Treatment Strategies in the Osteoporotic Spine.

This article reviews the appropriate assessment and management of osteoporotic compression fractures and discusses the implications of osteoporosis on initial patient evaluation, medical optimization for surgery, selection of instrumentation, and surgical technique. Adverse outcomes associated with osteoporosis are discussed. Failure to appropriately evaluate, optimize, and treat spine patients with osteoporotic bone can lead to disastrous complications. Weakened bone can lead to implant failure through cage subsidence and screw pullout, as well as, peri-implant fractures, failure of deformity correction, and proximal kyphosis. These risks must be taken into account when considering operative interventions in these patients.

Technique for insertion of a Scheker prosthesis for failed Sauve-Kapandji with a well fixed ulnar stem: A case report.

INTRODUCTION: The Scheker prosthesis is a distal radioulnar joint (DRUJ) arthroplasty used as a salvage option for many DRUJ pathologies. PRESENTATION OF CASE: We report the case of a patient who underwent insertion of a Scheker prosthesis for continued pain and limited motion at the wrist in the setting of a failed Sauve-Kapandji with a well fixed ulnar stem and DRUJ pseudo-arthrosis. DISCUSSION: This report aims to provide a technique for ulnar stem removal without compromising the bone needed for the Scheker prosthesis and for describing the location of a DRUJ osteotomy without compromising radio-lunate stability. CONCLUSION: The Scheker prosthesis is able to be safely inserted for DRUJ salvage after removal of a well fixed ulnar stem if careful removal prevents destruction of the ulna, as described here.

Degenerative Cervical Myelopathy: Evaluation and Management.

Degenerative cervical myelopathy is most commonly caused by cervical spondylosis, with a predominant elderly population, and is the most common cause of spinal cord impairment. Patients typically present with gait dysfunction, hand impairment, and/or the presence of long tract signs: clonus, Hoffman sign, Babinski sign, or inverted radial reflexes. One of the key surgical strategies is deciding an approach, which is based on patient characteristics and cause of pathologic condition. Without operative intervention, there is a high rate of neurological decline. Most surgeons recommended surgical treatment given the favorable outcomes and well understood natural history of disease.

A Pathway for the Diagnosis and Treatment of Lumbar Spinal Stenosis.

Lumbar spinal stenosis is a prevalent condition with varied presentation. Most common in older populations, symptoms typically include back, buttock, and posterior thigh pain. Diagnosis is typically based on physical examination and clinical history, but confirmed on imaging studies. Nonsurgical management includes nonsteroidal anti-inflammatories, physical therapy, and epidural injections. If nonoperative management fails or patient presentation involves worsening symptoms, surgical intervention, most commonly in the form of a laminectomy, may be indicated. Recent literature has demonstrated improved pain and functional outcomes with surgery compared with conservative treatment in the middle to long term.

Cisplatin exposure causes c-Myc-dependent resistance to CDK4/6 inhibition in HPV-negative head and neck squamous cell carcinoma.

The loss of p16 is a signature event in Human Papilloma Virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) that leads to increased Cyclin Dependent Kinase 4/6 (CDK) signaling. Palbociclib, a CDK4/6 inhibitor, is active for the treatment of a subset of HNSCC. In this study, we analyzed patient response data from a phase I clinical trial of palbociclib in HNSCC and observed an association between prior cisplatin exposure and CDK inhibitor resistance. We studied the effects of palbociclib on cisplatin-sensitive and -resistant HNSCC cell lines. We found that while palbociclib is highly effective against chemo-naive HNSCC cell lines and tumor xenografts, prior cisplatin exposure induces intrinsic resistance to palbociclib in vivo, a relationship that was not observed in vitro. Mechanistically, in the course of provoking a DNA damage-resistance phenotype, cisplatin exposure upregulates both c-Myc and cyclin E, and combination treatment with palbociclib and the c-Myc bromodomain inhibitor JQ1 exerts a synergistic anti-growth effect in cisplatin-resistant cells. These data show the benefit of exploiting the inherent resistance mechanisms of HNSCC to overcome cisplatin- and palbociclib resistance through the use of c-Myc inhibition.

Influence of preoperative opioid use on postoperative outcomes and opioid use after arthroscopic rotator cuff repair.

BACKGROUND: Recent orthopedic research has questioned the effect of opioid use on surgical outcomes. This study investigated this in the context of arthroscopic rotator cuff repair. We hypothesized that preoperative opioid use would be associated with inferior outcomes and greater postoperative opioid requirements. METHODS: A database query identified adult patients with full-thickness or partial-thickness supraspinatus tears surgically treated between 2011 and 2015. Preoperative and postoperative outcomes scores (active range of motion [AROM], American Shoulder and Elbow Surgeons [ASES], Constant scores, Simple Shoulder Test [SST], and visual analog scale [VAS] for pain) and postoperative opioid use were retrospectively recorded. Patients with less than 2 years of follow-up data at the time of the retrospective review were contacted for prospective ASES, SST, and VAS data collection. RESULTS: A total of 200 patients, 44 of whom received opioids preoperatively, were identified for inclusion. Patients prescribed preoperative opioids had consistently inferior preoperative and postoperative outcomes scores; however, the magnitudes of improvement were not significantly different between groups. Postoperatively, patients in the preoperative opioid group received 1.91 (95% confidence interval, 1.31-2.78) times more opioids over a postoperative course of treatment that was 2.73 (95% confidence interval, 1.62-4.59) times longer. In addition to having a greater proportion of women, this group also had significantly higher rates of certain comorbidities, including back pain, depression, degenerative joint disease, and chronic pain conditions. CONCLUSIONS: All patients demonstrated significant improvements in outcomes scores after surgical repair that were not significantly different between groups. However, patients taking opioids preoperatively did not ultimately reach the same level of functionality and had substantially greater opioid requirements postoperatively.

Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma.

ErbB3 has been widely implicated in treatment resistance, but its role as a primary treatment target is less clear. Canonically ErbB3 requires EGFR or ErbB2 for activation, whereas these two established treatment targets are thought to signal independently of ErbB3. In this study, we show that ErbB3 is essential for tumor growth of treatment-naive HNSCC patient-derived xenografts. This ErbB3 dependency occurs via ErbB3-mediated control of EGFR activation and HIF1α stabilization, which require ErbB3 and its ligand neuregulin-1. Here, we show that ErbB3 antibody treatment selects for a population of ErbB3-persister cells that express high levels of the transmembrane protein Trop2 that we previously identified as an inhibitor of ErbB3. Co-treatment with anti-ErbB3 and anti-Trop2 antibodies is synergistic and produces a greater anti-tumor response than either antibody alone. Collectively, these data both compel a revision of ErbB-family signaling and delineate a strategy for its effective inhibition in HNSCC.

Arginine Deprivation Inhibits the Warburg Effect and Upregulates Glutamine Anaplerosis and Serine Biosynthesis in ASS1-Deficient Cancers.

Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect. The reduction of glycolysis in cells otherwise dependent on aerobic glycolysis is correlated with reduced PKM2 expression and phosphorylation and upregulation of PHGDH. Concurrent arginine deprivation and glutaminase inhibition was found to be synthetic lethal across a spectrum of ASS1-deficient tumor cell lines and is sufficient to cause in vivo tumor regression in mice. These results identify two synthetic lethal therapeutic strategies exploiting metabolic vulnerabilities of ASS1-negative cancers.