Multicentric Castleman's disease as a cause for unclear febrile episodes in a 55-year-old HIV-infected man

Our case illustrates the difficulties involved in diagnosing multicentric Castleman's disease (MCD) in a human immunodeficiency virus-infected man with febrile episodes and malaise. In the absence of well-established treatment protocols, we have chosen a new treatment algorithm with rituximab, etoposide, and valganciclovir, which led to the remission of clinical symptoms. Yet, we advocate focused exploration for MCD in immunosuppressed patients with unclear febrile episodes, as recent advances in treatment are promisin

Wound fluid ceftriaxone concentrations after local application with calcium sulphate as carrier material in the treatment of orthopaedic device-associated hip infections.

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO <sub>4</sub> ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO <sub>4</sub> applied locally to treat ODAI. A total of 30 operations with ceftriaxone-loaded CaSO <sub>4</sub> had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Our study highlights new clinical data of locally administered ceftriaxone with CaSO <sub>4</sub> as carrier material. The near-constant release of ceftriaxone from CaSO <sub>4</sub> observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds.Cite this article: Bone Joint Res 2022;11(11):835-842

Characteristics and outcome of 16 periprosthetic shoulder joint infections

Purpose: Shoulder arthroplasties are increasingly performed, but data on periprosthetic joint infections (PJI) in this anatomical position are limited. We retrospectively investigated the characteristics and outcome of shoulder PJI after primary arthroplasty from 1998 to 2010 in a single centre. Methods: Periprosthetic joint infection was defined as periprosthetic purulence, presence of sinus tract or microbial growth. A Kaplan-Meier survival method was used to estimate relapse-free survival of prosthesis. Results: From 1,571 primary shoulder prostheses, we evaluated 16 patients with a PJI at different stages, i.e, early (n=4), delayed (n=6) and late (n=6) infections. The median patient age was 67 (range 53-86) years, and 69% were females. The most commonly isolated microorganism was Propionibacterium acnes in 38% of patients (monobacterial in four and polymicrobial in two patients). In 14 of the 16 patients, surgical interventions consisting of debridement and implant retention (6 patients), exchange (7) and explantation (1) were performed. Four patients had a relapse of infection with P. acnes (n=3) or Bacteroides fragilis (n=1). The relapse-free survival of the prosthesis was 75% (95% confidence interval 46-90%) after 1 and 2years, 100% in six patients following the treatment algorithm for hip and knee PJI and 60% in 10 patients not followed up. All but one of the relapses were previously treated without exchange of the prosthesis. Conclusions: As recommended for hip and knee PJI, we suggest treating shoulder PJI with a low-grade infection by microorganisms such as P. acnes with an exchange of the prosthesis. Cohort studies are needed to verify our result

Perioperative Antibiotikaprophylaxe bei elektiver Gelenkprothesenimplantation

Eine Gelenkprotheseninfektion ist eine schwerwiegende Komplikation, die nach einer Gelenkprothesenimplantation auftreten kann. Zu den Präventionsmassnahmen einer Infektion gehört eine Palette von Massnahmen wie zum Beispiel prä- und postoperative Checklisten, sorgfältige Operationspräparation, Haarentfernung und Hautdesinfektion, strikte Hygienemassnahmen, eine gute chirurgische Technik mit ­kurzer Operationsdauer, postoperativ Entfernen von Urinkatheter und eine korrekte Wundpflege nach Operation. Eine systemische präoperative Antibiotikaprophylaxe (AMP) ist ein Faktor, der zu diesen zahlreichen Präventionsmassnahmen gehört. SWISSNOSO veröffentlichte Richtlinien zu Verantwortlichkeiten und Ablauf der Verabreichung der AMP in den Jahren 2015 [1] und 2018 [2]. Deren Empfehlungen für den Fachbereich Orthopädie und Traumatologie des Bewegungsapparates sind in den Tabellen 1a und 1b wiedergegeben

Treatment outcomes of patients with Cutibacterium acnes-positive cultures during total joint replacement revision surgery: a minimum 2-year follow-up

INTRODUCTION Periprosthetic joint infection (PJI) is a devastating complication following total joint replacement (TJR). Cutibacterium acnes (C. acnes) is a low virulent skin commensal, commonly found during TJR revision surgery for "aseptic" causes. The purpose of the present study was to report the treatment outcomes of patients with C. acnes contamination or infection in the presence of a TJR treated with a revision surgery ± implant exchange ± prolonged (≥ 8 weeks) postoperative antibiotics. METHODS Medical records of patients with at least one positive C. acnes culture in intraoperative tissue samples or sonication fluid from a TJR revision surgery between January 2005 and December 2014 were retrospectively evaluated. The primary endpoint was infection eradication according to Delphi criteria. The diagnostic accuracy of preoperative TJR aspiration regarding the diagnosis of C. acnes PJI was also investigated. RESULTS A total of 52 TJR (28 shoulders, 17 hips, 7 knees) in 52 patients (35 males, 17 females) with an average age of 63 ± 11 (33-86) years were included. At an average follow-up of 67 ± 33 (24-127) months, the infection eradication of C. acnes PJI was 97% regardless of the surgical treatment or administration of prolonged postoperative antibiotics. The incidence of unsuspected C. acnes PJI was 28.8%. The sensitivity and specificity of preoperative joint aspiration in detecting C. acnes PJI were 59% and 88%, whereas the PPV and NNV were 83% and 67%, respectively. CONCLUSION Infection eradication of C. acnes PJI was very high at a minimum follow-up of 24 months, suggesting that C. acnes PJI could be adequately treated with a combination of revision surgery and prolonged postoperative antibiotics. The preoperative diagnosis of C. acnes PJI might be challenging with more than one-quarter of patients presenting without suspicion of C. acnes PJI. The appropriate treatment of patients with a single positive culture remains still unclear. A negative TJR aspiration should not rule out a C. acnes PJI, especially in the presence of clinical correlates of infection. LEVEL OF EVIDENCE Retrospective case-control study, Level III. IRB APPROVAL Kantonale Ethikkommission Zürich, BASEC Nr.:2017-00567

Characteristics and treatment outcomes of 69 cases with early prosthetic joint infections of the hip and knee

Purpose: Early prosthetic joint infection (PJI) can be treated with an intensive surgical debridement and implant retention (DAIR) of the prosthesis if (1) the prosthesis is stable, (2) the pathogen is not a difficult-to-treat microorganism, (3) symptoms have lasted for <3weeks and (4) a sinus tract is absent. Methods: We retrospectively evaluated the treatment outcome of early PJI in the hip and knee in a single orthopaedic centre. An early PJI was defined as a prosthesis infection within 3months after primary implantation or revision surgery for a non-infectious cause. Results: We identified 69 patients with confirmed early PJI, with a median age of 71 (range 33-84) years. Only 64% presented with ≥2 acute signs of infection. The most commonly isolated bacteria were coagulase-negative staphylococci (38%) and Staphylococcus aureus (25%). Surgical procedures included DAIR (50 cases, 69%) and two-stage exchange (19 cases, 31%). At last follow-up, five ofremaining living 67 patients (7.5%) had a relapse of infection. The overall relapse-free survival of the prosthesis after 2 yearswas 92.3% (95% confidence interval 82-97%) with no significant difference between DAIR and exchange of prosthesis. Conclusion: Our data suggest that an early PJI should be treated with DAIR as a less invasive procedure whenever possible according to the established treatment algorithm

Factors associated with rifampin resistance in staphylococcal periprosthetic joint infections (PJI): a matched case-control study

Purpose: Rifampin combination therapy plays an important role in the management of staphylococcal periprosthetic joint infection (PJI). However, the emergence of rifampin resistance is a feared complication. We retrospectively analysed predetermined potential risk factors in patients with rifampin-resistant staphylococcal PJI in a multicentre case-control study. Methods: Cases (n=48) were defined as PJI caused by rifampin-resistant staphylococci. Rifampin-susceptible controls (n=48) were matched for microorganism and type of prosthetic joint. Uni- and multivariable conditional logistic regression analyses were performed to estimate odds ratios (OR) with 95% confidence intervals (95% CI). Results: Forty-eight cases (31 men; median age 67years; age range 39-88years) with hip- (n=29), knee- (n=13), elbow- (n=4), shoulder- (n=1) or ankle-PJI (n=1) were enrolled in the study. Staphylococcus aureus and coagulase-negative staphylococci were isolated in ten and 38 episodes, respectively. Most of the cases (n=44, 92%) had a previous PJI, and 93 % (n=41) of these had been treated with rifampin. There was an independent association of emergence of rifampin resistance with male sex (OR 3.6, 95% CI 1.2-11),≥3 previous surgical revisions (OR 4.7, 95% CI 1.6-14.2), PJI treatment with high initial bacterial load (inadequate surgical debridement, <2weeks of intravenous treatment of the combination medication; OR 4.9, 95% CI 1.6-15) and inadequate rifampin therapy (OR 5.4, 95% CI 1.2-25). Conclusions: Based on our results, extensive surgical debridement and adequate antibiotic therapy are needed to prevent the emergence of rifampin resistanc

ChIP-on-chip analysis reveals angiopoietin 2 (Ang2, ANGPT2) as a novel target of steroidogenic factor-1 (SF-1, NR5A1) in the human adrenal gland

The nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) is a key regulator of adrenal and gonadal biology. Disruption of SF-1 can lead to disorders of adrenal development, while increased SF-1 dosage has been associated with adrenocortical tumorigenesis. We aimed to identify a novel subset of SF-1 target genes in the adrenal by using chromatin immunoprecipitation (ChIP) microarrays (ChIP-on-chip) combined with systems analysis. SF-1 ChIP-on-chip was performed in NCI-H295R human adrenocortical cells using promoter tiling arrays, leading to the identification of 445 gene loci where SF-1-binding regions were located from 10 kb upstream to 3 kb downstream of a transcriptional start. Network analysis of genes identified as putative SF-1 targets revealed enrichment for angiogenic process networks. A 1.1-kb SF-1-binding region was identified in the angiopoietin 2 (Ang2, ANGPT2) promoter in a highly repetitive region, and SF-1-dependent activation was confirmed in luciferase assays. Angiogenesis is paramount in adrenal development and tumorigenesis, but until now a direct link between SF-1 and vascular remodeling has not been established. We have identified Ang2 as a potentially important novel target of SF-1 in the adrenal gland, indicating that regulation of angiogenesis might be an important additional mechanism by which SF-1 exerts its actions in the adrenal gland

Multiexcitons confined within a sub-excitonic volume: Spectroscopic and dynamical signatures of neutral and charged biexcitons in ultrasmall semiconductor nanocrystals

The use of ultrafast gating techniques allows us to resolve both spectrally and temporally the emission from short-lived neutral and negatively charged biexcitons in ultrasmall (sub-10 nm) CdSe nanocrystals (nanocrystal quantum dots). Because of forced overlap of electronic wave functions and reduced dielectric screening, these states are characterized by giant interaction energies of tens (neutral biexcitons) to hundreds (charged biexcitons) of meV. Both types of biexcitons show extremely short lifetimes (from sub-100 picoseconds to sub-picosecond time scales) that rapidly shorten with decreasing nanocrystal size. These ultrafast relaxation dynamics are explained in terms of highly efficient nonradiative Auger recombination.Comment: 5 pages, 4 figures, to be published in Phys. Rev.