Identifying E3 Ligase Substrates With Quantitative Degradation Proteomics.

Controlled protein degradation by the ubiquitin-proteasome pathway is critical for almost all cellular processes. E3 ubiquitin ligases are responsible for targeting proteins for ubiquitylation and subsequent proteasomal degradation with spatial and temporal precision. While studies have revealed various E3-substrate pairs involved in distinct biological processes, the complete substrate profiles of individual E3 ligases are largely unknown. Here we report a new approach to identify substrates of an E3 ligase for proteasomal degradation using unnatural amino acid incorporation pulse-chase proteomics (degradomics). Applying this approach, we determine the steady-state substrates of the C-terminal to LisH (CTLH) E3 ligase, a multi-component complex with poorly defined substrates. By comparing the proteome degradation profiles of active and inactive CTLH-expressing cells, we successfully identify previously known and new potential substrates of CTLH ligase. Altogether, degradomics can comprehensively identify degradation substrates of an E3 ligase, which can be adapted for other E3 ligases in various cellular contexts.

Impact of a Fast-track Esophagectomy Protocol on Esophageal Cancer Patient Outcomes and Hospital Charges.

OBJECTIVE: To evaluate the effects of a fast-track esophagectomy protocol (FTEP) on esophageal cancer patients' safety, length of hospital stay (LOS), and hospital charges. BACKGROUND: FTEP involved transferring patients to the telemetry unit instead of the surgical intensive care unit (SICU) after esophagectomy. METHODS: We retrospectively reviewed 708 consecutive patients who underwent esophagectomy for primary esophageal cancer during the 4 years before (group A; 322 patients) or 4 years after (group B; 386 patients) the institution of an FTEP. Postoperative morbidity and mortality, LOS, and hospital charges were reviewed. RESULTS: Compared with group A, group B had significantly shorter median LOS (12 days vs 8 days; P < 0.001); lower mean numbers of SICU days (4.5 days vs 1.2 days; P < 0.001) and telemetry days (12.7 days vs 9.7 days; P < 0.001); and lower rates of atrial arrhythmia (27% vs 19%; P = 0.013) and pulmonary complications (27% vs 20%; P = 0.016). Multivariable analysis revealed FTEP to be associated with shorter LOS (P < 0.001) even after adjustment for predictors like tumor histology and location. FTEP was also associated with a lower rate of pulmonary complications (odds ratio = 0.655; 95% confidence interval = 0.456, 0.942; P = 0.022). In addition, the median hospital charges associated with primary admission and readmission within 90 days for group B ($65,649) were lower than that for group A ($79,117; P < 0.001). CONCLUSIONS: These findings suggest that an FTEP reduces patients' LOS, perioperative morbidity, and hospital charges.

Fannyhessea vaginae causing bacteraemia and vertebral osteomyelitis: first report of invasive disease in a male.

Introduction.Fannyhessea vaginae (formerly Atopobium vaginae) is an anaerobic organism commonly associated with female genital flora, with rare cases of invasive disease reported in females. Case report. We discuss the case of an 81-year-old male who presented with an acute history of back pain and signs of urinary tract infection in the context of intermittent self-urinary catheterisation. Multiple blood cultures grew Fannyhessea vaginae with a later finding of lumbar vertebral osteomyelitis as the cause of back pain. Treatment was commenced with ampicillin, later switched to ceftriaxone, with improvement of acute signs of infection. Conclusion. Gram-positive anaerobic organisms including Fannyhessea vaginae are possibly under-recognised causes of urinary tract particularly in older males. These bacteria may prove challenging to grow in standard protocols for urine culture; anaerobic or extended incubation could be considered particularly in complicated cases of urinary tract infection without an identifiable pathogen.

Mental Health and Dysphonia: Which Comes First, and Does That Change Care Utilization?

OBJECTIVES: Voice patients with voice disorders have a high prevalence of distress and mental health (MH) comorbidities, but it is unknown to what extent distress precedes or follows voice disorder diagnoses. Objectives were to compare 1) proportions of voice patients with MH diagnoses who received MH diagnoses first versus voice-related diagnoses first, 2) voice-related diagnoses and care utilization, and 3) time to specialty evaluation in each group. METHODS: Patients with voice and MH diagnoses were identified using International Classification of Diseases, Ninth and Tenth Revisions codes in a large health system data repository from January 2005 through July 2017. Sociodemographics, comorbidities, MH- and voice-related diagnoses, and voice-related care utilization were analyzed using descriptive statistics and multivariable regression modeling. RESULTS: Among the 11,419 patients with both voice and MH diagnoses, 63% (n = 7,251) received MH diagnoses prior to voice diagnoses, compared with 37% with a voice diagnosis first (P < 0.0001). The latter group received more specific voice-related diagnoses (e.g., laryngeal cancer [odds ratio (OR) 4.27], benign laryngeal neoplasm [OR 1.60]), and were more likely to ever see an otolaryngologist than those receiving MH diagnoses first (P < 0.0001). CONCLUSION: Most patients with voice and MH diagnoses received a MH diagnosis first. Patients who receive MH diagnoses first appeared to have different voice-related healthcare compared to those who received voice diagnoses first. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1243-1248, 2020.

Association of voice and mental health diagnoses with differences in voice-related care utilization.

OBJECTIVE: To compare healthcare utilization in voice patients with versus without mental health (MH) diagnoses STUDY DESIGN: Retrospective study using electronic medical records from large regional healthcare system. METHODS: We examined data on sociodemographic characteristics, comorbidities, voice-related diagnoses, and patterns of healthcare utilization (including medication use, tests and procedures, and outpatient visits). The study period spanned January 2005 through June 2017. RESULTS: A total of 24,672 patients had at least one voice-related diagnosis. Of these, 11,483 (47%) also had at least one MH diagnosis compared to 14% in the overall repository (P < 0.0001). The most common voice-related diagnoses were nonspecific dysphonia (80%), acute laryngitis (30%), and vocal fold paresis/paralysis (7%). The 11,483 patients with both voice-related and MH diagnoses were more likely to have acute laryngitis and/or nonspecific dysphonia; less likely to have laryngeal cancer and/or paresis/paralysis; and more likely to have seen a primary care provider, to have received medications, and to have undergone radiology studies. In contrast, the 13,189 patients with only voice-related diagnoses had more overall voice-related visits, were more likely to have seen an otolaryngologist, and were more likely to have undergone a voice evaluation with a speech language pathologist. CONCLUSION: Voice patients with MH diagnoses were less likely to see otolaryngology and more likely to have radiology studies than voice patients without MH diagnoses. Further study is warranted to characterize temporal sequences of care in this group of patients and determine whether these differences are attributable to referral patterns from primary care. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1496-1502, 2020.

Hearing outcomes in children with cleft palate and referred newborn hearing screen.

OBJECTIVES/HYPOTHESIS: To determine the prevalence of long-term hearing loss in patients with cleft palate who fail their universal newborn hearing screen. STUDY DESIGN: The study is a retrospective chart review from a tertiary pediatric center and tertiary children's hospital. METHODS: Newborns with cleft palate born between January 2002 and July 2012 were identified from a pediatric otolaryngology practice database. This cohort was then reduced to include only those patients who referred their universal newborn hearing screen. Postpressure equalization tube audiology results, follow-up audiology results, type of cleft, and comorbid conditions were collected for each patient who was both born with a cleft palate and referred their universal newborn hearing screen. RESULTS: A total of 317 newborns presented to the pediatric otolaryngology practice for cleft palate, with 89 (28%) having documented referred universal newborn hearing screen. At the time of data collection, 67 (75%) of 89 had normal hearing results, whereas 22 (25%) of 89 did not yet have normal hearing results. Fourteen patients had permanent hearing loss, and all 14 had a comorbid condition. Type of cleft and presence of a comorbid condition were correlated to hearing outcomes. CONCLUSIONS: Newborns with cleft palate who refer their universal newborn hearing screen could postpone diagnostic hearing testing until after placement of pressure equalization tubes, unless there is a clue to permanent hearing loss such as a comorbid condition.

Improving cancer care through public reporting of meaningful quality measures.

Historically, quality measures for cancer have followed a different route than overall quality measures in the health care system. Many specialized cancer treatment centers were exempt from standard reporting on quality measures because of the complexity of cancer. Additionally, it has been difficult to create meaningful quality measures for cancer because the disease can strike so many different organs; is discovered at and progresses through different stages; and is treated using different modalities, such as surgery, radiation, and chemotherapy. Over the past decade the National Quality Forum, a nonprofit organization dedicated to bettering the quality of US health care, has endorsed measures of quality for cancer providers and patients. The Affordable Care Act of 2010, which has sections specific to cancer reporting, will also further the development and public reporting of cancer quality measures-important steps in improving the delivery of cancer care.

A tale of 2 hospitals: a staggered cohort study of targeted interventions to improve compliance with antibiotic prophylaxis guidelines.

BACKGROUND: The purpose of this prospective study was to determine the effectiveness of targeted interventions to improve compliance with antibiotic prophylaxis guidelines (timing, spectrum, and discontinuation) at 2 university-affiliated hospitals. METHODS: Based on barriers identified previously, hospital-specific interventions were developed such as educational conferences, standardized forms, an extended time-out, and feedback. Guideline compliance and surgical site infection (SSI) data were recorded on all patients who underwent elective laparotomies for colorectal procedures, vascular operations, and hysterectomies during four 6-month study periods. Prestudy data from July to December 2006 served as a baseline. One year later, a prospective cohort study was performed. The interventions were introduced to the 2 hospitals in a staggered fashion with 2-month implementation periods before reassessing compliance during the 6-month study periods. General linear modeling was performed (P < .05 significant). RESULTS: Compliance with all 3 guidelines combined improved during the year preceding the study, after attention only, at both hospitals. Hospital-specific differences were found in the effectiveness of the intervention package on individual guidelines. Hospital 2 but not 1 improved in timing after the interventions; both hospitals improved in spectrum, and neither hospital improved in discontinuation. Overall compliance with all 3 antibiotic prophylactic measures was greater at hospital 1, but hospital 2 had lower SSI rates. CONCLUSION: Simply increasing attention to a quality problem can result in a significant and sustained improvement. Quality improvement interventions should be evaluated rigorously for effectiveness given hospital-specific differences in effectiveness and for correlation of guideline compliance with outcome.