Routine 2-Week Postoperative Radiographs After Geriatric Hip Fracture Fixation: Low Utility and High Cost.

BACKGROUND: Geriatric hip fractures are associated with a large financial burden on both patients and payors, yet minimal data exist regarding postoperative cost optimization and guidelines for delivering high-value care. We assessed the utility and cost of routine radiographs at the first postoperative visit (FPOV) after fixation of geriatric hip fractures. METHODS: We retrospectively evaluated patients with isolated geriatric hip fractures treated with internal fixation between January 2018 and September 2020. Medical records were reviewed to assess whether radiographs at the FPOV changed management. Direct costs of radiographs at the FPOV were estimated using Medicare Fee Schedule data. Indirect costs were estimated by assessing transportation costs. National costs were estimated by extrapolating institutional and Medicare data to the estimated 300,000 to 500,000 annual hip fractures in the United States. RESULTS: Two hundred forty-one patients were included. A majority had intertrochanteric fractures (80%), were injured because of a ground-level fall (94%), and received long intramedullary nails (73%). One patient (1/241, 0.41%) had their postoperative management changed by FPOV radiographs, and that patient had an acute reinjury before their FPOV. Patients discharged home (50/241, 21%) traveled mean 51.3 miles each way, and those discharged to another facility (191/241, 79%) traveled mean 24.1 miles each way. The national estimated direct cost of routine radiographs at the FPOV totaled $10.9 to $18.2 m annually. The national indirect costs are estimated to be $1.2 to $1.9 m annually for patients discharged home and $63.4 to $105.7 m annually for patients discharged to a facility. CONCLUSIONS: Routine radiographs at the FPOV after internal fixation of geriatric hip fractures may not change management and should only be obtained when specifically indicated. Elimination of routine radiographs and conduction of the FPOV virtually by telemedicine could result in national cost savings of estimated $75.5 to $125.8 m annually without compromising quality of care.

Riding the waves from epidemic to endemic: Viral mutations, immunological change and policy responses.

Nonpharmaceutical interventions (NPI) are an important tool for countering pandemics such as COVID-19. Some are cheap; others disrupt economic, educational, and social activity. The latter force governments to balance the health benefits of reduced infection and death against broader lockdown-induced societal costs. A literature has developed modeling how to optimally adjust lockdown intensity as an epidemic evolves. This paper extends that literature by augmenting the classic SIR model with additional states and flows capturing decay over time in vaccine-conferred immunity, the possibility that mutations create variants that erode immunity, and that protection against infection erodes faster than protecting against severe illness. As in past models, we find that small changes in parameter values can tip the optimal response between very different solutions, but the extensions considered here create new types of solutions. In some instances, it can be optimal to incur perpetual epidemic waves even if the uncontrolled infection prevalence would settle down to a stable intermediate level.

Relationship between the prosthesis scapular neck angle and clinical outcomes in reverse shoulder arthroplasty.

Background: Optimal glenosphere positioning in reverse shoulder arthroplasty (RSA) remains highly debated. We aimed to characterize the association between the prosthesis scapular neck angle (PSNA) and postoperative range of motion (ROM) and clinical outcome scores. Methods: A retrospective review of 284 RSAs using a single design with minimum 2-year follow-up was performed. Glenosphere tilt was measured postoperatively using PSNA. ROM and functional outcome scores were assessed preoperatively and at latest follow-up. The PSNA was dichotomized to inferior or superior groups (>90° vs ≤ 90°, respectively) and stratified into quartiles; ROM and outcome score measures were compared between groups controlling for inferior glenosphere overhang. Results: No range of PSNA was consistently associated with superior ROM, clinical outcome scores, or rates of complications including scapular notching. However, greater preoperative to postoperative improvement in active FE was found for superiorly (PSNA ≤ 90°) versus inferiorly tilted glenospheres (37° ± 33° vs 53° ± 35°, P = 0.005) and the greater improvement in active FE (57° ± 35°, P = 0.004) was further isolated to the first quartile (mean 85.1° ± 3.5°). Discussion: A lack of variation in clinical outcomes based on PSNA suggests negligible short-term (median follow-up 3.1 years) clinical significance when glenosphere tilt falls within the distribution of this cohort (mean 92.6° ± 6.2°).

The hammer and the jab: Are COVID-19 lockdowns and vaccinations complements or substitutes?

The COVID-19 pandemic has devastated lives and economies around the world. Initially a primary response was locking down parts of the economy to reduce social interactions and, hence, the virus' spread. After vaccines have been developed and produced in sufficient quantity, they can largely replace broad lock downs. This paper explores how lockdown policies should be varied during the year or so gap between when a vaccine is approved and when all who wish have been vaccinated. Are vaccines and lockdowns substitutes during that crucial time, in the sense that lockdowns should be reduced as vaccination rates rise? Or might they be complementary with the prospect of imminent vaccination increasing the value of stricter lockdowns, since hospitalization and death averted then may be permanently prevented, not just delayed? We investigate this question with a simple dynamic optimization model that captures both epidemiological and economic considerations. In this model, increasing the rate of vaccine deployment may increase or reduce the optimal total lockdown intensity and duration, depending on the values of other model parameters. That vaccines and lockdowns can act as either substitutes or complements even in a relatively simple model casts doubt on whether in more complicated models or the real world one should expect them to always be just one or the other. Within our model, for parameter values reflecting conditions in developed countries, the typical finding is to ease lockdown intensity gradually after substantial shares of the population have been vaccinated, but other strategies can be optimal for other parameter values. Reserving vaccines for those who have not yet been infected barely outperforms simpler strategies that ignore prior infection status. For certain parameter combinations, there are instances in which two quite different policies can perform equally well, and sometimes very small increases in vaccine capacity can tip the optimal solution to one that involves much longer and more intense lockdowns.

Periprosthetic humerus fractures after shoulder arthroplasty: an evaluation of available classification systems.

BACKGROUND: Periprosthetic proximal humerus fractures (PPHFs) are a detrimental complication of shoulder arthroplasty, yet their characterization and management have been poorly studied. We aimed to determine the intra- and interobserver reliability of 4 previously described PPHF classification systems to evaluate which classifications are the most consistent. METHODS: We retrospectively reviewed 32 patients (34 fractures) that were diagnosed with a PPHF between 1990 and 2017. Patient electronic medical records and research electronic data capture (REDCap) were used for data collection. Post-PPHF radiographs in multiple views for all 34 cases were organized into an encrypted, randomized Qualtrics survey. Four blinded fellowship-trained shoulder and elbow surgeons graded each fracture using previously reported classification systems by (1) Wright and Cofield (1995), (2) Campbell et al (1998), (3) Worland et al (1999), and (4) Groh et al (2008), along with selecting a preferred management strategy for each fracture. Grading was performed twice with at least 2 weeks between each randomized attempt. Intraobserver reliability was calculated as an unweighted Cohen kappa coefficient between attempt 1 and attempt 2 for each surgeon. Interobserver reliability and agreeability between surgeons' preferred management strategies were calculated for each classification system using Fleiss kappa coefficient. The kappa coefficients were interpreted using the Landis and Koch criteria. RESULTS: The average intraobserver kappa coefficient for each classification was as follows: Wright and Cofield = 0.703, Campbell = 0.527, Worland = 0.637, Groh = 0.699. The overall Fleiss kappa coefficient for interobserver reliability for each classification was as follows: Wright and Cofield = 0.583, Campbell = 0.488, Worland = 0.496, Groh = 0.483. Interobserver reliability was significantly greater with the Wright and Cofield classification. Using Landis and Koch criteria, all the classification systems assessed demonstrated only moderate interobserver agreement. Additionally, the mean interobserver agreeability kappa coefficient for preferred management strategy was 0.490, indicating only moderate interobserver agreement. CONCLUSION: There is only moderate interobserver reliability among the 4 PPHF classification systems and the preferred management strategy for the fractures assessed. Of the 4 PPHF classification systems, Wright and Cofield demonstrated the greatest mean intraobserver reliability and overall interobserver reliability. Our study highlights a need for the development of a PPHF classification system that can achieve high intra- and interobserver reliability and that can allow for a standardized treatment algorithm in the management of PPHFs.

Incidence of fatigue associated with immune checkpoint inhibitors in patients with cancer: a meta-analysis.

BACKGROUND: Fatigue is one of the most common adverse effects associated with cancer immunotherapy using checkpoint inhibitors (CPIs). Because treatment-related fatigue also frequently occurs in patients treated with non-immunological therapies, our study aimed to compare the incidence of fatigue in CPI-treated patients with that associated with non-immune therapies in randomised trials. METHODS: PubMed and ClinicalTrials.gov were searched for phase III studies using a CPI alone or in combination with chemotherapy or non-immunologic targeted therapy in the experimental arm and control arm using inactive therapies such as placebo or observation, chemotherapy, or non-immunologic targeted therapy. Adverse events listed in the full texts as well as those available from clinicaltrials.gov were reviewed for all identified studies. RESULTS: A total of 60 studies involving 41 435 patients were included in the analysis. All-grade fatigue was reported in 30.4% of patients [95% confidence interval (CI) 29.9% to 31.0%] in the immunotherapy arms of the analysed studies. Using anti-programmed cell death protein 1 agents as reference, the odds ratio (OR) for fatigue was significantly higher both for anti-cytotoxic T lymphocyte-associated antigen 4 agents (OR 1.46, 95% CI 1.04-2.04) and the combination of anti-cytotoxic T lymphocyte-associated antigen 4 and anti-programmed cell death protein agents (OR 1.43, 95% CI 1.12-1.83). Fatigue was significantly less likely to occur in patients treated with CPI compared with patients receiving chemotherapy (OR 0.79, 95% CI 0.73-0.85), but significantly was more common in patients receiving the combination of CPI/chemotherapy compared with patients receiving chemotherapy alone (OR 1.12, 95% CI 1.03-1.22). CONCLUSIONS: Although immunotherapy using CPIs was associated with treatment-related fatigue, the occurrence of all-grade fatigue was significantly higher in patients treated with chemotherapy compared with patients receiving CPIs. The risk of fatigue was higher for CPI/chemotherapy combinations than for chemotherapy alone. These results suggest that although the effects of CPIs and chemotherapy are additive, chemotherapy was the dominant cause of treatment-related fatigue in the analysed trials.

Effectiveness of Child-Focused Interventions for Externalizing Behavior: a Rapid Evidence Review.

Parent behavior management training (BMT) is well established as an effective, evidence-based treatment for children with externalizing behavior. Despite the wealth of data supporting BMT, many community providers use a variety of child-focused and non-directive interventions to target behavior problems. There is lack of clarity as to whether the evidence supporting child-focused externalizing treatments is sufficiently compelling to support offering these treatments rather than or in addition to BMT. This rapid evidence review compares the effectiveness of BMT with several common child-focused interventions for externalizing behavior including cognitive behavioral (CBT), social skill (SS), and play/dynamic (PT) approaches. PubMed, PsychINFO, and Web of Science were searched for English-language articles from year 2000 onwards for each intervention type. Inclusion criteria were child age (12 and under), presence of a child-focused behavioral treatment condition, and externalizing behavior as an outcome variable. A total of 30 studies met inclusion criteria and were coded (13 CBT, 10 SS, 7 PT). Results supported social skills interventions with accompanying BMT as effective in improving externalizing problems, with generally moderate effect sizes. Individual social skills interventions were promising but needing further evaluation compared to treatment as usual. CBT treatments with and without accompanying BMT showed moderate effects over waitlist but produced less consistently significant effects compared to more robust controls. Play therapy approaches showed inconsistent effects and require further evaluation. This review supports social skills plus BMT treatments as a child-focused intervention with probable efficacy for child externalizing problems. Implications for policy and community practice are discussed.

Testing a knowledge-based approach for inferring spatio-temporal characteristics of groundwater in the Australian State of Victoria.

Groundwater spatio-temporal characteristics are important information for groundwater development and management. However, such information is usually insufficient or even unavailable in many regions around the world due to insufficient or even lack of in-situ data such as from boreholes. Recently, a knowledge-based approach was proposed to infer 'where' and 'when' to find groundwater using Lake Victoria Basin (LVB) as an example for data-deficient regions. In this knowledge-based approach, groundwater model and inversion analysis of groundwater impact factors are used to infer groundwater storage potential and recharge timing. In the LVB's case, only 10 borehole data were used to test the spatio-temporal behaviours of groundwater, which are insufficient. In this contribution, therefore, using the Australian State of Victoria as an example, with over 15,000 boreholes data, the performance of the same knowledge-based approach is further tested in a well-controlled area. The results indicate that the knowledge-based approach is able to correctly infer regions with large groundwater storage potential suitable for extraction. The recharge timing of groundwater is also correctly indicated as the results show consistency with the borehole data. This provides further evidence of the reliability of the knowledge-based approach for inferring spatio-temporal characteristics of groundwater.

Recent Modifications of the Nuss Procedure: The Pursuit of Safety During the Minimally Invasive Repair of Pectus Excavatum.

OBJECTIVE: To review standardized Nuss correction of pectus excavatum and vacuum bell treatment over the last 10 years. SUMMARY OF BACKGROUND DATA: In 2010, we reported 21 years of the Nuss procedure in 1215 patients. METHODS: Over the last 10 years, 2008-2018, we evaluated 1885 pectus excavatum patients. Surgery was indicated for well-defined objective criteria. A consistent operation was performed by 8 surgeons in 1034 patients, median 15 years, (range 6-46); 996 were primary, and 38 redo operations. Surgical patients' mean computed tomography index was 5.46. Mitral valve prolapse was present in 5.4%, Marfan syndrome in 1.1% and scoliosis in 29%. Vacuum bell treatment was introduced for 218 patients who did not meet surgical criteria or were averse to surgery. RESULTS: At primary operation, 1 bar was placed in 49.8%; 2 bars, 49.4%; and 3 bars, 0.7%. There were no deaths. Cardiac perforation occurred in 1 patient who had undergone previous cardiac surgery. Paraplegia after epidural catheter occurred once. Reoperation for bar displacement occurred in 1.8%, hemothorax in 0.3%, and wound infection in 2.9%; 1.4% required surgical drainage. Allergy to stainless steel was identified in 13.7%. A good anatomic outcome was always achieved at bar removal. Recurrence requiring reoperation occurred in 3 primary surgical patients. Two patients developed carinate overcorrection requiring reoperation. Vacuum bell treatment produced better results in younger and less severe cases. CONCLUSIONS: A standardized Nuss procedure was performed by multiple surgeons in 1034 patients with good overall safety and results in primary repairs. Vacuum bell treatment is useful.

Inference of the spatio-temporal variability and storage potential of groundwater in data-deficient regions through groundwater models and inversion of impact factors on groundwater, as exemplified by the Lake Victoria Basin.

Groundwater is an important resource for supporting domestic water use for people's livelihoods and for maintaining ecosystems. Borehole observations provide the first-hand data that characterise the fluctuation, depth, and aquifer conditions of the groundwater. Unfortunately, such observations are not available or are insufficient for scientific use in many regions. Taking the Lake Victoria Basin (LVB) as an example of data-deficient regions, this study proposes a simple knowledge-based approach that uses the Global Land Data Assimilation System (GLDAS) Catchment Land Surface Model (CLSM) for the main data, with rainfall, hydrological, topographical and geological datasets as supports, by which to infer the spatio-temporal variability and storage potential of groundwater. The method is based on analysis and inversion of impact factors on groundwater, and the feasibility of such a method is proven by showing that the groundwater results from GLDAS CLSM can correctly indicate the seasonality, as well as the link to topographical and geological features. For example, both results from the water balance equation (WBE) and GLDAS CLSM indicate that there are two groundwater recharge seasons in the basin, e.g., March to May and September to November. Compared to the eastern side of the LVB, the western side has mountains blocking surface runoff, and thus, reasonably, has larger storage potential estimates in GLDAS CLSM. Due to the low degree of weathering of the basement rocks, it is expected that there is only small storage potential and variation of groundwater in the southeastern parts of the LVB. GLDAS CLSM also correctly reflects this behaviour. Additionally, the largest groundwater storage potential over the LVB is found in regions near the Kagera River and the western shoreline, since it associates with unconsolidated rocks and behaviours of large groundwater recharge from GLDAS CSLM during the wet year of 2006. The major limitation of this knowledge-based method is that the uncertainty in terms of magnitude on GLDAS CLSM groundwater changes cannot be assessed, in addition to the fact that the reliability of the results cannot be quantified in terms of specific numbers. Therefore, the results and interpretation of groundwater behaviours using such methods can only be a guide for 'where' and 'when' to find groundwater.

Halo vest immobilization - an institutional review of safety in acute cervical spine injury from 2013 to 2017.

Objective: Halo vest immobilization (HVI) remains an important treatment option for occipital-cervical injuries. It provides the surgeon with a safe and effective medical treatment options for challenging patients. The aim of this study was to evaluate the safety of HVI in these patients.Methods: This retrospective study identified adult patients treated with Halo vests immobilization (HVI) for acute cervical spine injury at our metropolitan level 1 trauma center from 2013 to 2017. This heterogenous cohort included 67 consecutive patients with acute cervical spine injury secondary to trauma or iatrogenic injury following surgical intervention with a mean age of 52 and a mean injury severity score (ISS) of 18. Forty-six percent of patients were treated with HVI as an adjunct therapy to surgical fixation (both short- and long-term immobilization), 45% of patients were treated with HVI as a primary medical treatment, and 9% of patients were treated with HVI instead of failed conservative medical treatment, such as cervical braces. Results: Pneumonia during the initial hospital stay was the most common complication (25%), followed by the correction of loose pins (22%) and pin site infections (18%). Overall, 51% of patients experienced at least one of these complications. There were significant associations between low initial GCS scores and the development of pneumonia (p < 0.001), high ISS scores and the development of pneumonia (p < 0.01), and duration of HVI and the occurrence of loose pins (p < 0.05). Four patients initially treated with HVI as primary medical treatment was converted to surgical treatment due to an intolerance of HVI or non-healing injuries.Conclusions:The HVI is a safe and effective treatment modality in a subset of patients with complex cervical junction and subaxial cervical spine pathology.

Trichomoniasis and adverse birth outcomes: a systematic review and meta-analysis.

BACKGROUND: Trichomoniasis commonly affects women of childbearing age and has been linked to several adverse birth outcomes. OBJECTIVE: To elucidate the association between trichomoniasis in pregnant women and adverse birth outcomes, including preterm delivery, prelabour rupture of membranes and low birthweight. SEARCH STRATEGY: MEDLINE, EMBASE and ClinicalTrials.gov were systematically searched in December 2020 without time or language restrictions. SELECTION CRITERIA: Original research studies were included if they assessed at least one of the specified adverse birth outcomes in pregnant women with laboratory-diagnosed trichomoniasis. DATA COLLECTION AND ANALYSIS: Estimates from included articles were either extracted or calculated and then pooled to produce a combined estimate of the association of trichomoniasis with each adverse birth outcome using the random effects model. Heterogeneity was assessed using the I2 statistic and Cochran's Q test. MAIN RESULTS: Literature search produced 1658 publications after removal of duplicates (n = 770), with five additional publications identified by hand search. After screening titles and abstracts for relevance, full text of 84 studies was reviewed and 19 met inclusion criteria for meta-analysis. Significant associations were found between trichomoniasis and preterm delivery (OR 1.27; 95% CI 1.08-1.50), prelabour rupture of membranes (OR 1.87; 95% CI 1.53-2.29) and low birthweight (OR 2.12; 95% CI 1.15-3.91). CONCLUSIONS: Trichomoniasis in pregnant women is associated with preterm delivery, prelabour rupture of membranes and low birthweight. Rigorous studies are needed to determine the impact of universal trichomoniasis screening and treatment during pregnancy on reducing perinatal morbidity. TWEETABLE ABSTRACT: This systematic review and meta-analysis found that in the setting of pregnancy, trichomoniasis is significantly associated with multiple adverse birth outcomes, including preterm delivery, low birthweight, and prelabour rupture of membranes.

Scanning Compton X-ray microscopy.

X-ray microscopy offers the opportunity to image biological and radiosensitive materials without special sample preparations, bridging optical and electron microscopy capabilities. However, the performance of such microscopes, when imaging radiosensitive samples, is not limited by their intrinsic resolution, but by the radiation damage induced on such samples. Here, we demonstrate a novel, to the best of our knowledge, radio-efficient microscope, scanning Compton X-ray microscopy (SCXM), which uses coherently and incoherently (Compton) scattered photons to minimize the deposited energy per unit of mass for a given imaging signal. We implemented SCXM, using lenses capable of efficiently focusing 60 keV X-ray photons into the sub-micrometer scale, and probe its radio-efficient capabilities. SCXM, when implemented in high-energy diffraction-limited storage rings, e.g., European Synchrotron Radiation Facility Extremely Brilliant Source and PETRA IV, will open the opportunity to explore the nanoscale of unstained, unsectioned, and undamaged radiosensitive materials.

Vitamin E analogs limit in vitro oxidant damage to bovine mammary endothelial cells.

Diseases that occur during the transition period are exacerbated when cows are unable to cope with an increased pro-oxidant load that results in oxidative stress. Dairy cattle are routinely supplemented with the vitamin E analog α-tocopherol to mitigate the severity of oxidative stress. Nonetheless, oxidative stress remains a disease predisposing condition for many dairy cattle. A better method of optimizing the antioxidant functions of vitamin E is needed. α-Tocopherol is only 1 of 8 analogs of vitamin E, all of which have varying antioxidant properties in other mammals, albeit a shorter physiological half-life compared with α-tocopherol. A primary bovine mammary endothelial cell oxidant challenge model was used to determine functions of certain vitamin E analogs. The aim of this study was to determine if other analogs, namely γ-tocopherol or γ-tocotrienol, have antioxidative functions in bovine cells and if these functions may protect cellular viability and endothelial function from oxidant damage. Physiological (10 µM) and supraphysiological (50 µM) concentrations of γ-tocopherol and γ-tocotrienol had a greater capacity to reduce accumulated reactive oxygen species derived from a nitric oxide donating pro-oxidant antagonist, when compared with α-tocopherol, after 30 min to 6 h of treatment. Further, γ-tocotrienol (10 µM) decreased cell cytotoxicity to a greater amount than other analogs at like concentrations, whereas γ-tocopherol (10 µM) reduced lipid peroxidation and apoptosis more effectively than other analogs. Last, α-tocopherol (5 and 10 µM) and γ-tocopherol (5 and 10 µM) significantly slowed pro-oxidant induced loss of endothelial cell barrier integrity over a 48-h period using an electrical cell-substrate impedance sensing system. Concerningly, γ-tocotrienol drastically reduced the endothelial barrier integrity at only 5 µM despite no apparent effect on cellular viability at like concentrations. γ-Tocotrienol, however, was also the only analog to show significant cytotoxicity and reductions in viability at supraphysiological doses (25 and 50 µM). Our results suggest that γ-tocopherol has antioxidant activities that reduces cellular damage and loss of function due to oxidant challenge as effectively as α-tocopherol. These data set the foundation for further investigation into the antioxidant properties of vitamin E analogs in other bovine cells types or whole animal models.

Insight into the current practice of ototoxicity monitoring during cisplatin therapy.

BACKGROUND: The aim of this study is to evaluate the current state of ototoxicity monitoring for patients receiving cisplatin chemotherapy in an academic medical center with particular attention to how closely monitoring adheres to national ototoxicity guidelines. METHODS: Case series including retrospective medical records review of patients (age > 18) treated with cisplatin at University of California Davis Medical Center between January 2014 and August 2017. Patient and ototoxicity related variables were analyzed. Patients that underwent a transfer of care during treatment and with less than 3 months of follow-up were excluded. RESULTS: Three hundred seventy-nine patients met study criteria, of which 104 (27.4%) had a prior history of hearing loss. Prior to treatment, 196 (51.7%) patients were counseled regarding the ototoxic nature of cisplatin and 92 (24.3%) patients had a pretreatment audiogram. During treatment, 91 (24%) patients had documented otologic complaints. Only 17 patients (4.5%) patients had an audiogram ordered during their cisplatin treatment period. 130 (34.3%) patients had otologic complaints following cisplatin treatment. Audiograms were ordered for 20 (7.8%), 13 (5.1%), and 16 (6.2%) patients at 1-month, 3-month, and 6-month follow-ups, respectively. No patients in the study cohort received baseline, treatment, and post-treatment audiograms as recommended by national ototoxicity monitoring protocols. Patients with Head and Neck Cancer (HNC) represented the largest subgroup that received cisplatin (n = 122, 32.2%) and demonstrated higher rates of ototoxicity counseling (n = 103, 84.4%) and pretreatment audiograms (n = 70, 57.4%) compared to the non HNC group (n = 36, 36.2%, P < 0.0001 and n = 22, 8.5%, P < 0.0001). CONCLUSIONS: There is poor adherence to national ototoxicity monitoring guidelines at a large academic medical center. This is a missed opportunity for intervention and aural rehabilitation. Improved education and collaboration between otolaryngology, audiology, and medical oncology is needed to develop and promote an effective ototoxicity-monitoring program.

Selective use of sternal elevation before substernal dissection in more than 2000 Nuss repairs at a single institution.

BACKGROUND/PURPOSE: Evaluate the safety of sternal elevation (SE) used selectively before creating the substernal tunnel during the Nuss procedure. METHODS: An IRB-approved (01-05-EX-0175-HOSP), single institution, retrospective review was performed (1/1/1997-11/20/2017). Primary and secondary Nuss repairs (i.e., previous Nuss, Ravitch, thoracotomy, or sternotomy) are included. SE use, cardiac injuries, and pectus bar infections are reported. Chi square and Fisher's exact test (FE) were used (critical p < .05). RESULTS: 2037 patients [(80% male; mean age 15.2 years (SD = 4.4, range 3-46); mean Haller index (HI) 5.3 (SD = 5.7, range 1.73-201)] underwent Nuss repair. SE was used before creating the substernal tunnel in 171 (8.4%): 160 (8.2%) of 1949 primary and 11 (12.5%) of 88 secondary repairs. SE use increased significantly [χ2(2) = 118.93; p < .001] over time and with increasing HI [χ2(3) = 59.9; p < .001]. No cardiac injuries occurred in primary repairs but two occurred in patients with previous sternotomy. Infection rates were not different with (2.9%) or without SE (1.8%) [χ2(1) =1.14; p = .285] and not higher with off-label VB (1.5%) versus other SE techniques (3.8%) [FE, p = .65)]. CONCLUSION: Selective use of sternal elevation before substernal dissection during the Nuss procedure is safe but may not prevent cardiac injuries in patients with previous sternotomy. Infection rates were not increased with SE. TYPE OF STUDY: Retrospective review. LEVEL OF EVIDENCE: IV.

Study of duplicated galU genes in Rhodococcus jostii and a putative new metabolic node for glucosamine-1P in rhodococci.

BACKGOUND: Studying enzymes that determine glucose-1P fate in carbohydrate metabolism is important to better understand microorganisms as biotechnological tools. One example ripe for discovery is the UDP-glucose pyrophosphorylase enzyme from Rhodococcus spp. In the R. jostii genome, this gene is duplicated, whereas R. fascians contains only one copy. METHODS: We report the molecular cloning of galU genes from R. jostii and R. fascians to produce recombinant proteins RjoGalU1, RjoGalU2, and RfaGalU. Substrate saturation curves were conducted, kinetic parameters were obtained and the catalytic efficiency (kcat/Km) was used to analyze enzyme promiscuity. We also investigated the response of R. jostii GlmU pyrophosphorylase activity with different sugar-1Ps, which may compete for substrates with RjoGalU2. RESULTS: All enzymes were active as pyrophosphorylases and exhibited substrate promiscuity toward sugar-1Ps. Remarkably, RjoGalU2 exhibited one order of magnitude higher activity with glucosamine-1P than glucose-1P, the canonical substrate. Glucosamine-1P activity was also significant in RfaGalU. The efficient use of the phospho-amino-sugar suggests the feasibility of the reaction to occur in vivo. Also, RjoGalU2 and RfaGalU represent enzymatic tools for the production of (amino)glucosyl precursors for the putative synthesis of novel molecules. CONCLUSIONS: Results support the hypothesis that partitioning of glucosamine-1P includes an uncharacterized metabolic node in Rhodococcus spp., which could be important for producing diverse alternatives for carbohydrate metabolism in biotechnological applications. GENERAL SIGNIFICANCE: Results presented here provide a model to study evolutionary enzyme promiscuity, which could be used as a tool to expand an organism's metabolic repertoire by incorporating non-canonical substrates into novel metabolic pathways.

Impacts of extreme climate on Australia's green cover (2003-2018): A MODIS and mascon probe.

Australia as a continent represents a semi-arid environment that is generally water-limited. Changes in rainfall pattern will inevitably occur due to rising temperatures caused by climate change, which has a direct impact on the distribution of Australia's vegetation (green cover). As variability in rainfall continues to increase, i.e., in frequency and/or magnitude, due to climate change, extreme climate events such as droughts are predicted to become more pervasive and severe that will have an adverse effect on vegetation. This study investigates the effects of extreme climate on Australia's green cover during 2003-2018 for the end of rainy seasons of April and October in the northern and southern parts, respectively, to (i) determine the state of vegetation and its changes, (ii) identify "hotspots", i.e., regions that constantly experienced statistically significant decrease in NDVI, and (iii), relate changes in the identified hotspots to GRACE-hydrological changes. These are achieved through the exploitation of the statistical tools of Principal Component Analysis (PCA) and Mann-Kendel Test on Gravity Recovery and Climate Experiment (GRACE) hydrological products on the one hand, and the utilization of Australia's rainfall product and Moderate Resolution Imaging Spectroradiometer Normalized Difference Vegetation Index (MODIS-NDVI) used here with its native spatial resolution of 0.002413∘ × 0.002413∘ on the other hand. Differences between 3-year intervals from 2003 to 2018 for both April and October datasets are used to quantify vegetation variations. Through area change analysis, the vegetation differences (2003-2018) indicate that April exhibited larger increase (13.77% of total vegetation area) than decrease (7.83%) compared to October, which experienced slightly larger decrease (9.41%) than increase (8.71%). South Australia and Western Australia emerge as "hotspots" in which vegetation statistically decreased in October, with no noticeable change in April. GRACE-based hydrological changes in both hotspots reflect a decreasing trend (2003-2009) and increasing trend (2009-2012) that peaks in 2011, which then transitions towards a gradually decreasing trend after 2012. Australia-wide climate variability (ENSO and IOD) influenced vegetation variations during the data period 2003 to 2018.

Invited review: Cytochrome P450 enzyme involvement in health and inflammatory-based diseases of dairy cattle.

Dairy cattle are at the greatest risk of developing diseases around the time of calving because of compromised immune responses and the occurrence of oxidative stress. Both the development of compromised immunity and oxidative stress are influenced directly or indirectly by the metabolism of polyunsaturated fatty acids (PUFA) and fat-soluble vitamins. The cytochrome P450 (CYP450) family of enzymes is central to the metabolism of both classes of these compounds, but to date, the importance of CYP450 in the health of dairy cattle is underappreciated. As certain CYP450 isoforms metabolize both PUFA and fat-soluble vitamins, potential interactions may occur between PUFA and fat-soluble vitamins that are largely unexplored. For example, one CYP450 that generates anti-inflammatory oxylipids from arachidonic acid additionally contributes to the activation of vitamin D. Other potential substrate interactions between PUFA and vitamins A and E may exist as well. The intersection of PUFA and fat-soluble vitamin metabolism by CYP450 suggest that this enzyme system could provide an understanding of how immune function and oxidant status interconnect, resulting in increased postpartum disease occurrence. This review will detail the known contributions of bovine CYP450 to the regulation of oxylipids with a focus on enzymes that may also be involved in the metabolism of fat-soluble vitamins A, D, and E that contribute to antioxidant defenses. Although the activity of specific CYP450 is generally conserved among mammals, important differences exist in cattle, such as the isoforms primarily responsible for activation of vitamin D that makes their specific study in cattle of great importance. Additionally, a CYP450-driven inflammatory positive feedback loop is proposed, which may contribute to the dysfunctional inflammatory responses commonly found during the transition period. Establishing the individual enzyme isoform contributions to oxylipid biosynthesis and the regulation of vitamins A, D, and E may reveal how the CYP450 family of enzymes can affect inflammatory responses during times of increased susceptibility to disease. Determining the potential effect of each CYP450 on disease susceptibility or pathogenesis may allow for the targeted manipulation of the CYP450 pathways to influence specific immune responses and antioxidant defenses during times of increased risk for health disorders.