12-year survival analysis of 322 Hintegra total ankle arthroplasties from an independent center

Background and purpose — Total ankle arthroplasties (TAAs) have larger revision rates than hip and knee implants. We examined the survival rates of our primary TAAs, and what different factors, including the cause of arthritis, affect the success and/or revision rate.Patients and methods — From 2004 to 2016, 322 primary Hintegra TAAs were implanted: the 2nd generation implant from 2004 until mid-2007 and the 3rd generation from late 2007 to 2016. A Cox proportional hazards model evaluated sex, age, primary diagnosis, and implant generation, pre- and postoperative angles and implant position as risk factors for revision.Results — 60 implants (19%) were revised, the majority (n = 34) due to loosening. The 5-year survival rate (95% CI) was 75% (69–82) and the 10-year survival rate was 68% (60–77). There was a reduced risk of revision, per degree of increased postoperative medial distal tibial angle at 0.84 (0.72–0.98) and preoperative talus angle at 0.95 (0.90–1.00), indicating that varus ankles may have a larger revision rate. Generation of implant, sex, primary diagnosis, and most pre- and postoperative radiological angles did not statistically affect revision risk.Interpretation — Our revision rates are slightly above registry rates and well above those of the developer. Most were revised due to loosening; no difference was demonstrated with the 2 generations of implant used. Learning curve and a low threshold for revision could explain the high revision rate.

Arthritis in the ankle often develops earlier than in the hip or knee, and 70% have a traumatic etiology (Saltzman et al. 2005, Brown et al. 2006). Total ankle arthroplasty (TAA) can be indicated for severe arthritis in the ankle joint, but the anatomical preconditions, like a small surface area and high stress from compression and torque (Bouguecha et al. 2011, Kakkar and Siddique 2011), makes it less durable than hip and knee prosthetics. The Hintegra TAA, a 3-component mobile bearing, uncemented implant (Hintermann et al. 2004) is widely used and results from the development center demonstrate survival rates of 94% and 84% after 5 and 10 years’ follow-up (Barg et al. 2013). This is considerably more than the survival rates from national registries. Labek et al. (2011) demonstrated that development centers report only half of the revision rate that can be found in the few existing national registers. In a systematic review of primary Agility total ankle arthroplasty (DePuy Synthes Orthopedics, Warsaw, IN, USA), the author (Roukis 2012) found that the incidence of complications increased from 7% to 12%, in studies where the inventor was excluded. Similar results were found by Prissel and Roukis (2013), who found an increased incidence of complications from 6% to 13% in studies where the inventor or faculty consultants were excluded. These studies indicated the risk of selection (inventor) and publication (conflict of interest) bias.Planning and surgical technique, including significant experience, are mandatory for a successful outcome. The better result from development centers may reflect, besides the above-mentioned bias, that there is a long learning curve and that the indication for revision surgery varies.We examined the survival rates of primary Hintegra TAAs performed at Hvidovre Hospital, with revision rate as outcome. We report primary diagnosis for primary TAA and examine whether sex, generation of the implant, preoperative angles and implant position affect the revision rate.     

Evaluation of Screening and Commercial Methods for Detection of Methicillin Resistance in Coagulase-Negative Staphylococci

The National Committee for Clinical Laboratory Standards recommends 48 h of incubation by the oxacillin salt agar screen (OSAS) method for the detection of methicillin-resistant coagulase-negative staphylococci (CoNS). An earlier identification of methicillin resistance is desirable. The time to detection of the mecA gene by PCR was compared with the times to detection by OSAS, by the oxacillin disk diffusion (ODD) method, and with MicroScan Gram Positive Combo type 6 panels (MicroScan Inc. Sacramento, Calif.) and Vitek GPS-SA cards (bioMérieux Vitek Inc., Hazelwood, Mo.). The combination of the Vitek card and the ODD method detected 92 of 99 methicillin-resistant strains of CoNS at 24 h; however, 6 mecA-positive strains were phenotypically methicillin susceptible. We conclude that most methicillin-resistant CoNS can be detected and the results can be reported after overnight incubation by a combination of methods.     

Performance of the TechLab C. DIFF CHEK-60 enzyme immunoassay (EIA) in combination with the C. difficile Tox A/B II EIA kit, the Triage C. difficile panel immunoassay, and a cytotoxin assay for diagnosis of Clostridium difficile-associated diarrhea

We compared a recently marketed enzyme immunoassay for glutamate dehydrogenase (GDH), TechLab's C. DIFF CHEK-60 (TL-GDH), in combination with the C. difficile Tox A/B II enzyme immunoassay (Tox-A/B) with (i) the Triage C. difficile test, which detects both GDH (TR-GDH) and toxin A (TR-Tox-A); (ii) an in-house cytotoxin assay (C-Tox); and (iii) stool cultures for C. difficile. All C. difficile isolates were tested for the presence of the toxin genes by PCR. If a toxin gene-positive strain of Clostridium difficile was recovered and a toxin was detected by any method, the result was considered to be truly positive. Eighty-seven of 93 and 79 of 93 C. difficile culture-positive samples were also TL-GDH and TR-GDH positive, respectively. No test was able to detect toxin in all samples with true-positive results. Tox-A/B and TR-Tox-A in combination with the GDH detection tests and C-Tox were able to identify 52 and 50 samples with true-positive results. Tox-A/B and TR-Tox-A would have missed 15 and 31% of cases of C. difficile-associated diarrhea, respectively, if used alone.     

Stimulation of chronic lymphatic leukaemia cells by pokeweed mitogen after treatment with neuraminidase-galactose oxidase.

CLL lymphocytes gave a low response upon stimulation with PHA or PWM in 3-day cultures. However, after treatment with neuraminidase-galactose oxidase (NGO), in the presence of PWM, CLL lymphocytes transformed into blasts and incorporated 3H-thymidine in 3-day cultures. This response of CLL lymphocytes was similar to that given by normal lymphocytes to PWM in 3-day cultures. The best stimulation of CLL lymphocytes was achieved when conditioned medium (CM) from normal T lymphocytes was present in PWM cultures. Purified B lymphocytes from CLL (T lymphocytes and monocytes removed) did not respond to PHA or PWM. However, after NGO treatment these cells were stimulated by PWM, but only in the presence of CM. PHA failed to stimulate NGO-treated CLL lymphocytes or purified B lymphocytes. This study shows that CLL lymphocytes, which usually fail to respond to mitogens, can be stimulated by PWM to proliferate after treatment with neuraminidase-galactose oxidase (NGO). This technique of B cell stimulation has been found useful in cytogenetic studies of B cell proliferative disorders.     

HLA PROFILE OF ETHNIC PAKISTANI POPULATION GROUPS

Acute rejection is a major determinant of chronic allograft dysfunction and graft survival. This study evaluated the effect of basiliximab (Simulect^®), a 156-kDa chimeric monoclonal antibody (human and murine) directed against the alpha chain of the interleukin (IL)-2 receptor of human lymphocytes, on acute rejection in pediatric renal transplantation. Data were collected from two pediatric renal transplantation centers. Forty transplantations (22 males and 18 females; mean age 14.8±3.6 years) were performed between 1996 and 2001. Twelve of the grafts came from cadaveric donors and 28 from living-related donors. Twenty-four of the patients were on hemodialysis, 15 were on peritoneal dialysis, and one case was a pre-emptive transplantation. All patients were placed on triple-drug immunosuppression [prednisolone + (azathioprine or mycophenolate mofetil) +(cyclosporine or tacrolimus)]. Basiliximab was also administered in 17 cases. The respective rates of biopsy-proven acute rejection in the basiliximab group and the standard-regimen group were 0% vs. 17.4% ( P >0.05) at 1 month post-transplantation; 0% vs. 26.1% ( P <0.05) at 3 months; and 0% vs. 26.1% ( P <0.05) at 6 months. Thirty and 16 patients had completed 1- and 3-year follow ups, respectively, at the time of writing; the 1- and 3-year graft survival rates were 96% (29/30) and 81% (13/16), respectively.
Basiliximab significantly reduced the rates of acute rejection at 3- and 6 months post-pediatric renal transplantation. It was well tolerated by all patients, and caused no significant adverse effects. The effect of basiliximab on long-term graft survival and chronic allograft dysfunction deserves further investigation.     

An investigation of depotentiation of long-term potentiation in the CA1 region of the hippocampus

We have investigated long-term synaptic depression in the CA1 region of rat hippocampal slices. Prolonged low-frequency stimulation (LFS; 900 stimuli delivered at 2 Hz) of the Schaffer collateral-commissural pathway in naïve slices did not induce long-term depression (LTD) of synaptic transmission. However, if long-term potentiation (LTP) was firstly induced in the pathway then LFS generated an LTD-like effect (i.e. depotentiation of LTP). Depotentiation could be induced 2 h (the longest time studied) after the induction of LTP and was stable for the duration of the experiment (followed for up to 40 min). The induction of depotentiation was not blocked by the N-methyl-d-aspartate receptor antagonist d-2-amino-5-phosphonopentanoate, the L-type voltage-gated Ca²⁺ channel blocker nimodipine or the nitric oxide synthase inhibitor N-nitro-l-arginine. However, the magnitude of depotentiation was reversibly reduced, in a stereoselective manner, by the specific metabotropic glutamate receptor (mGluR) antagonist (+)--methyl-4-carboxyphenylglycine. These results show that prolonged low frequency stimulation can result in an mGluR-dependent depotentiation of LTP.     

Comparison of mismatch amplification mutation assay with DNA sequencing for characterization of fluoroquinolone resistance in Neisseria gonorrhoeae

A mismatch amplification mutation assay (MAMA) was developed for identification of point mutations in quinolone resistance-determining region (QRDR) of gyrA at codons 91 and 95. MAMA PCR was used to detect mutations at codons 91 and 95 of gyrA in 117 Neisseria gonorrhoeae isolates (with ciprofloxacin MICs of 0.004 to >32 microg/ml) from Bangladesh during 1997 to 2001. The QRDR regions of the gyrA genes from 31 randomly selected isolates were sequenced, and the results were compared with those of MAMA PCR. Using mismatch PCR, a mutation at Ser91 could be detected in all 27 (resistant and intermediate) isolates, and an Asp95-to-Gly95 mutation could be detected in all 15 isolates, as detected by sequencing. MAMA PCR offers a simple, inexpensive, rapid, and easier alternative for detection of point mutations in fluoroquinolone resistance in N. gonorrhoeae.     

Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich antigen

In order to identify T cell epitopes within the Mycobacterium leprae 45-kD serine-rich antigen, we analysed responses to overlapping 17-mer peptides encompassing the whole antigen in non-exposed UK controls, Pakistani leprosy patients and tuberculosis patients in both the United Kingdom and Pakistan. This antigen has been described as M. leprae-specific, although it has a hypothetical homologue in M. tuberculosis. Human peripheral blood mononuclear cells were stimulated with peptide for 5 days and IFN-gamma measured in supernatants by ELISA. Some peptides were recognized more frequently by T cells from tuberculoid leprosy patients than those from UK controls, suggesting that such T cell epitopes might have diagnostic potential, while other peptides induced greater responses among UK control subjects. Short-term cell lines confirmed that these assays detected specific T cell recognition of these peptides. However, many tuberculosis patients also recognized these potentially specific peptides suggesting that there could be a true homologue present in M. tuberculosis.     

Extraintestinal Seeding of Salmonella enterica Serotype Typhi,Pakistan

We evaluated Salmonella enterica serotype Typhi strains isolated from all body sites in Pakistan during 2013–2018. Despite an increase in overall number of localized, extensively drug-resistant Salmonella Typhi in organ infections during 2018, there was no increase in the proportion of such isolates in comparison with non–extensively drug-resistant isolates.