Clinical Utility of the Behavioral Pain Assessment Tool in Patients Admitted in the Intensive Care Unit.

INTRODUCTION: Unnoticed and unrelieved pain is one of the main sources of psychological and physiological stress for intensive care unit (ICU) patients. The eight-item behavior pain assessment tool (BPAT) is a multicountry validated tool to assess pain in ICU patients. However, its feasibility and clinical utility for ICU patients in India need further research. AIMS AND OBJECTIVES: The Aims and objectives of the study were to assess pain using BPAT and its clinical utility in pain assessment and management in ICU patients. MATERIALS AND METHODS: Following ethical approval, 400 consecutive adult patients admitted in the ICUs in a tertiary care teaching hospital were assessed for pain severity using BPAT at intake, baseline pain and procedural pain. Patients <18 years and in deep coma on the Glasgow coma scale were excluded from the study. The patients with BPAT score ≥4 were given opioid analgesic, and their pain was reassessed after 2-3 hours. A feedback regarding feasibility and clinical utility was filled by the doctors. RESULTS: High interrater agreement for BPAT was observed with excellent kappa coefficients (>0.85) for each item. The BPAT significantly guided the pain management (p < 0.0001). More than 90% of doctors found BPAT easy to understand and use. In most of the cases (95.5%), doctors agreed that BPAT can improve the clinical management of ICU patients. CONCLUSION: The BPAT is a reliable, brief, and an easy-to-use pain assessment tool, which clinicians can use for guiding pain assessment and management in the ICU setting on a routine basis. CLINICAL SIGNIFICANCE: We recommend implementing BPAT in the clinical practice for better pain assessment and control in ICU patients. HOW TO CITE THIS ARTICLE: Mitra S, Jain K, Singh J, Saxena P, Nyima T, Selvam SR, et al. Clinical Utility of the Behavioral Pain Assessment Tool in Patients Admitted in the Intensive Care Unit. Indian J Crit Care Med 2020;24(8):695-700.

Nonlinear transcriptomic response to dietary fat intake in the small intestine of C57BL/6J mice.

BACKGROUND: A high caloric diet, in conjunction with low levels of physical activity, promotes obesity. Many studies are available regarding the relation between dietary saturated fats and the etiology of obesity, but most focus on liver, muscle and white adipose tissue. Furthermore, the majority of transcriptomic studies seek to identify linear effects of an external stimulus on gene expression, although such an assumption does not necessarily hold. Our work assesses the dose-dependent effects of dietary fat intake on differential gene expression in the proximal, middle and distal sections of the small intestine in C57BL/6J mice. Gene expression is analyzed in terms of either linear or nonlinear responses to fat intake. RESULTS: The highest number of differentially expressed genes was observed in the middle section. In all intestine sections, most of the identified processes exhibited a linear response to increasing fat intake. The relative importance of logarithmic and exponential responses was higher in the proximal and distal sections, respectively. Functional enrichment analysis highlighted a constantly linear regulation of acute-phase response along the whole small intestine, with up-regulation of Serpina1b. The study of gene expression showed that exponential down-regulation of cholesterol transport in the middle section is coupled with logarithmic up-regulation of cholesterol homeostasis. A shift from linear to exponential response was observed in genes involved in the negative regulation of caspase activity, from middle to distal section (e.g., Birc5, up-regulated). CONCLUSIONS: The transcriptomic signature associated with inflammatory processes preserved a linear response in the whole small intestine (e.g., up-regulation of Serpina1b). Processes related to cholesterol homeostasis were particularly active in the middle small intestine and only the highest fat intake down-regulated cholesterol transport and efflux (with a key role played by the down-regulation of ATP binding cassette transporters). Characterization of nonlinear patterns of gene expression triggered by different levels of dietary fat is an absolute novelty in intestinal studies. This approach helps identifying which processes are overloaded (i.e., positive, logarithmic regulation) or arrested (i.e., negative, exponential regulation) in response to excessive fat intake, and can shed light on the relationships linking lipid intake to obesity and its associated molecular disturbances.

A Phase 0 Study to Assess the Biodistribution and Pharmacokinetics of a Radiolabeled Antibody Targeting Human Kallikrein 2 in Participants with Metastatic Castration-Resistant Prostate Cancer.

Despite the inclusion of multiple agents within the prostate cancer treatment landscape, new treatment options are needed to address the unmet need for patients with metastatic castration-resistant prostate cancer (mCRPC). Although prostate-specific membrane antigen is the only cell-surface target to yield clinical benefit in men with advanced prostate cancer, additional targets may further advance targeted immune, cytotoxic, radiopharmaceutical, and other tumor-directed therapies for these patients. Human kallikrein 2 (hK2) is a novel prostate-specific target with little to no expression in nonprostate tissues. This first-in-human phase 0 trial uses an 111In-radiolabeled anti-hK2 monoclonal antibody, [111In]-DOTA-h11B6, to credential hK2 as a potential target for prostate cancer treatment. Methods: Participants with progressive mCRPC received a single infusion of 2 mg of [111In]-DOTA-h11B6 (185 MBq of 111In), with or without 8 mg of unlabeled h11B6 to assess antibody mass effects. Sequential imaging and serial blood samples were collected to determine [111In]-DOTA-h11B6 biodistribution, dosimetry, serum radioactivity, and pharmacokinetics. Safety was assessed within a 2-wk follow-up period from the time of [111In]-DOTA-h11B6 administration. Results: Twenty-two participants received [111In]-DOTA-h11B6 and are included in this analysis. Within 6-8 d of administration, [111In]-DOTA-h11B6 visibly accumulated in known mCRPC lesions, with limited uptake in other organs. Two treatment-emergent adverse events unrelated to treatment occurred, including tumor-related bleeding in 1 patient, which led to early study discontinuation. Serum clearance, biodistribution, and tumor targeting were independent of total antibody mass (2 or 10 mg). Conclusion: This first-in-human study demonstrates that tumor-associated hK2 can be identified and targeted using h11B6 as a platform as the h11B6 antibody selectively accumulated in mCRPC metastases with mass-independent clearance kinetics. These data support the feasibility of hK2 as a target for imaging and hK2-directed agents as potential therapies in patients with mCRPC.

Ultrasound-guided erector spinae plane block compared to serratus anterior muscle block for postoperative analgesia in modified radical mastectomy surgeries: A randomized control trial.

Background and Objectives: The present study was undertaken to compare the analgesic efficacy of erector spinae plane (ESP) block with serratus anterior muscle (SAM) block in patients undergoing modified radical mastectomy (MRM). We hypothesized that ESP block would provide better postoperative pain relief than SAM block following MRM. Methods: Eighty American Society of Anaesthesiologists (ASA) I-II adult females, scheduled for MRM, were randomly allocated to receive either ultrasound-guided ipsilateral single-shot ESP or SAM block after induction in the respective planes, using 20 ml of 0.25% ropivacaine. Both the groups received postoperative intravenous patient-controlled analgesia (IV-PCA) (morphine) for 24 h. The primary outcome was to assess pain severity using a visual analogue scale (VAS) score. Postoperative 24-h opioid consumption, time to first opioid analgesia, hemodynamic variables, total dose of antiemetics, and safety profile of both the blocks were also evaluated. Data analysis was carried out using Statistical Package for the Social Sciences version 21.0 (SPSS Inc. Chicago, Illinois, USA). Results: VAS scores were lower in the ESP block group, at rest and on movement, and the difference was statistically significant (p < 0.05). Postoperative morphine consumption was also significantly less in patients receiving ESP block as compared to SAM block (3.13 ± 1.44 mg vs 4.33 ± 1.69 mg; P = 0.001). The time to first analgesia request was significantly prolonged in the ESP group as compared to the SAM group (9.58 ± 4.11 h vs 6.46 ± 2.95 h; P = 0.001). No major side effects were observed in any of the study groups. Conclusions: ESP block provides better analgesia as compared to SAM block after MRM. Clinical trial registration number: CTRI/2019/03/018067.

Quantification of cell energetics in human subcutaneous adipose progenitor cells after target gene knockdown.

Pro-preadipocytes are adipocyte progenitor cells within subcutaneous adipose tissue that are conserved in human adipose tissue with distinct cellular energetics. Here, we detail a protocol to quantify cellular oxygen consumption rates of primary human cells harvested from adipose tissue. We describe steps for primary cell expansion, cell seeding, transfection, differentiation, and respirometry followed by Agilent Seahorse Analytics. The measurement of bioenergetic profiles and resulting data further expand our knowledge of the functional properties of primary cells isolated from adipose tissue. For complete details on the use and execution of this protocol, please refer to Chen et al. (2023).1.

A multi-omics dataset for the analysis of frontotemporal dementia genetic subtypes.

Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Systematic studies on human post-mortem brain tissue of patients with genetic subtypes of FTD are currently lacking. The Risk and Modyfing Factors of Frontotemporal Dementia (RiMod-FTD) consortium therefore has generated a multi-omics dataset for genetic subtypes of FTD to identify common and distinct molecular mechanisms disturbed in disease. Here, we present multi-omics datasets generated from the frontal lobe of post-mortem human brain tissue from patients with mutations in MAPT, GRN and C9orf72 and healthy controls. This data resource consists of four datasets generated with different technologies to capture the transcriptome by RNA-seq, small RNA-seq, CAGE-seq, and methylation profiling. We show concrete examples on how to use the resulting data and confirm current knowledge about FTD and identify new processes for further investigation. This extensive multi-omics dataset holds great value to reveal new research avenues for this devastating disease.