Antimicrobial prophylaxis with teicoplanin plus gentamicin in primary total joint arthroplasty.

Objectives: To compare prosthetic joint infection (PJI) and acute kidney injury (AKI) rates among cohorts before and after changing our hospital's antimicrobial prophylactic regimen from cefuroxime to teicoplanin plus gentamicin. Methods: We retrospectively studied all patients undergoing primary total joint arthroplasty at our hospital 18 months pre- and post-implementation of the change in practice. All deep infections identified during follow-up were assessed against the European Bone and Joint Infection Society (EBJIS) definitions for PJI. Survival analysis using Cox regression was employed to adjust for differences in baseline characteristics and compare the risk of PJI between the groups. AKIs were identified using pathology records and categorized according to the KDIGO (Kidney Disease - Improving Global Outcomes) criteria. AKI rates were calculated for the pre- and post-intervention periods. Results: Of 1994 evaluable patients, 1114 (55.9 %) received cefuroxime only (pre-intervention group) and 880 (44.1 %) patients received teicoplanin plus gentamicin (post-intervention group). The overall rate of PJI in our study was 1.50 % (30 of 1994), with a lower PJI rate in the post-intervention group (0.57 %; 5 of 880) compared with the pre-intervention group (2.24 %; 25 of 1114). A corresponding risk reduction for PJI of 75.2 % (95 % CI of 35.2-90.5; p=0.004) was seen in the post-intervention group, which was most pronounced for early-onset and delayed infections due to coagulase-negative staphylococci (CoNS) and cefuroxime-resistant Enterobacteriaceae. Significantly higher AKI rates were seen in the post-intervention group; however, 84 % of cases (32 of 38) were stage 1, and there were no differences in the rate of stage-2 or -3 AKI. Conclusions: Teicoplanin plus gentamicin was associated with a significant reduction in PJI rates compared with cefuroxime. Increases in stage-1 AKI were seen with teicoplanin plus gentamicin.

MAP2K1-mutated melanocytic tumors have reproducible histopathologic features and share similarities with melanocytic tumors with BRAF V600E mutations.

BACKGROUND: Melanocytic tumors driven by MAP2K1 in-frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, deep penetrating melanocytomas, and pigmented epithelioid melanocytoma. However, little is known about the characteristics of these tumors, especially in the absence of well-known second molecular "hits." Moreover, despite their frequent spitzoid cytomorphology, their potential categorization among the Spitz tumors is debatable. MATERIALS AND METHODS: We conducted a retrospective search through our molecular archives to identify sequenced melanocytic tumors with MAP2K1 in-frame deletions. We reviewed the clinical and histomorphological features of these tumors and compared them to similar neoplasms reported to date. In addition, we performed single-nucleotide polymorphism (SNP) array testing to identify structural chromosomal aberrations. RESULTS: Of 27 sequenced tumors, 6 (22%) showed a pathogenic MAP2K1 in-frame deletion (with or without insertion) and were included in this series. Five (83%) were females with lesions involving the upper limb. Histopathologically, all neoplasms were compounded with plaque-like or wedge-shaped silhouettes, spitzoid cytomorphology, and impaired cytologic maturation. All cases showed background actinic damage with sclerotic stroma replacing solar elastosis, variable pagetoid scatter, and occasional dermal mitotic figures (range 1-2/mm2 ). Five cases (83%) had a small component of nevic-looking melanocytes. Biologically, these tumors likely fall within the spectrum of unusual nevi. Five cases (83%) had a relatively high mutational burden and four (67%) showed an ultraviolet radiation signature. Four cases (67%) showed in-frame deletion involving the p.I103_K104del locus while two cases (33%) showed in-frame deletion involving the p.Q58_E62del locus. SNP array testing showed structural abnormalities ranging from 1 to 5 per case. Five of these cases showed a gain of chromosome 15 spanning the MAP2K1 gene locus. DISCUSSION AND CONCLUSION: Melanocytic tumors with MAP2K1 in-frame deletion could represent another spectrum of melanocytic tumors with close genotypic-phenotypic correlation. They are largely characterized by a spectrum that encompasses desmoplastic Spitz nevus as shown in our series and Spitz and Clark nevus as shown by others. Evolutionary, they share many similarities with tumors with BRAF V600E mutations, suggesting they are better classified along the conventional pathway rather than the Spitz pathway despite the frequent spitzoid morphology.

Utility of sequencing for ATP6AP1 and ATP6AP2 to distinguish between atypical granular cell tumor with junctional component and melanoma.

BACKGROUND: Granular cell tumor (GCT) is a S100+ neoplasm with atypical and malignant variants. Similar to melanocytic neoplasms, the tumors make nests and can have junctional components raising a differential diagnosis of melanoma. Nevi and melanomas may also have granular cell cytoplasm. MelanA is useful in distinguishing melanocytic from granular cell lineage, but increasingly MelanA/SOX10 negative melanomas have been recognized by correlation with molecular methods. METHODS: We encountered several cases with morphologic overlap between melanoma and atypical GCT necessitating additional molecular workup. We sequenced two cases and searched our archive for similar cases of GCT with overlapping features of melanocytic lineage. RESULTS: In our two index cases, we excluded melanoma driver mutations and identified frameshift or premature stop codons in ATP6AP1/2 pathognomonic of granular cell lineage. Data retrieved from Cosmic identified 24 melanomas with missense single nucleotide variants (SNVs) in ATP6AP1 but no frameshift or premature stop codons. Twenty-one melanomas had missense SNVs in ATP6AP2. One melanoma had a premature stop codon in ATP6AP2, but this lesion also had a melanoma-associated driver mutation NRASQ61K. We found 1 of 23 additional cases of GCT in our archives with a junctional component and no additional cases with maturation. CONCLUSIONS: Atypical and malignant GCT can have histopathologic overlap with melanoma. Frameshift and premature stop codons in ATP6AP1/2 are specific for granular cell lineage, and capable of excluding melanoma, in the absence of known melanoma-associated driver mutations.

Prophylactic antibiotics for massive endoprostheses in orthopaedic oncology.

The recently published Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial found no benefit in extending antibiotic prophylaxis from 24 hours to five days after endoprosthetic reconstruction for lower limb bone tumours. PARITY is the first randomized controlled trial in orthopaedic oncology and is a huge step forward in understanding antibiotic prophylaxis. However, significant gaps remain, including questions around antibiotic choice, particularly in the UK, where cephalosporins are avoided due to concerns of Clostridioides difficile infection. We present a review of the evidence for antibiotic choice, dosing, and timing, and a brief description of PARITY, its implication for practice, and the remaining gaps in our understanding.

Risk factors for recurrent infection in the surgical treatment of infected massive endoprostheses implanted for musculoskeletal tumours.

BACKGROUND: Infection is a devastating complication of endoprosthetic replacement (EPR) in orthopaedic oncology. Surgical treatments include debridement and/or one- or two-stage exchange. This study aims to determine the infection-free survival after surgical treatment for first and recurrent EPR infections and identify the risk factors associated with infection recurrence. METHODS: This single-centre cohort study included all patients with primary bone sarcomas or metastatic bone disease treated for infected EPR between 2010 and 2020. Variables included soft tissue status using McPherson classification, tumour type, silver coating, chemotherapy, previous surgery and microorganisms identified. Data for all previous infections were collected. Survival analysis, with time to recurrent infection following surgical treatment, was calculated at 1, 2 and 4 years. Cox regression analysis was used to assess the influence of different variables on recurrent infection. RESULTS: The cohort included 99 patients with a median age of 44 years (29-58 IQR) at the time of surgical treatment. The most common diagnoses were osteosarcoma and chondrosarcoma. One hundred and thirty-three surgical treatments for first or subsequent infections were performed. At 2 years of follow-up, overall success rates were as follows: two-stage exchange 55.3%, one-stage exchange 45.5%, DAIR with an exchange of modular components 44.6% and DAIR without exchange of modular components 24.7%. Fifty-one (52%) patients were infection-free at the most recent follow-up. Of the remaining 48 patients, 27 (27%) were on antibiotic suppression and 21 (21%) had undergone amputation. Significant risk factors for recurrent infection were the type of surgical treatment, with debridement alone as the highest risk (HR 4.75: 95%CI 2.43-9.30; P < 0.001); significantly compromised soft tissue status (HR 4.41: 95%CI 2.18-8.92; P = 0.001); and infections due to Enterococcus spp.. (HR 7.31: 95%CI 2.73-19.52); P = 0.01). CONCLUSIONS: Two-stage exchange with complete removal of all components where feasible is associated with the lowest risk of recurrent infection. Poor soft tissues and enterococcal infections are associated with higher risks of recurrent infection. Treatment demands an appropriate multidisciplinary approach. Patients should be counselled appropriately about the risk of recurrent infection before embarking on complex treatment.

An NTRK-1-associated soft tissue tumor showing distinctive nodules with peripheral accentuation of cellularity.

Lipofibromatosis-like neural tumor is a recently described entity defined by a low-cellularity spindle cell infiltrate in the subcutaneous fat with admixed inflammatory cells. This tumor is histopathologically similar to lipofibromatosis, but unlike lipofibromatosis shows reactivity for S100 and has an NTRK-1 kinase fusion. These lesions are locally aggressive but appear to have a negligible metastatic potential. Subsequently, a more cellular variant has been described with generally low mitotic rate. This variant also displays S100 reactivity and kinase fusions (typically involving NTRK-1), but it has a low risk of metastasis. In this report, we describe a case that aligns with the more cellular variant of NTRK-1 kinase fusion tumors on histopathologic, immunohistochemical, and molecular grounds, but in addition has distinctive nodules with peripheral accentuation of cellularity, reminiscent of those present in epithelioid malignant peripheral nerve sheath tumors. This latter feature is previously undescribed in NTRK kinase fusion soft tissue tumors and offers further support for the presumed neural differentiation of this neoplasm.

Coronavirus disease 2019 (COVID-19) polymerase chain reaction (PCR) screening of asymptomatic healthcare workers in a low-prevalence setting: A single-center UK cohort study.

In this cohort study of UK healthcare workers, we evaluated the use of fortnightly polymerase chain reaction (PCR) screening to facilitate the safe resumption of elective surgery in a low-prevalence setting. We found that adherence to serial testing was poor, and the resource required to identify 1 asymptomatic case was substantial.

Phase I and scintigraphy studies to evaluate safety, tolerability, pharmacokinetics, and lung deposition of inhaled GDC-0214 in healthy volunteers.

Several inflammatory cytokines that promote inflammation and pathogenesis in asthma signal through the Janus kinase 1 (JAK1) pathway. This phase I, randomized, placebo-controlled trial assessed the pharmacokinetics and safety of single and multiple ascending doses up to 15 mg twice daily for 14 days of a JAK1 inhibitor, GDC-0214, in healthy volunteers (HVs; n = 66). Doses were administered with a dry powder, capsule-based inhaler. An accompanying open-label gamma scintigraphy study in HVs examined the lung deposition of a single dose of inhaled Technetium-99m (99m Tc)-radiolabeled GDC-0214. GDC-0214 plasma concentrations were linear and approximately dose-proportional after both single and multiple doses. Peak plasma concentrations occurred at 15-30 min after dosing. The mean apparent elimination half-life ranged from 32 to 56 h across all single and multiple dose cohorts. After single and multiple doses, all adverse events were mild or moderate, and none led to treatment withdrawal. There was no clear evidence of systemic toxicity due to JAK1 inhibition, and systemic exposure was low, with plasma concentrations at least 15-fold less than the plasma protein binding-corrected IC50 of JAK1 at the highest dose. Scintigraphy showed that approximately 50% of the emitted dose of radiolabeled GDC-0214 was deposited in the lungs and was distributed well to the peripheral airways. 99m Tc-radiolabeled GDC-0214 (1 mg) exhibited a mean plasma Cmax similar to that observed in phase I at the same dose level. Overall, inhaled GDC-0214 exhibited pharmacokinetic properties favorable for inhaled administration.

Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study.

Background: An extrafine formulation triple therapy combination of beclomethasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) has been developed for the maintenance treatment of asthma and chronic obstructive pulmonary disease. This study used gamma scintigraphy to evaluate the intrapulmonary and extrapulmonary in vivo deposition of BDP/FF/GB, and the intrapulmonary regional distribution of the deposited formulation. Methods: This open-label uncontrolled nonrandomized single-dose study recruited 10 healthy volunteers and 9 patients with asthma. After a krypton-81m (81mKr) ventilation scan was conducted, subjects inhaled study drug (four inhalations of BDP/FF/GB 100/6/12.5 µg radiolabeled using technetium-99 m [99mTc]) through pressurized metered-dose inhaler, and a series of scintigraphic images were taken. The primary objective was to evaluate intrapulmonary drug deposition of BDP/FF/GB, determined as the percentage of nominal (i.e., metered) dose. Secondary endpoints included central/peripheral deposition ratio (C/P), and the standardized central/peripheral ratio (sC/P; 99mTc aerosol C/P/81mKr gas C/P). Results: All participants completed the study, with all scintigraphy procedures performed at one site. In patients with asthma, mean ± standard deviation intrapulmonary deposition was 25.50% ± 6.81%, not significantly different to that in healthy volunteers (22.74% ± 9.19%; p = 0.4715). Approximately half of the lung dose was deposited in the peripheral region of the lung (fraction deposited 0.52 ± 0.07 and 0.49 ± 0.06 in healthy volunteers and patients with asthma, respectively), resulting in C/P ratios of 0.94 ± 0.25 and 1.06 ± 0.25, respectively, with sC/P ratios of 1.80 ± 0.40 and 1.94 ± 0.38. Deposition patterns were similar in the two populations. BDP/FF/GB was well tolerated. Conclusions: This study confirmed that the extrafine particles delivered by BDP/FF/GB penetrate the peripheral areas of the lungs, with a similar proportion of particles deposited in the central and peripheral regions. Importantly, the deposition patterns were similar in healthy volunteers and patients with asthma, suggesting that disease characteristics are unlikely to impact drug deposition. Clinical Trial Registration number: NCT03795350.

BNT162b2 vaccine uptake and effectiveness in UK healthcare workers - a single centre cohort study.

In this single centre cohort study we assessed BNT162B2 vaccine uptake and effectiveness among UK healthcare workers (HCWs) during a time of high community COVID-19 prevalence. Early uptake among HCWs was 62.3% (1409/2260), however there were significant differences in uptake between age groups, ethnic origins, and job roles. Uptake increased to 72.9% after a vaccine hesitancy working group implemented specific measures. In the 42 days after vaccination, 49 new cases of COVID-19 were identified, of which 7 (14.3%) occurred in HCWs who were beyond 10 days of vaccination. Kaplan-Meier curves for partially vaccinated and unvaccinated groups were congruent until day 14 and continued to diverge up to 42 days. Cox regression analysis showed a 70.0% (95%CI 6.0-91.0; p=0.04) risk reduction for COVID-19 infection in partially vaccinated HCWs. Here we report early vaccination rates among HCWs are generally high although uptake is lower in certain groups. It is possible to improve vaccine uptake and efforts should focus on this, however, significant resource is required. The BNT162B2 vaccine is effective from 14 days post-vaccination in a frontline clinical setting and protection continues beyond 21 days post 1st dose without a 2nd dose, being given.

Clinical Experience of Implementing Oral Versus Intravenous Antibiotics (OVIVA) in a Specialist Orthopedic Hospital.

BACKGROUND: The Oral Versus Intravenous Antibiotics (OVIVA) Trial demonstrated that oral therapy, when used during the initial 6 weeks in the treatment in bone and joint infection (BJI), is noninferior to intravenous therapy. To date there are no reports describing reproducibility of these findings in a real-world setting. METHODS: We studied all patients diagnosed with BJI at our hospital 12 months pre- and postimplementation of the OVIVA trial findings into clinical practice. An infection consultant recommended antibiotic treatment and patients were followed up by an outpatient parenteral antibiotic therapy (OPAT) service. Prospective data from a local registry was used to analyze baseline clinical details, outcome, length of hospital stay (LOS), and costs. RESULTS: A cohort of 328 patients (145 pre- and 183 postimplementation) was analyzed. Postimplementation, 66.1% of patients were switched to a suitable oral antibiotic regimen. Definite failure at 1 year was 13.6% in the preimplementation group and 18.6% in the postimplementation group (P = .154). Postimplementation, definite failure was more common in patients requiring intravenous antibiotics due to lack of suitable oral options (intravenous, 26.7% and oral, 14.3%). Adverse drug reactions (ADRs) requiring closer monitoring or change to treatment were more common postimplementation (21.0% and 37.1%, respectively). ADR-related hospital readmissions were similar in both groups (2.1 and 2.2%). Comparing both groups, the postimplementation group showed a reduction of 4 days in the median LOS and a median cost reduction of £2764.28 per patient. CONCLUSIONS: The OVIVA trial findings can be safely implemented into clinical practice when patients on oral antibiotics are followed up by an established OPAT service. Two-thirds of patients were switched to a suitable oral antibiotic regimen. Implementation led to reductions in hospital LOS and antibiotic costs.

The management of infected shoulder arthroplasty by two-stage revision.

BACKGROUND: There remains no gold standard management for deep shoulder periprosthetic joint infection (PJI). This case series aims to present our experience of two-stage revision arthroplasty, including eradication of infection and reoperation rates. METHODS: We retrospectively reviewed patients undergoing revision arthroplasty for shoulder PJI between 2006 and 2015. Cases were confirmed using Musculoskeletal Infection Society (MSIS) and American Academy of Orthopaedic Surgeons (AAOS) guidelines. TSA removal, debridement and irrigation preceded antibiotic-loaded cement spacer insertion and a minimum of six weeks intravenous antibiotics. Reimplantation was performed as a second stage following a negative aspirate. RESULTS: Twenty-eight patients underwent a first stage procedure (mean age 69 years; 16 male, 12 female). Propionibacterium acnes, Methicillin-sensitive Staphylococcus aureus, Coagulase-negative Staphylococcus and Staphylococcus epidermidis were the commonest microorganisms cultured. Five cases had mixed growths and six cases provided no growth. Three patients did not proceed to a second stage. Twenty-five patients underwent reimplantation (mean interval 6.7 months), with 80% remaining infection-free (mean follow-up 38.3 months). DISCUSSION: Managing complex and late presentation shoulder PJI with two-stage revision is associated with high rates of infection eradication (80%). In the absence of a management consensus, our experience supports two-stage revision arthroplasty for eradicating infection in this complex patient group.

Snapshot PCR surveillance for SARS-CoV-2 in hospital staff in England.

BACKGROUND: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. METHODS: Cross-sectional 'snapshot' survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. FINDINGS: Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42-37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38-8.67; p = 0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. INTERPRETATION: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. FUNDING: Public Health England.

A case of Trueperella pyogenes causing prosthetic joint infection.

We present the first reported case of prosthetic joint infection caused by Trueperella pyogenes. This animal pathogen rarely causes human infection. Our patient was successfully treated with single-stage exchange and 12 weeks of rifampicin and moxifloxacin.

Dalbavancin to Treat Infected Massive Endoprostheses: A Case Report and Cost Comparison Analysis.

We report a case of an infected massive endoprosthetic replacement treated successfully with 2 stage surgery and off-label dalbavancin. Dalbavancin was used due to a limited number of antimicrobial options that could be administered safely in an outpatient setting and to avoid the need for daily dosing.

Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT.

BACKGROUND: Management of bone and joint infection commonly includes 4-6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. OBJECTIVE: To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. DESIGN: Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. SETTING: Twenty-six NHS hospitals. PARTICIPANTS: Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). INTERVENTIONS: Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. RESULTS: Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was -1.38% (90% confidence interval -4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. LIMITATIONS: The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. CONCLUSIONS: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. FUTURE WORK: Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN91566927. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Treatment of bone and joint infection usually requires a long course of antibiotics. Doctors usually give these by injection through a vein (intravenously) for the first 4­6 weeks, rather than by mouth (orally). Although intravenous (IV) administration is more expensive and less convenient for patients, most doctors believe that it is more effective. However, there is little evidence to support this. The OVIVA (Oral Versus IntraVenous Antibiotics) trial set out to challenge this assumption. A total of 1054 patients from 26 UK hospitals were randomly allocated to receive the first 6 weeks of antibiotic therapy either intravenously or orally. Irrespective of the route of administration, the choice of antibiotic was left to an infection specialist so as to ensure that the most appropriate antibiotics were given. Patients were followed up for 1 year. Thirty-nine participants were lost to follow-up. Among the remaining 1015 participants, treatment failure occurred in 14.6% of those treated intravenously and 13.2% of those treated with PO antibiotics. This difference could easily have occurred by chance. Even if it was not by chance, the difference does not suggest that PO therapy is associated with worse outcomes than IV therapy and is too small to conclude that PO therapy is better than IV therapy. Participants in the IV group stayed in hospital longer and 10% of them had complications related to the IV line used for administering the antibiotics. In addition, their treatment was, overall, more expensive. We conclude that PO antibiotic therapy has no disadvantages for the early management of bone and joint infection. It is also cheaper and associated with fewer complications.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

CD8-positive lymphomatoid papulosis (type D): Some lesions may lack CD30 expression and overlap histologically with mycosis fungoides.

BACKGROUND: CD8+ lymphomatoid papulosis is frequently indistinguishable histopathologically from primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma except for the expression of CD30. However, absent or weak expression of CD30 has been rarely reported in cases of CD8+ LyP. OBJECTIVE: We aim to study the clinical and pathologic features of cases of CD8+ LyP with no or minimal expression of CD30. MATERIAL AND METHODS: We identified all cases of CD8+ LyP diagnosed in our institution over a period of 10 years. Blinded comparison of clinical and histopathologic features of cases with and without CD30 expression was performed. RESULTS: Among seven cases (four patients) with definitive clinical and histopathologic diagnosis of CD8+ LyP, two cases (29%) had no expression of CD30. These two cases had more prominent epidermotropism, less epidermal ulceration, and less vascular damage relative to cases with CD30 expression and therefore resembled mycosis fungoides and type B LyP. CD5 and CD7 were frequently lost regardless of the CD30 status. Expression of cytotoxic markers was not different between the two groups. In the two cases with lack of CD30 expression, subsequent biopsies showed classic features of CD8+ LyP with strong expression of CD30. CONCLUSION: CD8+ LyP with lack of expression of CD30 may have distinct histopathologic features that resemble mycosis fungoides and LyP type B. Clinically, they are indistinguishable from their CD30+ counterparts, signifying the importance of clinical correlation to avoid the erroneous diagnosis of lymphoma. Interval biopsies may be needed to establish a definitive diagnosis.