For the Long Haul: Management of Long-Term Survivors after Melanoma Systemic Therapy.

PURPOSE OF REVIEW: This review summarizes the latest advancements in survivorship care for patients with advanced melanoma who received systemic therapy and emphasizes the areas where more research is needed. RECENT FINDINGS: Over the last decade there have been remarkable advances in the treatment of advanced and metastatic melanoma. Due to these novel treatments, including several immune checkpoint inhibitors and tyrosine kinase inhibitors, there are and will continue to be increasing numbers of long-term melanoma survivors who have been treated with systemic therapy. These patients will navigate new challenges are they are essentially among the first long term survivors after these novel therapies. Survivorship care focuses on improving the health-related quality of life of patients including the physical, emotional, social and functional effects of cancer that begin at diagnosis and continue through the end of life. Survivorship also includes screening for cancer recurrence and second cancers. As the number of melanoma survivors who received systemic therapy continues to grow, the survivorship care plan will become increasingly important for optimal care of patients even after their cancer treatments. Understanding the many domains of survivorship care for this group of patients is imperative for their care now and to identify unmet needs for future research.

A rare case of huge frontoethmoidal encephalocele projecting through mouth, with cleft palate.

Frontoethmoidal encephalocele represents protrusion of meninges and brain in a sac through a defect in the anterior skull base, mostly as swelling over the nose. Rarely it is associated with facial dysmorphism and palatal cleft. There are various perioperative concerns like airway difficulties, leaking from the swelling causing fluid and electrolyte disturbances, risk of infection, compression of the swelling causing a rise in intracranial pressure, bleeding, hypothermia, etc., In neonates, these challenges rise exponentially because of the inherent difficulties in dealing with this group of patients. Frontoethmoidal encephaloceles are common in low socioeconomic strata and are often missed in the antenatal period. We are reporting a rare case of frontoethmoidal encephalocele, with a huge swelling protruding through the cleft palate and occupying more than 50% of the face and oral cavity, making mask ventilation impossible.

Survivorship wellness: a multidisciplinary group program for cancer survivors.

PURPOSE: National mandates require cancer centers provide comprehensive survivorship care. We created an 8-session, group intervention, the Survivorship Wellness Group Program (SWGP), that covered 8 topics: nutrition, physical activity, stress, sleep/fatigue, sexuality/body image, emotional wellbeing/fear of cancer recurrence, spirituality/meaning, and health promotion/goal setting. This study examined the acceptability and preliminary outcomes of SWGP. METHODS: We evaluated SWGP using questionnaire data collected at program entry and 15-week follow-up. Questionnaires assessed acceptability and impact on anxiety, depression, quality of life, and perceived knowledge of topics. Enrollees who consented to participate in research and completed the baseline and 15-week follow-up were included in the analysis (N = 53). We assessed acceptability and preliminary outcomes using paired-samples t-tests. Due to the COVID-19 pandemic, SWGP transitioned to telehealth partway through data collection. Post-hoc analyses compared outcomes by intervention delivery. RESULTS: Participants completed an average of 7.44/8 classes. Participants reported a mean response of 3.42/4 regarding overall program satisfaction and 90.6% reported being "very likely" to recommend SWGP. SWGP was associated with decreases in anxiety and depression; increases in physical, emotional, functional, and overall quality of life; and increases in knowledge of all health behavior domains. No outcomes differed significantly between delivery in person versus telehealth. CONCLUSIONS: SWGP offers an acceptable and replicable model for cancer centers to meet national survivorship care guidelines. IMPLICATION FOR CANCER SURVIVORS: SWGP provides a comprehensive service for cancer survivors post-treatment, and was associated with better quality of life, fewer mental health symptoms, and increased knowledge in multiple domains of wellness.

Medication errors in the practice of paediatric anaesthesia - a narrative review.

Medication error has emerged as a significant problem in healthcare, especially in the past 2 decades. In anaesthesia, the paediatric age group is particularly at risk of such events because of complex age- and weight-based drug calculation, drug formulations, serial dilutions, and often limited staff experience in handling such patients. We searched PubMed, Cochrane, and Google Scholar for literature on medication errors in paediatric anaesthesia in children (< 18 years of age). Two authors searched for the articles independently, and a third author sorted any consensus differences. A total of 2979 articles were retrieved. We studied primary outcomes, the results, and conclusions of the various studies. A total of 21 relevant articles were selected finally. Following preventive strategies like colour coding, accurate dose calculations, verification by a second individual, and checking and encouraging self-reporting can improve perioperative safety in the paediatric population to a significant extent.

Prevalence and Impact of Poorly Controlled Modifiable Risk Factors Among Patients Who Underwent Atrial Fibrillation Ablation.

Managing atrial fibrillation (AF) risk factors (RFs) improves ablation outcomes in obese patients. However, real-world data, including nonobese patients, are limited. This study examined the modifiable RFs of consecutive patients who underwent AF ablation at a tertiary care hospital from 2012 to 2019. The prespecified RFs included body mass index (BMI) ≥30 kg/m2, >5% fluctuation in BMI, obstructive sleep apnea with continuous positive airway pressure noncompliance, uncontrolled hypertension, uncontrolled diabetes, uncontrolled hyperlipidemia, tobacco use, alcohol use higher than the standard recommendation, and a diagnosis-to-ablation time (DAT) >1.5 years. The primary outcome was a composite of arrhythmia recurrence, cardiovascular admissions, and cardiovascular death. In this study, a high prevalence of preablation modifiable RFs was observed. More than 50% of the 724 study patients had uncontrolled hyperlipidemia, a BMI ≥30 mg/m2, a fluctuating BMI >5%, or a delayed DAT. During a median follow-up of 2.6 (interquartile range 1.4 to 4.6) years, 467 patients (64.5%) met the primary outcome. Independent RFs were a fluctuation in BMI >5% (hazard ratio [HR] 1.31, p = 0.008), diabetes with A1c ≥6.5% (HR 1.50, p = 0.014), and uncontrolled hyperlipidemia (HR 1.30, p = 0.005). A total of 264 patients (36.46%) had at least 2 of these predictive RFs, which was associated with a higher incidence of the primary outcome. Delayed DAT over 1.5 years did not alter the ablation outcome. In conclusion, substantial portions of patients who underwent AF ablation have potentially modifiable RFs that were not well controlled. Fluctuating BMI, diabetes with hemoglobin A1c ≥6.5%, and uncontrolled hyperlipidemia portend an increased risk of recurrent arrhythmia, cardiovascular hospitalizations, and mortality after ablation.

Predictive value of interatrial block on electrocardiogram among obese patients undergoing atrial fibrillation ablation.

BACKGROUND: Determine a predictive value of interatrial block (IAB) on atrial fibrillation (AF) ablation outcomes in obese patients. METHODS: Medical records were retrospectively reviewed for 205 consecutive patients with body mass indices (BMI) ≥ 30 kg/m2 who underwent initial AF ablation. Evidence of partial IAB defined as P-wave duration (PWD) ≥ 120 ms and advanced IAB with PWD ≥ 120 ms and biphasic or negative P-wave in inferior leads was examined from sinus electrocardiograms (ECGs) within 1-year pre-ablation. The primary outcome was recurrent atrial arrhythmia after 3-month blanking period post-ablation. RESULTS: The mean BMI was 36.9 ± 5.7 kg/m2. Partial IAB and advanced IAB were observed in 155 (75.61%) and 42 (20.49%) patients, respectively. During the median follow-up of 1.35 (interquartile range 0.74, 2.74) years, 115 (56.1%) patients had recurrent atrial arrhythmias. In multivariable analysis adjusting for age, gender, persistent AF, use of antiarrhythmic drugs (AADs), left atrial volume index (LAVI), partial IAB, and advanced IAB were independent predictors of recurrent arrhythmia with hazard ratio (HR) of 2.80 (95% confidence interval [CI] 1.47-6.05; p = 0.001) and HR 1.79 (95% CI 1.11-2.82; p = 0.017), respectively. The results were similar in a subgroup analysis of patients who had no severe left atrial enlargement and a subgroup analysis of patients who were not on AADs. CONCLUSIONS: IAB is highly prevalent in patients with obesity and AF. Partial IAB, defined as PWD ≥ 120 ms, and advanced IAB with evidence of biphasic P-wave in inferior leads were independently associated with increased risk of recurrent arrhythmia after AF ablation. Its predictive value is independent of other traditional risk factors, LAVI, or use of AADs.

Sleep disturbance among breast cancer survivors and controls from midlife to early older adulthood: Pink SWAN.

PURPOSE: To compare sleep disturbance from 5 years pre- to 5 years post-diagnosis between breast cancer survivors (BCS) and women without cancer over the same period and to identify BCS subgroups exhibiting different sleep trajectories. METHODS: Analyses included data from 152 BCS and 2163 controls from 20 years of follow-up in the longitudinal Study of Women's Health Across the Nation (SWAN), a multi-racial/ethnic cohort study. SWAN participants were assessed approximately annually from 1995 to 2015 using a standardized protocol. Pink SWAN focused on women who reported no cancer at SWAN enrollment and developed incident breast cancer after enrollment or did not develop breast cancer. Nonparametric locally weighted scatterplot smoothing plots and linear mixed models were used to compare the prevalence of the most frequently reported sleep problem, frequently waking several times a night (a sleep maintenance problem) during the previous 2 weeks, between BCS and controls in the 5 years pre- to 5 years post-diagnosis. We characterized heterogeneity among BCS on this sleep problem using group-based trajectories and examined pre-diagnosis variables as predictors of group membership. RESULTS: No differences were found between BCS and controls in prevalence of frequent nighttime awakenings either before or after diagnosis. Among BCS, three trajectory groups were identified. Thirty-seven percent of BCS had consistently low prevalence of waking several times per night, 30% had high prevalence, and 33% had increasing prevalence which started 2 years pre-diagnosis. Prevalence of pre-diagnosis vasomotor symptoms, anxiety, depressive symptoms, and smoking differed among these groups. CONCLUSION: Among mid-aged women diagnosed with breast cancer, this diagnosis did not trigger/amplify a sleep maintenance problem. The majority of BCS had similar levels of this sleep problem from pre- to post-diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Although sleep maintenance problems were not amplified by a cancer diagnosis, a subset of BCS may have sleep issues that should be monitored and treated, as indicated.

Anxiety During the COVID-19 Pandemic: A Web-Based Survey of Thyroid Cancer Survivors.

OBJECTIVE: Cancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors' health care interactions and quality of life. METHODS: An anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the Thyroid Cancer Survivors' Association, Inc website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression. RESULTS: From May 6, 2020, to October 8, 2020, 413 participants consented to take the survey; 378 (92%) met the inclusion criteria: diagnosed with thyroid cancer or noninvasive follicular neoplasm with papillary-like nuclear features, located within the United States, and completed all sections of the survey. The mean age was 53 years, 89% were women, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during the COVID-19 pandemic, as were their interactions with doctors (79%). A minority (43%) were satisfied with the information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs 56.5; P < .05) and lower for the ability to participate in social activities (46.2 vs 48.1; P < .01), fatigue (55.8 vs 57.9; P < .01), and sleep disturbance (54.7 vs 56.1; P < .01). After adjusting for confounders, higher anxiety was associated with younger age (P < .01) and change in treatment plan (P = .04). CONCLUSION: During the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to treatment plans.

#CardioOncology: Twitter chat as a mechanism for increasing awareness of heart health for cancer patients.

Consideration of heart health for cancer survivors is increasingly important, as improved cancer survivorship has resulted in a growing number of survivors affected by cardiovascular disease. However, there is limited knowledge of cardio-oncology among both patients and a variety of health professionals. Thus, efforts are needed to increase awareness about cardio-oncology. Social media represents one potential opportunity to disseminate information about cardio-oncology to a large audience. We highlight one example of a social media educational/advocacy campaign conducted on Twitter (a "Twitter Chat") that garnered nearly 1.2 million impressions (views by Twitter users) in just 24 h. We provide both quantitative and qualitative data to support the efficacy of using Twitter for such educational/advocacy campaigns, and describe key features that contributed to its success. Twitter Chats inexpensively utilize innovative technology to provide education and foster community. Long-term studies are needed to understand whether Twitter Chats can change knowledge and behavior related to cardio-oncology.

CSF cell-free DNA EGFR testing using DdPCR holds promise over conventional modalities for diagnosing leptomeningeal involvement in patients with non-small cell lung cancer.

BACKGROUND: EGFR mutant NSCLC patients have leptomeningeal (LM) involvement in more than 9% cases. MATERIAL & METHODS: We conducted a study evaluating the diagnostic utility of cfDNA EGFR testing in CSF using DdPCR while comparing it against MRI and CSF cytology. We also looked for known EGFR mutations in the CSF sample. These mutations were also tested in paired plasma samples. We further compared which constituent of CSF (pellet/supernatant) had better yield. RESULTS: 21 patients comprised the study. Of these 17 patients were diagnosed to have LM involvement based on conventional criteria. All modalities had 100 % specificity and positive predictive value. However, MRI and CSF cytology had a poor negative predictive value. cfDNA had the highest sensitivity (92.3 %), negative predictive value (75 %), accuracy (94.1 %), and net comparative benefit. Paired plasma samples were available for 19 patients. Primary EGFR mutation was detectable in the CSF sample in 16/19 patients; however, the plasma sample was positive only in 7/19 patients. 3 samples were negative for primary EGFR mutation in both CSF and plasma. None of the CSF samples showed positivity for T790M mutation which could however be observed in two patients in plasma samples. Both supernatant and pellet were analysed for cfDNA mutation analysis in 18/21 patients. The intraclass correlation coefficient regarding the percentage fraction tumor-derived DNA of cfDNA observed was 0.83(95 % CI 0.29 to 0.95) between both samples. CONCLUSION: EGFR detection in CSF has a potential role in diagnosing LM involvement. T790 M resistance mutations are uncommon in CSF post first and second-generation TKIs. Both supernatant and pellet samples can be used for the extraction of cell-free DNA in CSF.

Health-related quality of life among breast cancer survivors and noncancer controls over 10 years: Pink SWAN.

BACKGROUND: The goal of this study was to compare health-related quality of life (HRQL) from diagnosis to 10 years postdiagnosis among breast cancer survivors (BCS) and women without cancer over the same period and to identify BCS subgroups exhibiting different HRQL trajectories. METHODS: Our analysis included 141 BCS and 2086 controls from the Study of Women's Health Across the Nation (SWAN), a multiracial/ethnic cohort study of mid-life women assessed approximately annually from 1995 to 2015. Pink SWAN participants reported no cancer at SWAN enrollment and developed (cases) or did not develop (controls) incident breast cancer after enrollment. We assessed HRQL with SF-36 Mental Component Summary and Physical Component Summary scores. We modeled each as a function of case/control status, years since diagnosis, years since diagnosis squared, and the interaction terms between case/control status and the 2 time variables in linear models. We characterized heterogeneity in postdiagnosis HRQL of cases using group-based trajectories. RESULTS: BCS had significantly lower HRQL compared with controls at diagnosis and 1 year postdiagnosis. By 2 years, BCS and controls no longer differed significantly. Among BCS, 2 trajectory groups were identified for both scores. For the Mental Component Summary, 88.4% of BCS had consistently good and 11.6% had very low scores. For the Physical Component Summary, 73.9% had good scores, and 26.1% had consistently low scores. Prediagnosis perceived stress and current smoking were related to being in the low mental trajectory group, and a higher number of comorbidities was related to being in the low physical trajectory group. CONCLUSION: Although the majority of BCS have HRQL similar to non-cancer controls after 2 years, subgroups of BCS continue to have low HRQL. Prediagnosis stress, comorbidities, and smoking are vulnerability factors for long-term, low HRQL in BCS.

Inflammatory biomarkers, geriatric assessment, and treatment outcomes in acute myeloid leukemia.

OBJECTIVES: To investigate changes in inflammatory biomarkers during induction therapy for older adults with acute myeloid leukemia (AML) and their associations with geriatric assessment (GA) measures and outcomes. METHODS: This was a single institution ancillary study to a prospective observational study (N = 20 consecutive adults aged ≥60 with newly diagnosed AML who received induction chemotherapy). Biomarkers (Interleukin-6 [IL-6], IL-6 soluble receptor [IL-6 sR], tumor necrosis factor alpha [TNFα], TNFα soluble receptor 1 [TNFα sR1], interleukin-3 [IL-3], C-reactive protein [CRP]) were collected at start of induction, weekly for three weeks, and post-induction and were compared over time using paired t-tests. GA was administered at baseline and post-induction, and correlated with biomarker levels using Spearman correlations. Survival was estimated using Kaplan-Meier and compared by categorized biomarker level using Wilcoxon tests. RESULTS: Biomarker levels were stable during induction, except for CRP and IL-6 sR. Declines in objectively measured physical function [Short Physical Performance Battery (SPPB); r = 0.71, p < 0.01] and increases in self-reported limitation in instrumental activities of daily living (r = 0.81, p < 0.01) were correlated with increased TNFα sR1. Declines in SPPB were correlated with increased CRP (r = -0.73, p < 0.01). Improvement in depression was correlated with increased IL-6 sR (r = -0.59 p = 0.02). Survival was shorter in those with baseline TNFα or CRP levels above the median (6.1 vs. 40.2 months and 5.5 vs. 27.6 months respectively, p = 0.04 for both). CONCLUSION: Among older adults with AML, the relationships between TNFα sR1, CRP, and IL-6 sR with change in physical and emotional health during treatment warrants further investigation.

Machine learning based quantification of ejection and filling parameters by fully automated dynamic measurement of left ventricular volumes from cardiac magnetic resonance images.

BACKGROUND: Although analysis of cardiac magnetic resonance (CMR) images provides accurate and reproducible measurements of left ventricular (LV) volumes, these measurements are usually not performed throughout the cardiac cycle because of lack of tools that would allow such analysis within a reasonable timeframe. A fully-automated machine-learning (ML) algorithm was recently developed to automatically generate LV volume-time curves. Our aim was to validate ejection and filling parameters calculated from these curves using conventional analysis as a reference. METHODS: We studied 21 patients undergoing clinical CMR examinations. LV volume-time curves were obtained using the ML-based algorithm (Neosoft), and independently using slice-by-slice, frame-by-frame manual tracing of the endocardial boundaries. Ejection and filling parameters derived from these curves were compared between the two techniques. For each parameter, Bland-Altman bias and limits of agreement (LOA) were expressed in percent of the mean measured value. RESULTS: Time-volume curves were generated using the automated ML analysis within 2.5 ± 0.5 min, considerably faster than the manual analysis (43 ± 14 min per patient, including ~10 slices with 25-32 frames per slice). Time-volume curves were similar between the two techniques in magnitude and shape. Size and function parameters extracted from these curves showed no significant inter-technique differences, reflected by high correlations, small biases (<10%) and mostly reasonably narrow LOA. CONCLUSION: ML software for dynamic LV volume measurement allows fast and accurate, fully automated analysis of ejection and filling parameters, compared to manual tracing based analysis. The ability to quickly evaluate time-volume curves is important for a more comprehensive evaluation of the patient's cardiac function.

Echocardiography and cardiovascular magnetic resonance based evaluation of myocardial strain and relationship with late gadolinium enhancement.

OBJECTIVES: We sought to: (1) determine the agreement in cardiovascular magnetic resonance (CMR) and speckle tracking echocardiography (STE) derived strain measurements, (2) compare their reproducibility, (3) determine which approach is best related to CMR late gadolinium enhancement (LGE). BACKGROUND: While STE-derived strain is routinely used to assess left ventricular (LV) function, CMR strain measurements are not yet standardized. Strain can be measured using dedicated pulse sequences (strain-encoding, SENC), or post-processing of cine images (feature tracking, FT). It is unclear whether these measurements are interchangeable, and whether strain can be used as an alternative to LGE. METHODS: Fifty patients underwent 2D echocardiography and 1.5 T CMR. Global longitudinal strain (GLS) was measured by STE (Epsilon), FT (NeoSoft) and SENC (Myocardial Solutions) and circumferential strain (GCS) by FT and SENC. RESULTS: GLS showed good inter-modality agreement (r-values: 0.71-0.75), small biases (< 1%) but considerable limits of agreement (- 7 to 8%). The agreement between the CMR techniques was better for GLS than GCS (r = 0.81 vs 0.67; smaller bias). Repeated measurements showed low intra- and inter-observer variability for both GLS and GCS (intraclass correlations 0.86-0.99; coefficients of variation 3-13%). LGE was present in 22 (44%) of patients. Both SENC- and FT-derived GLS and GCS were associated with LGE, while STE-GLS was not. Irrespective of CMR technique, this association was stronger for GCS (AUC 0.77-0.78) than GLS (AUC 0.67-0.72) and STE-GLS (AUC = 0.58). CONCLUSION: There is good inter-technique agreement in strain measurements, which were highly reproducible, irrespective of modality or analysis technique. GCS may better reflect the presence of underlying LGE than GLS.

Impact of Severe Pulmonary Arterial Hypertension on the Left Heart and Prognostic Implications.

BACKGROUND: Severe pulmonary arterial hypertension (sPAH) results in a dilated and dysfunctional right ventricle (RV) together with a small left ventricle (LV) with preserved systolic function. RV size and function parameters have an established association with poor prognosis in sPAH. We sought to determine the impact of RV geometry and function on LV mechanics and its relationship with mortality. METHODS: We studied 114 patients (54 ± 13 years) with sPAH, normal LV ejection fraction (LVEF), and complete two-dimensional transthoracic echocardiograms (TTE) and compared them with 70 normal controls of similar age and gender distribution. TTE measurements of atrial sizes, ventricular volumes and function, tricuspid and mitral regurgitation (TR, MR), and LV diastolic function were performed. Speckle-tracking strain was measured in all four chambers, including LV global longitudinal strain (GLS). Cox proportional hazards regression with forward selection was performed to determine the associations between measured indices and mortality over a 20-month follow-up period. Kaplan-Meier curves were generated for variables most associated with death. RESULTS: Compared with controls, sPAH patients had greater TR severity and right-chamber size with worse function. Of note, LVEF was normal in both groups. Left atrial peak strain and LV GLS were reduced in sPAH, with greater reductions in nonsurvivors. In multivariate analysis, right atrial volume index (hazard ratio [HR] = 1.02 [CI, 1.01-1.04], P < .01), RV free-wall strain (HR = 1.08; CI [1.01-1.15]; P = .03), and LV GLS (HR = 1.11 [CI, 1.01-1.22]; P = .04) were independently associated with mortality. CONCLUSIONS: Although PAH is predominantly a right heart disease, in our cohort of sPAH with normal LVEF, LV GLS was independently associated with death in addition to RV and right atrial abnormalities. These findings indicate that the role of left heart dysfunction in sPAH may be underappreciated in clinical practice.