AKI treated with kidney replacement therapy in critically Ill allogeneic hematopoietic stem cell transplant recipients.

Acute kidney injury (AKI) is a frequent complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but few studies have focused on AKI treated with kidney replacement therapy (AKI-KRT), particularly among critically ill patients. We investigated the incidence, risk factors, and 90-day mortality associated with AKI-KRT in 529 critically ill adult allo-HSCT recipients admitted to the ICU within 1-year post-transplant at two academic medical centers between 2011 and 2021. AKI-KRT occurred in 111 of the 529 patients (21.0%). Lower baseline eGFR, veno-occlusive disease, thrombotic microangiopathy, admission to an ICU within 90 days post-transplant, and receipt of invasive mechanical ventilation (IMV), total bilirubin ≥5.0 mg/dl, and arterial pH <7.40 on ICU admission were each associated with a higher risk of AKI-KRT. Of the 111 patients with AKI-KRT, 97 (87.4%) died within 90 days. Ninety-day mortality was 100% in each of the following subgroups: serum albumin ≤2.0 g/dl, total bilirubin ≥7.0 mg/dl, arterial pH ≤7.20, IMV with moderate-to-severe hypoxemia, and ≥3 vasopressors/inotropes at KRT initiation. AKI-KRT was associated with a 6.59-fold higher adjusted 90-day mortality in critically ill allo-HSCT vs. non-transplanted patients. Short-term mortality remains exceptionally high among critically ill allo-HSCT patients with AKI-KRT, highlighting the importance of multidisciplinary discussions prior to KRT initiation.

The HPV Serology Laboratory leads an initiative to standardize and harmonize human papillomavirus serology assays.

The HPV Serology Laboratory is leading a global partnership initiative aiming for standardization and harmonization of current serology assay platforms being used to assess immune responses to HPV vaccines. Serology standardization is particularly important given the increasing number of immunobridging trials relying on serology data for approval of new vaccine dosing schedules or vaccine formulations. The initiative was established in 2017 to enable comparisons of data between different vaccines and relevant studies as well as expedite the implementation of new vaccines and vaccine indications. The HPV Serology Laboratory has held or attended several meetings with partnering laboratories, including international meetings in 2017, 2018, and 2021.

Timing of invasive mechanical ventilation and death in critically ill adults with COVID-19: A multicenter cohort study.

PURPOSE: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality. MATERIALS AND METHODS: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox model. RESULTS: Among the 1879 patients included in this analysis (1199 male [63.8%]; median age, 63 [IQR, 53-72] years), 1526 (81.2%) initiated IMV early and 353 (18.8%) initiated IMV late. A total of 644 of the 1526 patients (42.2%) in the early IMV group died, and 180 of the 353 (51.0%) in the late IMV group died (adjusted HR 0.77 [95% CI, 0.65-0.93]). CONCLUSIONS: In critically ill adults with respiratory failure from COVID-19, early compared to late initiation of IMV is associated with reduced mortality.

Trends in Swallowing Outcomes Following Deintensified Treatment in Selected p16+ Oropharyngeal Carcinoma.

Objective: Identify trends in swallowing outcomes in p16+ oropharyngeal squamous cell carcinoma following neoadjuvant chemotherapy+surgery (NAC+S) versus neoadjuvant chemotherapy+surgery+radiation (NAC+S+R). Study Design: Cohort study. Setting: Single academic institution. Methods: Swallowing outcome was measured using a validated questionnaire, MD Anderson Dysphagia Inventory (MDADI). MDADI scores were compared between NAC+S and NAC+S+R groups in short-term (<1 year), middle-term (1-3 years), and long-term (>3 years). Clinical factors associated with MDADI scores were explored using a linear mixed model. Statistical significance was established at p < .05. Results: Sixty-seven patients met the inclusion criteria and were divided into 2 groups: NAC+S (57 [85.1%]) and NAC+S+R (10 [14.9%]). All patients had improved MDADI scores in the middle-term compared to short-term (NAC+S: score increase = 3.43, p = .002; NAC+S+R: score increase = 11.18, p = .044), long-term compared to short-term (NAC+S: score increase = 6.97, p < .001; NAC+S+R: score increase = 20.35, p < .001), and long-term compared to middle-term (NAC+S: score increase = 3.54, p = .043; NAC+S+R: score increase = 9.18, p = .026). NAC+S patients had better MDADI scores than NAC+S+R patients at short-term (83.80 vs 71.26, p = .001). There was no significant difference in swallowing function in the middle-term or long-term. Conclusion: Regardless of treatment type, swallowing will likely be improved in the middle-term and long-term compared to the short-term. Patients treated with NAC+S+R will have worse short-term swallowing function. However, in the middle-term and long-term, there is no significant difference in swallowing function between patients treated with NAC+S and NAC+S+R.

The second HPV serology meeting: Progress and challenges in standardization of human papillomavirus serology assays.

The HPV Serology Laboratory in the Frederick National Laboratory for Cancer Research is working in partnership with the scientific community with the goal of standardizing and harmonizing current HPV serology assay platforms in response to the increasing number of immunobridging trials relying on serology data for approval of new vaccine dosing schedules and new formulations. A virtual meeting was held on June 29-30, 2021, to review the progress of the standardization initiative thus far and to bridge scientific gaps and outstanding questions. The main aims and outcomes of the meeting were to discuss: 1) standardization of assays and reagents; 2) International Standard calibration procedures; 3) assay cut-off values; 4) current immunobridging clinical trials; and 5) gaps and challenges in standardization of HPV serology.

Systematic review of the use of human papillomavirus vaccine as adjuvant therapy for juvenile-onset recurrent respiratory papillomatosis.

INTRODUCTION: Juvenile-onset RRP (JoRRP) is considered a rare disease with high morbidity and healthcare costs. The management of RRP has received much scientific attention in recent years and several treatment methodologies have been explored, including therapeutic use of HPV vaccine. There has been increasing interest in the off-label use of the vaccine in virus-induced disease processes such as RRP, due to its immunomodulatory effect and activating role on the innate and adaptive immune system. This review explores the efficacy of the HPV vaccination as a therapeutic tool in the pediatric population. METHODS: The review of the English literature included three electronic databases, PubMed, SCOPUS, and Cochrane, without publication date restrictions. Studies and reports identified by the database search were reviewed and assessed by two independent reviewers. RESULTS: The literature searches identified 768 unique citations, from which 204 duplicates were removed (n = 564). A total of 547 articles were excluded as they did not meet our inclusion criteria. A total of 12 studies (3 experimental studies, 3 case series, 6 case reports) that met the inclusion criteria and reported one or more of the outcomes of interest were included for our review. The assessment of the outcome measures evaluated (number of surgeries during the follow-up period, ISI, SPM, Derkay or severity scores, and remission status) revealed that eight out of 12 studies included in the review showed varying degrees of potential benefits from the administration of the vaccine as a treatment modality compared to surgical interventions and/or concurrent adjuvant therapies alone. CONCLUSION: We conclude that while the therapeutic use of HPV vaccination has shown promise for some JoRRP patients, it overall remains uncertain with the currently available data. There is a need for a prospective multi-centric trial with a larger sample size to fully characterize the potential use of the vaccine in the management of JoRRP.

A rare case of Hidradenoma of the lower lip.

Hidradenoma are rare benign tumors with eccrine or apocrine differentiation that most often presents as a small, firm, solitary dermal nodule. At times, hidradenoma shows striking cytologic and histologic similarity to other neoplasms, including its malignant counterpart, hidradenocarcinoma. We present the first reported case of benign hidradenoma of the lower lip. The case illustrates important diagnostic features of hidradenoma and discusses the current understanding of its malignant potential and the appropriate management of such lesions.

Efficacy of ethanol ablation as a treatment of benign head and neck cystic lesions.

OBJECTIVE: To evaluate the efficacy and safety of ethanol ablation in the treatment of benign head and neck cystic lesions. METHODS: A total of 25 patients who received ethanol ablation (EA) of head and neck cystic lesions by an otolaryngologist at a single institution between October 2017 and October 2020 were identified. Patient demographics, clinical characteristics, treatment details, and treatment outcomes at follow up visits were obtained by retrospective review of electronic medical records. RESULTS: 25 patients who underwent ethanol ablation of head and neck cystic lesions were included, with a mean age of 49.1 years old (Interquartile range (IQR),32.5-65.5 years) and 12 males (47.0%). The most common cysts treated with EA were thyroglossal duct cysts (n = 8, 32.0%) and lymphoepithelial parotid cysts (n = 7, 28.0%). The mean volume prior to treatment was 10.57 mL (IQR, 1.58-8.81 mL). Mean volume following EA was 1.30 mL (range, 0.10-0.97 mL) with 74.40% cyst reduction by volume (IQR, 48.56-96.29%) (p = 0.002). The mean time to the last follow-up was 5 months (range, 3-6 months). One patient received surgery despite treatment success to obtain a definitive diagnosis of the mass. No other patients received further surgical management. The treatment success of EA, as defined by >70% volume reduction or the resolution of symptoms, was 92.0%. All patients were satisfied with the outcome and had no reported complications. CONCLUSION: EA is an effective and safe alternative to surgery for the treatment of head and neck cystic lesions that can be performed in an outpatient setting by an otolaryngologist.

Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers.

SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close homologue Brahma-related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. No small molecules have been reported that modulate SWI/SNF chromatin-remodeling activity via inhibition of its ATPase activity, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1-loss-of-function settings and should enable probing the role of SWI/SNF functions more broadly in different cancer contexts and those of other diseases.

A comparison of the effects of rhythm and robotic interventions on repetitive behaviors and affective states of children with Autism Spectrum Disorder (ASD).

Repetitive behaviors and poor affect regulation are commonly seen in children with Autism Spectrum Disorder (ASD). We compared the effects of two novel interventions - rhythm and robotic therapies, with those of a standard-of-care intervention, on the repetitive behaviors and affective states of 36 children with ASD between 5 and 12 years using a randomized controlled trial design. We coded for frequencies of sensory, negative, and stereotyped behaviors and the duration of positive, negative, and interested affective states in children during early, mid, and late training sessions. In terms of repetitive behaviors, in the early session, the rhythm and robot groups engaged in greater negative behaviors, whereas the comparison group engaged in greater sensory behaviors. With training, the rhythm group reduced negative behaviors whereas there were no training-related changes in the other groups. In terms of affective states, the rhythm and robot groups showed greater negative affect, whereas the comparison group demonstrated greater interested affect across all sessions. With training, the rhythm group showed a reduction in negative affect and an increase in interested affect whereas the robot group showed a reduction in positive affect. Overall, it appears that rhythm-based interventions are socially engaging treatment tools to target core impairments in autism.

The Effects of Rhythm and Robotic Interventions on the Imitation/Praxis, Interpersonal Synchrony, and Motor Performance of Children with Autism Spectrum Disorder (ASD): A Pilot Randomized Controlled Trial.

We assessed the effects of three interventions, rhythm, robotic, and standard-of-care, on the imitation/praxis, interpersonal synchrony, and overall motor performance of 36 children with Autism Spectrum Disorder (ASD) between 5 and 12 years of age. Children were matched on age, level of functioning, and services received, prior to random assignment to one of the three groups. Training was provided for 8 weeks with 4 sessions provided each week. We assessed generalized changes in motor skills from the pretest to the posttest using a standardized test of motor performance, the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2). We also assessed training-specific changes in imitation/praxis and interpersonal synchrony during an early and a late session. Consistent with the training activities practiced, the rhythm and robot groups improved on the body coordination composite of the BOT-2, whereas the comparison group improved on the fine manual control composite of the BOT-2. All three groups demonstrated improvements in imitation/praxis. The rhythm and robot groups also showed improved interpersonal synchrony performance from the early to the late session. Overall, socially embedded movement-based contexts are valuable in promoting imitation/praxis, interpersonal synchrony, and motor performance and should be included within the standard-of-care treatment for children with ASD.