Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

BACKGROUND: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. OBJECTIVES: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory. METHODS: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology. FINDINGS: ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon's Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. CONCLUSIONS/SIGNIFICANCE: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. TRIAL REGISTRATION: NCT04474132, https://clinicaltrials.gov/study/NCT04474132 ClinicalTrials.gov.

[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.

PURPOSE: The O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. METHODS: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). RESULTS: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. CONCLUSION: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.

Building Programs to Eradicate Toxoplasmosis Part IV: Understanding and Development of Public Health Strategies and Advances "Take a Village".

Purpose of Review: Review international efforts to build a global public health initiative focused on toxoplasmosis with spillover benefits to save lives, sight, cognition and motor function benefiting maternal and child health. Recent Findings: Multiple countries' efforts to eliminate toxoplasmosis demonstrate progress and context for this review and new work. Summary: Problems with potential solutions proposed include accessibility of accurate, inexpensive diagnostic testing, pre-natal screening and facilitating tools, missed and delayed neonatal diagnosis, restricted access, high costs, delays in obtaining medicines emergently, delayed insurance pre-approvals and high medicare copays taking considerable physician time and effort, harmful shortcuts being taken in methods to prepare medicines in settings where access is restricted, reluctance to perform ventriculoperitoneal shunts promptly when needed without recognition of potential benefit, access to resources for care, especially for marginalized populations, and limited use of recent advances in management of neurologic and retinal disease which can lead to good outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-022-00268-x.

Building Programs to Eradicate Toxoplasmosis Part I: Introduction and Overview.

Purpose of Review: Review building of programs to eliminate Toxoplasma infections. Recent Findings: Morbidity and mortality from toxoplasmosis led to programs in USA, Panama, and Colombia to facilitate understanding, treatment, prevention, and regional resources, incorporating student work. Summary: Studies foundational for building recent, regional approaches/programs are reviewed. Introduction provides an overview/review of programs in Panamá, the United States, and other countries. High prevalence/risk of exposure led to laws mandating testing in gestation, reporting, and development of broad-based teaching materials about Toxoplasma. These were tested for efficacy as learning tools for high-school students, pregnant women, medical students, physicians, scientists, public health officials and general public. Digitized, free, smart phone application effectively taught pregnant women about toxoplasmosis prevention. Perinatal infection care programs, identifying true regional risk factors, and point-of-care gestational screening facilitate prevention and care. When implemented fully across all demographics, such programs present opportunities to save lives, sight, and cognition with considerable spillover benefits for individuals and societies. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-022-00269-w.

Building Programs to Eradicate Toxoplasmosis Part III: Epidemiology and Risk Factors.

Purpose of Review: Review comprehensive data on rates of toxoplasmosis in Panama and Colombia. Recent Findings: Samples and data sets from Panama and Colombia, that facilitated estimates regarding seroprevalence of antibodies to Toxoplasma and risk factors, were reviewed. Summary: Screening maps, seroprevalence maps, and risk factor mathematical models were devised based on these data. Studies in Ciudad de Panamá estimated seroprevalence at between 22 and 44%. Consistent relationships were found between higher prevalence rates and factors such as poverty and proximity to water sources. Prenatal screening rates for anti-Toxoplasma antibodies were variable, despite existence of a screening law. Heat maps showed a correlation between proximity to bodies of water and overall Toxoplasma seroprevalence. Spatial epidemiological maps and mathematical models identify specific regions that could most benefit from comprehensive, preventive healthcare campaigns related to congenital toxoplasmosis and Toxoplasma infection.

Building Programs to Eradicate Toxoplasmosis Part II: Education.

Purpose of Review: Review work to create and evaluate educational materials that could serve as a primary prevention strategy to help both providers and patients in Panama, Colombia, and the USA reduce disease burden of Toxoplasma infections. Recent Findings: Educational programs had not been evaluated for efficacy in Panama, USA, or Colombia. Summary: Educational programs for high school students, pregnant women, medical students and professionals, scientists, and lay personnel were created. In most settings, short-term effects were evaluated. In Panama, Colombia, and USA, all materials showed short-term utility in transmitting information to learners. These educational materials can serve as a component of larger public health programs to lower disease burden from congenital toxoplasmosis. Future priorities include conducting robust longitudinal studies of whether education correlates with reduced adverse disease outcomes, modifying educational materials as new information regarding region-specific risk factors is discovered, and ensuring materials are widely accessible.

Combined acetabulum and pelvic ring injuries.

Combined fractures of the acetabulum and pelvic ring are more common than previously believed, with an incidence as high as 15.7%. Recent series that include combined injuries indicate that the incidence of lateral compression and anteroposterior compression pelvic ring injuries is similar and that transverse and both-column acetabular fractures are the most common acetabular fracture patterns. Combined injuries most often are the result of high-energy mechanisms, and, compared with patients who present with isolated pelvic or acetabular injury, patients with combined injury typically have higher injury severity scores, higher transfusion requirements, and lower systolic blood pressure, with reported mortality rates of 1.5% to 13%. Treatment requires a multidisciplinary approach. The first priority is resuscitation following the Advanced Trauma Life Support protocols. Once the patient is stable, acetabular fractures and pelvic ring injuries should be assessed individually, and the most appropriate treatment for each should be outlined. These treatments should then be integrated to develop the most appropriate overall treatment strategy. Although outcomes data are available for isolated acetabulum and pelvic ring disruptions, no such data currently exist for combined injuries.

Open reduction and internal fixation of tibial pilon fractures using a lateral approach.

OBJECTIVES: To assess the wound complications and reductions achieved in a cohort of patients with pilon fractures who were treated using a novel lateral approach. DESIGN: Retrospective review. SETTING: Two level 1 trauma centers affiliated with academic institutions. PATIENTS/METHODS: All 44 fractures (in 43 patients) treated by the senior authors with open reduction and internal fixation (ORIF) using the lateral approach as the primary approach were included. INTERVENTION: Data regarding medical comorbidities, mechanism of injury, soft-tissue injury sustained during the injury, treatment, wound healing, and secondary surgeries were recorded. Fractures were classified using the AO/OTA system with most being type C3. Eighteen fractures were open injuries (10 type 3). Fracture reductions were scored using the criteria of Teeny and Wiss. MAIN OUTCOME MEASUREMENTS: Quality of articular reduction and soft-tissue healing. RESULTS: An anatomic or good fracture reduction was achieved in 41 fractures (93%), and a fair reduction was obtained in 3 fractures. Two patients were successfully treated for deep infection (4.5%), and 2 patients developed a wound dehiscence (4.5%). There were no amputations. Twelve patients underwent secondary surgeries (27%). Five of these were for symptomatic screw removal (related to the fibular hardware in all cases), and the sixth was for planned removal of a syndesmotic-type screw (13.6%). Four were for nonunion, representing 9% of all cases. The remaining secondary surgeries (2 cases) were performed for infection. Overall, 13.6% of patients underwent a secondary surgical procedure to address nonunion or infection. CONCLUSIONS: When applied in a staged fashion, the lateral surgical approach for pilon fractures provides excellent protection of the soft-tissue envelopes by creating thick flaps while allowing excellent visualization for reconstruction of the anterior and lateral distal tibia.

Biomechanical evaluation of an expandable nail for the fixation of midshaft fractures.

BACKGROUND: The objective of this study was to compare the torsional stability of diaphyseal long bone fractures fixed with either a Fixion nail (DiscOTech, Monroe Township, NJ) or a standard locked Zimmer M/DN locked nail (Zimmer, Warsaw, IN). METHODS: Two fracture models were used to evaluate the bone-implant constructs. A transverse osteotomy was created in all tibiae, and a spiral fracture was created in all humeri. Paired specimens were randomly assigned to receive either a Fixion or Zimmer M/DN locked nail. Each implanted construct was cyclically loaded in torsion, and construct stiffness for each fracture type and each bone computed from the resulting load-displacement curves. RESULTS: Performance of the Fixon nail in the tibial transverse model was variable: 2 of 10 implanted constructs failed during testing, and average construct stiffness was significantly greater for the Zimmer nail. No significant difference was found between the stiffness of the Zimmer M/DN and Fixion implanted humeral constructs either with or without the interlock. CONCLUSIONS: Fracture type significantly affected the performance of the Fixion nail. Our results suggest that the Fixion nail is most suitable for use in fractures where torsional loads across the fracture site are shared between the nail and the bony ends of the fracture, as in a spiral fracture.

Case report: Echinococcus disease of the bone presenting as a femoral shaft nonunion.

Osseous hydatidosis (Echinococcus infection) is a rare parasitic bone infection that poses challenges in diagnosis and treatment. We present a novel case of osseous hydatidosis of the femoral shaft that was diagnosed at the time of surgery for a recalcitrant femoral shaft nonunion. We know of no reports of osseous hydatidosis presenting as a femoral shaft nonunion. A discussion of the challenges in diagnosis and treatment of osseous hydatidosis are discussed, and the literature on osseous hydatidosis is reviewed.

Hybrid locked plating of osteoporotic fractures of the humerus.

BACKGROUND: Locked plating techniques recently have gained popularity and offer a different biomechanical approach for fracture fixation compared with traditional compression plating. In certain clinical situations, it may be preferable to employ a "hybrid" construct, in which an unlocked screw is used to assist with reduction and locked screws are subsequently used to protect the initial reduction. In the present study, we used an unstable osteoporotic fracture model of the humerus to determine (1) whether a hybrid construct behaved more like a locked construct or a conventional unlocked construct and (2) whether there was a difference between locked and unlocked constructs. METHODS: Thirty third-generation Sawbones humeri were divided into three groups of ten humeri each. A locking plate with combination holes was applied to each bone with use of either a locked construct, an unlocked construct, or a hybrid construct. To simulate purchase in osteoporotic bone, all screw-holes were drilled to 0.3 mm less than the diameter of the screw used. Each specimen was then osteotomized in the middle part of the shaft, and a 5-mm segment was removed. Oscillating cyclic torsion testing was performed to +/-10 N-m for 1000 cycles, torsional stiffness was determined at periodic cyclic intervals, and the groups were compared. RESULTS: The locked and hybrid constructs demonstrated similar behavior. The initial stiffness was similar in these two groups. At ten cycles, the locked and hybrid constructs retained 96.3% and 95.4% of their initial stiffness, respectively. During the remainder of cycling the stiffness of the locked and hybrid constructs decreased in a linear fashion (R(2) = 0.89 and 0.88, respectively), and at 1000 cycles the stiffness of the locked and hybrid constructs averaged 80.0% and 79.2% of the initial values, respectively (p = 1.0). In contrast, the unlocked constructs initially were significantly less stiff than both the locked and hybrid constructs (p < 0.001). At ten cycles the unlocked constructs retained 80.4% of their initial stiffness, and at 1000 cycles they retained only 22.3% of their initial stiffness. CONCLUSIONS: Hybrid constructs are mechanically similar to locked constructs, and both are significantly more stable than unlocked constructs under torsional cyclic loading. CLINICAL RELEVANCE: Combining screws in the hybrid configuration used in the present study did not compromise the mechanical performance of the construct. Hybrid constructs may decrease cost and may provide additional clinical value when treating fractures in osteoporotic bone.

Acetabular fractures in the elderly: treatment recommendations.

Acetabular fractures in the elderly population are marked by a high degree of variability in terms of patient and fracture characteristics. Successful outcomes depend on application of highly individualized management principles by experienced teams. Reviewed are indications and outcomes associated with various management options, including closed treatment, open reduction internal fixation, and acute or staged total hip arthroplasty. Proper initial management choices are critical, as early failures and subsequent salvage surgery can be accompanied by significant morbidity. Clinical results after ORIF closely follow the quality of articular reduction and the ability to maintain a congruent reduction of the hip joint. Fracture characteristics predictive of anatomic articular reduction should be treated with ORIF. Fracture characteristics predictive of early post-traumatic arthritis should be treated with simultaneous ORIF and THA. Presented is one referral institution's treatment algorithm and management approach.

Lisfranc injuries.

Lisfranc/midfoot injuries are complex injuries that are frequently overlooked. The consequences of missing these injuries can lead to long-term deformity and disability. Timely diagnosis, whether by primary or later treating physicians, can ensure this does not happen. Proper physical examination and imaging studies allow the physician to find these injuries and determine if open treatment is required. Open treatment can be approached and performed in a number of ways, depending on geographical preference. However, one concept that remains across all the various techniques is perfect anatomical reduction before the fixation technique is applied. Intraoperative and postoperative variations are all secondary concerns after anatomical reduction.