How are Oral Antibiotics Being Used in Total Joint Arthroplasty? A Review of the Literature.

While the role and benefit of perioperative intravenous (IV) antibiotics in patients undergoing total joint arthroplasty (TJA) is well-established, oral antibiotic use in TJA remains a controversial topic with wide variations in practice patterns. With this review, we aimed to better educate the orthopedic surgeon on when and how oral antibiotics may be used most effectively in TJA patients, and to identify gaps in the literature that could be clarified with targeted research. Extended oral antibiotic prophylaxis (EOAP) use in high-risk primary, aseptic revision, and exchange TJA for infection may be useful in decreasing periprosthetic joint infection (PJI) rates. When prescribing oral antibiotics either as EOAP or for draining wounds, patient factors, type of surgery, and type of infectious organisms should be considered in order to optimally prevent and treat PJI. It is important to maintain antibiotic stewardship by administering the proper duration, dose, and type of antibiotics and by consulting infectious disease when necessary.

Musculoskeletal Injury in American Football: A Bibliometric Analysis of the Most Cited Articles.

Background: Textbook knowledge and clinical dogma are often insufficient for effective evidence-based decision making when treating musculoskeletal injuries in American football players, given the variability in presentation and outcomes across different sports and different levels of competition. Key evidence can be drawn directly from high-quality published articles to make the appropriate decisions and recommendations for each athlete's unique situation. Purpose: To identify and analyze the 50 most cited articles related to football-related musculoskeletal injury to provide an efficient tool in the arsenal of trainees, researchers, and evidence-based practitioners alike. Study Design: Cross-sectional study. Methods: The ISI Web of Science and SCOPUS databases were queried for articles pertaining to musculoskeletal injury in American football. For each of the top 50 most cited articles, bibliometric elements were evaluated: citation count and density, decade of publication, journal, country, multiple publications by the same first author or senior author, article content (topic, injury area), and level of evidence (LOE). Results: The mean ± SD number of citations was 102.76 ± 37.11; the most cited article, with 227 citations, was "Syndesmotic Ankle Sprains" published in 1991 by Boytim et al. Several authors served as a first or senior author on >1 publication, including J.S. Torg (n = 6), J.P. Bradley (n = 4), and J.W. Powell (n = 4). The American Journal of Sports Medicine published the majority of the 50 most cited articles (n = 31). A total of 29 articles discussed lower extremity injuries, while only 4 discussed upper extremity injuries. The majority of the articles (n = 28) had an LOE of 4, with only 1 article having an LOE of 1. The articles with an LOE of 3 had the highest mean citation number (133.67 ± 55.23; F = 4.02; P = .05). Conclusion: The results of this study highlight the need for more prospective research surrounding the management of football-related injury. The low overall number of articles on upper extremity injury (n = 4) also highlights an area for further research.

Patellar Tendon Injury: A Bibliometric Analysis of the Most-Cited Articles Demonstrates Relatively High Overall Level of Evidence.

Purpose: To identify and analyze the 50 most-cited articles in patellar tendon injury research. Methods: The ISI Web of Science and SCOPUS databases were used to conduct a search for articles pertaining to patellar tendon injury. For the top 50 most-cited articles, bibliometric data (title, first and senior author, citation count, journal, publication year, citation density, country of origin, Level of Evidence [LOE]) and topic of article were recorded. Results: The mean number of citations was 172.0 ± 88.2 (range 101-546). There was a statistically significant correlation between publication year and citation density (r = 0.61, P < .01). The earliest article was the third most-cited article (362 citations), published by Blazina et al. in 1973, which discussed the epidemiology of patellar tendinopathy. The first and second most-cited articles (546 and 466 citations, respectively) covered surgical outcomes of patellar tendinopathy and prevalence of patellar tendinopathy among elite athletes. A total of 14 articles (28%) discussed nonoperative management, whereas only 5 articles discussed surgical management (10%). The most frequent LOE category was a LOE of IV (n = 18, 36%), but 19 studies (38%) were LOE I or LOE II. Conclusions: Among the top 50 most-cited studies regarding patellar tendon injury, a relatively high number were of a high LOE (19 Level I or II, 38%), affirming that these articles in patellar tendon injury research are not only influential, but also of high-quality evidence. Clinical Relevance: This bibliometric analysis provides an efficient tool for educators, researchers, and evidence-based practitioners to identify and evaluate the most influential articles in patellar tendon injury research.

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).

Modulation of ATXN1 S776 phosphorylation reveals the importance of allele-specific targeting in SCA1.

Spinocerebellar ataxia type 1 (SCA1) is an adult-onset neurodegenerative disorder characterized by motor incoordination, mild cognitive decline, respiratory dysfunction, and early lethality. It is caused by the expansion of the polyglutamine (polyQ) tract in Ataxin-1 (ATXN1), which stabilizes the protein, leading to its toxic accumulation in neurons. Previously, we showed that serine 776 (S776) phosphorylation is critical for ATXN1 stability and contributes to its toxicity in cerebellar Purkinje cells. Still, the therapeutic potential of disrupting S776 phosphorylation on noncerebellar SCA1 phenotypes remains unstudied. Here, we report that abolishing S776 phosphorylation specifically on the polyQ-expanded ATXN1 of SCA1-knockin mice reduces ATXN1 throughout the brain and not only rescues the cerebellar motor incoordination but also improves respiratory function and extends survival while not affecting the hippocampal learning and memory deficits. As therapeutic approaches are likely to decrease S776 phosphorylation on polyQ-expanded and WT ATXN1, we further disrupted S776 phosphorylation on both alleles and observed an attenuated rescue, demonstrating a potential protective role of WT allele. This study not only highlights the role of S776 phosphorylation to regulate ATXN1 levels throughout the brain but also suggests distinct brain region-specific disease mechanisms and demonstrates the importance of developing allele-specific therapies for maximal benefits in SCA1.

Improving the properties of chitosan as support for the covalent multipoint immobilization of chymotrypsin.

Changing gel structure and immobilization conditions led to a significant improvement in the covalent multipoint attachment of chymotrypsin on chitosan. The use of sodium alginate, gelatin, or kappa-carrageenan, activation with glutaraldehyde, glycidol, or epichlorohydrin, and addition of microorganisms followed by cellular lysis allowed the modification of the gel structure. Immobilization yields, recovered activities, and stabilization factors at 55 and 65 degrees C were evaluated. Enzyme immobilization for 72 h at pH 10.05, 25 degrees C and reduction with NaBH 4 in chitosan 2.5%-carrageenan 2.5%, with addition of S. cerevisiae 5% and activation with epichlorohydrin led to the best derivative, which was 9900-fold more stable than the soluble enzyme. This support allowed an enzyme load up to 40 mg chymotrypsin x g gel (-1). The number of covalent bonds, formed by active groups in the support and lysine residues of the enzyme, can explain the obtained results. SEM images of the gel structures corroborate these conclusions.

[Diagnosis and treatment of acute pancreatitis: are the guidelines accepted?]. / Diagnose und Therapie der akuten Pankreatitis: Werden die Leitlinien akzeptiert?

BACKGROUND AND OBJECTIVE: Eight international guidelines exist for the diagnosis and treatment of acute pancreatitis, a disease that is often difficult to assess and treat, particularly when the necrotising variety of the disease is present. The knowledge of and compliance with these guidelines in Germany is unknown. METHOD: In order to assess the knowledge and compliance with acute pancreatitis guidelines, a structured questionnaire was sent out to the 190 members of the ALGK (Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte), a professional organisation of gastroenterology chairmen, who, in their respective institutions, are responsible for the diagnosis and treatment of acute pancreatitis. University hospitals were excluded to cover the entire severity spectrum of the disease and to avoid a referral bias. RESULTS: The questionnaire was responded by 182 (96 %) members. To a large extent (acceptance > 2/3 of the consultants), guideline recommendations were complied with. There was, nevertheless, disagreement regarding the prophylactic use of antibiotics (acceptance < 2/3 of the consultants), as to when a contrast-enhanced computed tomography was indicated, and the timing of cholecystectomy for biliary pancreatitis. The choice of pain therapy for patients with acute pancreatitis also remained equivocal. CONCLUSION: Based on the high response rate which excludes a non-responder bias, the results of our study reflect the current status of the diagnosis and therapy of acute pancreatitis in Germany and to what extent international guidelines are known and complied with. This study also highlights the need for additional clinical trials in areas of diagnostic or therapeutic uncertainty.

Recovered efficiency of filter control in dispersion-managed solitons for optical regeneration applications: analysis and experimental validation.

We demonstrate numerically that local conversion of dispersion-managed return-to-zero pulses into nonlinear Schrödinger solitons fully restores optical filtering control for energy stabilization, thus permitting the association of optical regeneration with dispersion-managed propagation. Experimental validation is achieved by means of 40-Gbit/s regenerated dispersion-managed loop transmission over 10,000 km.

Stability and optimization of dispersion-managed soliton control.

Dispersion-managed solitons with in-line all-optical regeneration are shown to be subject to amplitude and timing-jitter instabilities. We identify and discuss the different natures of these instabilities by means of a linear stability analysis, which is in good agreement with the full numerical solutions of the governing equations. Stable pulse propagation can be achieved through appropriate choices of dispersion map and pulse energy.