Inferior stabilization of cementless compared with cemented dual-mobility cups in elderly osteoarthrosis patients: a randomized controlled radiostereometry study on 60 patients with 2 years’ follow-up

Background and purpose — Elderly patients may benefit from a dislocation low-risk dual-mobility (DM) articulation in total hip arthroplasty, but the best cup fixation method is unknown. We compared cup migration for cemented and cementless DM cups using radiostereometry.Patients and methods — In a patient-blinded randomized trial, 60 patients (33 female) with osteoarthritis were allocated to cemented (n = 30) or cementless (n = 30) Avantage DM cup fixation. Criteria were age above 70 years, and T-score above –4. We investigated cup migration, periprosthetic bone mineral density (BMD), and patient-reported outcome measures (PROMs) until 24 months postoperative follow-up.Results — At 24 months mean proximal cup migration was 0.11 mm (95% CI 0.00–0.23) for cemented cups and 0.09 mm (CI –0.09 to 0.28) for cementless cups. However, cementless cups generally migrated more than cemented cups at 12 and 24 months. Cemented cups had no measurable migration from 3 months’ follow-up, while cementless cups had not yet stabilized at 24 months in all rotations. Cementless cups showed statistically significantly more maximum total point motion (MTPM) at 12- and 24-month follow-up compared with cemented cups in patients with low systemic BMD (p = 0.01). Periprosthetic BMD changes did not statisticially significantly correlate to proximal migration in either cup fixation group (p > 0.05). PROMs improved similarly in both groups.Interpretation — Cemented cups were well fixed at 3 months. The cementless cups migrated more in patients with low BMD, showed an inconsistent pattern of migration, and migrated in different directions during the first and second year without tendency to stabilization. Cemented fixation of the Avantage DM cup seems safer in elderly patients

The most common indication for revision of a conventional primary total hip arthroplasty (THA) is aseptic loosening of the components (SHAR 2016, NJR 2017, DHAR 2018).Implant fixation method (i.e., cemented or cementless) in primary THA seems mainly based on the surgeon’s preference and national trends. The Danish Hip Replacement Registry report shows a decrease in the use of cemented cup fixation in osteoarthrosis (OA) patients above 70 years (DHAR 2018). This trend has also been described in the United Kingdom (UK) and Australian Joint Registries, while in Sweden and Norway cemented cup fixation is still the preferred fixation method in elderly patients (SHAR 2016, NAR 2017, NJR 2017).The dual-mobility (DM) concept, with 2 articulation surfaces and increased jump distance, may decrease the dislocation rate and increase range of motion compared with standard single mobility (SM) THAs. The long-term survival and the best fixation method of the newer Avantage Reload DM cup in elderly patients is currently unknown but retrospective studies on other types of primary DM THAs suggest acceptable survival rates (Batailler et al. 2017) .Excessive early (2-year) implant micromotion measured with radiostereometric analysis (RSA) is a strong predictor for later implant loosening and poor survival (Karrholm et al. 1997, Nieuwenhuijse et al. 2012, Pijls et al. 2012), and our primary aim was to investigate the early RSA-measured migration of cemented and cementless Avantage DM cups in elderly (> 70 years old) OA patients until 24 months’ follow-up. Secondary endpoints included systemic and periprosthetic bone mineral density (BMD) measurements, and clinical outcome scores.     

In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of the Mucorales Order

The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5 of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus, 26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC₅₀s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤0.03 to 0.5), 0.06 (≤0.03 to 0.25), and 0.125 (≤0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher than those for posaconazole. However, in the clinical setting this may be compensated for by the higher exposure at standard dosing.     

Superior fixation and less periprosthetic stress-shielding of tibial components with a finned stem versus an I-beam block stem: a randomized RSA and DXA study with minimum 5 years’ follow-up

Background and purpose — The stem on the tibial component of total knee arthroplasty provides mechanical resistance to lift-off, shear forces, and torque. We compared tibial components with finned stems (FS) and I-beam block stems (IS) to assess differences in implant migration.

Patients and methods — In a patient-blinded RCT, 54 patients/knees (15 men) with knee osteoarthritis at a mean age of 77 years (70–90) were randomly allocated to receive tibial components with either a FS (n = 27) or an IS (n = 27). Through 5 to 7 years’ follow-up, implant migration was measured with RSA, periprosthetic bone mineral density (BMD) was measured with DXA, and surgeons reported American Knee Society Score (AKSS).

Results — At minimum 5 years’ follow-up, maximum total point motion (MTPM) was higher (p = 0.04) for IS (1.48?mm, 95% CI 0.81–2.16) than for FS (0.85?mm, CI 0.38–1.32) tibial components. Likewise, total rotation (TR) was higher (p = 0.03) for IS (1.51?, CI 0.78–2.24) than for FS (0.81?, CI 0.36–1.27). Tibial components with IS externally rotated 0.50° (CI –0.06 to 1.06) while FS internally rotated 0.09° (CI –0.20 to 0.38) (p = 0.03). Periprosthetic bone stress-shielding was higher (p < 0.01) up to 2 years’ follow-up for IS compared with FS in the regions medial to the stem (–13% vs. –2%) and posterior to the stem (–13% vs. –2%). Below the stem bone loss was also higher (p = 0.01) for IS compared with FS (–6% vs. +1%) up to 1-year follow-up. Knee score improved similarly in both groups up to 5 years’ follow-up.

Interpretation — Periprosthetic bone stress-shielding medial and posterior to the stem until 2 years, and tibial component migration at 5 years, was less for a finned compared with an I-shaped block stem design.

Trial registration: ClinicalTrials.gov identifier: NCT00175136.     

Pulmonary mucormycosis in the aftermath of critical COVID-19 in an immunocompromised patient: Mind the diagnostic gap

Mucormycosis has recently been recognized as a severe complication of COVID-19 with high fatality rates. We report a fatal case of COVID-19 associated mucormycosis (CAM) in a non-diabetic immunocompromised patient, who was first misdiagnosed and treated for COVID-19 associated aspergillosis (CAPA). The risk factors and initial clinical presentation of CAPA and CAM are similar, but CAM has a more aggressive course and CAPA and CAM are treated differently. Dedicated diagnostic workup is essential to ensure early treatment of CAM with surgical debridement and targeted antifungal therapy.     

Oxford medial unicompartmental knees display contact‐loss during step‐cycle motion and bicycle motion: A dynamic radiostereometric study

The Oxford medial unicompartmental knee is designed fully congruent, with the purpose of maintaining a large contact‐area throughout motion and minimize wear. No other study has investigated this design feature in‐vivo. We aimed to evaluate if contact‐loss was introduced between the articulating surfaces of the Oxford medial unicompartmental knee during bicycle‐ and step‐cycle motion, and whether this correlated with essential implant parameters, such as polyethylene (PE) wear, knee‐loadings, and clinical outcome. To study contact‐loss, 15 patients (12 males, mean age 69 years) with an Oxford medial unicompartmental knee (7 cemented, mean follow‐up 4.4 years) were examined with use of dynamic radiostereometry (RSA) (10 frames/s). PE wear was measured from static RSA and clinical outcome was evaluated with American Knee Society Score (AKSS) and Oxford Knee Score (OKS). Data on knee‐loadings were acquired from the literature. Contact‐loss was deteced in all patients during both exercises, and the trend of contact‐loss correlated with the knee‐loadings. Median contact‐loss was 0.8 mm (95%PI: 0.3; 1.5) for bicycle motion and 0.3 mm (95%PI: 0.24; 0.35) for step‐cycle motion, and did not correlate with the PE wear rate of mean 0.06 mm/year. Possible in‐congruency was seen in three patients. Clinical outcome scores correlated with contact‐loss during step‐cycle motion. In conclusion, contact‐loss was seen in all patients indicating a clinical tolerance during load. Contact‐loss followed the knee‐loadings, which could explain why no correlation was seen with PE wear, as an increase in load was acommadated by an increase in contact‐area (contact‐loss reduction). The size of contact‐loss may reflect clinical outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:357–364, 2018.     

Bone Mineral Density Measurements Around Osseointegrated Implants: A Precision Study and Validation of Scan Protocol for Transfemoral Amputees

Visual evaluation of bone changes around an osseointegration (OI) implant in femoral amputees examined on plain radiographs shows that periprosthetic bone resorption takes place during the first years after OI surgery, but the bone mineral density (BMD) change has not been previously quantified by dual-energy X-ray absorptiometry (DXA). Precision is vital when monitoring BMD changes around implants, and thus the aim of this study was to evaluate the precision and feasibility of a scan protocol for BMD measurements in proximity of OI implants. The proximal part of 2 human cadaveric femoral bones (specimens A and B) with OI implants were mounted in a positioning jig and DXA scans were repeated 5 times in increments of 5° from neutral (0°) to 20° flexion and rotation. BMD changes as a result of change in leg position were evaluated. Repeated patient examinations (n?=?20) were conducted in a clinical setting and the precision error was calculated for each of 7 periprosthetic custom-made regions of interest (ROIs). The precision of cadaveric BMD measurements in neutral position was <3.3%. Even 5° flexion or rotation in femur position caused significant changes in average BMD (p?<0.04). Depending on ROI, the percentage of coefficient of variation (%CV) and average BMD was?<6% at 10° flexion and rotation. At 20° flexion, %CV increased up to 12.7% and average BMD increased up to 9.9%. The clinical short-term precision root mean square standard deviation ranged from 0.031?g/cm² to 0.047?g/cm² and %CV ranged from 3.12% to 6.57% depending on ROI. Simulated hip flexion or rotation of the femur affected periprosthetic BMD measurements around OI implants in cadaveric femoral bones, which stresses the importance of a reproducible set-up during DXA scans to reduce measurement errors caused by variation in leg position. Adherence to the scan protocol with a relaxed position of the residual limb resulted in an acceptable short-term precision below 6.6%.     

Comparison of Caspofungin MICs by Means of EUCAST Method EDef 7.1 Using Two Different Concentrations of Glucose

According to the product insert for Cancidas (caspofungin acetate), the drug must not be diluted in solutions containing glucose as this decreases caspofungin stability. The aim of this study was to compare caspofungin MICs for a collection of yeasts by means of EUCAST method EDef7.1 but using two different concentrations of glucose: 2% versus 0.2%. MICs were identical or within one 2-fold dilution for 93 out of 95 strains (97.9%), showing that glucose does not interfere with susceptibility.In a previous work, a comparison of the major susceptibility testing methods for echinocandins was performed using a well-characterized panel of Candida strains (1). EUCAST method EDef 7.1 performed as one of the best methods for discriminating wild-type strains from isolates with mutations in FKS hot spot regions. However, for caspofungin the MICs obtained by EUCAST method EDef 7.1 were in general higher than those obtained using the CLSI M27A3 methodology. In addition, the number of very major errors (number of FSK hot spot mutants classified as susceptible according the wild-type upper limit values) was 50% for EUCAST method EDef 7.1 (1), while 7% of very major errors were obtained by means of CLSI M27A3 at 24 h (1, 2). Finally, this previous work also found that caspofungin MICs obtained by means of EUCAST method EDef 7.1 and CLSI M27A3 were, in general, higher than those obtained by Pfaller et al. in a previous work using CLSI M27A3 methodology (4), indicating a possible variability associated with caspofungin antifungal susceptibility testing (1). Thus, it was of interest to explore which variables influence the reproducibility of the susceptibility tests for caspofungin. Although it has been proven that both the EUCAST EDef 7.1 and CLSI M27 A3 (2, 5) methodologies generate similar results for amphotericin B and azole drugs (3, 6), this does not appear to be the case for caspofungin. The main differences between EUCAST method EDef 7.1 and CLSI M27A3 include different inocula (10⁵ versus 10³ CFU/ml, respectively) and glucose concentrations (2% versus 0.2%, respectively) (3, 6).The product insert for Cancidas states that the compound must not be diluted in solutions containing glucose because it decreases drug stability. As stated previously, the glucose concentration in the growth medium recommended for method EDef 7.1 in RPMI 1640 is 10 times higher than that recommended by the CLSI (5). As this concentration could have influenced the MIC values obtained by means of EUCAST method EDef 7.1 (5), the Antifungal Susceptibility Testing Subcommittee of EUCAST decided to set up a comparison test to examine whether the increased glucose concentration affects the MIC results. The test compared caspofungin MICs for a collection of well-characterized yeast isolates by means of EUCAST method EDef 7.1 (5) but using growth medium with two different concentrations of glucose: 2% versus 0.2%.     

The prognostic value of polycomb group protein B‐cell‐specific moloney murine leukemia virus insertion site 1 in stage II colon cancer patients

The aim of this study was to investigate the prognostic value of B‐cell‐specific moloney murine leukemia virus insertion site 1 (BMI1) protein expression in primary tumors of stage II colon cancer patients. BMI1 protein expression was assessed by immunohistochemistry in a retrospective patient cohort consisting of 144 stage II colon cancer patients. BMI1 expression at the invasive front of the primary tumors correlated with mismatch repair status of the tumors. Furthermore, BMI1 expression at the luminal surface correlated with T‐stage, tumor location, and the histological subtypes of the tumors. In a univariate Cox proportional hazard analysis, no statistical significant association between risk of relapse and BMI1 protein expression at the invasive front (HR: 1.12; 95% CI 0.78–1.60; p = 0.53) or at the luminal surface of the tumor (HR: 1.06; 95% CI 0.75–1.48; p = 0.70) was found. Likewise, there was no association between 5‐year overall survival and BMI1 expression at the invasive front (HR: 1.12; 95% CI 0.80–1.56; p = 0.46) or at the luminal surface of the tumor (HR: 1.16; 95% CI 0.86–1.60; p = 0.33). In conclusion, BMI1 expression in primary tumors of stage II colon cancer patients could not predict relapse or overall survival of the patients, thus having a limited prognostic value in stage II colon cancer patients.