Single-Stage Revision of Infected Total Femoral Replacement.

We present 2 cases of infected total femur prosthetic devices treated with a single-stage revision with extensive irrigation and debridement, followed by reimplantation with a prosthesis coated in antibiotic-impregnated cement. Single-stage total femoral replacement with antibiotic-eluting cement around the device was used for 2 cases of limb salvage arthroplasty to reduce complications, maintain patient function, and minimize hospital-associated cost. [Orthopedics. 2022;45(5):e280-e283.].

Lateral Locking Plate Fixation of Simple Weber B Fibula Fractures Without a Lag Screw Yields Excellent Radiographic Results.

BACKGROUND: The most common first-line fixation technique for simple Weber B fibula fractures is a lag screw with lateral neutralization plate. The most common surgical technique for unstable Weber B fibula fracture is one-third semi-tubular plate and cortical screws, implemented with lag screw when appropriate. However, the lag technique can be technically challenging in osteoporotic bone or within fibulas of smaller diameter, and in some cases can result in fragmentation at the fracture site, malreduction, or peroneal irritation. The purpose of this study is to examine an alternative first-line method for routine treatment of simple Weber B fibula fractures. METHODS: Fifty-two consecutive patients undergoing open reduction internal fixation (ORIF) of a Weber B fibula fracture by a single surgeon were included in this retrospective study. After reduction, a lateral locking plate was applied with cortical screws proximally and locking screws distally. No screw crossed the fracture in any case. Per published precedent, nonunion was defined as either a gap of >3 mm between fracture surfaces >6 months postoperatively or a fracture line >2 to 3 mm wide and sclerosing of the fracture surfaces. Similarly, malunion was defined as one or more of the following: talar tilt >2º, talar subluxation >2 mm, or tibiofibular clear space ≥5 mm. RESULTS: The mean (± standard deviation) age of the 52 included patients was 44.2 ± 16.2 years, the mean body mass index was 27.7 ± 6.6 kg/m2, and 63.5% of patients identified themselves as female sex. The mean follow-up was 6.2 (range: 1.5-15) months. In addition to undergoing fixation of the lateral malleolus, 21 patients also underwent fixation of the posterior malleolus, 27 underwent fixation of the medial malleolus, 29 underwent fixation across the syndesmosis, and 7 underwent repair of the deltoid. In all patients, bony anatomic union of the fibula and congruence of the mortise were achieved with no cases of malunion or nonunion. CONCLUSIONS: The Arbeitsgemeinschaft für Osteosynthesefragen (AO) fixation technique for simple Weber B fractures with a lag screw and lateral neutralization plating has provided good outcomes for decades. We present an alternative technique for ORIF of these fractures with a lateral locking plate and no lag screw. In our series, we evaluated radiographic union and alignment as our primary outcome measures and found no cases of nonunion or malunion. Prospective cohort testing of lateral locking plates versus traditional fixation in the context of patient-centered value is warranted.Level of Evidence: Level III.

Copy Number Variations in Adult-onset Neuropsychiatric Diseases.

Adult-onset neuropsychiatric diseases are one of the most challenging areas of medicine. While symptomatic treatments are available, for most of these diseases the exact pathomechanism is not known, thus, disease-modifying therapies are difficult to conceptualize and find. The two most common and best studied neuropsychiatric diseases affecting higher cortical functions in humans are schizophrenia and Alzheimer's disease; both diseases have high heritability, however, the genetic architecture is not fully elucidated. Robust Single Nucleotide Variant (SNV) studies have identified several loci with modest effect sizes. While Copy Number Variants (CNV) make an important contribution to genetic variation, CNV GWAS suffer from dependence on mainly SNP arrays with underperforming genotyping accuracy. We evaluated dynamic range of the assays for three types of CNV loci, including biallelic deletion, high copy gain, and fusion gene, to assess the depth of exploration of the contribution of CNVs to disease susceptibility. Despite the suboptimal genotyping, novel mechanisms are emerging and further large-scale studies with genotyping assays optimized for CNV detection are needed. Furthermore, the CHRFAM7A human-specific fusion gene association warrants large scale locus specific association studies in AD, schizophrenia, bipolar disorder and ADHD.

Timing of Wnt Inhibition Modulates Directed Differentiation of Medial Ganglionic Eminence Progenitors from Human Pluripotent Stem Cells.

In vitro differentiation of human pluripotent stem cell into relevant cell types is a desirable model system that has the human biological context, is a renewable source, and is scalable. GABA interneurons and basal forebrain cholinergic neurons, derivates of the medial ganglionic eminence (MGE), are implicated in diverse neuropsychiatric diseases. Various protocols have been proposed to generate MGE progenitors: the embryoid body- (EB-) based rosette-derived (RD), the adherent (AdD), and the nonadherent (NAdD) approaches. While Wnt inhibition is frequently incorporated into the strategy, the timing varies between protocols and there is a lack of standardized outcome reporting, which precludes direct comparison. Here, we report a head-to-head comparison in three distinct experimental models to establish whether Wnt inhibition during neural stem cell, NSC (stage 1), or neural progenitor cell, NPC (stage 2), formation facilitates MGE differentiation. Wnt inhibition at both stages promotes MGE progenitor differentiation when compared to no inhibition. However, NSC (stage 1) Wnt inhibition markedly reduces the number of MGE progenitors available for downstream applications in the RD and the NAdD protocols due to early inhibition of proliferation. NPC (stage 2) Wnt inhibition in the adherent system is comparable to the EB-based methods offering a techically less challenging alternative.