Comparing the Biomechanical Stability of Cerclage Cable with Plate Insert Versus Locking Screw in Periprosthetic Humeral Fracture.

BACKGROUND: In the setting of periprosthetic humeral fractures, the humeral stem of the implant represents a substantial challenge to the optimal method of proximal fixation. This study aimed to compare the initial biomechanical stability provided by cerclage cables with a locking plate insert versus bicortical locking screws (i.e., the gold standard for fixation) in fresh cadaveric humeri. METHODS: After calculating the sample size, we utilized 10 sets of cadaveric specimens and created a 5-mm osteotomy gap 120 mm distal to the tip of the greater tuberosity, simulating a Wright and Cofield type-B periprosthetic humeral fracture on each specimen. Using 3 locking screws for distal fragment fixation, identical in all specimens, the specimens were assigned to Group A (3 cerclage cables with a plate insert) or Group B (3 locking bicortical screws) for proximal fragment fixation. Biomechanical tests included stiffness in varus and valgus bending, torsion, and axial compression, and a single load to failure. RESULTS: No significant differences were observed in the biomechanical metrics between the 2 groups. CONCLUSIONS: Our study revealed that fixation with use of cerclage cables with a plate insert demonstrated biomechanical stability comparable with that of bicortical locking screw fixation when addressing the proximal fragment in Wright and Cofield type-B periprosthetic humeral fractures. CLINICAL RELEVANCE: For proximal fragment fixation of periprosthetic humeral fractures, cerclage cables with a plate insert can be utilized as an effective fixation method that offers initial fixation strength that is comparable to the use of 3 locking bicortical screws.

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.

Meningioma Originating From Choroid Plexus of Foramen of Luschka: A Rare Case Report and Tip of Differential Diagnosis.

Meningiomas are the most common benign brain tumors, and most of them originate from the dura mater. However, in some cases, they can originate from the choroid plexus, and they are rarely found in the posterior cranial fossa. A 63-year-old female patient presented with dizziness and swallowing difficulty and was found to have a homogeneously enhancing mass in the right posterior cranial fossa. Mass removal was performed through retrosigmoid suboccipital craniotomy, and the mass was confirmed to originate from the choroid plexus. The pathological diagnosis was meningothelial meningioma. The patient had temporary swallowing difficulty but recovered without any neurological sequelae. We report a rare case of a lower cerebellopontine angle meningioma without dural attachment originating from the choroid plexus of the foramen of Luschka.

Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.

Factors associated with degeneration of rotator cuff tendon : a histological study in patients with rotator cuff tear.

Factors associated with tendon degeneration have not been fully investigated. The purpose of this study was to identify factors associated with tendon degeneration in patients with rotator cuff tear. A total of 93 patients with a full-thickness rotator cuff tear (fRCT) were included in the study. A full-thickness supraspinatus tendon sample was harvested from the middle portion between the lateral edge and the musculotendinous junction, and assessed histologically. Association between the degree of tendon degeneration and factors in demographic, clinical, radiologic, and arthroscopic categories were investigated. The mean of the total degeneration score was significantly lower in patients with symptom duration of 6 months or less than longer than 6 months (13.1 ± 2.6 vs 14.4 ± 2.3, p = 0.010). This study showed that tendon degeneration significantly progressed 6 months after the onset of symptoms, and suggested early intervention to avoid further deterioration of tendon degeneration.

Retrospective Comparative Outcomes Analysis of Arthroscopic Versus Open Bone Graft and Fixation for Unstable Scaphoid Nonunions.

PURPOSE: To compare union rates and clinical and radiologic outcomes after arthroscopic and open bone grafting and internal fixation for unstable scaphoid nonunions. METHODS: Between March 2009 and November 2014, patients with unstable scaphoid nonunion underwent arthroscopic (group A) or open (group O) bone grafting and internal fixation. One senior surgeon alternatively performed either arthroscopic or open osteosynthesis for the same surgical indications. Visual analog scale score, grip strength, active range of motion, Mayo wrist score (MWS), and Disabilities of Arm, Shoulder, and Hand score were assessed preoperatively and postoperatively. Union was determined by computed tomography 8 to 10 weeks postoperatively with bridging trabecula at the nonunion site. Scapholunate angle (SLA), radiolunate angle (RLA), and lateral intrascaphoid angle (LISA), plus height/length ratio (HLR) served to gauge carpal bone alignment in preoperative and postoperative radiographs. Those outcomes of patients with carpal collapse deformities, who met following conditions; (1) LISA of >45° or HLR of >0.65 on computed tomography images or (2) SLA of >60° or RLA of >10° on plain radiographs, were also compared. RESULTS: Overall, 62 patients qualified for study (group A, 28; group O, 34). Union rates did not differ by patient subset (group A, 96.4%; group O, 97.1%; P â‰’ 1); and visual analog scale score, grip strength, range of motion, Mayo Wrist Score, and Disabilities of Arm, Shoulder, and Hand scores were similar at last follow-up. In radiographic assessments, SLA, RLA, and LISA were similar, whereas scaphoid HLR excelled through open technique (group A, 0.59 ± 0.07; group O, 0.55 ± 0.05; P = .002). Subgroup analysis of patients with carpal collapse deformities (group A, 9; group O, 14) showed that all radiographic measures in group A (vs group O) reflected lesser correction (SLA, 56.7° ± 7.3° vs 49.2°±9.1° [P = .049]; RLA, 9.2° ± 2.0° vs 5.7° ± 3.0° [P = .005]; LISA, 34.8° ± 4.8° vs 25.6° ± 13.0° [P = .028]; HLR, 0.66 ± 0.04 vs 0.54 ± 0.07 [P < .001]). CONCLUSIONS: Arthroscopic and open bone grafting and internal fixation in treating unstable scaphoid nonunions, did not show any significant differences in clinical and radiologic outcomes at the minimum of 2 years after operation. In scaphoid nonunions with carpal collapse deformities, open bone grafting restored better carpal alignment than arthroscopic bone grafting, although there were no differences in clinical outcomes between the 2 techniques. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Molecular characteristics of cancer stem-like cells derived from human breast cancer cells.

We characterized the cellular properties of cancer stem-like cells (CSLCs) isolated from immortalized MDA-MB453 human breast cancer cells in culture. We showed that although the expression of Octamer-binding transcription factor-4 (OCT4) correlates to stemness in these CSLCs, OCT4 knockdown does not induce their differentiation. Our results suggest that the differentiation program in MDA-MB453 CSLCs is blocked at a step upstream of the transcription of the OCT4 promoter, allowing CSLCs to maintain their population through asymmetric cell division during many repeated passages. Comparative expression analysis indicates that only a subset of genes and signaling pathways known to be associated with survival and maintenance of CSCs are selectively expressed in CSLCs, as compared with non-CSLCs fractionated from the same parental MDA-MB453 cells. These results suggest that selective expression of a limited number of genes may be sufficient for establishment and maintenance of CSLCs with high tumorigenicity.

Higher-order aberration changes after Implantable Collamer Lens implantation for myopia.

PURPOSE: To investigate the changes in higher-order aberrations (HOAs) induced by implantation of Implantable Collamer Lenses (STAAR Surgical) and to explain them in relation to the surgical incision and optical properties. DESIGN: Prospective, observational case study. METHODS: This study included 56 eyes undergoing Implantable Collamer Lens insertion for myopic correction. The corneal incision size was determined according to the amount of astigmatism. HOAs were measured before surgery and 3 months after surgery in 25 eyes having small superior incision (<3.2 mm) surgery and in 31 eyes with large superior incision (3.2 to 4.5 mm) surgery. Changes in spherical aberration, coma, trefoil, and total HOAs (third to sixth order) were analyzed. Laboratory measurements of aberration profiles of Implantable Collamer Lenses with different optical powers were performed to validate clinical measurements. RESULTS: In the small-incision group, trefoil (Z(3)(-3)) and spherical aberration changed significantly (P=.004). In the large-incision group, in addition to trefoil and spherical aberration, total HOA changed significantly (mean change, 0.13 ± 0.17; P=.001). Significant correlations were observed among the incision size, the astigmatism induced, and the trefoil induced. Induced trefoil showed a predominant pattern at the orientation of the incision meridian. Optical measurement of aberrations of the Implantable Collamer Lenses confirmed the postoperative negative spherical aberration. CONCLUSIONS: HOA changes after Implantable Collamer Lens insertion were increased trefoil and induced negative spherical aberration. These changes may be explained by the effect of the corneal incision and the negative spherical aberration in the Implantable Collamer Lens, respectively.

Spondyloepiphyseal dysplasia congenita with absent femoral head.

Spondyloepiphyseal dysplasia congenita (SEDC), an inherited chondrodysplasia, occurs through a mutation in the COL2A1 gene encoding the type II procollagen alpha1 chain, proalpha1 (II). Recently, the authors studied two Korean patients with SEDC. Both these patients had short stature, os odontoideum with or without atlantoaxial instability, platyspondyly, and epiphyseal dysplasia limited to the femoral heads. The more seriously affected patient had shorter height (125 cm), atlantoaxial instability associated with os odontoideum, flat feet, and cleft palate, absence of the femoral head on radiographic and magnetic resonance imaging (MRI), and dislocated proximal femur. The less seriously affected patient was taller (145 cm) and had no atlantoaxial instability, absence of the femoral head on radiography with visible cartilage anlage on MRI, and subluxated cartilaginous femoral head. A mutation analysis was performed using direct sequencing. Two novel dominant mutations were found in the COL2A1 gene of these two patients: G277V and G238S, respectively. Although glycine was substituted with valine and serine in the proalpha1 (II) of these two patients, their phenotypes were significantly different in physical and radiologic evaluations.