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Background: Acute kidney injury (AKI) remains a common sequela of sepsis necessitating use of continuous renal replacement therapy (CRRT). In the setting of AKI, renally adjusted antimicrobials (eg, β-lactams) are dose reduced to prevent toxicity; however, the extracorporeal clearance of CRRT may lead to subtherapeutic exposures of dose reduced antimicrobials. The present study sought to evaluate the time to dose adjustment to CRRT appropriate doses of antimicrobials after initiation of CRRT. Methods: A retrospective cohort study of patients on CRRT and anti-pseudomonal β-lactams was conducted. CRRT was conducted as continuous veno-venous hemodialysis (CVVHD) per institutional standards. Baseline characteristics were collected including dialysate flow rate. The primary outcome was time to CRRT appropriate dose adjustment. Secondary outcomes included the pharmacist shift (ie, day, evening, or night shift) that CRRT was ordered and initiated. Continuous data were reported as median (IQR). Results: Forty-four patients were included in the analysis. The median dialysate flow rate was 2.3 L/hour (2, 3.1). Of included patients, 75% received cefepime therapy while 25% received meropenem. The median time to CRRT appropriate dosing was 13 hours (6, 20). CRRT was most commonly ordered during day shift (68%) but not started until evening (59%). The observed delay in appropriate dose adjustment may predispose patients to suboptimal antimicrobial exposure and subsequently therapeutic failure. CRRT was often ordered during the day shift but not initiated until evening which led to identification of potential procedural improvements. Conclusions: These data led to the initiation of a pharmacy in basket consult to alert pharmacists in real time of CRRT orders so that once CRRT was started, doses could be appropriately adjusted. Future studies to assess the impact of this process change on both time to appropriate dose and clinical outcomes are warranted.

PurposeAnti-PD-1 therapy provides clinical benefit in 40–50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.MethodsClinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune microenvironment to predict disease control with monotherapy PD-1 inhibitors (pembrolizumab and nivolumab). The performance of the biomarker was internally validated using out-of-bag methods.ResultsThe biomarker significantly predicted disease control (65% in predicted non-progressors vs. 17% in predicted progressors, p < 0.001) and was significantly correlated with overall survival (OS; p = 0.004). In addition, the biomarker outperformed PD-L1 IHC across numerous metrics including sensitivity (0.79 vs 0.64, respectively; p = 0.005) and specificity (0.70 vs 0.61, respectively; p = 0.009).ConclusionThis novel assay uses tumor immune microenvironment expression data to predict disease control and OS with high sensitivity and specificity in patients with RM-HNSCC treated with anti-PD-1 monotherapy.

Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

ABSTRACT Introduction Individuals after a transtibial amputation (TTA) are at risk to develop a hip flexion contracture, which may adversely affect future ambulation with a prosthesis. Although patients have traditionally been advised to lie prone to maintain or improve hip extension, compensatory pelvic tilting may occur in prone lying (PL). We sought to compare hip extension range of motion (ROM) in PL to the modified Thomas test (MTT) position, because research implies that, in the MTT, patients are better able to control for compensatory pelvic tilting. We hypothesized that individuals after a TTA would have a greater peak hip extension angle in the MTT position compared with the PL position. Methods Ten individuals after a dysvascular TTA, mean age of 60 ± 8.42 years, participated in this study. The same physical therapist marked the femur and pelvis for goniometric measurement of peak hip extension angle by 12 raters blinded to each other's measurements. The markers remained unchanged as six raters measured all participants in PL and six different raters measured all participants in the MTT position. Results and Discussion The intraclass correlation (ICC) indicated high interrater reliability between the raters for the PL and MTT positions (ICC = 0.985 for PL and 0.976 for MTT). The average peak hip extension angle in PL was −14.0° ± 13.3°, standard error of mean = 4.3°; and in the MTT position was −8.6° ± 15.3°, standard error of mean = 4.8° (the negative mean connotes that, on average, participants did not have hip extension to neutral for either condition). We found a mean of 5.4° ± 6.6° more hip extension ROM for the MTT position compared with PL (P = 0.028). Conclusions Our findings show that, on average, patients after a TTA have significantly greater peak hip extension angle in the MTT position compared with the PL position. Thus, passive PL may not be as effective of a stretching position for preventing a hip flexion contracture after a TTA, because PL does not always extend the patient's hip to its maximum available ROM, due to the reduced ability to control the pelvis from tilting anteriorly. Clinical Relevance Adequate hip flexor length is positively correlated with gait parameters, which include increased velocity and step length in people using a prosthesis after transtibial amputation. This study implies that the MTT position may be a better method for improving and maintaining hip flexor length over the traditional strategy of passive PL.

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage‐sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi‐faceted complications due to haploinsufficiency of BPTF.

Colon and rectal disorders can be functional and inflammatory. This is the second paper of a three-part series14 and will focus on the diagnosis and treatment of rectal prolapse, fecal incontinence and inflammatory bowel disease.

1Wishard Health Service, Indianapolis, IN 2Cedarville University, Cedarville, OH 3Cox Health, Springfield, MO