The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

Impact of an automated, remote monitoring and coaching intervention in reducing hospice cancer family caregiving burden: A multisite randomized controlled trial.

BACKGROUND: Care for those with life-limiting cancer heavily involves family caregivers who may experience significant physical and emotional burden. The purpose of this study was to test the impact of Symptom Care at Home (SCH), an automated digital family caregiver coaching intervention, during home hospice, when compared to usual hospice care (UC) on the primary outcome of overall caregiver burden. Secondary outcomes included Caregiver Burden at weeks 1 and 8, Mood and Vitality subscales, overall moderate-to-severe caregiving symptoms, and sixth month spouse/partner bereavement outcomes. METHODS: Using a randomized, multisite, nonblinded controlled trial, 332 cancer family caregivers were enrolled and analyzed (159 SCH vs. 173 UC). Caregivers were primarily White (92%), female (69%), and spouse caregivers (53%). Caregivers provided daily reports on severity levels (0-10 scale) for their anxiety, depressed mood, fatigue, disturbed sleep, and caregiving interference with normal activities. These scores combined constituted the Caregiver Burden primary outcome. Based on reported symptoms, SCH caregivers received automated, tailored coaching about improving their well-being. Reports of moderate-to-severe caregiving symptoms also triggered hospice nurse notification. Secondary outcomes of Mood and Vitality were subcomponents of the Caregiver Burden score. A combined bereavement adjustment tool captured sixth month bereavement. RESULTS: The SCH intervention reduced overall Caregiver Burden compared to UC (p < .001), with a 38% reduction at 8 weeks and a medium-to-large effect size (d = .61). SCH caregivers experienced less (p < .001) disruption in both Mood and Vitality. There were higher levels of moderate-to-severe caregiving symptoms overtime in UC (OR, 2.722). All SCH caregivers benefited regardless of caregiver: sex, caregiver relationship, age, patient diagnosis and family income. SCH spouse/partner caregivers achieved better sixth month bereavement adjustment than UC (p < .007). CONCLUSIONS: The SCH intervention significantly decreased caregiving burden over UC and supports the maintenance of family caregiver mood and vitality throughout caregiving with extended benefit into bereavement.

The impacts of adrenoleukodystrophy newborn screening on the evaluation of adrenal dysfunction in male children: An integrative literature review.

PROBLEM: Adrenoleukodystrophy (ALD) is an x-linked genetic condition with a high risk of adrenal dysfunction recommended for newborn screening. This review aims to critically appraise and synthesize existing literature identifying the impacts of ALD newborn screening in the United States on the evaluation and treatment of adrenal dysfunction in male children. ELIGIBILITYCRITERIA: An integrative literature review was conducted using the Embase, PubMed, and CINAHL databases. English-language primary source studies published in the past decade and seminal studies were included. SAMPLE: Twenty primary sources met the inclusion criteria, including five seminal studies. RESULTS: Three major themes emerged from the review: 1) prevention of adrenal crisis, 2) unexpected outcomes, and 3) ethical impacts. CONCLUSIONS: ALD screening increases disease identification. Serial adrenal evaluation prevents adrenal crisis and death; data is needed to establish predictive outcomes in ALD prognosis. Disease incidence and prognosis will become more apparent as states increasingly add ALD screening to their newborn panel. IMPLICATIONS FOR PRACTICE: Clinicians need awareness of ALD newborn screening and state screening protocols. Families first learning of ALD through newborn screening results will require education, support, and timely referrals for appropriate care.

Survivorship of high tibial osteotomy in the treatment of osteoarthritis of the knee: a retrospective cohort study with fourteen years' follow-up.

PURPOSE: This study was to evaluate the survivorship of HTO for the treatment of medial compartment osteoarthritis (OA) in young and active patients from two teaching hospitals in a single city. METHODS: This is a retrospective cohort multicenter study looking at HTO for treatment of medial compartment OA. We analyzed a case series of HTO's performed by four surgeons in two centres over a 14-year period. Failure was defined as conversion to total knee replacement (TKR). All cases where additional procedures for instability of the knee were performed at the time of the index surgery were excluded. Time to failure was recorded, and a Kaplan-Meir (KM) analysis was performed to evaluate survivorship. Univariate binary regression analysis was undertaken to identify associations between risk factors and failure. RESULTS: A total of 96 patients were included in the study with a median age was 45 years. The survivorship at five years post-op was 90.3%, and at ten years post-op, it was 82%. Patients that were 14 years after surgery had a survivorship of 65%. Also, 18.8% of patients required the removal of their metalwork. The overall complication rate was 6.3%. The univariate regression analysis showed that higher age (p = 0.02) and larger corrections requiring the use of bone graft increased the risk of failure (p = 0.02). There was no statistically significant correlation between laterality, gender, complication rate, and pre-operative alignment to survivorship. CONCLUSION: This is one of the largest reported case series of HTO's with comparable survivorship at five and ten year follow-up compared to the reported literature. There was an association found between increasing age and larger corrections requiring bone graft at index procedure to increasing failure rate.

How technology can improve communication and health outcomes in patients with advanced cancer: an integrative review.

OBJECTIVE: Patients facing an advanced cancer diagnosis require clear communication with their clinicians. Technology has been utilized in many different capacities to navigate communication in cancer care, but few authors examine the specific areas of communication from a theoretical perspective. The purpose of this literature review was to (1) identify articles focused on technology-based communication strategies to improve health outcomes in individuals with advanced cancer, and (2) using Epstein and Street's framework, identify areas in which technology-based communication has been used to improve health outcomes, and (3) identify gaps that exist in technology-based communication care in patients with advanced cancer. METHODS: A systematic search was conducted which returned 446 articles. Using Epstein and Street's 2007 framework, the final sample was 39. RESULTS: Nine clinical trials, 29 observational studies, and 1 case study were identified. The articles were categorized into one area within Epstein and Street's areas of communication. Many of the articles examined the patient's and provider's acceptability and feasibility of technology-based methods of communication, while other articles examined their efficacy. CONCLUSIONS: While research studies were identified in each of the areas of communication, the majority of technology-based communication strategies were focused on the exchange of information between patients and their providers. Further research and the development of technology-based communication interventions assessed through clinical trials are needed in the areas of healing relationships and making decisions in cancer care. Additionally, the communication strategies found effective at improving health outcomes in advanced cancer should begin implementation into clinical practice, therefore reaching more patients.

Sexual dysfunction among gynecologic cancer survivors in a population-based cohort study.

Treatment for gynecologic cancer is associated with sexual dysfunction, which may present during and/or after treatment. The aim of this study was to investigate the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. We identified a cohort of 4863 endometrial, ovarian, and cervical cancer survivors diagnosed between 1997 and 2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors (N = 22,693). We used ICD-9 codes to identify sexual dysfunction. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for sexual dysfunction with adjustment for potential confounders. Approximately 6.6% of gynecologic cancer survivors had sexual dysfunction diagnoses 1-5 years after cancer diagnosis. Gynecologic cancer survivors had higher risks of overall sexual dysfunction (HR: 2.51, 95% CI: 2.16, 2.93), dyspareunia (HR: 3.27, 95% CI: 2.63, 4.06), and vaginal dryness (HR: 2.63, 95% CI: 2.21, 3.12) compared to a general population of women, 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HRRegional vs. Localized: 1.61, 95% CI: 1.19, 2.31), radiation therapy (HR: 1.73, 95% CI: 1.29, 2.31), and chemotherapy (HR: 1.80, 95% CI: 1.30, 2.50). This large cohort study confirms that there is an increased risk of sexual dysfunction among gynecologic cancer survivors when compared to the general population. Further investigation is needed to address the risk factors for sexual dysfunction and to improve patient-provider communication, diagnosis, documentation, and treatment of sexual dysfunction among gynecologic cancer survivors.

Ultrasound-Guided Serratus Anterior Plane Block (SAPB) Improves Pain Control in Patients With Rib Fractures.

OBJECTIVES: The serratus anterior plane block (SAPB) is an ultrasound-guided compartment block; limited data suggest that it can decrease pain in patients with rib fractures or chest wall pain. We sought to determine the effect of SAPB on pain and incentive spirometry (IS) maximal vital capacity in adult patients with rib fractures. METHODS: We enrolled a prospective sample of adult patients with at least two unilateral rib fractures who were being admitted for pain control. SAPB was performed by trained emergency physicians. Patients reported pain on an 11-point Numeric Rating Scale at rest and during IS, before, 15, and 60 minutes after SAPB. RESULTS: Mean pain scores decreased by 1.8 (SD 2.17, 95% confidence interval [CI]: 0.79-2.81) at 15 minutes and 2.5 (SD 2.69, 95% CI: 1.24-3.76) at 60 minutes. Compared to pre-block pain scores during IS, mean pain scores decreased by 1.95 (SD 1.99, 95% CI: 1.02-2.88) at 15 minutes and 2.4 (SD 2.42, 95% CI: 1.27-3.53) at 60 minutes. Mean maximum vital capacity increased by 232 mL (SD 406, 95% CI: 36-427) at 60 minutes. Zero SAPB-attributable complications were identified in the 24 hours post-enrollment. CONCLUSIONS: In patients with multiple rib fractures, SAPB reduced pain scores at rest and during IS, and increased maximal vital capacity. The SABP may be a safe and effective modality for pain control in trauma patients with multiple rib fractures.

Updates in the Management of Cryptogenic Stroke and Patent Foramen Ovale.

BACKGROUND: Stroke is a common neurological disorder and may present with visual symptoms. A thorough workup is warranted to determine the underlying cause of stroke to optimize secondary prevention. Despite a full workup, a high-risk mechanism may not be identified. Optimal treatment in this patient population has been the subject of recent research, particularly with regard to low-risk stroke mechanisms such as patent foramen ovale (PFO). EVIDENCE ACQUISITION: Using PubMed and published stroke guidelines, an evidence-based literature review was performed. RESULTS: In this review, we compare cryptogenic stroke with the newer concept of embolic stroke of undetermined source, summarize the most common causes presumed to underlie these strokes, and review the evidence for optimal antithrombotic management. We also review recent clinical trials demonstrating a benefit for percutaneous closure of PFO for secondary stroke prevention in select patients. CONCLUSIONS: Stroke management is based on evaluation of individual patient-risk factors. Evaluation and treatment is ideally directed by a vascular neurologist to ensure optimal secondary prevention, especially in cases where an underlying etiology is not identified on initial workup.

Comparative cohort study of volumetric modulated arc therapy for squamous cell cancer of unknown primary in the head and neck-Involved neck only versus mucosal irradiation.

OBJECTIVES: Target volumes for irradiation remain ill-defined for squamous cell cancer of unknown primary in the head and neck (SCCUP). The aim of this study was to compare involved neck only (INO) radiotherapy (RT) with irradiating involved neck plus potential mucosal primary sites and contralateral neck (MUC) in patients diagnosed and treated with modern diagnostics and techniques. DESIGN: This is a retrospective cohort study. Patients with a diagnosis of SCCUP with unilateral neck disease were included. RESULTS: Thirty patients were identified. All underwent FDG PET-CT. 47% of patients had HPV-positive SCC. 20 patients received RT to INO, 10 patients to MUC, all with volumetric modulated arc therapy (VMAT). A significantly lower dose for each organ at risk was delivered in INO-treated patients, with mean dose to contralateral parotid gland 57% less. The proportion of patients with late grade 2 or worse xerostomia was higher in MUC patients. The incidence of grade 2-3 mucositis (89% vs 45%) and grade 3 or worse dysphagia (50% vs 10%) was higher in MUC patients. Median follow-up was 31 months. No mucosal primaries emerged. Progression-free survival at 2 years was 74.7% for INO patients, 70% in the MUC group. Overall survival at 2 years was 79.7% in the INO group and 70% in the MUC patients. CONCLUSION: INO radiotherapy for patients with SCCUP of the head and neck is a safe treatment strategy resulting in clinically significant lower RT doses to OARS. Acute and late toxicities are reduced without detriment to patient survival.

Facilitating an International Research Experience Focused on Applied Nanotechnology and Surface Chemistry for American Undergraduate Students Collaborating with Mentors at a German Educational and Research Institution.

The "International Research Experience for Students (IRES)" at Doane University (DU) located in Crete, Nebraska, exposed undergraduate science, technology, engineering, and mathematics (STEM) students to international research at the Karlsruhe Institute of Technology (KIT) in Germany. The international collaboration team included three undergraduate researchers per year from DU, one faculty member and one postdoctoral fellow from DU, two faculty mentors at KIT, and several graduate, post-doctoral, and technical staff at KIT. Prior to departure to Germany, the students received extensive research training, as well as culture and language preparation from the mentors at DU. While in Germany, the students received an in-depth orientation to Karlsruhe, Germany, Europe, the research setting at KIT, and the international collaborators. The eight week summer projects over three years involved nanolithography, nano- to microsized array fabrication, organic synthesis using click chemistry, and surface modifications for sensing and other biomedical research applications. When the students returned from Germany, they continued to conduct research at DU and train other undergraduate students using the expertise acquired from KIT. The DU research students, including the IRES scholars, learned oral and written communication skills. They presented their KIT and DU research results at weekly seminars and at local and national meetings. An external assessment firm evaluated the program, the students, and mentors on a yearly basis before and after the summer research. This enabled all participants to continuously improve the learning objectives and the program execution including three program adjustments implemented in year 2 or 3. The survey data shows that the IRES program provided an enriching experience for the students in research and international culture and established a successful base of collaboration for mentors.

Management of Blunt Cerebrovascular Injury.

PURPOSE OF REVIEW: This review provides an updated summary of blunt cerebrovascular injury (BCVI) to guide clinicians in its early diagnosis and prevention and treatment of stroke associated with such injury. RECENT FINDINGS: Untreated BCVI causes stroke in 10-40% of patients, but more than half will not present with stroke symptoms initially. Risk of stroke is highest in the first 7 days, with a peak in the first 24 h. Computed tomography (CT) angiography is currently the screening modality of choice, although digital subtraction angiography may still be required in some cases. Antithrombotic therapy is the mainstay of treatment and has proven safety in trauma patients. In carefully selected patients, endovascular intervention may also be beneficial. BCVI is a potentially preventable cause of stroke. A high index of suspicion is needed as emergent screening during initial evaluation can provide a window for stroke prevention. Screening all patients with injuries that would otherwise prompt CT scans of the neck or chest is recommended. Treatment is guided by grade of injury. Early treatment with antithrombotics has been shown to be both effective and safe.

Symptomatic Carotid Occlusion Is Frequently Associated With Microembolization.

BACKGROUND AND PURPOSE: Symptomatic carotid artery disease is associated with significant morbidity and mortality. The pathophysiologic mechanisms of cerebral ischemia among patients with carotid occlusion remain underexplored. METHODS: We conducted a prospective observational cohort study of patients hospitalized within 7 days of ischemic stroke or transient ischemic attack because of ≥50% carotid artery stenosis or occlusion. Transcranial Doppler emboli detection was performed in the middle cerebral artery ipsilateral to the symptomatic carotid. We describe the prevalence of microembolic signals (MES), characterize infarct topography, and report clinical outcomes at 90 days. RESULTS: Forty-seven patients, 19 with carotid occlusion and 28 with carotid stenosis, had complete transcranial Doppler recordings and were included in the final analysis. MES were present in 38%. There was no difference in MES between those with carotid occlusion (7/19, 37%) compared with stenosis (11/28, 39%; P=0.87). In patients with radiographic evidence of infarction (n=39), 38% had a watershed pattern of infarction, 41% had a nonwatershed pattern, and 21% had a combination. MES were present in 40% of patients with a watershed pattern of infarction. Recurrent cerebral ischemia occurred in 9 patients (19%; 6 with transient ischemic attack, 3 with ischemic stroke). There was no difference in the rate of recurrence in those with compared to those without MES. CONCLUSIONS: Cerebral embolization plays an important role in the pathophysiology of ischemia in both carotid occlusion and stenosis, even among patients with watershed infarcts. The role of aggressive antithrombotic and antiplatelet therapy for symptomatic carotid occlusions may warrant further investigation given our findings.