Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

Barriers to overcoming immunotherapy resistance in glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, known for its poor prognosis and high recurrence rate. Current standard of care includes surgical resection followed by combined radiotherapy and chemotherapy. Although immunotherapies have yielded promising results in hematological malignancies, their successful application in GBM remains limited due to a host of immunosuppressive factors unique to GBM. As a result of these roadblocks, research efforts have focused on utilizing combinatorial immunotherapies that target networks of immune processes in GBM with promising results in both preclinical and clinical trials, although limitations in overcoming the immunosuppressive factors within GBM remain. In this review, we aim to discuss the intrinsic and adaptive immune resistance unique to GBM and to summarize the current evidence and outcomes of engineered and non-engineered treatments targeted at overcoming GBM resistance to immunotherapy. Additionally, we aim to highlight the most promising strategies of targeted GBM immunotherapy combinatorial treatments and the insights that may directly improve the current patient prognosis and clinical care.

Air pollution is associated with elevated HPA-Axis response to stress in anxious adolescent girls.

Research suggests that exposure to fine particulate air pollution (PM2.5) increases hypothalamic-pituitary-adrenal (HPA) axis activation in adults; it is unclear, however, whether PM2.5 is associated with HPA-axis functioning in psychosocial contexts, such as during the experience of social stress. One recent study of adolescents found that PM2.5 was associated with heightened autonomic reactivity to a social stress task, and that this association was strongest for adolescents with more severe internalizing symptoms. Here, we sought to replicate and extend these findings to HPA-axis stress responsivity in an independent sample of adolescent girls (N â€‹= â€‹130). We estimated PM2.5 concentrations at each participant's address using data from nearby air quality monitoring stations, and assessed participants' anxiety symptoms. We measured salivary cortisol in response to a social stress task and characterized HPA-axis functioning by computing area under the curve with respect to ground (AUCg) and with respect to increase (AUCi). Controlling for demographic factors, we found that PM2.5 was associated with heightened HPA-axis stress responsivity (both AUCg and AUCi) for girls who reported more severe levels of anxiety. We did not find a main effect of PM2.5 on HPA-axis functioning. These findings suggest that anxious adolescents are particularly vulnerable to the adverse effects of PM2.5 exposure on biological sensitivity to social stress.

Fine Particle Air Pollution and Physiological Reactivity to Social Stress in Adolescence: The Moderating Role of Anxiety and Depression.

OBJECTIVE: Exposure to high levels of fine particle air pollution (PM2.5) is associated with adolescent pathophysiology. It is unclear, however, if PM2.5 is associated with physiology within psychosocial contexts, such as social stress, and whether some adolescents are particularly vulnerable to PM2.5-related adverse effects. This study examined the association between PM2.5 and autonomic reactivity to social stress in adolescents and tested whether symptoms of anxiety and depression moderated this association. METHODS: Adolescents from Northern California (N = 144) participated in a modified Trier Social Stress Test while providing high-frequency heart rate variability and skin conductance level data. PM2.5 data were recorded from CalEnviroScreen. Adolescents reported on their own symptoms of anxiety and depression using the Youth Self-Report, which has been used in prior studies and has good psychometric properties (Cronbach's α in this sample was .86). RESULTS: Adolescents residing in neighborhoods characterized by higher concentrations of PM2.5 demonstrated greater autonomic reactivity (i.e., indexed by lower heart rate variability and higher skin conductance level) (ß = .27; b = .44, p = .001, 95% CI = 0.19 to 0.68) in response to social stress; this association was not accounted for by socioeconomic factors. In addition, adolescents who reported more severe anxiety and depression symptoms showed the strongest association between PM2.5 and autonomic reactivity to social stress (ß = .53; b = .86, p < .001, 95% CI = 0.48 to 1.23). CONCLUSIONS: Exposure to PM2.5 may heighten adolescent physiological reactivity to social stressors. Moreover, adolescents who experience anxiety and depression may be particularly vulnerable to the adverse effects of PM2.5 on stress reactivity.