Are Positive Biopsy Margins in Melanoma Significant?: A Cohort Study of Micro- Versus Macroscopic Margin Status and Their Impact on Residual Disease and Survival.

BACKGROUND: Presence of positive biopsy margins in melanoma can provoke anxiety over potential disease progression from delays to surgical excision, but their impact on outcomes is unknown. We aimed to compare the presence of residual melanoma in the surgical excision specimen and survival between patients with negative, microscopically positive, and macroscopically positive biopsy margins. METHODS: Patients with cutaneous melanoma who underwent surgical excision over a 13-year period were included. Biopsy characteristics, residual disease in the surgical specimen, and overall and recurrence-free survival were compared between patients with negative, microscopically positive (only scar visible), and macroscopically positive (visible remaining melanoma) biopsy margins. RESULTS: Of 901 patients, 42.4%, 33.3%, and 24.3% had negative, microscopically positive, and macroscopically positive margins, respectively. The incidence of residual invasive melanoma in the surgical specimen varied (P < 0.001), occurring in 5.5%, 17.0%, and 74.9% of patients, respectively. Both microscopically and macroscopically positive margins were associated with residual disease (P < 0.001) but only the latter predicted worse overall (P = 0.013) and recurrence-free survival (P = 0.009). Kaplan-Meier estimated survival was comparable between those with negative and microscopically positive margins, but overall (P = 0.006) and recurrence-free survival (P = 0.004) were significantly worse in the macroscopically positive margin group. These patients had worse prognosis melanoma, with 33.8% being stage III disease, and 23.2% having positive sentinel lymph nodes. CONCLUSIONS: Patients and physicians may be reassured in the presence of microscopically positive biopsy margins which are not associated with worse survival, However, patients with macroscopically positive margins have poorer prognosis and should be treated within an acceptable time frame.

Imiquimod-induced bullous pemphigoid: A case report.

A 72-year-old man treated with 3.5% imiquimod cream for scalp actinic keratoses developed the usual crusted and erosive reaction but developed bullae on the scalp, as well as the limbs and torso after several weeks into treatment. Biopsy confirmed bullous pemphigoid. He was treated with clobetasol ointment, prednisone and methotrexate, with eventual disease control. He had a severe disease course. Bullous pemphigoid is usually idiopathic, but can be induced by skin trauma, as well as by several medications; this is the first report of imiquimod as a trigger. Imiquimod is a toll-like receptor 7 agonist that induces cellular apoptosis and recruits pro-inflammatory cytokines including tumour necrosis factor-alpha and interferon-alpha, which have been implicated in autoimmunity. This case highlights an unusual but severe adverse effect from topical imiquimod.

New mycosis fungoides-like lymphomatoid reaction following COVID-19 vaccination: A case report.

Numerous cutaneous side effects arising from COVID-19 vaccination have been reported. Mycosis fungoides (MF) is a rare indolent form of cutaneous t-cell lymphoma. While the pathogenesis of MF is not well understood, it is thought to involve immune dysregulation. There have been reports of COVID-19 vaccination induced flares and recurrences of cutaneous lymphomas and lymphomatoid reactions. We present the first reported case of COVID-19 vaccine induced MF-like lymphomatoid reaction.

MSC-Derived Extracellular Vesicles to Heal Diabetic Wounds: a Systematic Review and Meta-Analysis of Preclinical Animal Studies.

INTRODUCTION: Extracellular vesicles from mesenchymal stromal cells (MSC-EVs) have shown promise in wound healing. Their use in diabetic wounds specifically, however, remains pre-clinical and their efficacy remains uncertain less clear. A systematic review of preclinical studies is needed to determine the efficacy of MSC-EVs in the treatment of diabetic wounds to accelerate the clinical translation of this cell-based therapy. METHODS: PubMed and Embase were searched (to June 23, 2020). All English-language, full-text, controlled interventional studies comparing MSC-EVs to placebo or a "no treatment" arm in animal models of diabetic wounds were included. Study outcomes, including wound closure (primary outcome), scar width, blood vessel number and density, and re-epithelialisation were pooled using a random effects meta-analysis. Risk of bias (ROB) was assessed using the SYRCLE tool for pre-clinical animal studies. RESULTS: A total of 313 unique records were identified from our search, with 10 full text articles satisfying inclusion criteria (n = 136 animals). The administration of MSC-EVs improved closure of diabetic wounds compared to controls with a large observed effect (Standardized Mean Difference (SMD) 5.48, 95% Confidence Interval (CI) 3.55-8.13). Healing was further enhanced using MSC-EVs enriched in non-coding RNAs or microRNAs compared to controls (SMD 9.89, 95%CI 7.32-12.46). Other outcomes, such as blood vessel density and number, scar width, and re-epithelialisation were improved with the administration of MSC-EVs, with a large effect. ROB across studies was unclear. CONCLUSION: MSC-EVs, particularly following enrichment for specific RNAs, are a promising treatment for diabetic wounds in pre-clinical studies and translation to the clinical domain appears warranted. REGISTRATION: PROSPERO #CRD42020199327 [248]. Forest plot demonstrating increased wound closure rates of diabetic wounds receiving genetically modified MSC-EVs that were enriched for specific RNAs. DFO = deferoxamine. Control groups were inactive (no treatment or saline) except for 3 studies which used hydrogels without MSC-EVs as control (Li M 2016; Shi 2017; Tao 2016).

Early Warning of Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation Using Heart Rate Variability and Serum Biomarkers.

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ~48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (~50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study.

Variation in management of post-operative atrial fibrillation (POAF) after thoracic surgery.

OBJECTIVES: New-onset post-operative atrial fibrillation (POAF) is a frequent adverse event following major thoracic surgery and is associated with increased risk of perioperative morbidity, length of stay and stroke. It is managed initially with rate and rhythm control therapy; however, optimal duration and the need for anticoagulation are poorly understood. This study aims to assess practice variation regarding POAF management and duration. METHODS: This retrospective, single-center cohort study included patients who underwent major thoracic surgery and developed POAF between 2008 and 2017, managed with rate and rhythm control therapy alone. Demographic, clinical, and surgical variables/outcomes, POAF management, and incidence of POAF recurrence in the 30-day post-operative period were collected. Chi-square and T-tests determined significance. RESULTS: Of 2054 patients undergoing thoracic surgery, 155 (75%) patients developed POAF. Different rate and rhythm control agents were used, most commonly metoprolol. 107 (69%) continued rate and rhythm control therapy upon hospital discharge for a mean of 56 days. Among the 48 patients with discontinuation of rate and rhythm control therapy on discharge, none demonstrated recurrence of POAF; in contrast to 3 of 107 patients who continued on therapy. Among patients with CHA2DS2-VASc score ≥ 2, 15% were prescribed anticoagulation on discharge. CONCLUSIONS: Use of rate and rhythm control therapy and anticoagulation for POAF is significantly varied in practice. Many patients are not continued on rate and rhythm control after hospital discharge, which does not appear to impact risk of POAF recurrence. Further research to inform guidelines for POAF management, including therapy duration and indications for anticoagulation is warranted.

Socioeconomic Status and Melanoma in Canada: A Systematic Review.

As melanoma is one of the leading cancers in average years of life lost per death from disease, screening and early diagnosis are imperative to decrease morbidity and mortality. Socioeconomic status (SES) has been shown to be associated with melanoma incidence. However, it is unclear if this association holds true in universal healthcare systems where screening, diagnostic, and treatment services are available to all patients. The objective of this systematic review was to evaluate the evidence on the association of SES and melanoma incidence in Canada. A comprehensive search of PubMed and EMBASE yielded 7 studies reporting on melanoma incidence or outcomes with respect to SES in Canada. High SES was associated with increased melanoma incidence across all studies, which encompassed all Canadian provinces, and time periods spanning from 1979 to 2012. Studies also reported an increasing incidence of melanoma over time. There were substantial discrepancies in melanoma incidence across Canadian provinces, after controlling for SES and demographic characteristics. Populations of lower SES and living within certain healthcare regions had increased risks of advanced melanoma at diagnosis. This review highlights the potential for inequities in access to care even within a universal healthcare system. Future research is needed to characterize specific risk factors within different patient groups and within the universal health system context in order to implement targeted strategies to lower melanoma incidence, morbidity, and mortality.

Intraoperative balloon occlusion of the aorta for blood management in sacral and pelvic tumor resection: A systematic review and meta-analysis.

BACKGROUND: Neoplasms of the sacrum and pelvis are challenging to manage due to their complex vascularity and size and are at high risk of bleeding during resection. Intra-aortic balloon occlusion (IABO) has been used in trauma to control massive blood loss, but its efficacy and safety in oncologic sacral and pelvic surgery are unknown. The primary objective of this systematic review and meta-analysis was to assess the effectiveness of IABO in providing hemorrhage control during resection of sacral and pelvic tumors. METHODS: This PROSPERO pre-registered study meta-analyzed all studies reporting on the use of IABO in the setting of pelvic and sacral tumour resection, in accordance with the PRISMA guidelines. The primary outcome of the meta-analysis was intraoperative blood loss, with secondary outcomes consisting of transfusion volume, post-operative blood loss, operative time, complication rate, and mortality. RESULTS: Across studies, IABO was associated with a large, significant reduction in intraoperative blood loss (SMD -0.81, 95% CI -1.01 to -0.60, P < 0.0001) and transfused red blood cell volume (SMD 0.92, 95% CI -1.30 to -0.53, P < 0.0001). Two studies reported that complication rates were comparable between patients receiving IABO and patient receiving conventional surgery (Odds ratio = 1.29, 95% CI: 0.59 to 2.83, P = 0.52). All studies descriptively reported improved visualization of the operative field with IABO. CONCLUSIONS: Our findings demonstrated that IABO is an effective technique to decrease blood loss and transfusion requirements during sacral and pelvic tumor surgery. Future clinical trials should be conducted to establish the safety of this method and explore potential contraindications.

Perioperative antimicrobial decision making: Focused ethnography study in orthopedic and cardiothoracic surgeries in an Australian hospital.

OBJECTIVE: Antimicrobial use in the surgical setting is common and frequently inappropriate. Understanding the behavioral context of antimicrobial use is a critical step to developing stewardship programs. DESIGN: In this study, we employed qualitative methodologies to describe the phenomenon of antimicrobial use in 2 surgical units: orthopedic surgery and cardiothoracic surgery. SETTING: This study was conducted at a public, quaternary, university-affiliated hospital. PARTICIPANTS: Healthcare professionals from the 2 surgical unit teams participated in the study. METHODS: We used focused ethnographic and face-to-face semi-structured interviews to observe antimicrobial decision-making behaviors across the patient's journey from the preadmission clinic to the operating room to the postoperative ward. RESULTS: We identified 4 key themes influencing decision making in the surgical setting. Compartmentalized communication (theme 1) was observed with demarcated roles and defined pathways for communication (theme 2). Antimicrobial decisions in the operating room were driven by the most senior members of the team. These decisions, however, were delegated to more junior members of staff in the ward and clinic environment (theme 3). Throughout the patient's journey, communication with the patient about antimicrobial use was limited (theme 4). CONCLUSIONS: Approaches to decision making in surgery are highly structured. Although this structure appears to facilitate smooth flow of responsibility, more junior members of the staff may be disempowered. In addition, opportunities for shared decision making with patients were limited. Antimicrobial stewardship programs need to recognize the hierarchal structure as well as opportunities to engage the patient in shared decision making.

External validity of a model to predict postoperative atrial fibrillation after thoracic surgery.

OBJECTIVES: A prediction model developed by Passman et al. stratifies patients' risk of postoperative atrial fibrillation (POAF) after major non-cardiac thoracic surgery using 3 simple factors (sex, age and preoperative resting heart rate). The model has neither undergone external validation nor proven to be relevant in current thoracic surgery practice. METHODS: A retrospective single-centre analysis of all patients who underwent major non-cardiac thoracic surgery (2008-2017) with prospective documentation of incidence and severity of POAF was used for external validation of Passman's derivation sample (published in 2005 with 856 patients). The model calibration was assessed by evaluating the incidence of POAF and patients' risk scores (0-6). RESULTS: A total of 2054 patients were included. Among them, POAF occurred in 164 (7.9%), compared to 147 (17.2%) in Passman's study. Differences in our sample compared to Passman's sample included mean heart rate (75.7 vs 73.7 bpm, P < 0.001), proportion of patients with hypertension (46.1 vs 29.4%, P < 0.001), proportion of extensive lung resections, particularly pneumonectomy (6.1 vs 21%, P < 0.001) and proportion of minimally invasive surgeries (56.6% vs 0%). The model demonstrated a positive correlation between risk scores and POAF incidence (risk score 1.2% vs 6.16%). CONCLUSIONS: The POAF model demonstrated good calibration in our population, despite a lower overall incidence of POAF compared to the derivation study. POAF rates were higher among patients with a higher risk score and undergoing procedures with greater intrathoracic dissection. This tool may be useful in identifying patients who are at risk of POAF when undergoing major thoracic surgery and may, therefore, benefit from targeted prophylactic therapy.

Treatment of Mycoplasma pneumoniae-Induced Rash and Mucositis With Cyclosporine [Formula: see text].

BACKGROUND: Mycoplasma pneumoniae-induced rash and mucositis (MIRM) is a relatively newly recognized clinical entity that typically presents with predominant mucositis accompanied by variable cutaneous involvement 7-9 days after the onset of prodromal symptoms. There are no evidence-based guidelines for treatment, and current standards of care may include supportive therapy, antibiotics, corticosteroids, and intravenous immunoglobulin . OBJECTIVE: This case series aims to describe the potential efficacy of cyclosporine A (CsA) in the treatment of MIRM. METHODS: The present case series details our use of CsA early in the course of MIRM in 3 pediatric patients. RESULTS: Rapid clinical resolution was observed following CsA therapy. CONCLUSIONS: We suggest that early initiation of CsA may be an effective therapeutic option for MIRM.

Sunscreen Application, Safety, and Sun Protection: The Evidence.

Recently in Canada, there has been an effort to create consistent messaging about sun safety as there is a lack of up-to-date evidence-based guidelines regarding sun-protection measures. This review aimed to provide updated, evidence-based recommendations on sunscreen application, safety, and sun protection regarding the following topics for which there is clinical uncertainty: physical barriers, sunscreen properties, sunscreen application, and risk-benefit analysis.