Arthroscopically assisted fixation of Hawkins type II talar neck fractures: a case series.

Aims: Arthroscopically controlled fracture reduction in combination with percutaneous screw fixation may be an alternative approach to open surgery to treat talar neck fractures. The purpose of this study was thus to present preliminary results on arthroscopically reduced talar neck fractures. Patients and Methods: A total of seven consecutive patients (four women and three men, mean age 39 years (19 to 61)) underwent attempted surgical treatment of a closed Hawkins type II talar neck fracture using arthroscopically assisted reduction and percutaneous screw fixation. Functional and radiological outcome were assessed using plain radiographs, as well as weight-bearing and non-weight-bearing CT scans as tolerated. Patient satisfaction and pain sensation were also recorded. Results: Primary reduction was obtained arthroscopically in all but one patient, for whom an interposed fracture fragment had to be removed through a small arthrotomy to permit anatomical reduction. The quality of arthroscopic reduction and restoration of the talar geometry was excellent in the remaining six patients. There were no signs of talar avascular necrosis or subtalar degeneration in any of the patients. In the whole series, the functional outcome was excellent in five patients but restricted ankle movement was observed in two patients. All patients had a reduction in subtalar movement. At final follow-up, all patients were satisfied and all but one patient were pain free. Conclusion: Arthroscopically assisted reduction and fixation of talar neck fractures was found to be a feasible treatment option and allowed early functional rehabilitation. Cite this article: Bone Joint J 2018;100-B:461-7.

Custom-made total ankle arthroplasty for the salvage of major talar bone loss.

AIMS: A failed total ankle arthroplasty (TAA) is often associated with much bone loss. As an alternative to arthrodesis, the surgeon may consider a custom-made talar component to compensate for the bone loss. Our aim in this study was to assess the functional and radiological outcome after the use of such a component at mid- to long-term follow-up. PATIENTS AND METHODS: A total of 12 patients (five women and seven men, mean age 53 years; 36 to77) with a failed TAA and a large talar defect underwent a revision procedure using a custom-made talar component. The design of the custom-made components was based on CT scans and standard radiographs, when compared with the contralateral ankle. After the anterior talocalcaneal joint was fused, the talar component was introduced and fixed to the body of the calcaneum. RESULTS: At a mean follow-up of 6.9 years (1 to 13), 11 ankles were stable with no radiological evidence of loosening. Only one was lost to follow-up. The mean arc of movement was 21° (10° to 35°). A total of nine patients (75%) were satisfied or very satisfied with the outcome, two (17%) were satisfied but with reservations and one (8%) was not satisfied. All but one patient had an improvement in the American Orthopaedic Foot and Ankle Society hindfoot score (p = 0.01). Just one patient developed deep infection, leading to arthrodesis. CONCLUSION: A custom-made talar component yielded satisfactory results with regard to function, stability and satisfaction. This should encourage the use of such components as an alternative to arthrodesis of the ankle in patients with a failed TAA. Cite this article: Bone Joint J 2017;99-B:231-6.

Treatment of extended osteochondral lesions of the talus with a free vascularised bone graft from the medial condyle of the femur.

Large osteochondral lesions (OCLs) of the shoulder of the talus cannot always be treated by traditional osteochondral autograft techniques because of their size, articular geometry and loss of an articular buttress. We hypothesised that they could be treated by transplantation of a vascularised corticoperiosteal graft from the ipsilateral medial femoral condyle. Between 2004 and 2011, we carried out a prospective study of a consecutive series of 14 patients (five women, nine men; mean age 34.8 years, 20 to 54) who were treated for an OCL with a vascularised bone graft. Clinical outcome was assessed using a visual analogue scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. Radiological follow-up used plain radiographs and CT scans to assess graft incorporation and joint deterioration. At a mean follow-up of 4.1 years (2 to 7), the mean VAS for pain had decreased from 5.8 (5 to 8) to 1.8 (0 to 4) (p = 0.001) and the mean AOFAS hindfoot score had increased from 65 (41 to 70) to 81 (54 to 92) (p = 0.003). Radiologically, the talar contour had been successfully reconstructed with stable incorporation of the vascularised corticoperiosteal graft in all patients. Joint degeneration was only seen in one ankle. Treatment of a large OCL of the shoulder of the talus with a vascularised corticoperiosteal graft taken from the medial condyle of the femur was found to be a safe, reliable method of restoring the contour of the talus in the early to mid-term.

[MRSA - hygiene management, diagnostics and treatment]. / MRSA - Hygiene-Management, Diagnostik und Therapie.

Methicillin-resistant Staphyococcus aureus strains remain a challenge to both patient care and infection control efforts. In addition to the defining resistance to beta-lactams several other antibiotic classes may be ineffective. Some resistance phenotypes exhibit a characteristic distribution pattern between healthcare-associated, community-associated, and livestock-associated MRSA strains. For patients with defined risk factors a search-, destroy-, follow-up-strategy is recommended in order to identify and eliminate MRSA colonization. Mupirocin nasal ointment and extensive hygiene measures are the mainstays of decolonization efforts. Besides vancomycin several other antimicrobials such as rifampin, trimethoprim-sulfamethoxazol, clindamycin, linezolid, and daptomycin are used to treat specific MRSA infections.

Biodistribution and dosimetry of 195mPt-cisplatin in normal volunteers. Imaging agent for single photon emission computed tomography.

UNLABELLED: 195mPt-cisplatin is regarded as a promising imaging agent for optimizing dosage in patients receiving cisplatin chemotherapy. METHODS: We investigated the whole-body distribution and radiation dosimetry of 195mPt-cisplatin in humans. Whole-body scans were obtained up to 144 h after intravenous injection of 112.4 MBq 195mPt-cisplatin in each of five subjects. Blood samples were taken at various times up to 144 h after injection. Urine was collected up to 114 h after injection for calculation of renal clearance and whole-body clearance. Time/activity curves were generated by fitting the organ-specific geometric mean counts, obtained from regions of interest, on the respective images as a function of the time after injection. OLINDA software package was applied to calculate the absorbed radiation dose for various organs. RESULTS: Most of the activity (32 ± 4%) was excreted in the urine during the first 5 h. The effective clearance half-life derived from extrapolation of the whole-body curve was 40 hours (1.7 days). On average, the highest dose was received by the kidneys (mean dose received 2.68 ± 1.5 mGy/MBq), followed by the spleen (mean dose received 1.6 ± 0.8 mGy/MBq) followed by the liver (mean dose received 1.45 ± 0.38 mGy/MBq). The estimated mean effective dose for the adult subject was 0.185 ± 0.034 mSv/MBq. CONCLUSION: 195mPt-cisplatin proved a safe radiopharmaceutical with a favourable biodistribution for early and delayed imaging of pathology above the diaphragm. The ED obtained was 0.185 ± 0.034 mSv/MBq. The highest organ dose was received by the kidneys (2.68 ± 1.5 mGy/MBq).

[Iris tumor of unknown origin]. / Unklarer Iristumor.

A 51-year-old woman presented with a non-specific tumor of the iris and intraocular inflammation of the left eye. The patient had a history of surgery for metastatic bowel cancer and was on chemotherapy. The lesion was excised and was found to contain fungal spores and hyphae. Microbiological testing identified growth of Candida albicans and the patient was treated with local and systemic voriconazole. After combined vitrectomy with cataract surgery, the patient's condition improved.

The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation.

SitC is one of the predominant lipoproteins in Staphylococcus aureus. Recently, SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In this study, we purified C-terminally His-tagged SitC (SitC-His) from Staphylococcus aureus. SitC-His induced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) release in human monocytes and also NF-κB activation in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes (MKs) but also induced intracellular accumulation of TLR2, which was time and concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2 in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2-independent uptake. Neither activation nor colocalization of SitC-His was observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His specifically colocalizes with TLR2, is internalized by host cells, induces proinflammatory cytokines, and triggers intracellular accumulation of TLR2.

Design and powering of cystic fibrosis clinical trials using rate of FEV(1) decline as an efficacy endpoint.

BACKGROUND: Rate of lung function decline (RLFD) (as FEV(1) percent predicted/yr) is a robust measure of CF therapeutic efficacy rarely used as a study endpoint, in part due to uncertainty of sample size requirements. METHODS: Sample size requirements for 1:1 randomizations to detect RLFD treatment effects from 20% to 80% were assessed in Epidemiologic Study of CF (ESCF) patients. Effects of measuring FEV(1) 1-4 times per year in studies of 1- to 4-year durations were assessed in 399 patients age ≥ 6 years with FEV(1) ≥ 70%. Impacts of inclusion/exclusion based on risk factors in 2369 ESCF patients were assessed over 1.5 years using semi-annual FEV(1) measures. RESULTS: Increasing study duration and exclusion of lower risk patients (e.g., no P. aeruginosa infection) both substantially reduced requirements. CONCLUSIONS: CF RLFD studies of 1.5 years in duration appear feasible provided that investigators account for the beneficial effects of subject inclusion/exclusion based on risk factors in power estimates.

Epithelial cells and innate antifungal defense.

The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. Clinical observations indicate that mucocutaneous Candida infections are commonly associated with defective cell-mediated immune responses. The importance of the innate immune system as a first-line defense against pathogenic challenge has long been recognized. Over the last decade, many key molecules mediating innate host defense have been identified. Central to these developments is the discovery of pattern recognition receptors such as Toll-like receptors and C-type lectin-receptors that induce innate immune responses and also modulate cellular and humoral adaptive immunity during Candida infections. Although a large amount of information is now available in systemic infections, little is known about localized infections. We address the most relevant pattern recognition receptors and their signaling mechanisms in oral epithelial cells, to gain a better understanding of their contributions to antifungal innate immunity.

The anti-tumour properties and biodistribution (as determined by the radiolabeled equivalent) of Au-compounds intended as potential chemotherapeutics.

The anti-tumour activity of the Au (I) phosphine complex [Au(dppe(2)]Cl was first discovered in the mid 1980s although promising results were obtained it did not pass clinical studies because of its toxicity to organs such as the liver and heart. The aim of this study was to determine whether the two novel gold compounds (MM5 and MM6), selected for this study, have higher selectivity for cancer cells with less toxicity towards normal cells than [Au(dppe)(2)]Cl, and also to determine whether they have improved bio distribution compared to [Au(dppe)(2)]Cl. The Au-compounds as potential chemotherapeutic drugs were evaluated by using radioactive tracers in the in vitro and in vivo studies. Results obtained from these experiments showed that the uptake of these experimental compounds was dependent on their octanol/water partition coefficient. However; the inhibition of cell growth did not correlate with the uptake of these compounds by the cells that were tested. In terms of the total uptake it was found that the compounds that were less lipophilic (MM5, MM6) were taken up less efficiently in cells than those that are more lipophilic. Therefore hydrophilic drugs are expected to have a limited biodistribution compared to lipophilic drugs. This might imply a more selective tumour uptake.

Ultrase MT12 and Ultrase MT20 in the treatment of exocrine pancreatic insufficiency in cystic fibrosis: safety and efficacy.

BACKGROUND: Cystic fibrosis causes exocrine pancreatic insufficiency, leading to malabsorption. Supplemental pancreatic enzyme therapy alleviates the concomitant malnutrition experienced by cystic fibrosis patients. It is recognized that patients experience variations in clinical response to different brands of enzymes. This has prompted the US Food and Drug Administration to require that enzyme supplements be subjected to New Drug Applications. AIM: To investigate the safety and efficacy of supplemental pancreatic enzyme therapy in cystic fibrosis subjects. METHODS: We compared two doses of one formulation of enteric-coated pancreatic enzymes: Ultrase MT12 (12,000 lipase units per capsule) and Ultrase MT20 (20,000 lipase units per capsule), to placebo in two separate safety and efficacy studies. RESULTS: Mean total fat, protein and carbohydrate intake did not differ significantly between the groups. A significant difference in both fat and protein absorption occurred with the enzyme therapy groups. The Ultrase MT12 and Ultrase MT20 groups experienced a mean fat and protein absorption 79.4% and 83.8%, and 87.3% and 88.6%, respectively. No adverse events related to study drug were reported. CONCLUSIONS: This study further supports the use of enzymes to treat pancreatic insufficiency in cystic fibrosis. Excellent fat and protein absorption was achieved with minimal adverse events and safe doses.

Beclomethasone diproprionate reduced airway inflammation without adrenal suppression in young children with cystic fibrosis: a pilot study.

Inhaled corticosteroids are commonly used in cystic fibrosis (CF), but there are few studies evaluating their safety in young children. We, therefore, prospectively administered beclomethasone diproprionate (BDP) to 12 clinically stable young children with CF to examine the safety of this therapy with respect to adrenal suppression and airway infection. To determine potential mechanisms of corticosteroid action in CF, we also examined airway markers of inflammation before and after inhaled steroid treatment. BDP 210 microg twice a day was given via spacer for 2 months. Twelve-hour serum and urine cortisols and response to low-dose synthetic ACTH cortisol stimulation were assessed. Bronchoalveolar lavage fluid (BALF) was examined pre- and posttreatment with BDP by quantitative bacteriology and indices of airway inflammation, including levels of total neutrophils, neutrophil elastase-alpha-1 antiprotease complexes (NEAP), CA 19-9 mucin-associated antigen, interleukin-8 (IL-8), and macrophage IL-8 mRNA. Following 2 months of treatment, serum and urine cortisol levels were unchanged. Response to low-dose ACTH cortisol stimulation was not significantly decreased at 30 min. Posttreatment BALF bacterial density was not statistically different from pretreatment; however, one patient who was initially culture negative became culture-positive with Hemophilus influenzae. BALF total neutrophil counts, corrected for epithelial lining fluid dilution, were decreased to approximately one third of pretreatment values (P = 0.03). NEAP and CA 19-9 mucin-associated antigen demonstrated similar decreases. BALF IL-8 levels and macrophage IL-8 mRNA levels were not statistically changed. These findings suggest that treatment with BDP 420 microg per day for 2 months in young children with CF does not affect urine and blood cortisol, causes no decrease in adrenal reserve, and does not result in a clinically significant increase in airway infection. In addition, the fall in bronchoalveolar lavage fluid inflammatory markers following BDP suggests possible modulation of neutrophil influx into the CF airway and provides justification for further studies of inhaled corticosteroids in CF.

Tumor growth pattern and thymidine phosphorylase expression are related with the risk of hematogenous metastasis in patients with Astler Coller B1/B2 colorectal carcinoma.

BACKGROUND: The benefit of adjuvant chemotherapy appears to be limited for patients with Astler Coller B1/B2 colorectal carcinoma but may be better in a subgroup of patients with a high recurrence risk. In the current case-control analysis, the authors evaluated whether patients with a high risk of hematogenous metastasis could be identified by means of a thorough histologic and immunohistochemical examination of the resection specimens. METHODS: A database was built for all patients treated in a general teaching hospital for colorectal carcinoma between 1985 and 1995. From this database, all patients with an Astler Coller B1 or B2 tumor who subsequently had developed hematogenous metastases were taken as cases. For each case, three matched controls (age, Astler Coller, year of diagnosis) without metachronous metastases were selected. The resection specimens of cases and controls were blindly examined by two observers for the following: World Health Organization (WHO) classification; differentiation grade; growth pattern; lymphocytic, fibroblastic, and eosinophilic reaction; angioinvasion; number of lymph nodes examined; expression of E-cadherin, vascular endothelial growth factor and thymidine phosphorylase (TP); P53; microvessel density. RESULTS: Twenty-two cases and 65 controls were included in the analysis. Tumor growth pattern and tumor TP expression both independently contributed to recurrence risk. With these 2 variables, 4 subgroups could be identified with a recurrence risk ranging from 0% to 42%. CONCLUSIONS: Tumor growth pattern and degree of TP expression both appear to be related to the recurrence risk. Prospective trials should point out whether these variables can be implemented in the decision making concerning adjuvant chemotherapy.

A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency.

OBJECTIVE: The safety and efficacy of Minimicrospheres, which are enteric-coated, delayed-release pancrelipase capsules, on fat absorption in pediatric/adolescent and adult cystic fibrosis (CF) patients was assessed. Exocrine pancreatic insufficiency, common in CF patients, causes steatorrhea due to insufficient release of pancreatic enzymes. METHODS: In the open-label phase, 97 CF patients with pancreatic insufficiency and steatorrhea were stabilized on a high-fat diet and administered pancrelipase. Seventy-four patients with >80% coefficient of fat absorption received placebo or pancrelipase in the double-blind phase. Fat intake and excretion, stool frequency and consistency, and clinical global improvement were recorded. RESULTS: Average daily fat intake was comparable between treatment groups within each age group (adults vs pediatric/adolescent), but placebo patients had a significant (p < 0.001) mean decrease in coefficient of fat absorption (adult, 36.9 percentage points; pediatric/adolescent, 34.9 percentage points) from open-label to double-blind treatment compared to pancrelipase patients (adult, 2 percentage points; pediatric/adolescent, 3.25 percentage points); this difference was caused by a greater (p < or = 0.001) increase in mean fecal fat excretion (grams per day) in the placebo groups compared to pancrelipase groups (adult: 61.9 vs 2.3; pediatric/adolescent: 45.4 vs 4.1). Change in mean stool frequency from open-label to double-blind phases was significantly different (p < or = 0.002) between treatment groups, with increases in placebo groups and no difference (adult) or decrease (pediatric/adolescent) in pancrelipase groups. Pancrelipase patients' stool consistency remained about the same from open-label to double-blind. Placebo patients' stool consistency decreased (became softer) from open-label pancrelipase to double-blind placebo. Clinical global improvement data showed that > or =83% of pancrelipase patients improved or remained unchanged. CONCLUSIONS: Enteric-coated, delayed-release (Minimicrospheres) pancrelipase capsules are an effective treatment for steatorrhea associated with pancreatic insufficiency in patients with cystic fibrosis.