Superinfections of the Spine: A Single-Institution Experience.

Background/Objectives: A superinfection occurs when a new, secondary organism colonizes an existing infection. Spine infections are associated with high patient morbidity and sometimes require multiple irrigations and debridements (I&Ds). When multiple I&Ds are required, the risk of complications increases. The purpose of this study was to report our experience with spine superinfections and determine which patients are typically affected. Methods: A retrospective case series of spine superinfections and a retrospective case-control analysis were conducted. Data were collected manually from electronic medical records. Spine I&Ds were identified. Groups were created for patients who had multiple I&Ds for (1) a recurrence of the same causative organism or (2) a superinfection with a novel organism. Preoperative demographic, clinical, and microbiologic data were compared between these two outcomes. A case series of superinfections with descriptive data was constructed. Lastly, two illustrative cases were provided in a narrative format. Results: A total of 92 patients were included in this analysis. Superinfections occurred after 6 out of the 92 (7%) initial I&Ds and were responsible for 6 out of the 24 (25%) repeat I&Ds. The preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) of the patients with a superinfection were significantly lower than those in the control group (p = 0.022 and p = 0.032). Otherwise, the observed differences in the preoperative variables were not statistically different. In the six cases of superinfection, the presence of high-risk comorbidities, a history of substance abuse, or a lack of social support were commonly observed. The superinfecting organisms included Candida, Pseudomonas, Serratia, Klebsiella, Enterobacter, and Staphylococcus species. Conclusions: Superinfections are a devastating complication requiring reoperation after initial spine I&D. Awareness of the possibility of superinfection and common patient archetypes can be helpful for clinicians and care teams. Future work is needed to examine how to identify, help predict, and prevent spine superinfections.

Total Hip Arthroplasty in Human Immunodeficiency Virus Positive Patients: A Systematic Review of Outcomes.

BACKGROUND: Total hip arthroplasty (THA) has become a common intervention for human immunodeficiency virus (HIV)-positive patients who have osteonecrosis of the femoral head. This paper provides a systematic review to assess survivorships, patient-reported outcomes (PROMs), infection rates, other complications, and immune competence for patients who had THAs who did and did not have HIV. METHODS: A comprehensive and systematic review of published studies investigating the outcomes of THA in HIV-positive patients (osteonecrosis and non-osteonecrosis patients) was performed adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 10 studies with 9,534 HIV-positive patients fulfilled the inclusion and exclusion criteria. Manuscript quality was assessed on 2 scales: the Coleman Methodology Score and the level of evidence derived from Center for Evidence-Based Medicine criteria. Data were extracted from studies in the 5 key areas of interest: survivorships, PROMs, infection rates, complications, and clusters of differentiation-4 (CD4+) counts and viral loads. RESULTS: Implant survivorship was between 95% and 100%. Postoperative Harris Hip Scores were significantly improved from preoperative values in HIV-positive patients. Postoperative PROMs and infections did not appear to be different between HIV-positive and HIV-negative patients. Many of the cohort studies demonstrate comparable complication rates to matched controls. Where described (7 reports), mean CD4+ counts ranged from 425 to 646 cells/mm3, with low viral loads (3 reports) and variations not found to influence outcomes. CONCLUSIONS: THA is an effective treatment for HIV-positive patients, many of whom suffer from osteonecrosis of the femoral head. The results demonstrate excellent implant survivorship, improved quality of life, and a low risk of infections and complications.

Reducing kidney uptake of radiolabelled exendin-4 using variants of the renally cleavable linker MVK.

BACKGROUND: Peptidic radiotracers are preferentially excreted through the kidneys, which often results in high persistent renal retention of radioactivity, limiting or even preventing therapeutic clinical translation of these radiotracers. Exendin-4, which targets the glucagon-like-peptide 1 receptor (GLP-1R) overexpressed in insulinomas and in congenital hyperinsulinism, is an example thereof. The use of the tripeptide MVK, which is readily cleaved between methionine and valine by neprilysin at the renal brush border membrane, already showed promising results in reducing kidney uptake as reported in the literature. Based on our previous findings we were interested how linker variants with multiple copies of the MV-motive influence renal washout of radiolabelled exendin-4. RESULTS: Three exendin-4 derivatives, carrying either one MVK, a MV-MVK or a MVK-MVK linker were synthesized and compared to a reference compound lacking a cleavable linker. In vivo results of a biodistribution in GLP-1R overexpressing tumour bearing mice at 24 h post-injection demonstrated a significant reduction (at least 57%) of renal retention of all 111In-labeled exendin-4 compounds equipped with a cleavable linker compared to the reference compound. While the insertion of the single linker MVK led to a reduction in kidney uptake of 70%, the dual approach with the linker MV-MVK slightly, but not significantly enhanced this effect, with 77% reduction in kidney uptake compared to the reference. In vitro IC50 and cell uptake studies were conducted and demonstrated that though the cleavable linkers negatively influenced the affinity towards the GLP-1R, cell uptake remained largely unaffected, except for the MV-MVK cleavable linker conjugate, which displayed lower cell uptake than the other compounds. Importantly, the tumour uptake in the biodistribution study was not significantly affected with 2.9, 2.5, 3.2 and 1.5% iA/g for radiolabelled Ex4, MVK-Ex4, MV-MVK-Ex4 and MVK-MVK-Ex4, respectively. CONCLUSION: Cleavable linkers are highly efficient in reducing the radioactivity burden in the kidney. Though the dual linker approach using the instillation of MV-MVK or MVK-MVK between exendin-4 and the radiometal chelator did not significantly outperform the single cleavable linker MVK, further structural optimization or the combination of different cleavable linkers could be a stepping stone in reducing radiation-induced nephrotoxicity.

Demographics and surgery-related complications lead to 30-day readmission rates among knee arthroscopic procedures.

PURPOSE: The study objectives were (1) to evaluate risk factors related to 30-day hospital readmissions after arthroscopic knee surgeries and (2) to determine the complications that may arise from surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database data from 2012 to 2017 were researched. Patients were identified using Current Procedural Terminology codes for knee arthroscopic procedures. Ordinal logistic fit regression and decision tree analysis were used to examine study objectives. RESULTS: There were 83,083 knee arthroscopic procedures between 2012 and 2017 obtained from the National Surgical Quality Improvement Program database. The overall readmission rate was 0.87%. The complication rates were highest for synovectomy and cartilage procedures, 1.6% and 1.3% respectively. A majority of readmissions were related to the procedure (71.1%) with wound complications being the primary reason (28.2%) followed by pulmonary embolism and deep vein thrombosis, 12.7% and 10.6%, respectively. Gender and body mass index were not significant factors and age over 65 years was an independent risk factor. Wound infection, deep vein thrombosis, and pulmonary embolism were the most prevalent complications. CONCLUSION: Healthcare professionals have a unique opportunity to modify treatment plans based on patient risk factors. For patients who are at higher risk of inferior surgical outcomes, clinicians should carefully weigh risk factors when considering surgical and non-surgical approaches. LEVEL OF EVIDENCE: III.

Recommendations for fluoride limits in drinking water based on estimated daily fluoride intake in the Upper East Region, Ghana.

Both dental and skeletal fluorosis caused by high fluoride intake are serious public health concerns around the world. Fluorosis is particularly pronounced in developing countries where elevated concentrations of naturally occurring fluoride are present in the drinking water, which is the primary route of exposure. The World Health Organization recommended limit of fluoride in drinking water is 1.5 mg F(-) L(-1), which is also the upper limit for fluoride in drinking water for several other countries such as Canada, China, India, Australia, and the European Union. In the United States the enforceable limit is much higher at 4 mg F(-) L(-1), which is intended to prevent severe skeletal fluorosis but does not protect against dental fluorosis. Many countries, including the United States, also have notably lower unenforced recommended limits to protect against dental fluorosis. One consideration in determining the optimum fluoride concentration in drinking water is daily water intake, which can be high in hot climates such as in northern Ghana. The results of this study show that average water intake is about two times higher in Ghana than in more temperate climates and, as a result, the fluoride intake is higher. The results also indicate that to protect the Ghanaian population against dental fluorosis, the maximum concentration of fluoride in drinking water for children under 6-8 years should be 0.6 mg F(-) L(-1) (and lower in the first two years of life), and the limit for older children and adults should be 1.0 mg F(-) L(-1). However, when considering that water treatment is not cost-free, the most widely recommended limit of 1.5 mg F(-) L(-1) - which is currently the limit in Ghana--may be appropriate for older children and adults since they are not vulnerable to dental fluorosis once the tooth enamel is formed.

Understanding handpump sustainability: Determinants of rural water source functionality in the Greater Afram Plains region of Ghana.

Safe drinking water is critical to human health and development. In rural sub-Saharan Africa, most improved water sources are boreholes with handpumps; studies suggest that up to one third of these handpumps are nonfunctional at any given time. This work presents findings from a secondary analysis of cross-sectional data from 1509 water sources in 570 communities in the rural Greater Afram Plains (GAP) region of Ghana; one of the largest studies of its kind. 79.4% of enumerated water sources were functional when visited; in multivariable regressions, functionality depended on source age, management, tariff collection, the number of other sources in the community, and the district. A Bayesian network (BN) model developed using the same data set found strong dependencies of functionality on implementer, pump type, management, and the availability of tools, with synergistic effects from management determinants on functionality, increasing the likelihood of a source being functional from a baseline of 72% to more than 97% with optimal management and available tools. We suggest that functionality may be a dynamic equilibrium between regular breakdowns and repairs, with management a key determinant of repair rate. Management variables may interact synergistically in ways better captured by BN analysis than by logistic regressions. These qualitative findings may prove generalizable beyond the study area, and may offer new approaches to understanding and increasing handpump functionality and safe water access.

The range fraction: an applied method to characterize regional groundwater responses to climate inputs.

An important component of ongoing water-resource investigations in the eastern Great Basin, USA, has been to ascertain the impact of future predicted climate change on groundwater availability. As a first step in that analysis, it was hypothesized that potentiometric fluctuations at certain wells would reflect annual-scale precipitation variation. Potentiometric behavior at a well depends on local hydrologic conditions, well construction, and human activities, in addition to natural recharge and regional water levels. Moreover, measurement data are limited for many wells. After preliminarily screening, a large body of well and climate station data, short-term potentiometric responses to annual-scale climate inputs, were identified at 18 wells using a simple visualization methodology developed during the study. For water levels displaying multi-annual trends, the signals were measured as deviations from a linear trendline. Groundwater responses lagged precipitation signals by less than 1 year to as much as 3 years, with most wells showing at most a 1- to 2-year delay. Response amplitude was variable and strongly depended on the hydrologic setting of each well.