ctDNA as an Adjunct to Posttreatment PET for Head and Neck Cancer Recurrence Risk Assessment.

OBJECTIVE: Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as an adjunct method to help overcome the limitations of positron emission tomography (PET) and select patients who are at high risk for recurrence. STUDY DESIGN: Retrospective Single Institutional Study. SETTING: University Hospital Setting. METHODS: Twenty-nine patients who underwent definitive treatment for squamous cell carcinoma of the head and neck (HNSCC) from 8/2021 to 01/2023 had ctDNA levels analyzed at 1 to 3, 6, 9, and 12 months after definitive treatment. A personalized, tumor-informed, multiplex polymerase chain reaction (PCR) next-generation sequencing (NGS) assay was used to detect the ctDNA levels. The primary outcome was recurrence-free probability (RFP), and the secondary outcomes were overall survival (OS), sensitivity, specificity, and the test's negative (NPV) and positive predictive values (PPV). RESULTS: The median age of patients was 65 years (interquartile range: 56-69), with majority being males (n = 22, 76%). The primary sites were larynx (n = 12), oropharynx (n = 10), and oral cavity (n = 6). Posttreatment ctDNA was detected in 7 patients, all of whom had disease recurrence. ctDNA detection after definitive treatment was associated with a higher risk of disease recurrence (hazard ratio: 9.94, 95% confidence interval: 1.56-63.3, P = .015). ctDNA identified recurrence with 100% specificity and 78% sensitivity. The NPV and PPV were 91% and 100%. PET had 78% sensitivity but only 68% specificity with 86% NPV, and 54% PPV. CONCLUSION: Based on our data, ctDNA can be an excellent adjunct test for posttreatment PET and can help guide physicians in cases where PET results are inconclusive and difficult to interpret.

Monoclonal Gammopathy of Undetermined Significance in Patients With Transthyretin Amyloidosis (ATTR): Analysis Using the iStopMM Criteria.

INTRODUCTION: To identify the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with transthyretin amyloid (ATTR). We used the iStopMM study revised reference ranges for serum free light-chain (sFLC) corrected for eGFR to identify ATTR patients with light-chain MGUS (LC-MGUS). Characteristics and frequencies of the ATTR cohort with underlying MGUS was compared to a cohort of MGUS patients without ATTR. PATIENTS AND METHODS: A retrospective analysis of ATTR and MGUS patients evaluated at our center between January 2014 to December 2021. A total of 149, predominantly male (87.5%) ATTR patients with a median age of 82 were included. This cohort was compared to 228 MGUS patients. RESULTS: Of the 149 ATTR patients, 27 (18.1%) had coexisting MGUS. Among ATTR patients with MGUS, 12/27 (44%) had LC-MGUS based on sFLC abnormalities assessed using the iStopMM reference ranges. Of the MGUS only cohort, 44/228 (19.3%) met criteria for LC-MGUS. Utilizing the iStopMM reference ranges, 6 ATTR patients did not meet criteria for abnormal sFLCs, uncovering a 20% false-positive rate. CONCLUSION: We noted higher rates of MGUS, particularly LC-MGUS, among ATTR patients when compared to our MGUS only cohort. The high prevalence remained after utilizing the iStopMM sFLC corrected for eGFR reference ranges. Additionally, 6 ATTR patients with renal-dysfunction would have met MGUS criteria if not evaluated using the iStopMM revised measures. These findings emphasize careful interpretation of sFLC abnormalities and encourage providers to keep ATTR on the differential when work-up uncovers sFLC aberrations.

Amyloidosis and COVID-19: experience from an amyloid program in Canada.

Severe acute respiratory syndrome coronavirus (SARS-CoV2) and associated COVID-19 infection continue to impact patients globally. Patients with underlying health conditions are at heightened risk of adverse outcomes from COVID-19; however, research involving patients with rare health conditions remains scarce. The amyloidoses are a rare grouping of protein deposition diseases. Light-chain and transthyretin amyloidosis are the most common disease forms, often present with systemic involvement of vital organs including the heart, nerves, kidneys, and GI tracts of affected individuals. The Amyloidosis Program of Calgary examined 152 ATTR patients and 103 AL patients analyzing rates of vaccination, COVID-19 testing, infection outcomes, influence referrals, and excess deaths. Results showed 15 total PCR-confirmed COVID-19 infections in the tested population of amyloid patients, with a higher frequency of infections among patient with AL compared to the ATTR cohort (26.2% vs 5.1%). Four patients (26.6%) required hospital admission for COVID-19 infection, 2 ATTR, and 2 AL patients. Of the confirmed cases, 1 (0.07%) unvaccinated ATTR patient died of a COVID-19 infection. An excess of deaths was found in both the ATTR and AL cohorts when comparing pre-pandemic years 2018 and 2019 to the pandemic years of 2020 and 2021. The finding suggests that amyloidosis patients are likely at a high risk for severe COVID-19 infection and mortality, especially those of advanced age, those on an active treatment with chemotherapy, and those with concomitant B-cell or plasma cell disorder. The impact of virtual healthcare visits and pandemic measures on the excess of deaths observed requires further research.

Treating CLL with Bruton Tyrosine Kinase Inhibitors: The Role of the Outpatient Oncology Nurse.

OBJECTIVES: To summarize the role of Bruton tyrosine kinase (BTK) inhibitors in the management of chronic lymphocytic leukemia with a focus on the nursing role in relation to patients with chronic lymphocytic leukemia being treated with BTK inhibitors. DATA SOURCES: These include published articles (PubMed) and national and international guideline documents. CONCLUSION: BTK inhibitors have revolutionized the therapy of chronic lymphocytic leukemia and have become the most frequently used therapy today. Despite the many advantages of BTK inhibitors, adverse events remain a leading cause of treatment discontinuation, particularly for the first-in-class BTK inhibitor. Second-generation BTK inhibitors appear to have a better tolerability profile but still require adverse event management given their prolonged duration of therapy. Awareness and management of side effects by the oncology care team is essential for ensuring both compliance and safety with ongoing treatment. IMPLICATIONS FOR NURSING PRACTICE: Chronic lymphocytic leukemia is a chronic illness with a long-life expectancy. For the patients who require therapy, BTK inhibitor therapy is a frequently applied treatment with impressive efficacy. BTK inhibitors are continued indefinitely until disease progression or significant toxicity; therefore, the overall principles of careful assessment for side effects, diligent management for these, and individualized patient support provided by oncology nurses is vital in this patient population.

Incorporating foot assessment in the comprehensive geriatric assessment.

BACKGROUND: Foot problems are common in older adults and associated with poorer physical function, falls, frailty and reduced quality of life. Comprehensive Geriatric Assessment (CGA), a multidisciplinary process that is considered the gold standard of care for older adults, does not routinely include podiatry assessment and intervention in hospitalized older adults. AIMS: To introduce foot assessment to inpatient CGA to determine prevalence of foot disease, foot disease risk factors and inappropriate footwear use, assess inter-rater reliability of foot assessments, determine current podiatry input and examine associations between patient characteristics and foot disease risks. METHODS: Prospective, observational cohort study of older adults on geriatric rehabilitation wards. Foot assessment completed using the Queensland Foot Disease Form (QFDF) in addition to routine CGA. RESULTS: Fifty-two patients (median age [inter-quartile range] 86.4 [79.2-90.3] years, 54% female) were included. Six patients (12%) had foot disease and 13 (25%) had a 'high risk' or 'at risk' foot. Foot disease risk factor prevalence was peripheral arterial disease 9 (17%); neuropathy 10 (19%) and foot deformity 11 (22%). Forty-one patients (85%) wore inappropriate footwear. Inter-rater agreement was substantial on presence of foot disease and arterial disease, fair to moderate on foot deformity and fair on neuropathy and inappropriate footwear. Eight patients (15%) saw a podiatrist during admission: 5 with foot disease, 1 'at risk' and 2 'low risk' for foot disease. Patients with an at risk foot or foot disease had significantly longer median length of hospital stay (25 [13.7-32.1] vs 15.2 [8-22.1] days, p = 0.01) and higher median Malnutrition Screening Test scores (2 [0-3] vs 0 [0-2], p = 0.03) than the low-risk group. Patients with foot disease were most likely to see a podiatrist (p < 0.001). CONCLUSION: Foot disease, foot disease risk factors and inappropriate footwear are common in hospitalized older adults, however podiatry assessment and intervention is mostly limited to patients with foot disease. Addition of routine podiatry assessment to the multidisciplinary CGA team should be considered. Examination for arterial disease and risk of malnutrition may be useful to identify at risk patients for podiatry review.

Foot disease and physical function in older adults: A systematic review and meta-analysis.

OBJECTIVES: To systematically assess the literature examining the association between foot disease (foot ulceration, infection, critical ischaemia and/or Charcot neuroarthropathy) and physical function in older adults. METHODS: Literature search of MEDLINE, Embase and CINAHL was performed. Studies were included if foot disease and physical function were assessed in participants of mean or median age ≥ 65 years. RESULTS: Of 2,574 abstracts screened, 19 studies (13 longitudinal, 6 cross-sectional) reporting on 5634 participants, 43% female, were included. Diabetes-related foot disease and critical ischaemia were most studied (n = 5017, 40% female). In 8 studies with control groups, foot disease was associated with poorer physical function. Meta-analysis of 5 studies (n = 1503, 45% female) found an association between foot disease and poorer physical function (SMD (95% CI): 1.00 (0.40, 1.62), P < 0.001). CONCLUSION: Foot disease is associated with poorer physical function in older adults. Future research should include broader study populations and intervention strategies.

Optimizing the delivery of early palliative care for hematology patients receiving a stem cell transplant: A role for a Nurse Practitioner.

A hematopoietic stem cell transplant (HSCT) is an intense treatment approach for patients with a hematologic malignancy and brings a significant risk for morbidity and mortality. HSCT brings hope of cure for patients; however, treatments are lengthy and burdensome from both a physical and psychosocial perspective. As the culture of HSCT has traditionally been cure-oriented, it leaves little room for a potential partnership with palliative care services, and when palliative care services are introduced, it is often too late for significant benefit. The need to standardize palliative care involvement for patients with hematologic malignancies receiving a HSCT has become necessary, yet there are challenges with the best way to create such a partnership. Nurse practitioners are a steadily growing professional body possessing the knowledge and skill necessary to fill the gap in palliative care delivery for HSCT patients. The proposed Nurse Practitioner Early Palliative Care for HSCT patients (NEST) algorithm will seek to provide a pathway in which to foster a partnership between hematology/HSCT teams and palliative services to yield the best care possible for patients.

Increased Pharyngeal Reflux in Patients Treated for Laryngeal Cancer: A Pilot Study.

OBJECTIVE: Laryngopharyngeal reflux may cause significant morbidity in the head and neck cancer population. The goal was to determine if pharyngeal reflux is increased as a result of treatment for laryngeal cancer. STUDY DESIGN: A prospective clinical trial. SETTING: Tertiary care center. SUBJECTS: Head and neck cancer patients treated at LSU Health-Shreveport with a plan for total laryngectomy. METHODS: Pharyngeal pH probes with resultant reflux scores were utilized in patients with laryngeal/pharyngeal cancer with a plan for total laryngectomy. RESULTS: Twenty-four patients were enrolled, of whom 10 underwent postlaryngectomy pH probe monitoring. The mean upright Ryan score for patients with prior radiotherapy was 238.4 (n = 8), compared with 22.0 (n = 16) in those without prior radiotherapy (P = .02). The supine score was 12.7 in the radiotherapy group and 2.7 in those without radiotherapy (P = .12). For those who completed the postlaryngectomy pH study (n = 10), the mean preoperative upright Ryan score was 106.32 ± 279.1 versus a postoperative score of 209.0 ± 352.6 (P = .04). The mean supine preoperative Ryan score in this group was 3.9 ± 3.47, as opposed to 8.1 ± 9.6 postoperatively (P = .13) CONCLUSIONS: This study suggests that treatment of laryngeal cancer may increase the incidence of pharyngeal reflux. Consider screening for reflux in patients previously treated for laryngeal cancer.

Natural killer cells regulate T-cell proliferation during human parainfluenza virus type 3 infection.

Human parainfluenza virus type 3 (HPIV3) is a major respiratory pathogen in humans. Failure to induce immunological memory associated with HPIV3 infection has been attributed to inhibition of lymphocyte proliferation. We demonstrate that the inability of mixed lymphocytes to respond to virally infected antigen-presenting cells is due to an interleukin-2-dependent, nonapoptotic mechanism involving natural killer (NK) cells and their influence is exerted in a contact-dependent manner. These results suggest a novel regulatory mechanism for NK cells during HPIV3 infection, offering an explanation for viral persistence and poor memory responses.

Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective suppression of interleukin 12 p35 transcription in murine bone marrow-derived dendritic cells.

Infection with influenza virus strongly predisposes an individual to bacterial superinfection, which is often the significant cause of morbidity and mortality during influenza epidemics. Little is known about the immunomodulating properties of the virus that lead to this phenomenon, but the effect of the viral components on the development of immune dendritic cells (DCs) may prove vital. In this study, activation of and cytokine secretion by bacterial lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) following treatment with the influenza virus major antigen haemagglutinin (HA) were examined. HA selectively inhibits the release of LPS-induced interleukin 12 (IL12) p70, which is independent of IL10 secretion. Suppression occurs at the transcriptional level, with selective inhibition of p35- and not p40-subunit mRNA expression. The downregulation of IL12 p70 by influenza HA is a novel and unexplored pathway that may be relevant in the predisposition to bacterial superinfection associated with influenza virus infections.

Evaluating a 'service elective' in clinical teaching for medical students.

Many medical students wish to begin developing clinical teaching skills before residency. Faculty at the University of California, Irvine developed a 60-hour, longitudinal 'service elective' in teaching skills, which 50 third-year and fourth-year students have completed since 2001. Students learned to enact and rate eight stations of an objective structured teaching examination (OSTE) for generalist resident physicians, broadening this practical training with in-class exercises. To evaluate the elective, structured, written questionnaires were administered. Participating students gave the elective a mean rating of 5.24 on a seven-point Likert-type scale, which fell between 'very good' (5) and 'excellent' (6). Narrative comments showed that students believed the elective--and in particular the OSTE training--prepared them well for teaching as residents.