Ebola virus disease mathematical models and epidemiological parameters: a systematic review.

Ebola virus disease poses a recurring risk to human health. We conducted a systematic review (PROSPERO CRD42023393345) of Ebola virus disease transmission models and parameters published from database inception to July 7, 2023, from PubMed and Web of Science. Two people screened each abstract and full text. Papers were extracted with a bespoke Access database, 10% were double extracted. We extracted 1280 parameters and 295 models from 522 papers. Basic reproduction number estimates were highly variable, as were effective reproduction numbers, likely reflecting spatiotemporal variability in interventions. Random-effect estimates were 15·4 days (95% CI 13·2-17·5) for the serial interval, 8·5 days (7·7-9·2) for the incubation period, 9·3 days (8·5-10·1) for the symptom-onset-to-death delay, and 13·0 days (10·4-15·7) for symptom-onset-to-recovery. Common effect estimates were similar, albeit with narrower CIs. Case-fatality ratio estimates were generally high but highly variable, which could reflect heterogeneity in underlying risk factors. Although a substantial body of literature exists on Ebola virus disease models and epidemiological parameter estimates, many of these studies focus on the west African Ebola epidemic and are primarily associated with Zaire Ebola virus, which leaves a key gap in our knowledge regarding other Ebola virus species and outbreak contexts.

High-resolution epidemiological landscape from ~290,000 SARS-CoV-2 genomes from Denmark.

Vast amounts of pathogen genomic, demographic and spatial data are transforming our understanding of SARS-CoV-2 emergence and spread. We examined the drivers of molecular evolution and spread of 291,791 SARS-CoV-2 genomes from Denmark in 2021. With a sequencing rate consistently exceeding 60%, and up to 80% of PCR-positive samples between March and November, the viral genome set is broadly whole-epidemic representative. We identify a consistent rise in viral diversity over time, with notable spikes upon the importation of novel variants (e.g., Delta and Omicron). By linking genomic data with rich individual-level demographic data from national registers, we find that individuals aged  < 15 and  > 75 years had a lower contribution to molecular change (i.e., branch lengths) compared to other age groups, but similar molecular evolutionary rates, suggesting a lower likelihood of introducing novel variants. Similarly, we find greater molecular change among vaccinated individuals, suggestive of immune evasion. We also observe evidence of transmission in rural areas to follow predictable diffusion processes. Conversely, urban areas are expectedly more complex due to their high mobility, emphasising the role of population structure in driving virus spread. Our analyses highlight the added value of integrating genomic data with detailed demographic and spatial information, particularly in the absence of structured infection surveys.

The interaction of disease transmission, mortality, and economic output over the first 2 years of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused over 7.02 million deaths as of January 2024 and profoundly affected most countries' Gross Domestic Product (GDP). Here, we study the interaction of SARS-CoV-2 transmission, mortality, and economic output between January 2020 and December 2022 across 25 European countries. METHODS: We use a Bayesian mixed effects model with auto-regressive terms to estimate the temporal relationships between disease transmission, excess deaths, changes in economic output, transit mobility and non-pharmaceutical interventions (NPIs) across countries. RESULTS: Disease transmission intensity (logRt) decreases GDP and increases excess deaths, where the latter association is longer-lasting. Changes in GDP as well as prior week transmission intensity are both negatively associated with each other (-0.241, 95% CrI: -0.295 - -0.189). We find evidence of risk-averse behaviour, as changes in transit and prior week transmission intensity are negatively associated (-0.055, 95% CrI: -0.074 to -0.036). Our results highlight a complex cost-benefit trade-off from individual NPIs. For example, banning international travel is associated with both increases in GDP (0.014, 0.002-0.025) and decreases in excess deaths (-0.014, 95% CrI: -0.028 - -0.001). Country-specific random effects, such as the poverty rate, are positively associated with excess deaths while the UN government effectiveness index is negatively associated with excess deaths. INTERPRETATION: The interplay between transmission intensity, excess deaths, population mobility and economic output is highly complex, and none of these factors can be considered in isolation. Our results reinforce the intuitive idea that significant economic activity arises from diverse person-to-person interactions. Our analysis quantifies and highlights that the impact of disease on a given country is complex and multifaceted. Long-term economic impairments are not fully captured by our model, as well as long-term disease effects (Long COVID).

Promoting healthy populations as a pandemic preparedness strategy: a simulation study from Mexico.

Background: The underlying health status of populations was a major determinant of the impact of the COVID-19 pandemic, particularly obesity prevalence. Mexico was one of the most severely affected countries during the COVID-19 pandemic and its obesity prevalence is among the highest in the world. It is unknown by how much the COVID-19 burden could have been reduced if systemic actions had been implemented to reduce excess weight in Mexico before the onset of the pandemic. Methods: Using a dynamic epidemic model based on nationwide data, we compare actual deaths with those under hypothetical scenarios assuming a lower body mass index in the Mexican population, as observed historically. We also model the number of deaths that would have been averted due to earlier implementation of front-of-pack warning labels or due to increases in taxes on sugar-sweetened beverages and non-essential high-energy foods in Mexico. Findings: We estimate that 52.5% (95% prediction interval (PI) 43.2, 61.6%) of COVID-19 deaths were attributable to obesity for adults aged 20-64 and 23.8% (95% PI 18.7, 29.1%) for those aged 65 and over. Had the population BMI distribution remained as it was in 2000, 2006, or 2012, COVID-19 deaths would have been reduced by an expected 20.6% (95% PI 16.9, 24.6%), 9.9% (95% PI 7.3, 12.9%), or 6.9% (95% PI 4.5, 9.5%), respectively. If the food-labelling intervention introduced in 2020 had been introduced in 2018, an expected 6.2% (95% PI 5.2, 7.3%) of COVID-19 deaths would have been averted. If taxes on sugar-sweetened beverages and high-energy foods had been doubled, trebled, or quadrupled in 2018, COVID-19 deaths would have been reduced by an expected 4.1% (95% PI 2.5, 5.7%), 7.9% (95% PI 4.9, 11.0%), or 11.6% (95% PI 7.3, 15.8%), respectively. Interpretation: Public health interventions targeting underlying population health, including non-communicable chronic diseases, is a promising line of action for pandemic preparedness that should be included in all pandemic plans. Funding: This study received funding from Bloomberg Philanthropies, awarded to Juan A. Rivera from the National Institute of Public Health; Community Jameel, the UK Medical Research Council (MRC), Kenneth C Griffin, and the World Health Organization.

The early determinants of career choices for medical students following an obstetrics and gynaecology placement: Mixed methods study.

OBJECTIVE: To explore the impact of attending a clinical placement in considering a career in obstetrics and gynaecology. DESIGN: Mixed methods study. SETTING: London Medical School. POPULATION: Fifth year medical students attending a clinical placement in obstetrics and gynaecology. METHODS: Between January 2021 and January 2022, questionnaires were used and semi-structured focus groups conducted, which were audio-recorded. Descriptive statistics were conducted and a framework analysis on transcribed focus groups. MAIN OUTCOME MEASURE: The impact of the clinical placement on career choice. RESULTS: Six main themes were identified from the analysis; three contributing to considering a career in obstetrics and gynaecology; pregnancy is not an illness, extraordinary experience of observing childbirth and variable specialty and three themes emerged contributing to not considering a career; lack of work-life balance, high stakes specialty and the emotional toll. Even at an undergraduate level, medical students exhibited concerns about the long-term feasibility of achieving work-life balance and avoiding professional burnout, which was partly attributed to the responsibility of looking after both the woman and their baby. CONCLUSIONS: Obstetrics and gynaecology is perceived as an exciting and variable speciality by medical students. Students' experiences on the labour ward during a clinical placement appear to contribute to the consideration of a career in obstetrics and gynaecology. Students should be given opportunities to discuss their concerns about obstetrics, particularly over the potential psychological impact of adverse/traumatic birth events. It is crucial to provide a realistic introduction to obstetrics, to recruit enthusiastic junior doctors who will be resilient to the pressures of the speciality, to avoid burnout and minimise attrition rates.

Marburg virus disease outbreaks, mathematical models, and disease parameters: a systematic review.

The 2023 Marburg virus disease outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this lethal pathogen. We did a systematic review (PROSPERO CRD42023393345) of peer-reviewed articles reporting historical outbreaks, modelling studies, and epidemiological parameters focused on Marburg virus disease. We searched PubMed and Web of Science from database inception to March 31, 2023. Two reviewers evaluated all titles and abstracts with consensus-based decision making. To ensure agreement, 13 (31%) of 42 studies were double-extracted and a custom-designed quality assessment questionnaire was used for risk of bias assessment. We present detailed information on 478 reported cases and 385 deaths from Marburg virus disease. Analysis of historical outbreaks and seroprevalence estimates suggests the possibility of undetected Marburg virus disease outbreaks, asymptomatic transmission, or cross-reactivity with other pathogens, or a combination of these. Only one study presented a mathematical model of Marburg virus transmission. We estimate an unadjusted, pooled total random effect case fatality ratio of 61·9% (95% CI 38·8-80·6; I2=93%). We identify epidemiological parameters relating to transmission and natural history, for which there are few estimates. This systematic review and the accompanying database provide a comprehensive overview of Marburg virus disease epidemiology and identify key knowledge gaps, contributing crucial information for mathematical models to support future Marburg virus disease epidemic responses.

Full-Endoscopic Removal of Migrated and Pseudoarthrotic Lumbar Interbody Cages: Case Reports and Technical Note.

BACKGROUND: The removal of a lumbar interbody cage in revision spine surgery can be challenging, as there is an increased risk of nerve injury and a protracted outcome. The aim of this study was to evaluate the feasibility and preliminary results of uniportal full-endoscopic surgery for the removal of migrated and/or pseudarthrotic lumbar interbody cages. METHODS: Three complex revision surgery cases with migrated and pseudarthrotic lumbar interbody cages are presented, and the endoscopic surgical technique is described. The clinical outcome was assessed with a visual analog scale and Oswestry Disability Index (ODI) at 1-, 3-, 6-, and 12-month follow-up, while the radiologic outcome was assessed with pre- and postoperative x-ray and computed tomographic images. Full-endoscopic surgery was performed to extract the interbody cage, bypassing scar tissue of previous surgeries with the trans-Kambin approach. Foraminoplasty with manual reamers and/or a high-speed burr under direct endoscopic vision was performed to ensure the safety of the exiting nerve root during cage extraction. The retrieved cage was replaced with a large footprint, expandable titanium cage using the trans-Kambin approach. RESULTS: In all 3 cases, different types of interbody cages (1 titanium, 2 polyetheretherketone, and 1 expandable titanium cage) were removed under direct endoscopic view. In 1 case, we were only able to partially remove an impacted polyetheretherketone cage from the interbody disc endoscopically. The postoperative outcome significantly (P < 0.05) improved compared with preoperative scores in all 3 cases with a follow-up of 6 and 12 months, respectively. CONCLUSION: In most cases, lumbar interbody cages can be safely removed with endoscopic surgery with good preliminary clinical outcome. Nonetheless, further clinical research with long-term follow-up is required. CLINICAL RELEVANCE: Results indicate the feasibility of full-endoscopic removal of migrated and pseudoarthrotic lumbar interbody cages.

Intrinsic randomness in epidemic modelling beyond statistical uncertainty.

Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.

Data needs for integrated economic-epidemiological models of pandemic mitigation policies.

The COVID-19 pandemic and the mitigation policies implemented in response to it have resulted in economic losses worldwide. Attempts to understand the relationship between economics and epidemiology has led to a new generation of integrated mathematical models. The data needs for these models transcend those of the individual fields, especially where human interaction patterns are closely linked with economic activity. In this article, we reflect upon modelling efforts to date, discussing the data needs that they have identified, both for understanding the consequences of the pandemic and policy responses to it through analysis of historic data and for the further development of this new and exciting interdisciplinary field.

Thoracolumbar Interfascial Plane Block Results in Opioid-Free Postoperative Recovery After Percutaneous/Endoscopic Transforaminal Lumbar Interbody Fusion Surgery.

OBJECTIVE: To evaluate efficacy in reducing postoperative pain and opioid analgesia of a novel interdisciplinary strategy combining preoperative thoracolumbar interfascial plane (TLIP) block and percutaneous/endoscopic transforaminal lumbar interbody fusion surgery and to determine time to first postoperative ambulation and hospital length of stay. METHODS: In this retrospective review, 42 patients who underwent elective single-level percutaneous/endoscopic transforaminal lumbar interbody fusion surgery between 2015 and 2021 were divided into 2 groups: TLIP group with 17 patients who underwent TLIP block and non-TLIP group with 25 patients. Both groups received the same postoperative analgesia with morphine as patient-controlled rescue medication. Visual analog scale and Oswestry Disability Index scores were evaluated. Statistical evaluation was performed with Student t test. RESULTS: In contrast to the non-TLIP group, in the TLIP group, postoperative mean visual analog scale back score and mean Oswestry Disability Index score significantly decreased from 6.6 to 3.3 (P < 0.01) and 32.8 to 23.6 (P < 0.01), respectively, at hospital discharge. No differences were found between the groups at 1 month. Overall mean follow-up time was 29 ± 18 months (range, 3-78 months). Patients in the non-TLIP group were administered a median postoperative 24-hour morphine dose equivalent of 23 mg (range, 8-31 mg), while patients in the TLIP group did not require opioid analgesia (P < 0.01). Patients in the TLIP group started postoperative ambulation at a median of 4.1 hours (range, 2.5-26 hours) with a median hospital length of stay of 24 hours (range, 20-48 hours) (P = 0.112). CONCLUSIONS: TLIP block significantly improves patient outcome at hospital discharge after transforaminal lumbar interbody fusion surgery without postoperative administration of opioids. A prospective study is recommended to confirm our preliminary results.

The impact of non-pharmaceutical interventions on SARS-CoV-2 transmission across 130 countries and territories.

BACKGROUND: Non-pharmaceutical interventions (NPIs) are used to reduce transmission of SARS coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, empirical evidence of the effectiveness of specific NPIs has been inconsistent. We assessed the effectiveness of NPIs around internal containment and closure, international travel restrictions, economic measures, and health system actions on SARS-CoV-2 transmission in 130 countries and territories. METHODS: We used panel (longitudinal) regression to estimate the effectiveness of 13 categories of NPIs in reducing SARS-CoV-2 transmission using data from January to June 2020. First, we examined the temporal association between NPIs using hierarchical cluster analyses. We then regressed the time-varying reproduction number (Rt) of COVID-19 against different NPIs. We examined different model specifications to account for the temporal lag between NPIs and changes in Rt, levels of NPI intensity, time-varying changes in NPI effect, and variable selection criteria. Results were interpreted taking into account both the range of model specifications and temporal clustering of NPIs. RESULTS: There was strong evidence for an association between two NPIs (school closure, internal movement restrictions) and reduced Rt. Another three NPIs (workplace closure, income support, and debt/contract relief) had strong evidence of effectiveness when ignoring their level of intensity, while two NPIs (public events cancellation, restriction on gatherings) had strong evidence of their effectiveness only when evaluating their implementation at maximum capacity (e.g. restrictions on 1000+ people gathering were not effective, restrictions on < 10 people gathering were). Evidence about the effectiveness of the remaining NPIs (stay-at-home requirements, public information campaigns, public transport closure, international travel controls, testing, contact tracing) was inconsistent and inconclusive. We found temporal clustering between many of the NPIs. Effect sizes varied depending on whether or not we included data after peak NPI intensity. CONCLUSION: Understanding the impact that specific NPIs have had on SARS-CoV-2 transmission is complicated by temporal clustering, time-dependent variation in effects, and differences in NPI intensity. However, the effectiveness of school closure and internal movement restrictions appears robust across different model specifications, with some evidence that other NPIs may also be effective under particular conditions. This provides empirical evidence for the potential effectiveness of many, although not all, actions policy-makers are taking to respond to the COVID-19 pandemic.

Thermogenic diagnosis of periprosthetic joint infection by microcalorimetry of synovial fluid.

BACKGROUND: Synovial fluid culture is the standard investigation for the preoperative diagnosis of periprosthetic joint infection (PJI). However, the culture has limited sensitivity and requires several days until result. We evaluated the value of isothermal microcalorimetry for real-time diagnosis of PJI based on heat produced by microbial growth in synovial fluid. METHODS: Patients undergoing aspiration of prosthetic hip or knee joint before revision surgery were prospectively included between 2014 and 2015. The performance of microcalorimetry was compared to synovial fluid culture using McNemar's chi-squared test. Pearson's correlation coefficient was calculated for synovial fluid leukocyte count and microcalorimetric heat. RESULTS: Of 107 included patients (58 knee and 49 hip prosthesis), PJI was diagnosed in 46 patients (43%) and aseptic failure in 61 patients (57%) according to institutional criteria. In 26 PJI cases (56%) the pathogen grew in synovial fluid and intra-operative cultures. The sensitivity of synovial fluid culture and microcalorimetry was both 39% and the results were concordant in 98 patients (92%). In patients with PJI, microcalorimetry missed 4 pathogens which grew in synovial fluid culture, whereas culture missed 4 pathogens detected by microcalorimetry. A linear correlation (r = 0.366) was found between leukocyte count and microcalorimetric heat in synovial fluid (p < 0.001). The median time to positivity of microcalorimetry was 9 h (range, 1-64 h) vs. 3 days for cultures (range, 1-14 days). CONCLUSION: Microcalorimetry of synovial fluid allows thermogenic diagnosis of periprosthetic joint infection in synovial fluid. The diagnostic performance of synovial fluid microcalorimetry is comparable to culture and delivers results considerably faster. TRIAL REGISTRATION: This prospective study was registered on August 21, 2015 with the public clinical trial identification NCT02530229.

Value of multiplex PCR for detection of antimicrobial resistance in samples retrieved from patients with orthopaedic infections.

BACKGROUND: The performance of multiplex PCR (mPCR) for detection of antimicrobial resistance from clinical isolates is unknown. We assessed the ability of mPCR to analyse resistance genes directly from clinical samples. Patients with orthopedic infections were prospectively included. Phenotypical and genotypical resistance was evaluated in clinical samples (synovial and sonication fluid) where identical pathogens were identified by culture and mPCR. RESULT: A total of 94 samples were analysed, including 60 sonication fluid and 34 synovial fluid samples. For coagulase-negative staphylococcus strains, mPCR detected resistance to oxacillin in 10 of 23 isolates (44%) and to rifampin in none of 6 isolates. For S. aureus isolates, detection rate of oxacillin and rifampin-resistance was 100% (2/2 and 1/1, respectively). Fluoroquinolone-resistance was confirmed by mPCR in all 3 isolates of Enterobacteriaceae, in enterococci resistance to aminoglycoside-high level was detected in 1 of 3 isolates (33%) and in streptococci resistance to macrolides/lincosamides in none of 2 isolates. The overall sensitivity for different pathogens and antimicrobials was 46% and specificity 95%, the median concordance was 80% (range, 57-100%). Full agreement was observed for oxacillin in S. aureus, vancomycin in enterococci, carbapenems/cephalosporins in Enterobacteriaceae and rifampin in Cutibacterium species. CONCLUSION: The overall sensitivity for detection of antimicrobial resistance by mPCR directly from clinical samples was low. False-negative mPCR results occurred mainly in coagulase-negative staphylococci, especially for oxacillin and rifampin. However, the specificity of mPCR was high and a positive result reliably predicted antimicrobial resistance. Including universal primers in the PCR test assay may improve the detection rate but requires additional sequencing step. TRIAL REGISTRATION: www.clinicaltrials.gov No. NCT02530229, registered at 21 August 2015 (retrospectively registered).

Full Percutaneous Transforaminal Lumbar Interbody Fusion Using the Facet-sparing, Trans-Kambin Approach.

STUDY DESIGN: This was a prospective, multicenter, consecutive case series' study. OBJECTIVE: The objective of this study was to evaluate a novel facet-sparing, percutaneous transforaminal lumbar interbody fusion (pTLIF) technique consisting of percutaneous insertion of an expandable interbody cage through an endoscopic cannula with the trans-Kambin approach and complemented with percutaneous transpedicular screws and rods. SUMMARY OF BACKGROUND DATA: Lumbar interbody fusion by open or minimally invasive surgery is the usual treatment for degenerative disk disease but requires a relatively long recovery period. The transforaminal trans-Kambin approach is a standard in endoscopic spine surgery for safe intradiscal access without facet resection. METHODS: Preoperative and postoperative Visual Analogue Scale (VAS) and Oswestry Disability Index scores were quantitatively assessed at 1, 3, 6, and 12 months after surgery and then every 12 months for patients treated with pTLIF between 2009 and 2018 in 2 health care centers. An immediate postoperative control computed tomography scan was performed, whereas conventional postoperative x-ray controls were performed at 1 month and 1 year. Statistical evaluation was performed with the Student t test. RESULTS: A total of 51 patients (mean age, 59.3 y) were evaluated. The overall mean VAS score for axial lumbar pain improved from 6.6 to 1.8 (P<0.01), mean VAS score for leg pain from 5.5 to 1.2 (P<0.01), and mean Oswestry Disability Index scores from 30.3 to 11.8 (P<0.01) postoperatively with a mean follow-up of 27.9 months (range, 1-77.8 mo). Median estimated blood loss was 103.6 mL. Postoperative complications included 12 (22%) cases with transitory ipsilateral dysesthesia, 2 (4%) cases with transitory ipsilateral muscle weakness, and 3 (6%) clinically asymptomatic cases with radiologic cage subsidence. Median hospital stay was 1.4 days (range, 1-3.2 d). CONCLUSIONS: Postoperative scores for pTLIF significantly improved with minimal blood loss and no long-term complications. On the basis of this experience, the facet-sparing pTLIF is a reliable and safe technique with early hospital discharge, opening the way to outpatient instrumented spine surgery. LEVEL OF EVIDENCE: Level III.

Multiplex Polymerase Chain Reaction and Microcalorimetry in Synovial Fluid: Can Pathogen-based Detection Assays Improve the Diagnosis of Septic Arthritis?

OBJECTIVE: To prospectively evaluate automated multiplex PCR and isothermal microcalorimetry tests for rapid and accurate diagnosis of septic arthritis. METHODS: Patients with acute arthritis were prospectively included from October 2014 to September 2015. In synovial fluid (SF), leukocyte count and differential, culture, PCR, and microcalorimetry were determined. Septic arthritis was diagnosed by positive SF culture or (1) local clinical signs and symptoms, (2) increased SF leukocyte count, and (3) exclusion of noninfectious causes of inflammatory arthropathy. The performance of individual tests was compared with McNemar's test. RESULTS: Among 57 patients, 22 (39%) were diagnosed with septic arthritis. SF culture grew a pathogen in 10 patients (46%), PCR was positive in 5 (23%), and microcalorimetry in 10 (46%). Compared to SF culture, 49 concordant pairs were found for both methods (PCR and microcalorimetry; 86% agreement). In SF, PCR failed to detect Staphylococcus aureus (2 patients), Streptococcus pneumoniae (1 patient), Streptococcus dysgalactiae (1 patient), and Clostridium clostridioforme (1 patient). Microcalorimetry failed to detect S. dysgalactiae (1 patient), Streptococcus agalactiae (1 patient), and C. clostridioforme (1 patient). No statistical differences between the performance of SF culture, and PCR and microcalorimetry, respectively, were found. The processing time for PCR was 5 h and for microcalorimetry a median of 8.8 h (range, 2.3-64 h), whereas cultures required a median of 4.5 days (range, 3-14 days). CONCLUSION: Performance of SF PCR was inferior while microcalorimetry was similar to culture but provided results considerably faster. [Clinical trial registration number (https://www.clinicaltrials.gov): NCT02530229].

Value of PCR in sonication fluid for the diagnosis of orthopedic hardware-associated infections: Has the molecular era arrived?

INTRODUCTION: Bone healing disturbance following fracture fixation represents a continuing challenge. We evaluated a novel fully automated polymerase chain reaction (PCR) assay using sonication fluid from retrieved orthopedic hardware to diagnose infection. PATIENTS AND METHODS: In this prospective diagnostic cohort study, explanted orthopedic hardware materials from consecutive patients were investigated by sonication and the resulting sonication fluid was analyzed by culture (standard procedure) and multiplex PCR (investigational procedure). Hardware-associated infection was defined as visible purulence, presence of a sinus tract, implant on view, inflammation in peri-implant tissue or positive culture. McNemar's chi-squared test was used to compare the performance of diagnostic tests. For the clinical performance all pathogens were considered, whereas for analytical performance only microorganisms were considered for which primers are included in the PCR assay. RESULTS: Among 51 patients, hardware-associated infection was diagnosed in 38 cases (75%) and non-infectious causes in 13 patients (25%). The sensitivity for diagnosing infection was 66% for peri-implant tissue culture, 84% for sonication fluid culture, 71% (clinical performance) and 77% (analytical performance) for sonication fluid PCR, the specificity of all tests was >90%. The analytical sensitivity of PCR was higher for gram-negative bacilli (100%), coagulase-negative staphylococci (89%) and Staphylococcus aureus (75%) than for Cutibacterium (formerly Propionibacterium) acnes (57%), enterococci (50%) and Candida spp. (25%). CONCLUSION: The performance of sonication fluid PCR for diagnosis of orthopedic hardware-associated infection was comparable to culture tests. The additional advantage of PCR was short processing time (<5 h) and fully automated procedure. With further improvement of the performance, PCR has the potential to complement conventional cultures.

Synovial fluid multiplex PCR is superior to culture for detection of low-virulent pathogens causing periprosthetic joint infection.

INTRODUCTION: Analysis of joint aspirate is the standard preoperative investigation for diagnosis of periprosthetic joint infection (PJI). We compared the diagnostic performance of culture and multiplex polymerase chain reaction (PCR) of synovial fluid for diagnosis of PJI. PATIENTS AND METHODS: Patients in whom aspiration of the prosthetic hip or knee joint was performed before revision arthroplasty were prospectively included. The performance of synovial fluid culture and multiplex PCR was compared by McNemar's chi-squared test. RESULTS: A total of 142 patients were included, 82 with knee and 60 with hip prosthesis. PJI was diagnosed in 77 patients (54%) and aseptic failure in 65 patients (46%). The sensitivity of synovial fluid culture and PCR was 52% and 60%, respectively, showing concordant results in 116 patients (82%). In patients with PJI, PCR missed 6 high-virulent pathogens (S. aureus, streptococci, E. faecalis, E. coli) which grew in synovial fluid culture, whereas synovial fluid culture missed 12 pathogens detected by multiplex PCR, predominantly low-virulent pathogens (Cutibacterium acnes and coagulase-negative staphylococci). In patients with aseptic failure, PCR detected 6 low-virulent organisms (predominantly C. acnes). CONCLUSION: While the overall performance of synovial fluid PCR was comparable to culture, PCR was superior for detection of low-virulent bacteria such as Cutibacterium spp. and coagulase-negative staphylococci. In addition, synovial fluid culture required several days for growth, whereas multiplex PCR provided results within 5hours in an automated manner.

Feasibility of Full Percutaneous Segmental Stabilization of the Lumbar Spine With a Combination of an Expandable Interbody Cage and an Interspinous Spacer: Preliminary Results.

INTRODUCTION: We evaluated the feasibility of a full percutaneous approach with an expandable interbody cage and an interspinous spacer for a segmental stabilization of the anterior and posterior columns of the lumbar spine, respectively, with local anesthesia. METHODS: Patients were prospectively included between 2012 and 2018 in this single-center, feasibility case series. An expandable interbody cage was inserted with endoscopy-based, facet-sparing percutaneous transforaminal lumbar interbody fusion (pTLIF). An interspinous spacer was percutaneously placed through the same skin incision. Pre- and postoperative Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) outcomes at 1, 3, 6, 12, and 24 months were obtained and evaluated with the Student t test. Postoperative outcome was classified according to modified Macnab criteria. RESULTS: A total of 16 patients were included, presenting mean preoperative scores for VAS back of 6.9 ± 2.5, VAS leg 7.9 ± 1.2, and ODI 30.1 ± 4.5. Postoperative mean scores for VAS back of 1.9 ± 2.1, VAS leg 2.1 ± 3.4, and ODI 14.8 ± 13.0 significantly (P < .001) decreased with a mean follow-up of 18.1 ± 16.6 months (range 1-65.2). Postoperative outcome was excellent and good for 13 (81%) cases, fair for 2 (13%), and poor for 1 (6%) case with a preoperative spondylolisthesis, which required revision surgery due to persisting instability. Postoperative complications included 3 cases with transitory, ipsilateral dysesthesia and 2 cases with radiologic cage subsidence but no clinical symptoms. Median postoperative time until hospital discharge was 16 hours. CONCLUSION: Our preliminary results for this full percutaneous technique show a similar outcome compared to conventional surgery with a fast patient recovery and early postoperative hospital discharge, opening the way to instrumented, outpatient surgery.

Percutaneous Transforaminal Lumbar Interbody Fusion (pTLIF) with a Posterolateral Approach for the Treatment of Denegerative Disk Disease: Feasibility and Preliminary Results.

BACKGROUND: Interbody fusion by open discectomy is the usual treatment for degenerative disk disease but requires a relatively long recovery period. The transforaminal posterolateral approach is a well-known standard in endoscopic spine surgery that allows direct access to the disk with progressive tissue dilation. The aim of this study was to assess the feasibility of percutaneous transforaminal interbody fusion (pTLIF) with insertion of an expandable or a standard rigid interbody implant for patients with degenerative disk disease with or without spondylolisthesis and for revision surgery. METHODS: Between 2009 and 2014, the pTLIF procedure was performed in 30 patients. Ten patients underwent insertion of a rigid implant (group A) and the remaining 20 underwent insertion of an expandable titanium interbody implant as the initial procedure (n = 10) (group B) or after failed back surgery (n = 10) (group C). Patient outcomes were scored with visual analogic scale (VAS), Oswestry disability index (ODI) and modified Macnab criteria. RESULTS: The mean follow-up period was 38 (17) (range 11 to 67) months. The outcome was excellent in 18, good in 10 and fair in 2. No poor results and no major complications were reported. No differences in VAS and ODI scores according to the study group were found. Median postoperative time until hospital discharge was 26 hours (20 to 68 hours). Postoperative values for VAS and ODI scores improved significantly (p<0.05) compared to preoperative data in all study groups. CONCLUSIONS: These preliminary results have shown the feasibility and efficacy of the pTLIF procedure using a posterolateral approach for the treatment of degenerative disk disease with or without spondylolisthesis up to grade 2 and in revision surgery. No significant differences in outcome were observed between an expandable and a rigid cage. Median postoperative time until hospital discharge was faster compared to standard TLIF (26 hours vs. 9.3 days).