Combined joint fusion for index and middle carpometacarpal instability in elite boxers

Isolated instability of the index and middle finger carpometacarpal joints is uncommon. An unpublished injury pattern in a consecutive series of 13 elite boxers is described, with mid-term radiological and functional results of two novel surgical treatments. All the boxers (from Australia and the UK) were unable to compete owing to pain and weakness. Four boxers were managed initially by open reduction and temporary K-wire fixation. Nine boxers underwent primary carpometacarpal arthrodesis. All were able to return to their previous level of competition. One boxer who had undergone a soft tissue reconstruction competed at international level but required an arthrodesis because of recurrent symptoms. In elite boxers, simple reduction and wiring may be appropriate for an acute injury causing index or middle finger carpometacarpal joint instability, however, arthrodesis is the treatment of choice when instability and degenerative changes are present.

Community-onset Staphylococcus aureus infections presenting to general practices in South-eastern Australia

Community-acquired Staphylococcus aureus infections are a public health concern, yet little is known about infections that do not present to hospital. We identified community-onset S. aureus infections via specimens submitted to a community-based pathology service. Referring doctors confirmed eligibility and described infection site, severity and treatment. Isolates were characterized on antibiotic resistance, PFGE, MLST/SCCmec, and Panton–Valentine leukocidin (PVL), representing 106 community-onset infections; 34 non-multiresistant methicillin-resistant S. aureus (nmMRSA) (resistant to <3 non-β-lactam antibiotics), 15 multiply antibiotic-resistant MRSA (mMRSA) and 57 methicillin-sensitive S. aureus (MSSA). Most (93%) were skin and soft tissue infections. PVL genes were carried by 42% of nmMRSA isolates [95% confidence interval (CI) 26–61] and 15% of MSSA (95% CI 8–28). PVL was associated with infections of the trunk, head or neck (56·4% vs. 24·3%, P= 0·005) in younger patients (23 vs. 52 years, P< 0·001), and with boils or abscesses (OR 8·67, 95% CI 2·9–26·2), suggesting underlying differences in exposure and/or pathogenesis.

Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents

Background Cabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. Objective To describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents. Design, setting, and participants We report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. Outcome measurements and statistical analysis Changes in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. Results and limitations The post-endocrine-therapy patients received abiraterone (n = 32), sequential abiraterone and enzalutamide (n = 5) or enzalutamide (n = 4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1-10 cycles) were delivered, with ≥50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n = 18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. Conclusions This is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. Patient summary We looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments. © 2013 European Association of Urology.

Childhood cancer in Argentina: survival 2000–2007

 Introduction: Information on the epidemiology of childhood cancer in Latin America is limited. The Argentinean Oncopaediatric Registry (ROHA) is a population-based registry active since 2000. This paper describes the 3-year survival experience of children diagnosed with cancer in Argentina during 2000–2007 by major morphological subgroup, age, sex, and geographical region of residence.
Methods: Newly diagnosed paediatric cancer cases are registered in ROHA (estimated coverage is 93% of the country’s cases). Three-year overall survival was estimated using Kaplan–Meier methods. Univariate Cox models were used to compare subgroup survival.
Results: Between 2000 and 2007, a total of 10,181 new cancer diagnoses in children aged 0–14 years were reported to the registry. Three-year overall survival (95%CI) for all cancers was 61.7% (60.7; 62.7). Specific survival for the most frequent morphological types was: leukaemias 63.3% (61.6; 64.9), lymphomas and related neoplasms 75.3% (72.7; 77.7), brain neoplasms 46.3% (43.9; 48.7), soft-tissue sarcomas 52.3% (48.0; 56.5), neuroblastomas 49.6% (44.6; 54.3), renal tumours 76.7% (72.2; 80.6), and malignant bone tumours 47.2% (42.3; 51.9). Overall survival was associated with age but not sex and varied by geographical region. Compared to other regions, patients who resided in the capital city had a significantly higher survival: 69.6% (65.8; 73.0) versus 63.5% (59.4; 67.4) in Patagonia, 63.2% (61.9; 64.5) in the central region, 58.0% (54.2; 61.7) in Cuyo, 55.6% (52.5; 58.6) in the north-east, and 55.4% (52.4; 58.2) in the north-west (all P values <0.005).
Conclusions: Of children diagnosed with cancer in Argentina, 62% survived at least 3 years after diagnosis. Even though this figure is lower than that reported for more developed countries, survival patterns by diagnosis, age and sex were quite similar. Survival was lower in the two northern regions, which are areas with higher poverty levels.

Progressive computed tomography (CT) appearances preceding malignant spinal cord compression (MSCC) in men with castration-resistant prostate cancer

AIM: To test the hypothesis that computed tomography (CT)-based signs might precede symptomatic malignant spinal cord compression (MSCC) in men with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: A database was used to identify suitable mCRPC patients. Staging CT images were retrospectively reviewed for signs preceding MSCC. Signs of malignant paravertebral fat infiltration and epidural soft-tissue disease were defined and assessed on serial CT in 34 patients with MSCC and 58 control patients. The presence and evolution of the features were summarized using descriptive statistics. RESULTS: In MSCC patients, CT performed a median of 28 days prior to the diagnostic magnetic resonance imaging (MRI) demonstrated significant epidural soft tissue in 28 (80%) patients. The median time to MSCC from a combination of overt malignant paravertebral and epidural disease was 2.7 (0-14.6) months. Conversely, these signs were uncommon in the control cohort. CONCLUSIONS: Significant malignant paravertebral and/or epidural disease at CT precede MSCC in up to 80% of mCRPC patients and should prompt closer patient follow-up and consideration of early MRI evaluation. These CT-based features require further prospective validation.

Canadian Society for Exercise Physiology position stand : the use of instability to train the core in athletic and nonathletic conditioning

The use of instability devices and exercises to train the core musculature is an essential feature of many training centres and programs. It was the intent of this position stand to provide recommendations regarding the role of instability in resistance training programs designed to train the core musculature. The core is defined as the axial skeleton and all soft tissues with a proximal attachment originating on the axial skeleton, regardless of whether the soft tissue terminates on the axial or appendicular skeleton. Core stability can be achieved with a combination of muscle activation and intra-abdominal pressure. Abdominal bracing has been shown to be more effective than abdominal hollowing in optimizing spinal stability. When similar exercises are performed, core and limb muscle activation are reported to be higher under unstable conditions than under stable conditions. However, core muscle activation that is similar to or higher than that achieved in unstable conditions can also be achieved with ground-based free-weight exercises, such as Olympic lifts, squats, and dead lifts. Since the addition of unstable bases to resistance exercises can decrease force, power, velocity, and range of motion, they are not recommended as the primary training mode for athletic conditioning. However, the high muscle activation with the use of lower loads associated with instability resistance training suggests they can play an important role within a periodized training schedule, in rehabilitation programs, and for nonathletic individuals who prefer not to use ground-based free weights to achieve musculoskeletal health benefits.

A prescription for resistance: management of Staphylococcal skin abscesses by general practitioners in Australia

Objectives: We investigated the management of staphylococcal abscesses (boils) by general practitioners (GPs) in the context of rising antibiotic resistance in community strains of Staphylococcus aureus.
Design, Setting, Participants: We analyzed patient-reported management of 66 cases of uncomplicated skin abscesses from the frequency matched methicillinresistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) Community- Onset Staphylococcus aureus Household Cohort (COSAHC) study (Melbourne, Australia, 2008–2012). Susceptibilities in all cases were known: 50/66 abscesses were caused by MRSA. In order to investigate GP-reported management of staphylococcal abscesses, we surveyed a random subset of GPs, from the COSAHC study (41), and of GPs (39) who used the same community-based pathology service (December 2011– May 2012). Main outcome measures: Patient outcomes, antibiotics prescribed, antibiotic resistance profiles of infecting strains, rates of incision and drainage (I&D), and attitudes to ordering microbiological cultures.
Results: MRSA was three times more likely to be cultured from an abscess than MSSA. Patient-reported management revealed 100% were prescribed antibiotics and only 60.6% had I&D. Of those 85% who remembered their prescription(s), 81% of MRSA cases and 23% of MSSA cases initially received inactive antibiotics. Repeat GP visits where antibiotics were changed occurred in 45 MRSA and 7 MSSA cases, although at least 33% of subsequent prescriptions were inactive for the MRSA infections. Patients treated with I&D and antibiotics did no better than those treated with only I&D, regardless of the antibiotic activity. In the GP surveys, 89% reported I&D, with or without antibiotics, to be their preferred management. Only 29.9% of GPs would routinely swab abscesses.

What do infectious diseases physicians do? a 2-week snapshot of inpatient consultative activities across Australia, New Zealand and Singapore

The practice of an infectious diseases (ID) physician is evolving. A contemporary understanding of the frequency and variety of patients and syndromes seen by ID services has implications for training, service development and setting research priorities. We performed a 2-week prospective survey of formal ID physician activities related to direct inpatient care, encompassing 53 hospitals throughout Australia, New Zealand and Singapore, and documented 1722 inpatient interactions. Infections involving the skin and soft tissue, respiratory tract and bone/joints together accounted for 49% of all consultations. Suspected/confirmed pathogens were primarily bacterial (60%), rather than viral (6%), fungal (4%), mycobacterial (2%) or parasitic (1%). Staphylococcus aureus was implicated in 409 (24%) episodes, approximately four times more frequently than the next most common pathogen. The frequency of healthcare-related infections (35%), immunosuppression (21%), diabetes mellitus (19%), prosthesis-related infections (13%), multiresistant pathogens (13%) and non-infectious diagnoses (9%) was high, although consultation characteristics varied between geographical settings and hospital types. Our study highlights the diversity of inpatient-related ID activities and should direct future teaching and research. ID physicians' ability to offer beneficial consultative advice requires broad understanding of, and ability to interact with, a wide range of referring specialities.

Methicillin-susceptible Staphylococcus aureus endocarditis isolates are associated with clonal complex 30 genotype and a distinct repertoire of enterotoxins and adhesins.

BACKGROUND: Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. METHODS: IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. RESULTS: 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all). CONCLUSIONS: MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.

In situ localization associates biologically active plant natriuretic peptide immuno-analogues with conductive tissue and stomata

Plant natriuretic peptide immuno-analogues (irPNP) have previously been shown to affect a number of biological processes including stomatal guard cell movements, ion fluxes and osmoticum-dependent water transport. Tissue printing and immunofluorescent labelling techniques have been used here to study the tissue and cellular localization of irPNP in ivy (Hedera helix L.) and potato (Solanum tuberosum L.). Polyclonal antibodies active against human atrial natriuretic peptide (anti-hANP) and antibodies against irPNP from potato (anti-StPNP) were used for immunolabelling. Tissue prints revealed that immunoreactants are concentrated in vascular tissues of leaves, petioles and stems. Phloem-associated cells, xylem cells and parenchymatic xylem cells showed the strongest immunoreaction. Immunofluorescent microscopy with fluorescein isothiocyanate (FITC)-conjugated goat anti-rabbit IgG supported this finding and, furthermore, revealed strong labelling to stomatal guard cells and the adjacent apoplastic space as well. Biologically active immunoreactants were also detected in xylem exudates of a soft South African perennial forest sage (Plectranthus ciliatus E. Mey ex Benth.) thus strengthening the evidence for a systemic role of the protein. In summary, in situ cellular localization is consistent with physiological responses elicited by irPNPs reported previously and is indicative of a systemic role in plant homeostasis.

Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds

Several chronic bioassays have been conducted in multiple strains of mice in which various concentrations of arsenate or arsenite were administered in the drinking water without a tumorigenic effect. However, one study (Ng et al., 1999) reported a significant increase in tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. A physiologically based pharmacokinetic model for arsenic in the mouse has previously been developed (Gentry et al., 2004) to investigate potential differences in tissue dosimetry of arsenic species across various strains of mice. Initial results indicated no significant differences in blood, liver, or urine dosimetry in B6C3F1 and C57Bl/6 mice for acute or subchronic exposure. The current work was conducted to compare model-predicted estimates of tissue dosimetry to additional kinetic information from the (C57Bl/6 x CBA)F1 and TgAc mouse. The results from the current modeling indicate that the pharmacokinetic parameters derived based on information in the B6C3F1 mouse adequately describe the measured concentrations in the blood/plasma, liver, and urine of both the (C57Bl/6 x CBA)F1 and TgAc mouse, providing further support that the differences in response observed in the chronic bioassays are not related to strain-specific differences in pharmacokinetics. One significant finding was that no increases in skin or lung concentrations of arsenic species in the (C57Bl/6 x CBA)F1 strain were observed following administration of low concentrations (0.2 or 2 mg/L) of arsenate in the drinking water, even though differences in response in the skin were reported. These data suggest that pharmacodynamic changes may be observed following exposure to arsenic compounds without an observable change in tissue dosimetry. These results provided further indirect support for the existence of inducible arsenic efflux in these tissues.

Receptor mediated tumor targeting : an emerging approach for cancer therapy

Receptor-mediated tumor targeting has received major attention in the field of cancer drug delivery in the past few years. Receptors, as molecular target has opened new opportunities for cellular or intracellular targeting of drug loaded delivery systems conjugated with targeting moieties i.e. ligand. This receptor mediated targeting of cancer drug through nano carrier sys¬tems to cancerous tissue offer protection and improves the pharmacokinetics of various drugs and help to overcome the systemic toxicity and adverse effects that result from the non-selective nature of most current cancer therapeutic agents. The article reviews the scope of receptor mediated targeting of anticancer drug loaded in various nanocarriers and also summarize recent perspective and challenges in the field of nanocarrier-aided drug delivery and drug targeting for cancer therapy.

Contribution of fibroblast and mast cell (afferent) and tumor (efferent) IL-6 effects within the tumor microenvironment

Hyperactive inflammatory responses following cancer initiation have led to cancer being described as a ‘wound that never heals’. These inflammatory responses elicit signals via NFκB leading to IL-6 production, and IL-6 in turn has been shown to induce epithelial to mesenchymal transition in breast cancer cells in vitro, implicating a role for this cytokine in cancer cell invasion. We previously have shown that conditioned medium derived from cancer-associated fibroblasts induced an Epithelial to Mesenchymal transition (EMT) in PMC42-LA breast cancer cells and we have now identify IL-6 as present in this medium. We further show that IL-6 is expressed approximately 100 fold higher in a cancer-associated fibroblast line compared to normal fibroblasts. Comparison of mouse-specific (stroma) and human-specific (tumor) IL-6 mRNA expression from MCF-7, MDA MB 468 and MDA MB 231 xenografts also indicated the stroma rather than tumor as a significantly higher source of IL-6 expression. Mast cells (MCs) feature in inflammatory cancer-associated stroma, and activated MCs secrete IL-6. We observed a higher MC index (average number of mast cells per xenograft section/average tumor size) in MDA MB 468 compared to MDA MB 231 xenografts, where all MC were observed to be active (degranulating). This higher MC index correlated with greater mouse-specific IL-6 expression in the MDA MB 468 xenografts, implicating MC as an important source of stromal IL-6. Furthermore, immunohistochemistry on these xenografts for pSTAT3, which lies downstream of the IL-6 receptor indicated frequent correlations between pSTAT3 and mast cell positive cells. Analysis of publically available databases for IL-6 expression in patient tissue revealed higher IL-6 in laser capture microdissected stroma compared to adjacent tissue epithelium from patients with inflammatory breast cancer (IBC) and invasive non-inflammatory breast cancer (non-IBC) and we show that IL-6 expression was significantly higher in Basal versus Luminal molecular/phenotypic groupings of breast cancer cell lines. Finally, we discuss how afferent and efferent IL-6 pathways may participate in a positive feedback cycle to dictate tumor progression.

Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice: Real-time PCR quantitation

Orthotopic or intracardiac injection of human breast cancer cell lines into immunocompromised mice allows study of the molecular basis of breast cancer metastasis. We have established a quantitative real-time PCR approach to analyze metastatic spread of human breast cancer cells inoculated into nude mice via these routes. We employed MDA-MB-231 human breast cancer cells genetically tagged with a bacterial β-galactosidase (Lac-Z) retroviral vector, enabling their detection by TaqMan® real-time PCR. PCR detection was linear, specific, more sensitive than conventional PCR, and could be used to directly quantitate metastatic burden in bone and soft organs. Attesting to the sensitivity and specificity of the PCR detection strategy, as few as several hundred metastatic MDA-MB-231 cells were detectable in 100 μm segments of paraffin-embedded lung tissue, and only in samples adjacent to sections that scored positive by histological detection. Moreover, the measured real-time PCR metastatic burden in the bone environment (mouse hind-limbs, n=48) displayed a high correlation to the degree of osteolytic damage observed by high resolution X-ray analysis (r 2=0.972). Such a direct linear relationship to tumor burden and bone damage substantiates the so-called `vicious cycle' hypothesis in which metastatic tumor cells promote the release of factors from the bone which continue to stimulate the tumor cells. The technique provides a useful tool for molecular and cellular analysis of human breast cancer metastasis to bone and soft organs, can easily be extended to other cell/marker/organ systems, and should also find application in preclinical assessment of anti-metastatic modalities.

Tumor progression locus 2 (Tpl2) deficiency does not protect against obesity-induced metabolic disease

Obesity is associated with a state of chronic low grade inflammation that plays an important role in the development of insulin resistance. Tumor progression locus 2 (Tpl2) is a serine/threonine mitogen activated protein kinase kinase kinase (MAP3K) involved in regulating responses to specific inflammatory stimuli. Here we have used mice lacking Tpl2 to examine its role in obesity-associated insulin resistance. Wild type (wt) and tpl22/2 mice accumulated comparable amounts of fat and lean mass when fed either a standard chow diet or two different high fat (HF) diets containing either 42% or 59% of energy content derived from fat. No differences in glucose tolerance were observed between wt and tpl22/2 mice on any of these diets. Insulin tolerance was similar on both standard chow and 42% HF diets, but was slightly impaired in tpl22/2 mice fed the 59% HFD. While gene expression markers of macrophage recruitment and inflammation were increased in the white adipose tissue of HF fed mice compared with standard chow fed mice, no differences were observed between wt and tpl2 mice. Finally, a HF diet did not increase Tpl2 expression nor did it activate Extracellular Signal-Regulated Kinase 1/2 (ERK1/2), the MAPK downstream of Tpl2. These findings argue that Tpl2 does not play a non-redundant role in obesity associated metabolic dysfunction.