Re-evaluating TRP channel mechanosensitivity.

Transient receptor potential (TRP) channels are implicated in a wide array of mechanotransduction processes. However, a question remains whether TRP channels directly sense mechanical force, thus acting as primary mechanotransducers. We use several recent examples to demonstrate the difficulty in definitively ascribing mechanosensitivity to TRP channel subfamilies. Ultimately, despite being implicated in an ever-growing list of mechanosignalling events in most cases limited robust or reproducible evidence supports the contention that TRP channels act as primary transducers of mechanical forces. They either (i) possess unique and as yet unspecified structural or local requirements for mechanosensitivity; or (ii) act as mechanoamplifiers responding downstream of the activation of a primary mechanotransducer that could include Ca2+-permeable mechanosensitive (MS) channels or other potentially unidentified mechanosensors.

Performance of MYC, BCL2, and BCL6 break-apart FISH in small biopsies with large B-cell lymphoma: a retrospective Cytopathology Hematopathology Interinstitutional Consortium study.

Introduction: Fluorescence in situ hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have MYC, BCL2, or BCL6 rearrangements. Small-volume biopsies such as fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are increasingly used to diagnose lymphoma and obtain material for ancillary studies such as FISH. However, the performance of FISH in small biopsies has not been thoroughly evaluated or compared to surgical biopsies. Methods: We describe the results of MYC, BCL2, and BCL6 FISH in a series of 222 biopsy specimens, including FNAB with cell blocks, CNBs, and surgical excisional or incisional biopsies from 208 unique patients aggregated from 6 academic medical centers. A subset of patients had FNAB followed by a surgical biopsy (either CNB or excisional biopsy) obtained from the same or contiguous anatomic site as part of the same clinical workup; FISH results were compared for these paired specimens. Results: FISH had a low hybridization failure rate of around 1% across all specimen types. FISH identified concurrent MYC and BCL2 rearrangements in 20 of 197 (10%) specimens and concurrent MYC and BCL6 rearrangements in 3 of 182 (1.6%) specimens. The paired FNAB and surgical biopsy specimens did not show any discrepancies for MYC or BCL2 FISH; of the 17 patients with 34 paired cytology and surgical specimens, only 2 of the 49 FISH probes compared (4% of all comparisons) showed any discrepancy and both were at the BCL6 locus. One discrepancy was due to necrosis of the CNB specimen causing a false negative BCL6 FISH result when compared to the FNAB cell block that demonstrated a BCL6 rearrangement. Discussion: FISH showed a similar hybridization failure rate in all biopsy types. Ultimately, MYC, BCL2, or BCL6 FISH showed 96% concordance when compared across paired cytology and surgical specimens, suggesting FNAB with cell block is equivalent to other biopsy alternatives for evaluation of DLBCL or HGBCL FISH testing.

Diverse inorganic carbon uptake strategies in Antarctic seaweeds: Revealing species-specific responses and implications for Ocean Acidification.

Seaweeds are important components of coastal benthic ecosystems along the Western Antarctic Peninsula (WAP), providing refuge, food, and habitat for numerous associated species. Despite their crucial role, the WAP is among the regions most affected by global climate change, potentially impacting the ecology and physiology of seaweeds. Elevated atmospheric CO2 concentrations have led to increased dissolved inorganic carbon (Ci) with consequent declines in oceanic pH and alterations in seawater carbonate chemistry, known as Ocean Acidification (OA). Seaweeds possess diverse strategies for Ci uptake, including CO2 concentrating mechanisms (CCMs), which may distinctly respond to changes in Ci concentrations. Conversely, some seaweeds do not operate CCMs (non-CCM species) and rely solely on CO2. Nevertheless, our understanding of the status and functionality of Ci uptake strategies in Antarctic seaweeds remains limited. Here, we investigated the Ci uptake strategies of seaweeds along a depth gradient in the WAP. Carbon isotope signatures (δ13C) and pH drift assays were used as indicators of the presence or absence of CCMs. Our results reveal variability in CCM occurrence among algal phyla and depths ranging from 0 to 20 m. However, this response was species specific. Among red seaweeds, the majority relied solely on CO2 as an exogenous Ci source, with a high percentage of non-CCM species. Green seaweeds exhibited depth-dependent variations in CCM status, with the proportion of non-CCM species increasing at greater depths. Conversely, brown seaweeds exhibited a higher prevalence of CCM species, even in deep waters, indicating the use of CO2 and HCO3-. Our results are similar to those observed in temperate and tropical regions, indicating that the potential impacts of OA on Antarctic seaweeds will be species specific. Additionally, OA may potentially increase the abundance of non-CCM species relative to those with CCMs.

An incentive-based text-messaging intervention to reduce maternal alcohol use during pregnancy and lactation in South Africa (MaRISA study): Findings from a single-arm pilot study.

BACKGROUND: South Africa has the highest rate of fetal alcohol spectrum disorders (FASD) globally. As with alcohol use during pregnancy, alcohol consumption while breastfeeding adversely impacts infant development. We pilot tested an incentive-based text-messaging intervention to reduce alcohol use during pregnancy and lactation in South Africa. METHODS: A single-arm pilot trial was conducted over 3 months in healthcare facilities in Cape Town, South Africa. Pregnant and breastfeeding participants tested positive for recent alcohol use by urinalysis. The three-month intervention had two components, contingency management of alcohol abstinence confirmed by urinalysis twice weekly and weekly health-related text messaging from an evidence-based brief intervention. We collected twice weekly urine samples for measurement of ethyl glucuronide (EtG), an alcohol biomarker, and measures of self-reported alcohol and drug use, violence exposure, and mental health at six weeks and three months post-enrollment. RESULTS: Sixty participants were enrolled, of whom 31 were pregnant and 29 lactating. The number of days with four or more drinks in the past month decreased from 9 days at baseline, on average, to 1-3 days (p-value range: 0.144-0.010) at follow-up timepoints. There were statistically significant increases in the proportions of participants with alcohol-negative urine tests (p < 0.001). The percentages of participants breastfeeding while using alcohol decreased from baseline to the end of 3 months in the overall sample and among those enrolled postpartum, though these were not significant (p-value range: 0.255-0.147). Maternal depression scores also decreased among participants enrolled postpartum (p = 0.054). Emotional abuse by the main partner, but neither physical nor sexual abuse, significantly decreased at both follow-ups in the overall sample (p = 0.032) and among participants enrolled while pregnant (p = 0.015). CONCLUSIONS: This study is among the first to pilot test an incentive-based text-messaging intervention for maternal alcohol use and other outcomes such as depression and violence exposure. Further testing is warranted in a well-powered, randomized controlled trial.

Older adults with communication disabilities and their use of communication support at doctor's visits: a nationally representative study.

PURPOSE: Older adults with communication disabilities (CDs) experience barriers to receiving care and face a paucity of accommodations for their disability. Utilizing someone that supports communication with healthcare providers (communication support persons) may be a way that this group self-supports their disability. We examined if this utilization was independently associated with CDs among older adults. We also sought to understand if socioeconomic factors were associated with utilization. METHODS: We used the 2015 National Health and Aging Trends Survey (NHATS) to conduct a cross-sectional analysis of Medicare beneficiaries (n = 5954) with functional hearing, expressive, or cognitive difficulties. We calculated a weighted, population prevalence and an adjusted prevalence ratio (APR) controlling for sociodemographic, health and other disability factors. RESULTS: Among community dwelling older adults, having CDs was associated with higher utilization of a communication support person at medical visits (APR: 1.41 [CI: 1.27 - 1.57]). Among adults with CDs, Black adults and women had lower levels of utilization as compared to White adults and men, respectively. CONCLUSION: Communication support persons may be a way that older adults with CDs self-support their disability. However, not all older adults with CDs bring someone and variation by social factors could suggest that unmet support needs exist.

Over half of older adults with communication disabilities do not utilize a communication support person at doctors' visits, and utilization differs by race and gender.Rehabilitation professionals should educate their older adult patients with communication disabilities on this practice and collaborate with speech-language pathologists (SLPs) and audiologists (AuDs) on how to accommodate this population's disability.SLPs and AuDs can directly train support persons, other rehabilitation professionals, and physicians on accommodating these patients. For patients who don't bring a support person, SLPs and AuDs can plan alternative communication disability supports to use in healthcare settings, so that all older adults with CDs can equitably access their healthcare.

Oral Prostacyclin Pathway Agents Used in PAH: A Targeted Literature Review.

Purpose: Pulmonary arterial hypertension (PAH) is a rare and progressive pulmonary vascular disease that can result in right heart failure and death. Oral prostacyclins play an important role in the management of intermediate-low risk PAH. This targeted literature review (TLR) aimed to identify and compare evidence supporting use of oral prostacyclin pathway agents (PPAs: selexipag and oral treprostinil) in intermediate-low risk PAH. Methods: A targeted literature review was conducted. Literature databases (MEDLINE, Embase, and Cochrane reviews) were searched for studies describing clinical practice and treatment outcomes for oral treprostinil and selexipag globally, published in English (2012 to 2022). Electronic searches were supplemented by manual-searches of targeted conferences (2020 to 2022), and reference lists of identified publications were reviewed. One reviewer assessed studies for eligibility. Results: In total, 95 publications met inclusion criteria: 47 full-text articles (selexipag n = 22; oral treprostinil n = 16; selexipag and oral treprostinil n = 9) and 48 conference materials. Selexipag and oral treprostinil target the prostacyclin pathway differently; their label-supporting trials had different primary endpoints (disease progression and hospitalization vs exercise capacity and disease progression), differing baseline therapy (0, 1 or 2 vs 0 or 1 baseline treatments), titration duration and dosing (personalized dose capped at 1600 ug twice daily (BID) vs increasing doses over time with no maximum dose), respectively. While both oral PPAs have demonstrated reduced risk of disease progression, only selexipag showed reduction in hospitalization rates. Oral PPAs have been shown to reduce healthcare costs in real-world clinical practice. This difference is reflected in labeled indications. Conclusion: Given differences in trial- and real-world outcomes, number of prior therapies, and dosing, personalizing the choice of oral PPA is critical to maximizing the benefit for individual patients.

PAH is a condition that causes heart failure. It is important to take medicines to slow down this process. For people with early disease, there are some medicines that can be taken as a tablet rather than as an injection to slow down disease progression. The differences between two of the tablet options ­ selexipag and oral treprostinil, are unclear. We reviewed publications describing how, when and why these medicines are used and how well they work, to improve our understanding of the value of these medicines to people with PAH.

How Health Care Organizations Are Implementing Disability Accommodations for Effective Communication: A Qualitative Study.

BACKGROUND: Prior studies have documented that, despite federal mandates, clinicians infrequently provide accommodations that enable equitable health care engagement for patients with communication disabilities. To date, there has been a paucity of empirical research describing the organizational approach to implementing these accommodations. The authors asked US health care organizations how they were delivering these accommodations in the context of clinical care, what communication accommodations they provided, and what disability populations they addressed. METHODS: In this study, 19 qualitative interviews were conducted with disability coordinators representing 15 US health care organizations actively implementing communication accommodations. A conventional qualitative content analysis approach was used to code the data and derive themes. RESULTS: The authors identified three major themes related to how US health care organizations are implementing the provision of this service: (1) Operationalizing the delivery of communication accommodations in health care required executive leadership support and preparatory work at clinic and organization levels; (2) The primary focus of communication accommodations was sign language interpreter services for Deaf patients and, secondarily, other hearing- and visual-related accommodations; and (3) Providing communication accommodations for patients with speech and language and cognitive disabilities was less frequent, but when done involved more than providing a single aid or service. CONCLUSION: These findings suggest that, in addition to individual clinician efforts, there are organization-level factors that affect consistent provision of communication accommodations across the full range of communication disabilities. Future research should investigate these factors and test targeted implementation strategies to promote equitable access to health care for all patients with communication disabilities.

Immune Checkpoint Inhibitors in Hepatocellular Carcinoma and Their Hepatic-Related Side Effects: A Review.

Primary liver cancer is one of the leading causes of cancer mortality worldwide, with hepatocellular carcinoma (HCC) being the most prevalent type of liver cancer. The prognosis of patients with advanced, unresectable HCC has historically been poor. However, with the emergence of immunotherapy, specifically immune checkpoint inhibitors (ICIs), there is reason for optimism. Nevertheless, ICIs do not come without risk, especially when administered in patients with HCC, given their potential underlying poor hepatic reserve. Given their novelty in the management of HCC, there are few studies to date specifically investigating ICI-related side effects on the liver in patients with underlying HCC. This review will serve as a guide for clinicians on ICIs' role in the management of HCC and their potential side effect profile. There will be a discussion on ICI-related hepatotoxicity, the potential for hepatitis B and C reactivation with ICI use, the potential for the development of autoimmune hepatitis with ICI use, and the risk of gastrointestinal bleeding with ICI use. As ICIs become more commonplace as a treatment option in patients with advanced HCC, it is imperative that clinicians not only understand the mechanism of action of such agents but also understand and are able to identify hepatic-related side effects.

Predictive Value of Preoperative Pain Sketches in Lower Extremity Amputees Undergoing Secondary Targeted Muscle Reinnervation for Treatment of Neuropathic Pain.

BACKGROUND: Targeted Muscle Reinnervation (TMR) is an effective surgical treatment for neuropathic pain in amputees. Qualitative descriptions of pain, depicted by pain sketches, could enhance the understanding of symptomatic improvement following surgery. Our aim is to assess whether pre-operative pain sketches, drawn by lower extremity (LE) amputees, can predict surgical outcomes following Secondary TMR surgery. STUDY DESIGN: Eligible patients were LE amputees who underwent Secondary TMR surgery between 2017 and 2023. Pain sketches and pain scores were prospectively collected both before and after surgery. The pain trajectory, as categorized by pre-operative pain sketches, was analyzed and assessed for improvement, defined as reaching the Minimal Clinically Important Difference (MCID). The transition into different pain sketches and the occurrence of phantom drawings were evaluated for their association with improvement. RESULTS: Fifty-eight patients were included, of which 18 (31.1%) depicted diffuse pain (DP), 26 (44.8%) depicted focal pain (FP), and 18 (24.1%) depicted radiating pain (RP) in their pre-operative sketch. FP sketches were associated with the lowest pre- and post-operative pain scores and most frequently developed into sketches indicating "no pain". RP sketches were associated with the least pain improvement, the lowest likelihood of achieving the MCID, and were more prevalent in patients with diabetes or depression. RP sketches were associated with phantom drawings; no other sketch types developed into RP sketches at the final follow-up. CONCLUSIONS: In LE amputees who underwent Secondary TMR, pre-operative pain sketches could serve as a helpful tool in predicting pain outcomes. RP sketches seemed to be associated with worse outcomes, and FP sketches with the most improvement.

Using Bio-inline Reactor to Evaluate Sanitizer Efficacy in Removing Dual-species Biofilms Formed by Escherichia coli O157:H7 and Listeria monocytogenes.

The efficacy of a sanitizer in biofilm removal may be influenced by a combination of factors such as sanitizer exposure time and concentration, bacterial species, surface topography, and shear stresses. We employed an inline biofilm reactor to investigate the interactions of these variables on biofilm removal with chlorine. The CDC bioreactor was used to grow E. coli O157:H7 and L. monocytogenes biofilms as a single species or with Ralstonia insidiosa as a dual-species biofilm on stainless steel, PTFE, and EPDM coupons at shear stresses 0.368 and 2.462 N/m2 for 48 hours. Coupons were retrieved from a CDC bioreactor and placed in an inline biofilm reactor and 100, 200, or 500 ppm of chlorine was supplied for 1- and 4 min. Bacterial populations in the biofilms were quantified pre- and posttreatment by plating on selective media. After chlorine treatment, reduction (Log CFU/cm2) in pathogen populations obtained from three replicates was analyzed for statistical significance. A 1-min chlorine treatment (500 ppm), on dual-species E. coli O157:H7 biofilms grown at high shear stress of 2.462 N/m2 resulted in significant E. coli O157:H7 reductions on SS 316L (2.79 log CFU/cm2) and PTFE (1.76 log CFU/cm2). Similar trend was also observed for biofilm removal after a 4-min chlorine treatment. Single species E. coli O157:H7 biofilms exhibited higher resistance to chlorine when biofilms were developed at high shear stress. The effect of chlorine in L. monocytogenes removal from dual-species biofilms was dependent primarily on the shear stress at which they were formed rather than the surface topography of materials. Besides surface topography, shear stresses at which biofilms were formed also influenced the effect of sanitizer. The removal of E. coli O157:H7 biofilms from EPDM material may require critical interventions due to difficulty in removing this pathogen. The inline biofilm reactor is a novel tool to evaluate the efficacy of a sanitizer in bacterial biofilm removal.

Engaging Communities in Emerging Infectious Disease Mitigation to Improve Public Health and Safety.

The COVID-19 pandemic highlighted the need for potent community-based tools to improve preparedness. We developed a community health-safety climate (HSC) measure to assess readiness to adopt health behaviors during a pandemic. We conducted a mixed-methods study incorporating qualitative methods (e.g., focus groups) to generate items for the measure and quantitative data from a February 2021 national survey to test reliability, multilevel construct, and predictive and nomologic validities. The 20-item HSC measure is unidimensional (Cronbach α = 0.87). All communities had strong health-safety climates but with significant differences between communities (F = 10.65; p<0.001), and HSC levels predicted readiness to adopt health-safety behaviors. HSC strength moderated relationships between HSC level and behavioral indicators; higher climate homogeneity demonstrated stronger correlations. The HSC measure can predict community readiness to adopt health-safety behaviors in communities to inform interventions before diseases spread, providing a valuable tool for public health authorities and policymakers during a pandemic.

Quantitative Characterization of Chain-Flipping of Acyl Carrier Protein of Escherichia coli Using Chemical Exchange NMR.

The acyl carrier protein of Escherichia coli, termed AcpP, is a prototypical example of type II fatty acid synthase systems found in many bacteria. It serves as a central hub by accepting diverse acyl moieties (4-18 carbons) and shuttling them between its multiple enzymatic partners to generate fatty acids. Prior structures of acyl-AcpPs established that thioester-linked acyl cargos are sequestered within AcpP's hydrophobic lumen. In contrast, structures of enzyme-bound acyl-AcpPs showed translocation of AcpP-tethered acyl chains into the active sites of enzymes. The mechanistic underpinnings of this conformational interplay, termed chain-flipping, are unclear. Here, using heteronuclear NMR spectroscopy, we reveal that AcpP-tethered acyl chains (6-10 carbons) spontaneously adopt lowly populated solvent-exposed conformations. To this end, we devised a new strategy to replace AcpP's thioester linkages with 15N-labeled amide bonds, which facilitated direct "visualization" of these excited states using NMR chemical exchange saturation transfer and relaxation dispersion measurements. Global fitting of the corresponding data yielded kinetic rate constants of the underlying equilibrium and populations and lifetimes of solvent-exposed states. The latter were influenced by acyl chain composition and ranged from milliseconds to submilliseconds for chains containing six, eight, and ten carbons, owing to their variable interactions with AcpP's hydrophobic core. Although transient, the exposure of AcpP-tethered acyl chains to the solvent may allow relevant enzymes to gain access to its active thioester, and the enzyme-induced selection of this conformation will culminate in the production of fatty acids.

Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells.

BACKGROUND: Circulating tumor cells (CTCs) hold immense promise for unraveling tumor heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to cancer patients, enabling the screening of larger blood volumes. To leverage DLA's full potential, this study introduces a novel approach for CTC enrichment from DLAs. METHODS: DLA was applied to six advanced stage NSCLC patients. For an unbiased CTC enrichment, a two-step approach based on negative depletion of hematopoietic cells was used. Single-cell (sc) whole-transcriptome sequencing was performed, and CTCs were identified based on gene signatures and inferred copy number variations. RESULTS: Remarkably, this innovative approach led to the identification of unprecedented 3,363 CTC transcriptomes. The extensive heterogeneity among CTCs was unveiled, highlighting distinct phenotypes related to the epithelial-mesenchymal transition (EMT) axis, stemness, immune responsiveness, and metabolism. Comparison with sc transcriptomes from primary NSCLC cells revealed that CTCs encapsulate the heterogeneity of their primary counterparts while maintaining unique CTC-specific phenotypes. CONCLUSIONS: In conclusion, this study pioneers a transformative method for enriching CTCs from DLA, resulting in a substantial increase in CTC numbers. This allowed the creation of the first-ever single-cell whole transcriptome in-depth characterization of the heterogeneity of over 3,300 NSCLC-CTCs. The findings not only confirm the diagnostic value of CTCs in monitoring tumor heterogeneity but also propose a CTC-specific signature that can be exploited for targeted CTC-directed therapies in the future. This comprehensive approach signifies a major leap forward, positioning CTCs as a key player in advancing our understanding of cancer dynamics and paving the way for tailored therapeutic interventions.

Prospective derivation and validation of a NECROtizing Soft tissue InfectionS (NECROSIS) score: An EAST multicenter trial.

BACKGROUND: Although several risk indices have been developed to aid in the diagnosis of NSTIs, these instruments suffer from varying levels of reproducibility and failure to incorporate key clinical variables in model development. The objective of this study was to derive and validate a clinical risk index score - NECROSIS - for identifying NSTIs in emergency general surgery (EGS) patients being evaluated for severe skin and soft tissue infections. METHODS: We performed a prospective study across 16 sites in the US of adult EGS patients with suspected NSTIs over a 30-month period. Variables analyzed included demographics, admission vitals and labs, physical exam, radiographic, and operative findings. The main outcome measure was the presence of NSTI diagnosed clinically at the time of surgery. Multivariate analysis was performed to identify independent predictors for the presence of NSTI using the Hosmer-Lemeshow test and the Akaike information criteria. RESULTS: Of 362 patients, 297 (82%) were diagnosed with a NSTI. Overall mortality was 12.3%. Multivariate analysis identified 3 independent predictors for NSTI: systolic blood pressure ≤ 120 mmHg, violaceous skin, and WBC ≥15 (x103/uL). Multivariate modelling demonstrated Hosmer-Lemeshow goodness of fit (p = 0.9) with a c-statistic for the prediction curve of 0.75. Test characteristics of the NECROSIS score were similar between the derivation and validation cohorts. CONCLUSION: NECROSIS is a simple and potentially useful clinical index score for identifying at-risk EGS patients with NSTIs. Future validation studies are warranted. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria, Level III.

Hand hygiene perceptions, preferences, and practices among hospital staff in the Dominican Republic in the context of COVID-19: a qualitative study.

Background: Proper hand hygiene (HH), which includes sanitizing with alcohol-based hand rub (ABHR) (or handwashing with soap and water if ABHR is unavailable), is key for preventing healthcare-associated infections (HCAI), including COVID-19. Understanding drivers of HH is key to improving adherence. Aim: This study aims to explore drivers and barriers to HH practice at two hospitals in the Dominican Republic in the context of the COVID-19 pandemic to inform development of HH behaviour change interventions. Methods: We conducted in-depth interviews with 20 hospital staff during September 2021. We used the COM-B (capability, opportunity, motivation, behaviour) model to explore HH experiences and preferences. Interviews were recorded, transcribed, coded, and analysed using a thematic approach. Results: A total of 11 parent codes and 27 sub-codes were identified, and 1145 coded segments were analysed. Use of handwashing with soap and water and/or sanitizing with ABHR was reported by all participants; handwashing was generally preferred. Participants expressed knowledge of proper HH methods (capability), but inconsistent supplies and lack of time presented HH challenges (opportunity). Interviewees described practicing HH to protect themselves and their families from COVID-19 and other infections (reflective motivation) or out of habit (automatic motivation). Discussion: By understanding and addressing underlying factors affecting HH, hospitals can decrease the risk of HCAIs. Our findings suggest that interventions implemented to improve HH in these hospitals should target motivation and opportunity. These findings informed a multimodal intervention to increase ABHR access and implement message-tested communications campaigns; end-point assessments will provide insights into the intervention's impact.

Pragmaticism in Cancer Clinical Trials.

Clinical trials are essential for advancing oncology treatment strategies and have contributed significantly to the decline in cancer mortality rates over the past decades. Traditional explanatory trials, focused on establishing intervention efficacy in ideal settings, often lack generalizability and may not reflect real-world patient care scenarios. Furthermore, increasing complexity in cancer clinical trial design has led to challenges such as protocol deviations, slow enrollment leading to lengthened durations of trial, and escalating costs. By contrast, pragmatic trials aim to assess intervention effectiveness in more representative patient populations under routine clinical conditions. Here, we review the principles, methodologies, challenges, and advantages of incorporating pragmatic features (PFs) into cancer clinical trials. We illustrate the application of pragmatic trial designs in oncology and discuss the QUASAR collaborative, TAPUR study, and the ongoing PRAGMATICA-LUNG trial. Although not all oncology trials may be amenable to adopting fully pragmatic designs, integration of PFs when feasible will enhance trial generalizability and real-world applicability. Project Pragmatica and similar initiatives advocate for the integration of real-world practice with clinical trials, fostering a nuanced approach to oncology research that balances efficacy and effectiveness assessments, ultimately with a goal of improving patient outcomes.

Acute Kidney Injury in a Previously Healthy 56-Year-Old Male Following a Direct Visual Internal Urethrotomy of a Bulbar Stricture.

Acute kidney injury (AKI) is a frequent finding in acutely ill and hospitalized patients arising from various etiologies. Anuric AKI, a more pronounced form of AKI in which less than 100 cc of urine is produced per day, is most frequently encountered in hospitalized, septic, and post-surgical patients, often secondary to shock or bilateral urinary tract obstruction. The development of anuric AKI in previously healthy patients after outpatient urological procedures presents a unique challenge to physicians, as many outpatient procedures require the routine perioperative administration of multiple nephrotoxic medications. Further complicating this clinical scenario, some surgical procedures that intrinsically involve iatrogenic injury to the kidney, ureter, bladder, or nearby organ can rarely lead to a phenomenon known as reflex anuria, an anuric state typically associated with AKI. Here, we report an unusual case of a previously healthy 56-year-old male who developed anuric AKI two days after direct visual internal urethrotomy (DVIU) for the treatment of a bulbar stricture. Non-contrast CT revealed no signs of an obstructive process, and laboratory findings supported an intrarenal cause of AKI. Consideration was given to non-steroidal anti-inflammatory drugs (NSAID)-induced nephrotoxicity, gentamicin-associated acute tubular necrosis, and propofol infusion syndrome, in addition to their potential synergistic effects. We also explore this as the first reported case of reflex anuria occurring at the level of the bulbar urethra, as most cases have involved direct injury to the kidney or ureter. Over the course of 10 days, our patient responded well to treatment with supportive measures and dialysis, with his vomiting, electrolyte abnormalities, renal state, and anuria eventually improving.

Using structured problem solving to promote fluid consumption in the prevention of urinary stones with hydration (PUSH) trial.

BACKGROUND: Structured Problem Solving (SPS) is a patient-centered approach to promoting behavior change that relies on productive collaboration between coaches and participants and reinforces participant autonomy. We aimed to describe the design, implementation, and assessment of SPS in the multicenter Prevention of Urinary Stones with Hydration (PUSH) randomized trial. METHODS: In the PUSH trial, individuals with a history of urinary stone disease and low urine output were randomized to control versus a multicomponent intervention including SPS that was designed to promote fluid consumption and thereby prevent recurrent stones. We provide details specifically about training and fidelity assessment of the SPS coaches. We report on implementation experiences related to SPS during the initial conduct of the trial. RESULTS: With training and fidelity assessment, coaches in the PUSH trial applied SPS to help participants overcome barriers to fluid consumption. In some cases, coaches faced implementation barriers such as variable participant engagement that required tailoring their work with specific participants. The coaches also faced challenges including balancing rapport with problem solving, and role clarity for the coaches. CONCLUSIONS: We adapted SPS to the setting of kidney stone prevention and overcame challenges in implementation, such as variable patient engagement. Tools from the PUSH trial may be useful to apply to other health behavior change settings in nephrology and other areas of clinical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03244189.