Effect of Cleft Palate Repair Timing on Inpatient Complication Rate: Review of a National Database.

OBJECTIVES: Timing of cleft palate repair is controversial. We aim to assess whether timing of cleft palate repair affects rates of inpatient complications, length of stay (LOS), and cost of stay. METHODS: The Healthcare Cost and Utilization Project Kids' Inpatient Database 2009 was queried for all admissions with a primary diagnosis of cleft palate during which cleft palate repair was performed as a primary procedure. Age 6 months or less was termed "early" repair, while age >6 months was termed "standard" repair. Patients age >3 years old, inpatient stays >30 days, and those stays in which a cleft lip repair was performed were excluded. Logistic regressions were used to model the probability of complications. Generalized linear models and a natural log link function were used for LOS and hospital charges, using SAS 9.4. RESULTS: We included 223 early and 1482 standard repair patients. Early repairs were exclusively performed in urban hospitals (P < 0.001). Eighty-nine patients experienced a total of 100 complications, including respiratory failure (N = 53), airway obstruction (N = 18), and oropharyngeal hemorrhage (N = 13). We found no significant difference in complication rate or total hospital charges in the 2 groups. The earlier repair group had a slightly longer LOS (P = 0.048). CONCLUSION: Over 85% of United States cleft palate repairs are performed after 6 months of age. All early repairs were performed at urban hospitals, and had slightly longer LOS. There was a 5.1% overall complication rate. Available data revealed no significant difference in complication rates between early repair and standard repair groups. LEVEL OF EVIDENCE: 3b.

The Effect of Vaginal Microablative Fractional CO2 Laser Treatment on Vaginal Cytology.

BACKGROUND AND OBJECTIVES: Most recently vaginal laser treatment was introduced as a new option for women with genitourinary syndrome of menopause, vaginal dryness. Our objective was to assess the effects of intravaginal CO2 laser treatment on vaginal cytology. STUDY DESIGN/MATERIALS AND METHODS: Fifty-two women with symptoms of vaginal dryness were enrolled and underwent vaginal laser treatment using a fractional CO2 laser. Patients received three vaginal laser treatments 4 weeks apart. Vaginal cytology was obtained before the first treatment and 4 weeks after each additional treatment. Vaginal dryness was assessed by using a Visual Analog Scale (VAS). RESULTS: Out of the 52 women enrolled, 34 were in menopause. Postmenopausal women had significantly lower vaginal maturation values (VMV) compared with premenopausal women at the baseline visit (mean ± standard deviation [SD], 42 ± 23 vs. 68 ± 13, P < 0.01). The vaginal dryness VAS was higher (worse) in postmenopausal women compared with premenopausal cases (mean ± SD, 5.7 ± 4 vs. 2.4 ± 3, P < 0.01). The VMV did not change significantly over time after vaginal laser treatment. However vaginal dryness VAS improved significantly after each treatment. Both in the premenopausal and postmenopausal groups, vaginal dryness scores improved significantly from baseline after the three treatments (postmenopausal 5.7 ± 4 vs. 1.6 ± 2.5, P < 0.01 and premenopausal 2.4 ± 3 vs. 0.2 ± 0.5, P < 0.01). Those patients who had improvement in VMV had significantly better (lower) dryness VAS compared with those women without an improvement in VMV after the three treatments (mean ± SD, 0.3 ± 0.8 vs. 1.6 ± 2.6, P = 0.04). CONCLUSIONS: Vaginal dryness VAS improved significantly in a cohort of premenopausal and postmenopausal women undergoing vaginal CO2 laser treatment despite no significant change in vaginal cytology. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Breast-Specific Gamma Imaging Versus MRI: Comparing the Diagnostic Performance in Assessing Treatment Response After Neoadjuvant Chemotherapy in Patients With Breast Cancer.

OBJECTIVE: The purpose of this retrospective study was to evaluate the diagnostic performance of breast-specific gamma imaging (BSGI) and breast MRI in assessing for residual tumor after neoadjuvant chemotherapy (NAC) in patients with breast cancer. MATERIALS AND METHODS: A total of 114 patients underwent BSGI and MRI for initial staging as well as after undergoing NAC. Of those, 112 underwent subsequent definitive breast surgery. Thirty of the 114 patients had a complete pathologic response to NAC. RESULTS: BSGI and MRI had comparable sensitivities in detecting residual tumor after NAC (70% vs 83%). BSGI had a higher specificity than MRI in accurately determining complete response after NAC (90% vs 60%). CONCLUSION: BSGI may be a useful adjunctive tool for predicting a complete pathologic response to NAC.

Prevalence of Sonographic Markers of Placenta Accreta Spectrum in Low-Risk Pregnancies.

OBJECTIVE: This study was aimed to evaluate the prevalence of sonographic markers for placenta accreta spectrum (PAS) in pregnancies at low-risk for PAS. STUDY DESIGN: Pregnant women at low-risk for PAS presenting for routine second trimester ultrasound who enrolled in the study were evaluated prospectively for sonographic markers of PAS during two ultrasounds at 18 to 24 and 28 to 34 weeks. Frequencies of PAS markers were compared between the second and third trimester and between those with and without prior cesarean deliveries (CD). RESULTS: Overall, 174 women were included. Several markers were seen frequently in the second trimester: vascular cervical invasion (57%), lacunae (46%), subplacental hypervascularity (37%), and irregularity of the posterior bladder wall (37%). Other markers were seen infrequently or not at all: loss of the retroplacental clear zone, uterovesical interface < 1 mm, bridging vessels, placental bulge or focal exophytic mass. Frequencies of markers did not differ between women with and without prior CD. Lacunae were larger and more numerous in the third trimester. Two or more PAS markers were observed in 98% of second trimester ultrasounds. CONCLUSION: Several PAS sonographic markers occur commonly in low-risk pregnancies. In the absence of risk factors, the independent predictive value of these markers is questionable.

Prevalence and Predictors of Provider-Initiated HIV Test Offers Among Heterosexual Persons at Increased Risk for Acquiring HIV Infection - Virginia, 2016.

Since 2006, CDC has recommended routine, provider-initiated human immunodeficiency virus (HIV) screening (i.e., HIV screening at least once in lifetime) for all patients aged 13-64 years in all health care settings (1). Whereas evidence related to the frequency of HIV testing is available, less is known about the prevalence and predictors of providers' HIV test offers to patients (2). National HIV Behavioral Surveillance (NHBS) data from Virginia were used to examine the prevalence and predictors of provider-initiated HIV test offers to heterosexual adults aged 18-60 years at increased risk for HIV acquisition. In a sample of 333 persons who visited a health care provider in the 12 months before their NHBS interview, 194 (58%) reported not receiving an HIV test offer during that time, approximately one third of whom (71, 37%) also reported never having had an HIV test in their lifetime. In multivariable analysis, the prevalence of HIV test offers was significantly lower among men than among women (adjusted prevalence ratio [aPR] = 0.72; 95% confidence interval [CI] = 0.53-0.97). Provider-initiated HIV test offers are an important strategy for increasing HIV testing among heterosexual populations; there is a need for increased provider-initiated HIV screening among heterosexual adults who are at risk for acquiring HIV, especially men, who were less likely than women to be offered HIV screening in this study.

Association between pelvic organ prolapse types and levator-urethra gap as measured by 3D transperineal ultrasound.

OBJECTIVES: To evaluate the association between pelvic organ prolapse (POP) types and levator-urethra gap (LUG) as measured by 3-dimensional transperineal tomographic ultrasound. METHODS: A retrospective study was carried out on 98 women with symptomatic POP. Three-dimensional transperineal tomographic ultrasound images and POP quantification coordinates were reviewed. Each vaginal compartment was staged for the degree of prolapse, and total number of involved compartments identified. LUG was measured on 3-dimensional tomographic sonograms as the distance between the center of the urethra and the levator insertion bilaterally. Based on prior studies, an abnormal LUG of 25 mm or greater indicated levator avulsion. The LUG and the presence or absence of unilateral/bilateral avulsions was analyzed with reference to the clinical diagnosis of prolapse (single versus multicompartment, and mild [stage II] versus severe [stage III-IV]). Generalized logit models were used to evaluate the association between avulsion and prolapse type and stage. RESULTS: The LUG was substantially larger in women with multicompartment compared to single-compartment POP (28.9 ± 4.1 mm versus 22.7 ± 4.1 mm, P < .01). Similarly, LUG was substantially larger in women with severe (stage III-IV) compared to mild (stage II) POP (28.8 ± 4.7 mm versus 23.3 ± 4.5 mm, P < .01). Women with severe prolapse were 32 times more likely than women with mild prolapse to have bilateral levator avulsion. Those with POP involving all 3 vaginal compartments were 76 times more likely than single-compartment POP to have bilateral levator avulsions. CONCLUSIONS: Bilateral levator ani avulsion as diagnosed by LUG measurements of 25 mm or greater at rest is associated with multicompartment, severe prolapse.

Statewide assessment of surgical outcomes and the acute care surgery model.

BACKGROUND: The acute care surgery (ACS) model has been widely implemented with single institution studies demonstrating improved outcomes. Recent multicenter studies have raised questions about the economics and efficacy of ACS. This study compares traditional and ACS outcomes across an entire state. METHODS: A retrospective review of Virginia's Health Information administrative database was completed. Adults admitted with appendicitis or cholecystitis between 2008 and 2014 were included. Hospital administration was contacted to determine surgical model. To compare patient characteristics, t-test and chi-square analyses were used. Total charges and length of stay (LOS) differences between ACS and traditional were examined using generalized linear models, whereas logistic regression was used for the presence of complications and 30-day mortality. RESULTS: Overall, the ACS model showed an increased proportion of uninsured patients with a higher rate of comorbidities. In the appendicitis subgroup, (n = 22,011; ACS n = 1993), ACS patients had higher total charges ($30,060 versus $28,460, P = 0.013), longer LOS (3.31 versus 2.92 d, P < 0.001), and higher chance of complications (odds ratio [OR] = 1.2, P = 0.016) and mortality (OR = 2.4, P = 0.029). After adjustment for comorbidities and insurance, mortality was no longer significantly different. In the cholecystitis group (n = 6936; ACS n = 777), ACS patients had a longer LOS (4.55 versus 4.13 d; P = 0.009) without significant differences in mortality, complications, or cost. There were no significant differences after adjustment for patient characteristics. CONCLUSIONS: ACS patients in Virginia have a higher rate of medical comorbidities and uninsured status, with slightly worse outcomes than the traditional model for appendicitis. Further studies to determine which patients benefit the most from ACS are warranted.

Transperineal Sonography and Urodynamic Findings in Women With Lower Urinary Tract Symptoms After Sling Placement.

OBJECTIVES: To evaluate dynamic 2-dimensional (2D) transperineal pelvic sonographic findings and urodynamic studies in women with lower urinary tract symptoms after midurethral sling placement. METHODS: Transperineal pelvic sonography and urodynamic studies were reviewed from women with a midurethral sling and lower urinary tract symptoms. The shape and sonographic dynamic change of the sling from the rest position to the maximum Valsalva maneuver and back to rest were recorded. Patients were categorized into 3 groups: group I, at rest, the sling lies parallel to the urethral lumen, and during Valsalva, the sling becomes C shaped; group 2, both at rest and during Valsalva, the sling runs parallel to the urethral lumen; and group 3, at rest, the sling is C shaped, and during Valsalva, this curved shape is maintained. For analytical purposes group 3 was compared with groups 1 and 2. Multiple logistic regressions were used to evaluate the association between transperineal pelvic sonography and urodynamic studies. RESULTS: Seventy-seven women were enrolled. The detrusor pressure at the maximum flow rate was significantly higher in group 3 than groups 1 and 2 (mean ± SD, 36 ± 16 versus 19 ± 11 mm H2 O; P < .001). The odds of high detrusor pressure (>20 mm H2 O) in group 3 was approximately 12 times the odds of those in groups 1 and 2. After adjusting for other variables using a multiple logistic regression analysis, a statistically significant association between group 3 and high detrusor pressure persisted (odds ratio, 29.7; 95% confidence interval, 2.949-299.6; P = .0040) persisted. CONCLUSIONS: Transperineal dynamic 2D sonography can help predict women with high-pressure voiding after midurethral sling placement and aid in the diagnosis of bladder outlet obstruction.

The Role of Early Gestation Ultrasound in the Assessment of Fetal Anatomy in Maternal Obesity.

OBJECTIVES: The 2012 Eunice Kennedy Shriver National Institute of Child Health fetal imaging consensus suggested that fetal anatomy ultrasound in obese pregnancies be performed at 20 to 22 weeks, with follow-up in 2 to 4 weeks if anatomy is incomplete. It was postulated that imaging in early gestation may improve visualization, although no prospective trials had been done to date. METHODS: We performed a prospective longitudinal blinded trial comparing an early gestation ultrasound (13 + 0 to 15 + 6 weeks) with the traditional second-trimester ultrasound for completion of the fetal anatomy survey in obese patients. Inclusion criteria included singleton gestation, body mass index (BMI) more than 30, less than 16 + 0 weeks' gestation, and no karyotype abnormality; exclusion criteria included age younger than 18 years, more than 16 weeks' gestation at time of consent, and BMI less than 30. Participants received a transvaginal and/or transabdominal sonogram for fetal anatomic survey at 13 + 0 to 15 + 6 weeks' gestation (US1). Images from US1 were blinded to physicians and sonographers performing subsequent examinations. All participants underwent the traditional transabdominal sonogram at 18 to 24 weeks (US2). If US2 failed to complete the anatomic survey, a repeat transabdominal sonogram (2-US2) was performed 2 to 4 weeks later. RESULTS: A total of 152 pregnancies met the criteria. Anatomy completion rate was 57.2% for US1 and 62.5% for US2, which was not statistically significant, even when stratified by BMI. Excluding the philtrum, the US1 performed better than US2 for class III obesity (65.5% versus 45.5% [P = .035]). Combination of US1 + US2 yielded a higher completion rate than US2 + 2-US2 (94.1% versus 83.6% [P = .0023]). CONCLUSIONS: In the setting of maternal obesity, the addition of an ultrasound in early gestation may be of highest benefit for patients with class III obesity (BMI > 40 kg/m2 ).

Exploring Racial, Gender, and Insurance Disparities in Patients with Osteoporotic Fractures.

The objective of this study is to examine racial, gender, and insurance disparities in hospital outcomes among patients diagnosed with osteoporotic fractures aged 55 years and older. A total of 36,153 patients were included in this study. The sample was constructed from de-identified patient-level data for 2011 through 2014 from the Virginia Health Information (VHI) inpatient discharge database. Differences in mortality and 30-day readmission across race, gender, and insurance status were examined using logistic regression and generalized linear models for hospital charges and length of stay. Whites and Asians had a shorter stay than Blacks [5.2 days (95% confidence interval (CI) 5.1-5.3) and 5.0 days (95% CI 4.7-5.2) vs. 5.6 days (95% CI 5.4-5.7)], while Hispanics had a significantly longer stay [6.0 days (95% CI 5.6-6.5)]. On average, total charges were the highest among Blacks [$37,916 (95% CI 36,784-39,083)]. All outcomes were poorer for men than women. Privately and publicly insured patients were more likely to be readmitted [odds ratio (OR) 1.6 (95% CI 1.0-2.6) and OR 2.0 (95% CI 1.3-3.2)] and had a shorter stay than the uninsured [4.9 days (95% CI 4.8-5.0) and 5.2 days (95% CI 5.1-5.3) vs. 5.7 days (95% CI 5.4-6.0)], while privately insured patients had considerably lower total charges than those who were uninsured [$34,163 (95% CI 33,214-35,139) vs. $36,335 (95% CI 34,334-38,452)]. As evidenced from this study, there are racial, gender, and insurance disparities in health outcomes. These results and further exploration of these disparities could provide information necessary for strategies to improve these outcomes in at-risk patients diagnosed with osteoporotic fractures.

Factors associated with the accuracy of self-reported osteoporosis in the community.

We examined the agreement between self-reported osteoporosis and bone mineral density (BMD) results through dual-energy x-ray absorptiometry (DXA) using data from a national representative sample taken from the US communities. Six-year data from the continuous National Health and Nutrition Examination Survey 2005-2006, 2007-2008, and 2009-2010 were merged. Participants included adults 50 years of age or older whose data appeared in both questionnaire and medical examination data files. Self-reported osteoporosis was defined by an affirmative response to a question in the osteoporosis questionnaire then compared with BMD-defined osteoporosis, defined by BMD values taken from the examination data. Agreement between self-reported osteoporosis and DXA results were low. Kappa was only 0.24 (95 % confidence interval = 0.21-0.27), and sensitivity and positive predictive value were 28.0 and 40.8 %, respectively. When stratified by gender or age group, agreement remained poor. Self-report of osteoporosis would not be suitable for accurate prevalence estimates for osteoporosis regardless of gender or age group.

Determinants of Elevated Alkaline Phosphatase in Patients Infected with HIV.

OBJECTIVES: A retrospective cross-sectional study was performed to assess the prevalence of elevated alkaline phosphatase (ALP) in patients infected with human immunodeficiency virus (HIV) and to determine the relation between ALP and specific antiretroviral therapy (ART). METHODS: A total of 2990 patients were included in this study. Data were collected from a major academic institution's HIV clinic using the most recent searchable values from patients' medical records. Included patients were 18 to 89 years old, had HIV, and their ALP results were available. Elevated ALP was defined as ALP >120 IU/L. Logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of elevated ALP level. RESULTS: In our total population of 2990, 15.4% (n = 459) had elevated ALP. In the bivariate analyses, older age (≥60 years; OR 4.1, 95% CI 2.6-6.4), female sex (OR 1.6, 95% CI 1.3-1.9), Other race (not African American) vs white (OR 1.9, 95% CI 1.8-3.3), elevated creatinine (OR 2.9, 95% CI 2.1-4.1), laboratory evidence of liver disease (OR 2.1, 95% CI 1.7-2.6), CD4 count <200 cells per cubic millimeter (OR 2.5, 95% CI 2.0-3.2), hepatitis C infection (OR 1.9, 95% CI 1.4-2.5), laboratory markers of bone turnover (OR 1.9, 95% CI 1.2-3.1), and non-nucleoside reverse-transcriptase inhibitors use (OR 1.2, 95% CI 1.02-1.15) were significantly associated with elevated ALP. Only the association with laboratory markers of bone turnover remained significant in the multivariate analysis, however. CONCLUSIONS: The results suggest that comorbidities and demographic variables have stronger associations with elevated ALP than specific antiretroviral therapy. Future research should be conducted to define the clinical significance of elevated ALP among patients infected with HIV.

Frequency and clinical relevance of PET/CT incidentalomas.

RATIONALE AND OBJECTIVES: To assess the frequency of clinically significant incidental CT findings on PET/CT. MATERIALS AND METHODS: Reports of 345 cases of baseline standard skull base to thighs PET/CT exams done over the course of a 6 month period at an outpatient facility affiliated with a large tertiary care level 1 trauma medical center were retrospectively reviewed. Incidental CT findings were assigned a level of clinical significance on a scale of 1-5, from doubtful significance to very significant. CT findings already known from prior CT reports were not included. CT findings corresponding to PET findings were also excluded. A score of 3 or greater was considered significant and reportable. RESULTS: Out of 345 cases, 171 (50%) had a least one CT finding rated at or above a score of 3 on our scale of significance, while 96 (28%) were found to have at least one CT finding with score at or above 4, and 25 cases (7%) showed at least one CT finding rated 5. CONCLUSION: A substantial percentage of baseline PET/CT studies contain previously undiagnosed, significant incidental findings on the CT images.

Screening elders in the emergency department at risk for mistreatment: a pilot study.

Impaired functional status is associated with risk of elder mistreatment. Screening for functional impairment in elderly patients admitted to emergency departments could be performed to identify patients at risk for elder mistreatment who might benefit from further evaluation. This study utilized a modified Identification of Seniors at Risk (ISAR) screening tool to identify the proportion of elderly at risk for mistreatment due to functional difficulties presenting to two emergency departments in southeastern Virginia, one urban, the other rural. Of a 180-patient cohort (90 per site), 82 screened positive (46%), ISAR > 2 (range 0-6), indicating nearly half of all patients enrolled are at risk for mistreatment. Patients presenting to the urban emergency departments were potentially more at risk than their rural counterparts (p < 0.01). Health care professionals, particularly in urban settings, should consider screening seniors with a simple tool to identify patients at risk of elder mistreatment.

An open-label pilot study of apremilast for the treatment of moderate to severe lichen planus: a case series.

BACKGROUND: Current treatments for chronic lichen planus (LP) are often ineffective and may have significant adverse side effects. An alternative safe and effective treatment for recalcitrant LP is needed. OBJECTIVES: We sought to study the safety and efficacy of apremilast in the treatment of moderate to severe LP. METHODS: Ten patients with biopsy-proven LP received 20 mg of apremilast orally twice daily for 12 weeks with 4 weeks of treatment-free follow-up. The primary efficacy end point was the proportion of patients achieving a 2-grade or more improvement in the Physician Global Assessment (PGA) after 12 weeks of treatment. RESULTS: Three (30%) of the 10 patients achieved a 2-grade or more improvement in the PGA after 12 weeks of treatment; however, all patients demonstrated statistically significant clinical improvement with respect to secondary parameters between baseline and the end of treatment. LIMITATIONS: It may be difficult to generalize the results of this study to a larger patient population with LP because of our small sample size and lack of a control group. In addition, a longer treatment period or higher dose may have been needed for therapeutic efficacy. The safety and efficacy of long-term apremilast therapy is currently unknown. CONCLUSION: Apremilast may be efficacious in the treatment of LP, but double-blinded, controlled trials are necessary to thoroughly evaluate its safety and efficacy.

Prospective assessment of the gastroesophageal microbiome in VLBW neonates.

BACKGROUND: The distal GI microbiota of hospitalized preterm neonates has been established to be unique from that of healthy full-term infants; the proximal GI, more specifically gastroesophageal colonization has not been systematically addressed. We prospectively evaluated early colonization of gastroesophageal portion of the GI tract of VLBW infants. METHODS: This study involved 12 infants admitted to a level III NICU with gestational age (GA) 27 +/- 0.5 weeks and birth weight 1105 +/- 77 grams. The gastroesophageal microbial flora was evaluated using 16S rDNA analysis of aspirates collected in a sterile manner during the first 28 days of life. RESULTS: Bacteria were detected in 9 of the 12 neonates. Ureaplasma was the dominant species in the first week of life, however, staphylococci were the predominant bacteria overall. By the fourth week, Gram (-) bacteria increased in abundance to account for 50% of the total organisms. Firmicutes were present in the majority of the neonates and persisted throughout the 4 weeks comprising nearly half of the sequenced clones. Noticeably, only two distinct species of Staphylococcus epidermidis were found, suggesting acquisition from the environment. CONCLUSIONS: In our neonates, the esophagus and stomach environment changed from being relatively sterile at birth to becoming colonized by a phylogenetically diverse microbiota of low individual complexity. By the fourth week, we found predominance of Firmicutes and Proteobacteria. Bacteria from both phyla (CONS and Gram (-) organisms) are strongly implicated as causes of hospital-acquired infections (HAI). Evaluation of the measures preventing colonization with potentially pathogenic and pathogenic microorganisms from the hospital environment may be warranted and may suggest novel approaches to improving quality in neonatal care.

Interactive preventive health record to enhance delivery of recommended care: a randomized trial.

PURPOSE: Americans receive only one-half of recommended preventive services. Information technologies have been advocated to engage patients. We tested the effectiveness of an interactive preventive health record (IPHR) that links patients to their clinician's record, explains information in lay language, displays tailored recommendations and educational resources, and generates reminders. METHODS: This randomized controlled trial involved 8 primary care practices. Four thousand five hundred patients were randomly selected to receive a mailed invitation to use the IPHR or usual care. Outcomes were measured using patient surveys and electronic medical record data and included IPHR use and service delivery. Comparisons were made between invited and usual-care patients and between users and nonusers among those invited to use the IPHR. RESULTS: At 4 and 16 months, 229 (10.2%) and 378 (16.8%) of invited patients used the IPHR. The proportion of patients up-to-date with all services increased between baseline and 16 months by 3.8% among intervention patients (from 11.4% to 15.2%, P <.001) and by 1.5% among control patients (from 11.1% to 12.6%, P = .07), a difference of 2.3% (P = .05). Greater increases were observed among patients who used the IPHR. At 16 months, 25.1% of users were up-to-date with all services, double the rate among nonusers. At 4 months, delivery of colorectal, breast, and cervical cancer screening increased by 19%, 15%, and 13%, respectively, among users. CONCLUSIONS: Information systems that feature patient-centered functionality, such as the IPHR, have potential to increase preventive service delivery. Engaging more patients to use systems could have important public health benefits.

Site-Specific Intact N-Linked Glycopeptide Characterization of Prostate-Specific Membrane Antigen from Metastatic Prostate Cancer Cells.

The composition of N-linked glycans that are conjugated to the prostate-specific membrane antigen (PSMA) and their functional significance in prostate cancer progression have not been fully characterized. PSMA was isolated from two metastatic prostate cancer cell lines, LNCaP and MDAPCa2b, which have different tissue tropism and localization. Isolated PSMA was trypsin-digested, and intact glycopeptides were subjected to LC-HCD-EThcD-MS/MS analysis on a Tribrid Orbitrap Fusion Lumos mass spectrometer. Differential qualitative and quantitative analysis of site-specific N-glycopeptides was performed using Byonic and Byologic software. Comparative quantitative analysis demonstrates that multiple glycopeptides at asparagine residues 51, 76, 121, 195, 336, 459, 476, and 638 were in significantly different abundance in the two cell lines (p < 0.05). Biochemical analysis using endoglycosidase treatment and lectin capture confirm the MS and site occupancy data. The data demonstrate the effectiveness of the strategy for comprehensive analysis of PSMA glycopeptides. This approach will form the basis of ongoing experiments to identify site-specific glycan changes in PSMA isolated from disease-stratified clinical samples to uncover targets that may be associated with disease progression and metastatic phenotypes.

Commutability limitations influence quality control results with different reagent lots.

BACKGROUND: Good laboratory practice includes verifying that each new lot of reagents is suitable for use before it is put into service. Noncommutability of quality control (QC) samples with clinical patient samples may preclude their use to verify consistency of results for patient samples between different reagent lots. METHODS: Patient sample results and QC data were obtained from reagent lot change verification records for 18 QC materials, 661 reagent lot changes, 1483 reagent lot change-QC events, 82 analytes, and 7 instrument platforms. The significance of between-lot differences in the results for QC samples compared with those for patient samples was assessed by a modified 2-sample t test adjusted for heterogeneity of QC and patient sample measurement variances. RESULTS: Overall, 40.9% of reagent lot change-QC events had a significant difference (P < 0.05) between results for QC samples compared with results for patient samples between 2 reagent lots. For QC results with differences <1.0 SD interval (83.1% of total), 37.7% were significantly different from the changes observed for patient samples. For QC results with differences ≥1.0 SD interval (16.9% of total), 57.0% were significantly different from those for patient samples. CONCLUSIONS: Occurrence of noncommutable results for QC materials was frequent enough that the QC results could not be used to verify consistency of results for patient samples when changing lots of reagents.