The contralateral oblique fluoroscopic view is associated with a lower incidence of postdural puncture headache in patients undergoing percutaneous spinal cord stimulation.

BACKGROUND: Spinal cord stimulation (SCS) is a minimally invasive therapy that is increasingly used to treat refractory neuropathic pain. Although this technique has a low incidence of serious long-term adverse sequelae, the risk of complications such as inadvertent dural puncture remains. OBJECTIVES: The goal of this article was to determine the impact of the contralateral oblique (CLO) fluoroscopic view incidence of postdural puncture headache (PDPH) during spinal cord stimulator implantation as compared to lateral fluoroscopic view. METHODS: This was a single academic institution retrospective analysis of electronic medical records spanning an approximate 20-year time period. Operative and postoperative notes were reviewed for details on dural puncture, including technique and spinal level of access, the development of a PDPH, and subsequent management. RESULTS: Over nearly two decades, a total of 1637 leads inserted resulted in 5 PDPH that were refractory to conservative measures but responded to epidural blood patch without long-term complications. The incidence of PDPH per lead insertion utilizing loss of resistance and lateral fluoroscopic guidance was 0.8% (4/489). However, adoption of CLO guidance was associated with a lower rate of PDPH at 0.08% (1/1148), p < 0.02. CONCLUSIONS: The incorporation of the CLO view to guide epidural needle placement can decrease the odds of a PDPH during percutaneous SCS procedures. This study further provides real-world data supporting the potential enhanced accuracy of epidural needle placement in order to avoid unintentional puncture or trauma to deeper spinal anatomic structures.

Nusinersen for Patients With Spinal Muscular Atrophy: 1415 Doses via an Interdisciplinary Institutional Approach.

BACKGROUND: Spinal deformity and prior spinal fusion pose technical challenges to lumbar puncture (LP) for nusinersen administration for patients with spinal muscular atrophy (SMA). In this retrospective study over two study phases, we evaluated (1) factors associated with difficult LP or unscheduled requirement for image guidance and (2) effectiveness of a triage pathway for selective use of image guidance and nonstandard techniques, particularly for patients with spinal instrumentation/fusion to the sacrum. METHODS: With institutional review board approval, electronic health records, imaging, and administrative databases were analyzed for patients receiving nusinersen from January 2012 through September 2021. Descriptive statistics and univariate analyses were used. RESULTS: From January 2012 to March 2018 (phase 1), among 82 patients with SMA, 461 of 464 (99.4%) LP attempts were successful. Univariate analyses associated difficulty with prior spinal instrumentation, higher body mass index, and severity of the spinal deformity. Based on this experience, starting in April 2018 (phase 2), 125 patients were triaged selectively for ultrasound, fluoroscopy, or Dyna computed tomography. Patients with spinal instrumentation/fusion to the sacrum were treated primarily via intrathecal ports (137 doses) or transforaminal LP (55 doses). From April 2018 through September 2021, 704 of 709 (99.3%) LPs were successful. In total from January 2012 to September 2021, 1415 doses were administered. Over 50% of LPs were performed by neurology nurse practitioners without image guidance. Safety outcomes were excellent. CONCLUSIONS: A stratified approach resulted in successful intrathecal nusinersen delivery and efficient resource allocation for patients with SMA, with or without complex spinal anatomy.

Case-Control Study of Tumor Stage-Dependent Outcomes for Cutaneous Squamous Cell Carcinoma in Immunosuppressed and Immunocompetent Patients.

BACKGROUND: Immunosuppressed patients have worse outcomes from cutaneous squamous cell carcinomas (cSCCs), although unclear whether it is due to the development of more high-stage tumors or worse outcomes for a given stage. OBJECTIVE: Analyze the impact of immunosuppression on the development of cSCCs and tumor stage-dependent outcomes. MATERIALS AND METHODS: Single-institution 1:2 case-control study of primary invasive cSCCs from 2005 to 2015 in 106 mixed-cause immunosuppressed patients and 212 control subjects matched to age, gender, and race. RESULTS: Four hundred twelve cSCCs from 106 immunosuppressed patients and 291 tumors from 212 matched immunocompetent patients were included. Both cohorts had similar T-stage distribution, with <5% high-stage tumors, that is, AJCC-7 T2, AJCC-8 T3, and BWH T2b/T3. Immunosuppression significantly increased the likelihood of poor outcomes (POs) (aggregate of local recurrence (LR), nodal and distant metastasis, and squamous cell carcinoma-related deaths) for low-stage tumors, that is, AJCC-7 T1 (odds ratio [OR], 4.29), AJCC-8 T1 (OR, 3.45), AJCC-8 T2 (OR, 3.75), BWH T1 (OR, 3.53), and BWH T2a (OR, 3.41) tumors. There was no significant difference in the treatment: most tumors were treated with Mohs (71% vs 75%) or excision (21% vs 20%) in both cohorts. CONCLUSION: Immunosuppressed patients have an increased risk of POs, specifically LRs, from low-stage cSCCs. Definitive treatment of cSCCs is recommended.

Comparison of the American Joint Committee on Cancer Seventh Edition and Brigham and Women's Hospital Cutaneous Squamous Cell Carcinoma Tumor Staging in Immunosuppressed Patients.

BACKGROUND: The American Joint Committee on Cancer 7th edition (AJCC-7) and Brigham and Women's Hospital (BWH) staging criteria for cutaneous squamous cell carcinoma (cSCC) have not been validated in immunosuppressed patients. OBJECTIVE: To compare the AJCC-7 and BWH staging systems for cSCCs in immunosuppressed patients. MATERIALS AND METHODS: A single-institution retrospective cohort study of cSCCs in immunosuppressed patients. Risks of local recurrence (LR), nodal metastasis (NM), in-transit metastasis, and any poor outcome (PO) were compared among AJCC-7 and BWH tumor T stages. RESULTS: One hundred six patients had 412 primary invasive cSCCs. Eighty-five percent were AJCC-7 T1, and 15% T2. Risks of NM and PO for AJCC-7 T1 versus T2 were 0.9% versus 5% and 12.8% versus 23.3%, respectively, p < .05. Eighty-one percent of tumors were BWH T1, 18% T2a, 1% T2b, and 0.2% T3. Risk of LR for BWH T1 versus T2a was 11.4% versus 20.3%, p < .01. Risk of NM increased from 0.3% for T1 to 4.1%, 25%, and 100% for T2a, T2b, and T3, p < .05. Ninety percent of PO occurred in low-stage BWH T1/T2a. CONCLUSION: Low T-stage cSCCs account for most POs. Brigham and Women's Hospital staging criteria better risk stratifies cSCCs in immunosuppressed patients for risk of NM and LR.

Progress of molecular targeted therapies for prostate cancers.

Prostate cancer remains the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in men in the United States. The current standard of care consists of prostatectomy and radiation therapy, which may often be supplemented with hormonal therapies. Recurrence is common, and many develop metastatic prostate cancer for which chemotherapy is only moderately effective. It is clear that novel therapies are needed for the treatment of the malignant forms of prostate cancer that recur after initial therapies, such as hormone refractory (HRPC) or castration resistant prostate cancer (CRPC). With advances in understanding of the molecular mechanisms of cancer, we have witnessed unprecedented progress in developing new forms of targeted therapy. Several targeted therapeutic agents have been developed and clinically used for the treatment of solid tumors such as breast cancer, non-small cell lung cancer, and renal cancer. Some of these reagents modulate growth factors and/or their receptors, which are abundant in cancer cells. Other reagents target the downstream signal transduction, survival pathways, and angiogenesis pathways that are abnormally activated in transformed cells or metastatic tumors. We will review current developments in this field, focusing specifically on treatments that can be applied to prostate cancers. Finally we will describe aspects of the future direction of the field with respect to discovering biomarkers to aid in identifying responsive prostate cancer patients.

A primary cilia-dependent etiology for midline facial disorders.

Human faces exhibit enormous variation. When pathological conditions are superimposed on normal variation, a nearly unbroken series of facial morphologies is produced. When viewed in full, this spectrum ranges from cyclopia and hypotelorism to hypertelorism and facial duplications. Decreased Hedgehog pathway activity causes holoprosencephaly and hypotelorism. Here, we show that excessive Hedgehog activity, caused by truncating the primary cilia on cranial neural crest cells, causes hypertelorism and frontonasal dysplasia (FND). Elimination of the intraflagellar transport protein Kif3a leads to excessive Hedgehog responsiveness in facial mesenchyme, which is accompanied by broader expression domains of Gli1, Ptc and Shh, and reduced expression domains of Gli3. Furthermore, broader domains of Gli1 expression correspond to areas of enhanced neural crest cell proliferation in the facial prominences of Kif3a conditional knockouts. Avian Talpid embryos that lack primary cilia exhibit similar molecular changes and similar facial phenotypes. Collectively, these data support our hypothesis that a severe narrowing of the facial midline and excessive expansion of the facial midline are both attributable to disruptions in Hedgehog pathway activity. These data also raise the possibility that genes encoding ciliary proteins are candidates for human conditions of hypertelorism and FNDs.