Management of severe periacetabular bone loss combined with pelvic discontinuity in revision hip arthroplasty

Purpose

Revision of failed total hip arthroplasty with massive acetabular bone loss resulting in pelvic discontinuity represents a rare but challenging problem. The objective of this study was to present short to mid-term results of revision total hip arthroplasty with a custom-made acetabular implant in a consecutive series of patients with pelvic discontinuity.

Methods

We retrospectively reviewed 18 consecutive patients with massive acetabular bone loss (Paprosky Type 3B) resulting in pelvic discontinuity reconstructed with revision total hip arthroplasty using a custom-made acetabular component. The prosthesis was created on the basis of a thin-cut 1-mm computed tomography (CT) scan of the pelvis. Initial stability of the implant was obtained by screw fixation. Harris hip score and sequential radiographs were used to evaluate the clinical and radiographic results.

Results

At an average follow up of 30 months (range 17–62 months) 16 of 18 (88.9 %) custom-made implants were considered radiographically stable without signs of acetabular migration of more than 2 mm in the horizontal or vertical direction, implant rotation or screw breakage. Complications included two periprosthetic joint infections treated with explantation of the implant. Three patients had recurrent dislocations postoperatively. The mean Harris hip score improved from 28?±?12 points preoperatively to 69?±?13 points at the time of last follow up.

Conclusion

Treatment of acetabular bone loss and pelvic discontinuity with a custom-made acetabular component can provide a durable solution with good clinical and radiographic results.     

Degarelix as an Intermittent Androgen Deprivation Therapy for One or More Treatment Cycles in Patients with Prostate Cancer

Background

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients.

Objective

To evaluate the efficacy and safety of degarelix as IAD for one or more treatment cycle(s) in prostate cancer patients requiring androgen deprivation.

Design, setting, and participants

This open-label uncontrolled multicenter study included patients with prostate-specific antigen (PSA) >4 to 50 ng/ml or PSA doubling time <24 mo. Induction included 7-mo treatment. Off-treatment period started when PSA was ≤4 ng/ml and lasted up to 24 mo based on PSA and testosterone levels. Treatment was reinitiated when PSA was >4 ng/ml.

Intervention

Each induction period included a starting dose of degarelix 240 mg, and thereafter 80 mg once a month for 6 mo, followed by off-treatment periods.

Outcome measurements and statistical analysis

The primary end point was time to PSA >4 ng/ml. Secondary end points were subgroup analysis of the primary end point, time to testosterone >0.5 and >2.2 ng/ml, quality of life (QoL), and sexual function during the first off-treatment period.

Results and limitations

Of 213 patients in the first induction period, 191 entered the first off-treatment period, 35 patients entered the second induction, and 30 entered the second off-treatment period. Only two patients entered the third cycle. Median time to PSA >4 ng/ml and duration of first off-treatment period was 392 d each. Significant differences in time to PSA >4 ng/ml were observed between subgroups stratified by prognostic factors (previous curative treatment, cancer stage, PSA levels, and Gleason scores). Time to testosterone >0.5 and >2.2 ng/ml was 112 and 168 d, respectively. Change in QoL remained nonsignificant, and sexual function gradually improved during the off-treatment period. Adverse events were fewer during the off-treatment period and subsequent treatment cycles.

Conclusions

IAD with degarelix resulted in an improvement in sexual function commensurate with increased testosterone levels while PSA remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Patient summary

Guidelines for prostate cancer treatment suggest that intermittent androgen deprivation (IAD) can be considered for certain patients. IAD with degarelix resulted in improved sexual function commensurate with increased testosterone levels while prostate-specific antigen remained suppressed. The treatment for one treatment cycle or more was well tolerated.

Trial registration

Clinicaltrials.gov identifier NCT00801242.     

The Role of Waste Management in Control of Rabies: A Neglected Issue

Despite being vaccine preventable, the global burden of dog rabies remains significant, and historically it is the rural and marginalized communities in developing countries of Africa and Asia that are most threatened by the disease. In recent years, the developing world has been experiencing unprecedented increases in urbanization, with a correspondingly massive increase in municipal solid waste generation, among other things. Inefficient and inadequate waste collection and management, due to lack of resources and planning, led to significant increases in the volumes of waste on the streets and in open dumps, where it serves as food sources for free-roaming dogs. In this commentary, we discuss examples of poor waste management and the likely impact on rabies control efforts through the sustenance of free-roaming dogs in some dog rabies-endemic countries. We aim to stress the importance of implementing strategies that effectively address this particular issue as an important component of humane dog population management, as it relates to aspirations for the control and elimination of dog rabies per se.     

Rabies Prophylactic and Treatment Options: An In Vitro Study of siRNA- and Aptamer-Based Therapeutics

If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective mass dog vaccination needs to be complemented by effective prophylaxis for individuals exposed to rabies. Aptamers and short-interfering RNAs (siRNAs) have been successful in therapeutics, but few studies have investigated their potential as rabies therapeutics. In this study, siRNAs and aptamers—using a novel selection method—were developed and tested against rabies virus (RABV) in a post-infection (p.i.) scenario. Multiple means of delivery were tested for siRNAs, including the use of Lipofectamine and conjugation with the developed aptamers. One siRNA (N53) resulted in an 80.13% reduction in viral RNA, while aptamer UPRET 2.03 demonstrated a 61.3% reduction when used alone at 2 h p.i. At 24 h p.i., chimera UPRET 2.03-N8 (aptamer-siRNA) resulted in a 36.5% inhibition of viral replication. To our knowledge, this is the first study using siRNAs or aptamers that (1) demonstrated significant inhibition of RABV using an aptamer, (2) tested Lipofectamine RNAi-Max as a means for delivery, and (3) produced significant RABV inhibition at 24 h p.i. This study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin (RIG) replacements or therapeutic options for RABV and provides strong evidence towards their further investigation.     

Linking the Electrical Conductivity and Non-Stoichiometry of Thin Film Ce1−xZrxO2−δ by a Resonant Nanobalance Approach

Bulk ceria-zirconia solid solutions (Ce_1−xZr_xO_2−δ, CZO) are highly suited for application as oxygen storage materials in automotive three-way catalytic converters (TWC) due to the high levels of achievable oxygen non-stoichiometry δ. In thin film CZO, the oxygen storage properties are expected to be further enhanced. The present study addresses this aspect. CZO thin films with 0 ≤ x ≤ 1 were investigated. A unique nano-thermogravimetric method for thin films that is based on the resonant nanobalance approach for high-temperature characterization of oxygen non-stoichiometry in CZO was implemented. The high-temperature electrical conductivity and the non-stoichiometry δ of CZO were measured under oxygen partial pressures pO₂ in the range of 10⁻²⁴–0.2 bar. Markedly enhanced reducibility and electronic conductivity of CeO₂-ZrO₂ as compared to CeO_2−δ and ZrO₂ were observed. A comparison of temperature- and pO₂-dependences of the non-stoichiometry of thin films with literature data for bulk Ce_1−xZr_xO_2−δ shows enhanced reducibility in the former. The maximum conductivity was found for Ce_0.8Zr_0.2O_2−δ, whereas Ce_0.5Zr_0.5O_2-δ showed the highest non-stoichiometry, yielding δ = 0.16 at 900 °C and pO₂ of 10⁻¹⁴ bar. The defect interactions in Ce_1−xZr_xO_2−δ are analyzed in the framework of defect models for ceria and zirconia.     

Magnetic-resonance-imaging-based three-dimensional muscle reconstruction of hip abductor muscle volume in a person with a transfemoral bone-anchored prosthesis: A feasibility study

Background: Persons with transfemoral amputation typically have severe muscle atrophy of the residual limb. The effect of bone-anchored prosthesis use on existing muscle atrophy is unknown. A potentially feasible method to evaluate this is magnetic resonance imaging (MRI)-based three-dimensional (3D) muscle reconstruction. We aimed to (1) examine the feasibility of MRI-based 3D muscle reconstruction technique in a person with a cobalt–chrome–molybdenum transfemoral bone-anchored prosthesis; and (2) describe the change of hip abductor muscle volume over time. Methods: In this single case, 1-year follow-up study we reconstructed the 3D hip abductor muscle volumes semiautomatically from MRI scans at baseline, 6- and 12-month follow-up. The number of adverse events, difficulties in data analysis, time investment and participants’ burden determined the level of feasibility. Results: We included a man (70 years) with a transfemoral amputation who received a bone-anchored prosthesis after 52 years of socket prosthesis use. No adverse events occurred. The accuracy of the 3D reconstruction was potentially reduced by severe adipose tissue interposition. Data analysis was time-intensive (115 h). Participants’ burden was limited to 3-h time investment. Compared to baseline, the total hip abductor volume of both the residual limb (6 month: 5.5%; 12 month: 7.4%) and sound limb (6 month: 7.8%; 12 month: 5.5%) increased. Conclusion: The presented technique appears feasible to follow muscle volume changes over time in a person with a cobalt–chrome–molybdenum transfemoral bone-anchored prosthesis in an experimental setting. Future research should focus on analysis of muscle tissue composition and the feasibility in bone-anchored prostheses of other alloys.     

Pocket hematoma after pacemaker or implantable cardioverter defibrillator surgery: influence of patient morbidity, operation strategy, and perioperative antiplatelet/anticoagulation therapy

STUDY OBJECTIVES: Pocket hematoma is a common complication after pacemaker or implantable cardioverter defibrillator (ICD) implantation. Thus, we investigated the influence of patient comorbidity, implantation strategy, operator experience, antiplatelet therapy, and anticoagulation therapy on hematoma rate. DESIGN: Between 1990 and 2002, a total of 3,164 devices (pectoral pacemakers, 2,792; ICDs, 372) were implanted at our institution. Predictors of hematoma occurrence were determined prospectively and were analyzed by multivariate regression analysis. Operator experience was graded by individual implantation number, as follows: low, < 50; medium, 50 to 100; and high, > 100. RESULTS: The incidence of pocket hematoma was 4.9%, leading to prolonged hospitalization in 2.0% of all patients. Reoperation for pocket hematoma was required in 1.0% of patients. High-dose heparinization (hazard ratio [HR], 4.2), combined acetylsalicylic acid (ASA)/thienopyridine treatment after coronary stenting (HR, 5.2), and low operator experience (HR, 1.6) were independently predictive of hematoma development. Therapy with ASA alone did not increase the hematoma rate compared to patients who did receive antiplatelet or anticoagulation therapy (3.1% vs 2.5%, respectively; difference not significant). In patients with nonvalvular atrial fibrillation, postoperative high-dose heparinization substantially increased the hematoma rate (10.7% vs 2.9%, respectively; p < 0.001) without reducing the rate of arterial embolism within the first month after implantation (0.18% vs 0.21%, respectively; difference not significant). The infection rate (0.28% within 3 months after implantation) was not influenced by the presence of the pocket hematoma. CONCLUSIONS: The use of high-dose heparinization and combined ASA/thienopyridine treatment are highly predictive for the occurrence of intraoperative bleeding and pocket hematoma in patients who have undergone pacemaker and ICD surgery. We propose recommendations for the management of antiplatelet and anticoagulation therapy in patients undergoing these interventions.     

Acceleration of plague outbreaks in the second pandemic

Historical records reveal the temporal patterns of a sequence of plague epidemics in London, United Kingdom, from the 14th to 17th centuries. Analysis of these records shows that later epidemics spread significantly faster (“accelerated”). Between the Black Death of 1348 and the later epidemics that culminated with the Great Plague of 1665, we estimate that the epidemic growth rate increased fourfold. Currently available data do not provide enough information to infer the mode of plague transmission in any given epidemic; nevertheless, order-of-magnitude estimates of epidemic parameters suggest that the observed slow growth rates in the 14th century are inconsistent with direct (pneumonic) transmission. We discuss the potential roles of demographic and ecological factors, such as climate change or human or rat population density, in driving the observed acceleration.

Plague epidemics have afflicted human populations since at least the sixth century (1, 2). These events have had dramatic and long-lasting effects on human demography and behavior, especially those outbreaks associated with the second pandemic (14th to 19th centuries) in Europe and Asia (1, 3–5), and have inspired many theoretical studies of the ecology and evolution of infectious disease (6–13). We are now in the third pandemic (Modern Plague), with outbreaks continuing to occur in some parts of the world (14–18). Plague also remains a source of concern due to the bioterror potential of the causative agent, Yersinia pestis (19, 20).Recent advances in paleogenomics have definitively established that historical plague pandemics were caused by Y. pestis (21, 22), as proposed in the 19th century after Yersin discovered the bacterium’s link to bubonic plague (23). Researchers have reconstructed the evolutionary history of plague and other pathogens by sequencing and reconstructing nearly complete pathogen genomes from persistent DNA fragments (21, 24, 25). The strain isolated from victims of the Black Death (London 1348) is remarkably similar to extant human strains (Modern Plague): the core genomes^*of these strains are ≈99.99% similar (21), which makes it challenging to identify important evolutionary or ecological patterns from genomic investigations alone. Here we complement genetic studies by exploring more traditional (historical, demographic, and epidemiological) sources of information from a 300-y span of plague outbreaks in the same location (London), revealing a striking change in plague transmission dynamics over the course of the Renaissance period, namely, a fourfold increase in the initial growth rate of outbreaks.We quantify this change without making any assumptions about the underlying transmission processes, exploiting methodology that we have developed previously for this purpose (26). We then consider how this inference can contribute to the debate concerning whether plague transmission was primarily indirect (via rat fleas) or direct (pneumonic human-to- human). We argue that strictly pneumonic transmission in the 14th century is implausible but that beyond this the best that can be done at present is to highlight the biological complexities and uncertainties that limit the potential for further inferences.     

Somatostatin receptor subtypes in human pheochromocytoma: subcellular expression pattern and functional relevance for octreotide scintigraphy

The stable somatostatin analog octreotide has been successfully used for imaging and treatment of a variety of human tumors. In pheochromocytoma, data on somatostatin receptor subtyping have thus far been sparse. Pheochromocytomas often express more than one somatostatin receptor, and it is uncertain by which receptor subtype the functional responses of octreotide are mediated. Here, we have examined somatostatin receptor protein expression in a panel of 52 pheochromocytomas from 35 randomly selected patients by immunostaining with specific polyclonal anti-sst(1-5) and monoclonal mouse anti-SS-14 antibodies. Staining pattern, distribution and subcellular localization of somatostatin receptor subtypes were investigated. Seventeen patients received (111)In-octreotide scintigraphy. Although the vast majority of tumors (90%) showed positive immunohistochemical staining for sst(3), immunoreactive sst(2A) receptors were only seen in 13 tumors (25%). All other somatostatin receptor subtypes were less frequently detected. Interestingly, among sst(3)-positive tumors strikingly different subcellular distributions of immunoreactive sst(3) receptors were observed. In most cases, immunoreactive sst(3) receptors were distributed throughout the cytosol. Scintigraphic localization of tumors larger than 1 cm in diameter was always successful in the presence of immunoreactive sst(2A) receptors. In the absence of sst(2A), true-positive octreotide scintigraphy was only seen in the presence of membrane-associated sst(3) immunoreactivity. Our findings suggest that selective expression of functional membrane-associated sst(3) receptors is sufficient for high tracer uptake during octreotide scintigraphy in a subgroup of human pheochromocytomas. These tumors may represent a potential target treatment with somatostatin receptor agonists with improved sst(3) activity.