patients undergoing PNN cryoablation for AR or NAR after appropriate medical therapy were included for analysis. Demographics, medical therapies, baseline rhinitis symptom (total nasal symptom score [TNSS]), and disease-specific QOL (mini-rhinoconjunctivitis quality of life questionnaire [mini-RQLQ]) were recorded. The Wilcoxon signed-rank test was used to test for significant changes in baseline test scores posttreatment. Absolute and relative improvement in outcomes was determined for each participant. Secondary outcomes were assessed with univariate and multivariate analyses. RESULTS: Fourteen patients were enrolled with a mean follow-up of 16.5 weeks. The TNSS and mini-RQLQ scores significantly improved after PNN cryoablation (median δs [interquartile range]: -4 [3] and -1.61 [1.08], respectively; both P = .0002). The minimal clinically important difference for the TNSS and mini-RQLQ was obtained in 92.9% of patients in each category. Relative mean percentage (%) improvement after PNN cryoablation in the TNSS and mini-RQLQ was 40.7% and 40.5% (standard deviation = 24.9 and 29.5, respectively), respectively, for all patients. Patients with NAR (n = 10) reported mean improvement of 41.3% (29.1) as measured by the TNSS and 49.6% (25.9) by mini-RQLQ. Patients with AR reported mean percentage improvement in TNSS and mini-RQLQ scores of 39.5% (12.1) and 24.6% (28.5), respectively. Patients who had been prescribed a nasal anticholinergic for management prior to PNN cryoablation had statistically significantly increased improvement in mini-RQLQ scores from pre- to post-procedure (P = .0387). CONCLUSION: Surgical cryoablation of the PNN significantly improves both symptoms and disease-specific QOL in majority of patients with AR and NAR.

Utility of combined gadoxetic acid and ferumoxytol-enhanced liver MRI for preoperative detection of colorectal cancer liver metastases: a pilot study.

BACKGROUND: Colorectal cancer (CRC) is the second-leading cause of cancer-related death worldwide and resection of CRC metastases confined to the liver is the treatment of choice when feasible. Ferumoxytol is an off-label contrast agent that opacifies vasculature and may be helpful in distinguishing metastases from small hemangiomas and blood vessels on gadoxetic acid-enhanced magnetic resonance imaging (MRI). PURPOSE: To compare the diagnostic accuracy of MRI using a standard gadoxetic acid protocol and a combined gadoxetic acid/ferumoxytol protocol in patients with suspected colorectal hepatic metastases. MATERIAL AND METHODS: In this institutional review board-approved, single-institution, retrospective study, eight patients underwent gadoxetic acid-enhanced liver MRI, supplemented with additional T1-weighted ferumoxytol enhanced sequences. Two radiologists in consensus identified all metastases using all available sequences, which served as the reference standard. Two different radiologists reviewed each exam twice, once using the standard protocol and once with additional ferumoxytol sequences. The detection rate was estimated as the predicted probability of a metastasis along with the 95% confidence interval (CI) using hierarchical logistic regression models. RESULTS: A total of 49 metastases were identified. The mean diameter was 10 mm, measured in greatest axial dimension (median=7 mm; range=2-70 mm). Readers 1 and 2 had detection rates of 69.6% (95% CI = 48.2-85.0) and 53.1% (95% CI = 35.2-70.3) for gadoxetic acid alone and 98.0% (95% CI = 86.3-99.7) and 83.5% (95% CI = 59.3-94.7) for combined protocol. CONCLUSION: In this preliminary investigation, adding ferumoxytol-enhanced sequences to gadoxetic acid liver MRI protocol increased the detection rate of CRC hepatic metastases and may aid in preoperative decision making.

Clinical interventions are more accurate than quantitative measurements for defining hemorrhage with dilation and evacuation.

OBJECTIVES: To assess if quantitative blood loss (QBL) with dilation and evacuation (D&E) procedures correlated with clinically relevant outcomes or hemorrhage. STUDY DESIGN: We used a de-identified database to review D&E procedures performed at UC Davis Health from April 2019 through March 2020. Surgeons determined QBL during procedures and estimated blood loss, when excessive, during post-procedure recovery. We extracted patient demographic and procedure-related information. We defined clinically relevant bleeding as cases with bleeding-related interventions within 24 hours post-procedure including use of ≥2 uterotonics, tranexamic acid administration, cervical injury requiring repair, uterine balloon tamponade, blood transfusion, uterine artery embolization, hospitalization, or return to operating room; the latter 5 criteria defined hemorrhage. We used χ2 test for trend to evaluate bleeding outcomes. RESULTS: We evaluated 431 procedures with a mean gestational age of 19 weeks and 3 days. Clinically relevant bleeding outcomes occurred in 6/319 (2%), 15/97 (15%) and 7/12 (58%) patients with total blood loss <250mL, 250-500mL and >500mL, respectively (p<0.0001); 11 had bleeding related to cervical injuries. Hemorrhage occurred in 0, 4/97 (4%) and 5/12 (42%) patients, respectively (p<0.0001). Patients with relevant bleeding outcomes had QBLs ranging from 150-1800mL (median QBL 312.5mL, interquartile range [IQR] 250-550mL) while those without clinically relevant bleeding ranged from 10-900mL (median QBL 150mL, IQR 75-200mL). CONCLUSION: Most patients (75%) with clinically relevant bleeding outcomes had QBL ≤500mL. Although higher QBL correlates with clinical interventions, the need for significant interventions rather than a single blood loss amount should be used to define hemorrhage with D&E procedures. IMPLICATIONS: Clinical hemorrhage is best defined by the necessary clinical interventions required to manage bleeding rather than any quantified amount of blood loss.

Upper Instrumented Vertebrae, Number of Levels Fused, and Plate Morphology Do Not Affect Severity of Chronic Dysphagia After Anterior Cervical Spine Surgery.

BACKGROUND: Disordered swallowing, or dysphagia, is the most common complication after anterior cervical spine (ACS) surgery. Many operative factors are associated with development of dysphagia. The aim of this study was to explore how number of levels instrumented, specific levels fused, and plate morphology affect chronic dysphagia after ACS surgery. METHODS: Consecutive patients referred to a tertiary center for otolaryngology evaluation for chronic dysphagia after ACS surgery between 2012 and 2017 were enrolled. Basic demographic data were obtained. Plain radiographs were reviewed for number of levels fused, upper instrumented vertebrae, and plate morphology. Plate morphology was categorized as a closed, small window, large window, or no profile plate. The 10-item Eating Assessment Tool (EAT-10) was used to assess dysphagia severity. RESULTS: Of 171 patients referred for dysphagia, 126 met inclusion criteria; 54% were female, with a mean age of 63 years (range, 32-88 years). Mean EAT-10 score was 18.5 ± 10.1. Mean time from spine surgery to videofluoroscopic swallow study for dysphagia was 58.3 months. Mean number of levels fused was 2.2 ± 0.9. There were no significant differences in EAT-10 scores in single-level versus multilevel fusion (19.0 vs. 18.4, P = 0.76) as well as with regard to upper instrumented vertebrae or plate morphology. CONCLUSIONS: In this series of patients with chronic dysphagia following ACS surgery, the severity of dysphagia as measured by the EAT-10 was not affected by upper instrumented vertebrae, number of levels fused, or plate morphology.

Identification of Demographic and Clinical Prognostic Factors in Traumatic Intraventricular Hemorrhage.

BACKGROUND: The presence of traumatic intraventricular hemorrhage (tIVH) following traumatic brain injury (TBI) is associated with worse neurological outcome. The mechanisms by which patients with tIVH have worse outcome are not fully understood and research is ongoing, but foundational studies that explore prognostic factors within tIVH populations are also lacking. This study aimed to further identify and characterize demographic and clinical variables within a subset of patients with TBI and tIVH that may be implicated in tIVH outcome. METHODS: In this observational study, we reviewed a large prospective TBI database to determine variables present on admission that predicted neurological outcome 6 months after injury. A review of 7,129 patients revealed 211 patients with tIVH on admission and 6-month outcome data. Hypothesized risk factors were tested in univariate analyses with significant variables (p < 0.05) included in logistic and linear regression models. Following the addition of either the Rotterdam computed tomography or Glasgow Coma Scale (GCS) score, we employed a backward selection process to determine significant variables in each multivariate model. RESULTS: Our study found that that hypotension (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.13-0.94, p = 0.04) and the hemoglobin level (OR = 1.33, 95% CI = 1.09-1.63, p = 0.006) were significant predictors in the Rotterdam model, whereas only the hemoglobin level (OR = 1.29, 95% CI = 1.06-1.56, p = 0.01) was a significant predictor in the GCS model. CONCLUSIONS: This study represents one of the largest investigations into prognostic factors for patients with tIVH and demonstrates that admission hemoglobin level and hypotension are associated with outcomes in this patient population. These findings add value to established prognostic scales, could inform future predictive modeling studies, and may provide potential direction in early medical management of patients with tIVH.