Prognostic factors of head and neck cutaneous squamous cell carcinoma: a systematic review

Background: Head and neck cutaneous squamous cell carcinoma (HNCSCC) is a non-melanoma skin cancer that is mostly caused by solar ultraviolet radiation exposure. While it usually has an excellent prognosis, a subset of patients (5%) develops nodal metastasis and has poor outcomes. The aim of this study was to systematically review the literature and evaluate the prognostic factors of HNCSCC in order to better understand which patients are the most likely to develop metastatic disease. Methods: A comprehensive literature search was performed on PubMed and EMBASE to identify the studies that evaluated the prognostic factors of HNCSCC. Prognostic factors were deemed significant if they had a reported p-value of < 0.05. Proportions of studies that reported a given factor to be statistically significant were calculated for each prognostic factor. Results: The search yielded a total of 958 citations. Forty studies, involving a total of 8535 patients, were included in the final analysis. The pre-operative/clinical prognostic factors with the highest proportion of significance were state of immunosuppression (73.3%) and age (53.3%); while post-operative/pathological prognostic factors of importance were number of lymph nodes involved with carcinoma (70.0%), margins involved with carcinoma (66.7%), and tumor depth (50.0%). Conclusion: This systematic review is aimed to aid physicians in assessing the prognosis of HNCSCC and identifying the subsets of patients that are most susceptible to metastasis. It also suggests that immunosuppressed patients with a high-risk feature on biopsy, such as invasion beyond subcutaneous fat, could possibly benefit from a sentinel lymph node biopsy. Keywords: Carcinoma; Mohs surgery; Sentinel lymph node biopsy; Skin neoplasms; Squamous cell; Squamous cell carcinoma of head and neck

Prognosis tools for short-term adverse events in older emergency department users : result of a Québec observational prospective cohort

Background: The “Program of Research on the Integration of Services for the Maintenance of Autonomy” (PRISMA-7) and “Emergency room evaluation and recommendations” (ER2) are both clinical tools used in Québec Emergency Departments (EDs) for screening of older ED users at higher risk of poor outcomes, such as prolonged length of stay (LOS) in EDs and in hospital. The study aimed to: 1) examine whether the PRISMA-7 and ER2 risk levels were associated with length of stays in ED and hospital, as well as hospital admission; and 2) compare the criteria performance (i.e., sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios and area under receiver operating characteristic curve) of the PRISMA-7 and ER2 high-risk levels for these three ED adverse events in Québec older patients visiting ED on a stretcher. Methods: A total of 1905 older patients who visited the ED of the Jewish General Hospital (Montreal, Québec, Canada) on stretchers were recruited in this prospective observational cohort. Upon their ED arrival, PRISMA-7 and ER2 were performed. The outcomes were LOS in ED and in hospital, and hospital admission. Results: The PRISMA-7 and ER2 risk levels were associated with length of stay in ED and hospital as well as with hospital admission. Prolonged stays and higher hospitalization rates were associated with high-risk levels, whereas those in low-risk level groups had significantly shorter LOS and a lower rate of hospital admission (P < 0.006). While performance measures were poor for both assessment tools, ER2 had a greater prognostic testing accuracy compared with PRISMA-7. Conclusion: PRISMA-7 and ER2 were both associated with incidental short-term ED adverse events but their overall prognostic testing accuracy was low, suggesting that they cannot be used as prognostic tools for this purpose.Published versio

"Emergency Room Evaluation and Recommendations" (ER2) tool for the screening of older emergency department visitors with major neurocognitive disorders: results from the ER² database

Purpose: The Emergency Room Evaluation and Recommendation (ER2) is an application in the electronic medical file of patients visiting the Emergency Department (ED) of the Jewish General Hospital (JGH; Montreal, Quebec, Canada). It screens for older ED visitors at high risk of undesirable events. The aim of this study is to examine the performance criteria (i.e., sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], positive likelihood ratio [LR+], negative likelihood ratio [LR-] and area under the receiver operating characteristic curve [AUROC]) of the ER2 high-risk level and its "temporal disorientation" item alone to screen for major neurocognitive disorders in older ED visitors at the JGH. Methods: Based on a cross-sectional design, 999 older adults (age 84.9 ± 5.6, 65.1% female) visiting the ED of the JGH were selected from the ER2 database. ER2 was completed upon the patients' arrival at the ED. The outcomes were ER2's high-risk level, the answer to ER2's temporal disorientation item (present vs. absent), and the diagnosis of major neurocognitive disorders (yes vs. no) which was confirmed when it was present in a letter or other files signed by a physician. Results: The sensitivities of both ER2's high-risk level and temporal disorientation item were high (≥0.91). Specificity, the PPV, LR+, and AROC were higher for the temporal disorientation item compared to ER2's high-risk level, whereas a highest sensitivity, LR-, and NPV were obtained with the ER2 high-risk level. Both area under the receiver operating characteristic curves were high (0.71 for ER2's high-risk level and 0.82 for ER2 temporal disorientation item). The odds ratios (OR) of ER2's high-risk level and of temporal disorientation item for the diagnosis of major neurocognitive disorders were positive and significant with all OR above 18, the highest OR being reported for the temporal disorientation item in the unadjusted model [OR = 26.4 with 95% confidence interval (CI) = 17.7-39.3]. Conclusion: Our results suggest that ER2 and especially its temporal disorientation item may be used to screen for major neurocognitive disorders in older ED users.Published versionThe study was financially supported by private donations (Oberfeld family) and the Foundation of the Jewish General Hospital (Montreal, QC, Canada)

Inhibition of astroglial NF-κB enhances oligodendrogenesis following spinal cord injury.

BACKGROUND: Astrocytes are taking the center stage in neurotrauma and neurological diseases as they appear to play a dominant role in the inflammatory processes associated with these conditions. Previously, we reported that inhibiting NF-κB activation in astrocytes, using a transgenic mouse model (GFAP-IκBα-dn mice), results in improved functional recovery, increased white matter preservation and axonal sparing following spinal cord injury (SCI). In the present study, we sought to determine whether this improvement, due to inhibiting NF-κB activation in astrocytes, could be the result of enhanced oligodendrogenesis in our transgenic mice. METHODS: To assess oligodendrogenesis in GFAP-IκBα-dn compared to wild-type (WT) littermate mice following SCI, we used bromodeoxyuridine labeling along with cell-specific immuno-histochemistry, confocal microscopy and quantitative cell counts. To further gain insight into the underlying molecular mechanisms leading to increased white matter, we performed a microarray analysis in naïve and 3 days, 3 and 6 weeks following SCI in GFAP-IκBα-dn and WT littermate mice. RESULTS: Inhibition of astroglial NF-κB in GFAP-IκBα-dn mice resulted in enhanced oligodendrogenesis 6 weeks following SCI and was associated with increased levels of myelin proteolipid protein compared to spinal cord injured WT mice. The microarray data showed a large number of differentially expressed genes involved in inflammatory and immune response between WT and transgenic mice. We did not find any difference in the number of microglia/leukocytes infiltrating the spinal cord but did find differences in their level of expression of toll-like receptor 4. We also found increased expression of the chemokine receptor CXCR4 on oligodendrocyte progenitor cells and mature oligodendrocytes in the transgenic mice. Finally TNF receptor 2 levels were significantly higher in the transgenic mice compared to WT following injury. CONCLUSIONS: These studies suggest that one of the beneficial roles of blocking NF-κB in astrocytes is to promote oligodendrogenesis through alteration of the inflammatory environment