Breast cancer exploits neural signaling pathways for bone-to-meninges metastasis.

The molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, which limits the development of effective therapies. In this work, we show that BCCs in mice can invade the LM by abluminal migration along blood vessels that connect vertebral or calvarial bone marrow and meninges, bypassing the blood-brain barrier. This process is dependent on BCC engagement with vascular basement membrane laminin through expression of the neuronal pathfinding molecule integrin α6. Once in the LM, BCCs colocalize with perivascular meningeal macrophages and induce their expression of the prosurvival neurotrophin glial-derived neurotrophic factor (GDNF). Intrathecal GDNF blockade, macrophage-specific GDNF ablation, or deletion of the GDNF receptor neural cell adhesion molecule (NCAM) from BCCs inhibits breast cancer growth within the LM. These data suggest integrin α6 and the GDNF signaling axis as new therapeutic targets against breast cancer LM metastasis.

Late-week Multilevel Anterior Cervical Discectomy and Fusion Associated with Increased Length of Stay.

STUDY DESIGN: Retrospective analysis of clinical data from a single institution. OBJECTIVE: To assess the day of surgery during the week as a possible predictor of length of stay (LOS) following anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Surgeries later in the week may result in longer LOS and higher costs for joint arthroplasty, yet this is unclear following spine surgery. Procedures performed later in the week may lead to weekend admissions when there are limited services that may contribute to an extended LOS. We attempt to identify associations between day of surgery and LOS, readmission, and complications following single- and multilevel ACDF. MATERIALS AND METHODS: Patients at a single institution undergoing ACDF by 7 primary surgeons in both orthopedic and neurosurgery spine departments between 2015 and 2019 were retrospectively reviewed. Patients were stratified by surgery day at either the beginning (Monday/Tuesday) or end (Thursday/Friday) of the week and by single- or multilevel ACDF. Surgery for trauma, infections, adjacent level disease, or revision were excluded. Patient demographics, Charlson Comorbidity Index (CCI), LOS, postoperative complications, and readmission rates were assessed. RESULTS: Six hundred fifty-two patients underwent ACDF. For single-level ACDF, 222 were reviewed, with 112 having surgery at the beginning and 110 at the end of the week. For multilevel ACDF, 431 were reviewed, with 192 having surgery at the beginning and 239 at the end of the week. No differences in pre- or postoperative variables were determined for single-level ACDF. Despite no differences in pre-operative variables, CCI, operative duration, or number of levels, late-week multilevel ACDF had longer average LOS (2.8±3.0 days) compared to early-week surgery (2.0±2.0 days) (P=0.018). CONCLUSIONS: Late-week multilevel ACDF was associated with an increased LOS, as it may prove beneficial to surgical planning. This conflicts with previous reports that day of week was not associated with LOS following ACDF. LEVEL OF EVIDENCE: III.

Subinternship in Diagnostic Radiology: Bringing the Shadowers Out of the Shadows.

RATIONALE AND OBJECTIVES: Diagnostic radiology subinternships are uncommon. We started a diagnostic radiology subinternship at our institution in 2020 and present 3 years of data assessing the impact of the course on students' perceptions of and interest in diagnostic radiology. MATERIALS AND METHODS: The initial course design consisted of daily shadowing shifts, small group lectures with attending radiologists, asynchronous self-paced learning assignments, an ultrasound skills session, multidisciplinary tumor board attendance, and completion of 2 formal case presentations. "Junior resident" shifts, where students dictated studies under attending supervision, an emergency radiology call shift, and an ultrasound procedures shift were subsequently added in response to student feedback. Students were asked to complete surveys before and after completing the course. RESULTS: Forty-seven fourth-year medical students completed the course over 3 years. The first 2 groups were predominantly male, whereas the third group showed near even gender representation (54% male). 21 (45%) chose to apply to diagnostic radiology for residency. Student reported interest in diagnostic radiology as a career, valuation of diagnostic radiology as a specialty, comfort with imaging interpretation, and perceptions of the availability of patient interaction and procedures in diagnostic radiology all significantly increased after participation in the course. Students ranked the junior resident shifts and small group attending lectures as the most valuable course components. CONCLUSION: Implementation of a diagnostic radiology subinternship significantly improved students' interest in and perceptions of the field. We encourage the creation of similar courses in other radiology departments and stress the importance of active learning experiences.

A Case of Sarcoidosis Mimicking Lymphoma Confounded by Cognitive Decline.

Sarcoidosis is a disease with an unknown cause that affects multiple organ systems and has a varied clinical presentation. Often, its symptomatology mimics other disease processes, such as lymphoma, tuberculosis, and amyloidosis. The reticuloendothelial involvement and typical B symptoms of weight loss, fatigue, night sweats, and lymphadenopathy can make sarcoidosis often easily confused with lymphoma. Sarcoidosis has a myriad of central nervous system (CNS) effects, which are often not recognized as symptoms of the disease. These neuropsychiatric symptoms can include, but are not limited to, cognitive decline, headaches, and personality changes. In this report, we discuss a case of a patient who presented with symptoms consistent with indolent lymphoma but was eventually diagnosed with sarcoidosis with extrapulmonary manifestations.

Anatomic Reconstruction of the Anterior Oblique and the Dorsoradial Ligaments for Painful Subluxating Carpometacarpal Joint of the Thumb.

Thumb carpometacarpal osteoarthritis (CMC OA) is a common pathology of the hand that is characterized by pain, loss of grip and pinch strength, and deformity. Although conservative management is often preferred in earlier stage of CMC OA, surgical techniques can be used when symptoms are not fully relieved, especially with subluxation. We report a case series of 26 patients (32 operations) with Eaton stage I and II CMC OA who underwent a novel surgical technique that anatomically restores the CMC joint with autologous double ligament reconstruction. All cases were retrospectively reviewed as a prospective study and performed at a single regional health system from 2012 to 2016. Preoperative and postoperative radiographs, grip and pinch strength measurements, and DASH scores were collected to evaluate the outcomes. The mean CMC subluxation ratio decreased from 0.59±0.14 to 0.35±0.21 (P<0.0001). The mean grip strength increased from 44.34±17.36 pounds to 52.97±18.92 pounds (P=0.017), and the mean pinch strength increased from 10.16±4.59 pounds to 12.75±4.52 pounds (P=0.00027). The mean DASH scores decreased from 42.32±14.99 to 19.94±14.47 (P<0.0001). The average follow-up period was 39.44±14.94 months. Three patients had postoperative thumb stiffness that resolved with physical therapy. One patient had postoperative pain, attributed to carpal tunnel syndrome. One surgery required revision. All other patients (84.38%) reported significant improvement in pain and the ability to return to previous levels of work. This surgical technique is therefore a feasible option for patients with Eaton stage I or II CMC OA, and should be recommended for wider surgical use.