Halicin remains active against Staphylococcus aureus in biofilms grown on orthopaedically relevant substrates.

Aims: Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods: S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results: Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion: Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection.

Body-Plan Reorganization in a Sponge Correlates with Microbiome Change.

Mounting evidence suggests that animals and their associated bacteria interact via intricate molecular mechanisms, and it is hypothesized that disturbances to the microbiome influence animal development. Here, we show that the loss of a key photosymbiont (i.e., bleaching) upon shading correlates with a stark body-plan reorganization in the common aquarium cyanosponge Lendenfeldia chondrodes. The morphological changes observed in shaded sponges include the development of a thread-like morphology that contrasts with the flattened, foliose morphology of control specimens. The microanatomy of shaded sponges markedly differed from that of control sponges, with shaded specimens lacking a well-developed cortex and choanosome. Also, the palisade of polyvacuolar gland-like cells typical in control specimens was absent in shaded sponges. The morphological changes observed in shaded specimens are coupled with broad transcriptomic changes and include the modulation of signaling pathways involved in animal morphogenesis and immune response, such as the Wnt, transforming growth factor ß (TGF-ß), and TLR-ILR pathways. This study provides a genetic, physiological, and morphological assessment of the effect of microbiome changes on sponge postembryonic development and homeostasis. The correlated response of the sponge host to the collapse of the population of symbiotic cyanobacteria provides evidence for a coupling between the sponge transcriptomic state and the state of its microbiome. This coupling suggests that the ability of animals to interact with their microbiomes and respond to microbiome perturbations has deep evolutionary origins in this group.

Obesity Classification of the Body Mass Index Does Not Predict Participation Restrictions at Work.

OBJECTIVE: The objective was to explore the differences of the three body mass index (BMI) obesity classes regarding sociodemographic data, medical and psychological well-being, but especially participation restrictions at work. METHODS: A specialist in psychosomatic medicine reported on the health and occupational status of 190 patients (BMI >30), who were treated as inpatients in a psychosomatic rehabilitation unit. RESULTS: Significant increases in severity or work limitations were found for higher BMI groups concerning metabolic, cardiologic, and orthopedic comorbidity. There were no differences regarding indicators of occupational participation. Independent of the obesity status, about three quarters were seen as fit for work. CONCLUSIONS: The initial hypothesis is rejected, as no difference concerning objective parameters of work participation were found between the BMI classes. The data suggest that BMI class I to BMI class III do not allow predictions of the ability to work.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Development of melanoma clinical quality indicators for the Australian melanoma clinical outcomes registry (MelCOR): A modified Delphi study.

BACKGROUND: Clinical quality registries aim to identify significant variations in care and provide anonymised feedback to institutions to improve patient outcomes. Thirty-six Australian organisations with an interest in melanoma, raised funds through three consecutive Melanoma Marches, organised by Melanoma Institute Australia, to create a national Melanoma Clinical Outcomes Registry (MelCOR). This study aimed to formally develop valid clinical quality indicators for the diagnosis and early management of cutaneous melanoma as an important step in creating the registry. METHODS: Potential clinical quality indicators were identified by examining the literature, including Australian and international melanoma guidelines, and by consulting with key melanoma and registry opinion leaders. A modified two-round Delphi survey method was used, with participants invited from relevant health professions routinely managing melanoma as well as relevant consumer organisations. RESULTS: Nineteen participants completed at least one round of the Delphi process. 12 of 13 proposed clinical quality indictors met the validity criteria. The clinical quality indicators included acceptable biopsy method, appropriate excision margins, standardised pathology reporting, indications for sentinel lymph node biopsy, and involvement of multidisciplinary care and referrals. CONCLUSION: This study provides a multi-stakeholder consensus for important clinical quality indicators that define optimal practice that will now be used in the Australian Melanoma Clinical Outcomes Registry (MelCOR).

Developing an Australian Melanoma Clinical Outcomes Registry (MelCOR): a protocol paper.

INTRODUCTION: Australia has the highest incidence of melanoma in the world with variable care provided by a diverse range of clinicians. Clinical quality registries aim to identify these variations in care and provide anonymised, benchmarked feedback to clinicians and institutions to improve patient outcomes. The Australian Melanoma Clinical Outcomes Registry (MelCOR) aims to collect population-wide, clinical-level data for the early management of cutaneous melanoma and provide anonymised feedback to healthcare providers. METHODS AND ANALYSIS: A modified Delphi process will be undertaken to identify key clinical quality indicators for inclusion in the MelCOR pilot. MelCOR will prospectively collect data relevant to these quality indicators, initially for all people over the age of 18 years living in Victoria and Queensland with a melanoma diagnosis confirmed by histopathology, via a two-stage recruitment and consent process. In stage 1, existing State-based cancer registries contact the treating clinician and provide an opportunity for them to opt themselves or their patients out of direct contact with MelCOR. After stage 1, re-identifiable clinical data are provided to the MelCOR under a waiver of consent. In stage 2, the State-based cancer registry will approach the patient directly and invite them to opt in to MelCOR and share identifiable data. If a patient elects to opt in, MelCOR will be able to contact patients directly to collect patient-reported outcome measures. Aggregated data will be used to provide benchmarked, comparative feedback to participating institutions/clinicians. ETHICS AND DISSEMINATION: Following the successful collection of pilot data, the feasibility of an Australia-wide roll out will be evaluated. Key quality indicator data will be the core of the MelCOR dataset, with additional data points added later. Annual reports will be issued, first to the relevant stakeholders followed by the public. MelCOR is approved by the Alfred Ethics Committee (58280/127/20).

Electron-Optical In Situ Imaging for the Assessment of Accuracy in Electron Beam Powder Bed Fusion.

The current study evaluates the capabilities of electron-optical (ELO) in situ imaging with respect to monitoring and prediction of manufacturing precision in electron beam powder bed fusion. Post-process X-ray computed tomography of two different as-built parts is used to quantitatively evaluate the accuracy and limitations of ELO imaging. Additionally, a thermodynamic simulation is performed to improve the understanding of ELO data and to assess the feasibility of predicting dimensional accuracy numerically. It is demonstrated that ELO imaging captures the molten layers accurately (deviations <100 µm) and indicates the creation of surface roughness. However, some geometrical features of the as-built parts exhibit local inaccuracies associated with thermal stress-induced deformation (deviations up to 500 µm) which cannot be captured by ELO imaging. It is shown that the comparison between in situ and post-process data enables a quantification of these effects which might provide the possibility for developing effective countermeasures in the future.

Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals.

Hox genes are highly conserved transcription factors renowned for their roles in the segmental patterning of the embryonic anterior-posterior (A/P) axis. We report functions for Hox genes in A/P tissue segmentation and transverse fission behavior underlying asexual reproduction in adult planarian flatworms, Schmidtea mediterranea. Silencing of each of the Hox family members identifies 5 Hox genes required for asexual reproduction. Among these, silencing of hox3 genes results in supernumerary fission segments, while silencing of post2b eliminates segmentation altogether. The opposing roles of hox3 and post2b in segmentation are paralleled in their respective regulation of fission behavior. Silencing of hox3 increases the frequency of fission behavior initiation while silencing of post2b eliminates fission behavior entirely. Furthermore, we identify a network of downstream effector genes mediating Hox gene functions, providing insight into their respective mechanisms of action. In particular, we resolve roles for post2b and effector genes in the functions of the marginal adhesive organ in fission behavior regulation. Collectively, our study establishes adult stage roles for Hox genes in the regulation of tissue segmentation and behavior associated with asexual reproduction.

Mycoplasma hominis hematoma infection in patient following kidney transplant.

Mycoplasma species, specifically Mycoplasma hominis (M. hominis), are commonly associated with genitourinary (GU) tract infectious syndromes. However, Mycoplasma spp. can also be involved in extragenital infections, primarily in immunosuppressed patients. A 61 year old female was successfully treated with moxifloxacin and doxycycline combination therapy for an infected hematoma secondary to M. hominis following a renal transplant. Microbiology technologists noted the growth of pinpoint, translucent non-hemolytic colonies, but no organisms seen on Gram stain. These findings prompted the updated culture report of, "Growth on culture plates, gram stain suggestive of organism lacking cell wall." Empiric antimicrobials were initiated to cover both Mycoplasma spp. and Ureaplasma spp before resulting M. hominis. Initiating empiric therapy directed against Mycoplasma spp. following Gram stain results and before organism speciation may prevent a lapse in effective therapy. This is especially important as perioperative antimicrobial prophylaxis regimens consist of beta-lactam regimens directed against common GI and GU pathogens, which lack activity against Mycoplasma spp.

Adenosine deaminase negative pleural tuberculosis: a case report.

BACKGROUND: A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value. CASE PRESENTATION: We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven Mycobacterium tuberculosis. CONCLUSIONS: This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.

Endogenous Candida endophthalmitis: Who is really at risk?

OBJECTIVES: The Infectious Disease Society of America recommends that all patients with candidemia undergo a dilated retinal exam to exclude endogenous Candida endophthalmitis. Our objective was to determine if there are significant risk factors in candidemic patients for developing endogenous Candida endophthalmitis METHODS: We conducted a retrospective study of all candidemic patients at three academic medical centers between 2012 and 2017. We extracted risk factors for Candida endophthalmitis based on prior literature and compared them between patients with and without endophthalmitis. We then built a multivariate logistic regression model to assess which ones were significant. RESULTS: We found 771 patients with candidemia. 120 (15.6%) of these patients were diagnosed with Candida endophthalmitis. In our logistic regression analysis, central venous catheter presence (OR 8.35), intravenous drug use (OR 4.76), immunosuppression (OR 2.40), total parenteral nutrition recipient (OR 2.28), race (OR 1.65), age (OR 1.02), and gender (OR 0.57) were risk factors for developing Candida endophthalmitis. Additionally, Candida albicans was more likely to result in Candida endophthalmitis (OR 1.86). CONCLUSIONS: This cohort represents the largest study of risk factors for candidemic patients who developed endogenous Candida endophthalmitis. Based on our findings, clinicians should develop targeted and cost-effective strategies for endophthalmitis screening.

Positive early clinical outcomes of bone marrow aspirate concentrate for osteoarthritis using a novel fenestrated trocar.

BACKGROUND: This study sought to assess early clinical outcomes for knee osteoarthritis (OA) patients undergoing bone marrow aspirate concentrate (BMAC) treatment using a novel closed-end, fenestrated trocar (FT) that does not require centrifugation. METHODS: A prospective cohort of 17 knee OA patients undergoing BMAC treatment with the FT system from March 2018 to March 2019 was retrospectively evaluated. Approximately 10 mL of BMAC was harvested, no centrifugation was performed, and the BMAC was injected into the affected knee. Clinical outcomes were assessed at baseline, six weeks, and 12 weeks. This study has no affiliation with/vested-interest in the FT system. RESULTS: There were significant improvements in nearly all outcomes from baseline to 12 weeks. Specific improvements included Knee Injury and OA Outcome Score (KOOS) activities-of-daily-living (61.1 ± 9.2 [mean ± 95% confidence interval] to 89.3 ± 6, p = 0.001), quality-of-life (32.7 ± 9.3 to 66.1 ± 17.9, p = 0.003), sports/recreation (36.9 ± 10.6 to 72.6 ± 26.3, p = 0.006), and pain (53.8 ± 9.3 to 83 ± 10.2, p = 0.001); Lysholm scores (55.5 ± 8.4 to 77.3 ± 10.5, p = 0.009); and visual analog pain scores (5.68 ± 1.14 to 2.07 ± 1.86, p = 0.003). Individually, at least 75% of patients exhibited improvement in all KOOS categories at six weeks and at least 85% at 12 weeks. CONCLUSIONS: BMAC treatment with an FT system that does not require centrifugation resulted in significant improvements in early pain and function scores for knee OA. The symptomatic improvements in this study were similar to or greater than what has been reported using traditional needles. These data may provide clinicians with comfort in using an FT system and provide motivation for future randomized-controlled trials comparing aspiration techniques.

Invasive Fungal Infection After Lung Transplantation: Epidemiology in the Setting of Antifungal Prophylaxis.

BACKGROUND: Lung transplant recipients commonly develop invasive fungal infections (IFIs), but the most effective strategies to prevent IFIs following lung transplantation are not known. METHODS: We prospectively collected clinical data on all patients who underwent lung transplantation at a tertiary care academic hospital from January 2007-October 2014. Standard antifungal prophylaxis consisted of aerosolized amphotericin B lipid complex during the transplant hospitalization. For the first 180 days after transplant, we analyzed prevalence rates and timing of IFIs, risk factors for IFIs, and data from IFIs that broke through prophylaxis. RESULTS: In total, 156 of 815 lung transplant recipients developed IFIs (prevalence rate, 19.1 IFIs per 100 surgeries, 95% confidence interval [CI] 16.4-21.8%). The prevalence rate of invasive candidiasis (IC) was 11.4% (95% CI 9.2-13.6%), and the rate of non-Candida IFIs was 8.8% (95% CI 6.9-10.8%). First episodes of IC occurred a median of 31 days (interquartile range [IQR] 16-56 days) after transplant, while non-Candida IFIs occurred later, at a median of 86 days (IQR 40-121 days) after transplant. Of 169 IFI episodes, 121 (72%) occurred in the absence of recent antifungal prophylaxis; however, IC and non-Candida breakthrough IFIs were observed, most often representing failures of micafungin (n = 16) and aerosolized amphotericin B (n = 24) prophylaxis, respectively. CONCLUSIONS: Lung transplant recipients at our hospital had high rates of IFIs, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. These data suggest benefit in providing systemic antifungal prophylaxis targeting Candida for up to 90 days after transplant and extending mold-active prophylaxis for up to 180 days after surgery.

Wnt and TGFß coordinate growth and patterning to regulate size-dependent behaviour.

Differential coordination of growth and patterning across metazoans gives rise to a diversity of sizes and shapes at tissue, organ and organismal levels. Although tissue size and tissue function can be interdependent1-5, mechanisms that coordinate size and function remain poorly understood. Planarians are regenerative flatworms that bidirectionally scale their adult body size6,7 and reproduce asexually, via transverse fission, in a size-dependent manner8-10. This model offers a robust context to address the gap in knowledge that underlies the link between size and function. Here, by generating an optimized planarian fission protocol in Schmidtea mediterranea, we show that progeny number and the frequency of fission initiation are correlated with parent size. Fission progeny size is fixed by previously unidentified mechanically vulnerable planes spaced at an absolute distance along the anterior-posterior axis. An RNA interference screen of genes for anterior-posterior patterning uncovered components of the TGFß and Wnt signalling pathways as regulators of the frequency of fission initiation rather than the position of fission planes. Finally, inhibition of Wnt and TGFß signalling during growth altered the patterning of mechanosensory neurons-a neural subpopulation that is distributed in accordance with worm size and modulates fission behaviour. Our study identifies a role for TGFß and Wnt in regulating size-dependent behaviour, and uncovers an interdependence between patterning, growth and neurological function.

HIV-Associated Vacuolar Encephalomyelopathy.

We report a case of human immunodeficiency virus (HIV)-associated vacuolar encephalomyelopathy with progressive central nervous system dysfunction and corresponding vacuolar degeneration of the spinal cord, cranial nerves, and brain, the anatomic extent of which has not previously been described.

Cardiovascular Implantable Electronic Device Infections.

Infections associated with cardiac implantable electronic devices are increasing and are associated with significant morbidity and mortality. This article reviews the epidemiology, microbiology, and risk factors for acquisition of these infections. The complex diagnostic and management strategies associated with these serious infections are reviewed with an emphasis on recent updates and advances, as well as existing controversies. Additionally, the latest in preventative strategies are reviewed.

Short-Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing in a Patient with Varicella-Zoster Virus Encephalomyelitis.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome (SUNCT) is a type of trigeminal autonomic cephalalgia. Its etiology is generally idiopathic, though rarely it has been associated with viral infections. We describe the fourth case reported in the literature of SUNCT in association with viral meningoencephalitis.

Chronic Exertional Compartment Syndrome in the Forearm of a Collegiate Softball Pitcher.

BACKGROUND: Chronic exertional compartment syndrome (CECS) is a recognized condition in the lower limb, with many reports in the literature. However, very few instances include CECS of the upper limb. This article presents the case of a collegiate softball pitcher presenting with CECS in her right forearm. To our knowledge, this is the first case report of a softball player with CECS, with only one similar incident in a major league baseball player. PURPOSE: The rarity of this condition normally places it low on the differential diagnosis. However, we hope that the presentation of this case and the review of the literature will aid in making swift and accurate diagnoses of CECS in future patients. We discuss the importance of three specific modalities in the diagnosis of this patient, what diagnostic criteria proved less conclusive, and the paradoxical course the syndrome presented with. STUDY DESIGN: Case Review RESULTS: Over a six-month period, the patient presented with peculiar presentations and exam results. A broad list of differential diagnoses had to be narrowed down through the presence or absence of relevant findings. These included cessation of exercise for 1 month, physical therapy, anti-inflammatory medicines, an electromyography/electromyogram (EMG), nerve conduction study (NCS), non-exercise magnetic resonance imaging (MRI) of the forearm, cervical MRI, and cervical computed tomography (CT) angiogram. After the above interventions were attempted and the relative findings of three important modalities were summarized, a fasciotomy and release of the dorsal, volar, and mobile wad compartments was performed. The patient's symptoms were relieved, and she eventually returned to full play in softball at the university. CONCLUSIONS: The three diagnostic criteria we believed to be most helpful in this case, and for future cases of CECS in the forearm, include the clinical presentation, pre- and post-exercise MRI, and pre- and post-exercise compartment pressure measurements. CLINICAL RELEVANCE: Chronic exertional compartment syndrome of the forearm is extremely rare, especially in the female athlete. This case report and review of the literature may be helpful to the clinician facing similar cases. It describes which clinical tests are most helpful for diagnosis and which findings may be distracting.