LncRNA Nostrill promotes interferon-γ-stimulated gene transcription and facilitates intestinal epithelial cell-intrinsic anti-Cryptosporidium defense.

Intestinal epithelial cells possess the requisite molecular machinery to initiate cell-intrinsic defensive responses against intracellular pathogens, including intracellular parasites. Interferons(IFNs) have been identified as cornerstones of epithelial cell-intrinsic defense against such pathogens in the gastrointestinal tract. Long non-coding RNAs (lncRNAs) are RNA transcripts (>200 nt) not translated into protein and represent a critical regulatory component of mucosal defense. We report here that lncRNA Nostrill facilitates IFN-γ-stimulated intestinal epithelial cell-intrinsic defense against infection by Cryptosporidium, an important opportunistic pathogen in AIDS patients and a common cause of diarrhea in young children. Nostrill promotes transcription of a panel of genes controlled by IFN-γ through facilitating Stat1 chromatin recruitment and thus, enhances expression of several genes associated with cell-intrinsic defense in intestinal epithelial cells in response to IFN-γ stimulation, including Igtp, iNos, and Gadd45g. Induction of Nostrill enhances IFN-γ-stimulated intestinal epithelial defense against Cryptosporidium infection, which is associated with an enhanced autophagy in intestinal epithelial cells. Our findings reveal that Nostrill enhances the transcription of a set of genes regulated by IFN-γ in intestinal epithelial cells. Moreover, induction of Nostrill facilitates the IFN-γ-mediated epithelial cell-intrinsic defense against cryptosporidial infections.

Despite the improved clinical sensitivity of the Roche benzodiazepines II assay it cannot replace mass spectrometry in all patient populations.

Introduction: Benzodiazepines are frequently prescribed and misused therefore urine drug screening (UDS) is performed in many patient populations. Most current benzodiazepine immunoassays have poor sensitivity, particularly for detecting the metabolites of newer benzodiazepines such as lorazepam in urine. Objectives: We aimed to verify the clinical performance of the new qualitative Roche Benzodiazepines II (BNZ2) immunoassay, as well as compare its performance to the Roche Benzodiazepines Plus (BENZ) assay in two patient populations: UDS in the emergency department (ED) and compliance monitoring. Methods: An initial verification study was performed, selecting for samples containing clonazepam and lorazepam metabolites. Performance of the BNZ2 and BENZ assays was compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the reference method. Sensitivity, specificity, false positive rate (FPR) and false negative rate (FNR) were determined. Results: We verified the performance claims in the initial verification and demonstrated similar precision, with coefficient of variations (CVs) of 12.8% and 7.7% for negative and positive controls, respectively. Furthermore, we observed higher clinical sensitivity and lower FNR with the BNZ2 assay in both the ED and compliance monitoring populations due to improved cross-reactivity for lorazepam and clonazepam metabolites. Despite these improvements, the BNZ2 assay was unable to detect 27% of specimens positive by LC-MS/MS, including specimens from patients using benzodiazepines without prescription. Discussion: Due to its improved performance and rapid turnaround time, the BNZ2 assay should be implemented for UDS in the ED. However, the assay should not replace LC-MS/MS testing for compliance monitoring, as unsuspected benzodiazepine use may go undetected.

Qualitative and Psychometric Evaluation of 29-Item Patient-Reported Outcomes Measurement Information System® to Assess General Health-Related Quality of Life in Patients With Moderately to Severely Active Inflammatory Bowel Disease.

OBJECTIVES: To evaluate content validity and psychometric properties of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) to determine its suitability in inflammatory bowel disease (IBD) clinical trials. METHODS: Content validity of PROMIS-29 was evaluated using qualitative interviews, including concept elicitation and cognitive debriefing, among patients living with Crohn's disease (Crohn's disease n = 20) or ulcerative colitis (UC, n = 19). PROMIS-29 validity, reliability, and responsiveness were assessed using data from phase II clinical trials of Crohn's disease (N = 360) and UC (N = 518). RESULTS: Common (≥74%) symptoms reported in qualitative interviews were increased stool frequency, fatigue, abdominal pain/cramping, blood/mucus in stool, bowel urgency, and diarrhea. Disease impact aligned with PROMIS-29 content (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles/activities). Cognitive debriefing indicated that PROMIS-29 instructions were easily understood, items were relevant, and the recall period was appropriate. Psychometric evaluations demonstrated that PROMIS-29 scores indicating worse symptoms/functioning were associated with lower health-related quality of life and greater disease activity and severity. PROMIS-29 domain scores correlated (rs ≥ 0.40) with IBD Questionnaire domains and EuroQol-5-Dimension-5-Level dimensions measuring similar concepts. Test-retest reliability among patients with stable disease was moderate-to-excellent (0.64-0.94) for nearly all domains in all studies. PROMIS-29 was responsive to change in disease status from baseline to week 12. Thresholds for clinically meaningful improvement ranged from ≥3 to ≥8, depending on domain. CONCLUSIONS: PROMIS-29 is valid, reliable, and responsive for assessing general health-related quality of life and treatment response in IBD clinical trials.

Therapeutic Role of Nusinersen on Respiratory Progression in Pediatric Patients With Spinal Muscular Atrophy Type 2 and Nonambulant Type 3.

Background and Objectives: Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020. Methods: This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age ≤18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected. Results: Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH (p = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH (p = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, p = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up. Discussion: This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned. Classification of Evidence: This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort.

Comparing Polymerase Chain Reaction Testing of Nasopharyngeal Swab and Lower Respiratory Tract Specimens for the Diagnosis of Pneumocystis jirovecii Pneumonia.

Using nasopharyngeal (NP) swab samples instead of lower respiratory tract specimens for polymerase chain reaction (PCR) to diagnose Pneumocystis jirovecii pneumonia (PJP) may be better tolerated and improve diagnostic accessibility. In this 2-year Australian retrospective cohort study of patients with clinically suspected PJP, P jirovecii PCR on NP swab samples had perfect specificity but low sensitivity (0.66).

Epigenetic signatures of social status in wild female spotted hyenas (Crocuta crocuta).

In mammalian societies, dominance hierarchies translate into inequalities in health, reproductive performance and survival. DNA methylation is thought to mediate the effects of social status on gene expression and phenotypic outcomes, yet a study of social status-specific DNA methylation profiles in different age classes in a wild social mammal is missing. We tested for social status signatures in DNA methylation profiles in wild female spotted hyenas (Crocuta crocuta), cubs and adults, using non-invasively collected gut epithelium samples. In spotted hyena clans, female social status influences access to resources, foraging behavior, health, reproductive performance and survival. We identified 149 differentially methylated regions between 42 high- and low-ranking female spotted hyenas (cubs and adults). Differentially methylated genes were associated with energy conversion, immune function, glutamate receptor signalling and ion transport. Our results provide evidence that socio-environmental inequalities are reflected at the molecular level in cubs and adults in a wild social mammal.

Not heading in the right direction: Five hundred psychiatrists' views on resourcing, demand, and workforce across New Zealand mental health services.

OBJECTIVE: To explore the views of psychiatrists (including trainees) regarding the current state and future direction of specialist mental health and addictions services in Aotearoa New Zealand. METHODS: Psychiatrists and trainee psychiatrists (registrars) in Aotearoa New Zealand were surveyed in August 2021. Of 879 eligible doctors, 540 participated (83% qualified and 17% trainee psychiatrists), a response rate of over 60%. Data were analysed quantitatively and with content analysis. RESULTS: Psychiatrists thought specialist mental health and addictions services had been neglected during recent reforms, with 94% believing current resourcing was insufficient, and only 3% considering future planning was heading in the right direction. The demand and complexity of on-call work had markedly increased in the preceding 2 years. Ninety-eight percent reported that people needing specialist treatment were often (85%) or sometimes (13%) unable to access the right care due to resourcing constraints. The pressures were similar across sub-specialties. A key theme was the distress (sometimes termed 'moral injury') experienced by psychiatrists unable to provide adequate care due to resource limitations, 'knowing what would be a good thing to do and being unable to do it . . . is soul destroying'. Recommendations were made for addressing workforce, service design and wider issues. CONCLUSION: Most psychiatrists in Aotearoa New Zealand believe the mental health system is not currently fit for purpose and that it is not heading in the right direction. Remedies include urgently addressing identified staffing challenges and boosting designated funding to adequately care for the 5% of New Zealanders with severe mental health and addiction needs.

Identification of Small Molecule Ligand Binding Sites On and In the ARNT PAS-B Domain.

Transcription factors are generally challenging to target with small molecule inhibitors due to their structural plasticity and lack of catalytic sites. Notable exceptions to this include a number of transcription factors which are naturally ligand-regulated, a strategy we have successfully exploited with the heterodimeric HIF-2 transcription factor, showing that a ligand-binding internal pocket in the HIF-2α PAS-B domain could be utilized to disrupt its dimerization with its partner, ARNT. Here, we explore the feasibility of directly targeting small molecules to the structurally similar ARNT PAS-B domain, potentially opening a promising route to simultaneously modulate several ARNT-mediated signaling pathways. Using solution NMR screening of an in-house fragment library, we previously identified several compounds that bind ARNT PAS-B and, in certain cases, antagonize ARNT association with the TACC3 transcriptional coactivator. However, these ligands only have mid-micromolar binding affinities, complicating characterization of their binding sites. Here we combine NMR, MD simulations, and ensemble docking to identify ligand-binding 'hotspots' on and within the ARNT PAS-B domain. Our data indicate that the two ARNT/TACC3 inhibitors, KG-548 and KG-655, bind to a ß-sheet surface implicated in both HIF-2 dimerization and coactivator recruitment. Furthermore, KG-548 binds exclusively to the ß-sheet surface, while KG-655 binds to the same site but can also enter a water-accessible internal cavity in ARNT PAS-B. Finally, KG-279, while not a coactivator inhibitor, exemplifies ligands that preferentially bind only to the internal cavity. Taken together, our findings provide a comprehensive overview of ARNT PAS-B ligand-binding sites and may guide the development of more potent coactivator inhibitors for cellular and functional studies.

Overcoming the hurdles: surmounting acquired resistance to anti-EGFR therapy in metastatic colorectal cancer.

Colorectal cancer is the third most prevalent cancer type in the United States, with an alarming incidence and mortality rate, especially among individuals younger than 50 years. The epidermal growth factor receptor (EGFR), essential for cell proliferation and survival, has surfaced as a promising therapeutic target for metastatic colorectal cancer and has demonstrated success in various clinical trials. Monoclonal antibodies such as cetuximab and panitumumab have proven to be effective against EGFR by blocking vital downstream signaling pathways and inhibiting gene transcription and cell proliferation. Despite this promise, most patients eventually develop resistance to anti-EGFR treatment, thereby limiting its long-term efficacy. Genomic alterations, such as mutations in KRAS, NRAS, and BRAF, often bypass the EGFR receptor, promoting resistance to therapy. Although our understanding of primary resistance to anti-EGFR therapy has improved, acquired resistance remains a significant hurdle. This review explores the potential mechanisms underpinning this acquired resistance and strategies to overcome it.

Surgical resection criteria and neoadjuvant therapies for intrahepatic cholangiocarcinoma.

The staging of intrahepatic cholangiocarcinoma (ICC) is complex, and there is no consensus among international cancer groups on how to most appropriately select candidates with nonmetastatic disease for surgical resection. Factors contributing to a higher stage of disease include larger tumor size, multiple tumors, vascular invasion (either portal venous or arterial), biliary invasion, involvement of local hepatic structures, serosal invasion, and regional lymph node metastases. For patients selected to undergo surgery, it is well-documented that R0 resection translates to a survival benefit. Estimating the risk of post-hepatectomy liver failure and post-surgical residual liver function is vital and may preclude some patients with significant tumor burden from undergoing surgery. Numerous serum and biliary biomarkers of the disease can help detect recurrence in patients undergoing surgical resection. Systemic and locoregional neoadjuvant treatments to facilitate better surgical outcomes have yielded mixed results regarding improving resectability and overall survival. Additional research is needed to identify optimal neoadjuvant treatment approaches and to evaluate which patients will benefit most from these strategies. Therapies targeting genetic mutations and protein aberrations found by tumor molecular profiling may offer additional options for future neoadjuvant treatment.

Lower Double-Wall Puncture Rate During Ultrasound-Guided Internal Jugular Vein Cannulation Using Sharper, Narrower-Gauge, and/or Length-Optimized Needles: A 6-Year Quality Improvement Clinical Series in Adult Patients.

Background: During internal jugular vein (IJV) cannulation, needle tip injury to vulnerable subjacent cervical anatomic structures can be prevented if the cannulating needle tip is not permitted, even momentarily, to penetrate the deep portion of the IJV wall, an event known as double-wall puncture (DWP), also called posterior wall puncture. Methods: We conducted a 6-year ultrasound-guided IJV cannulation quality improvement project, seeking to minimize the occurrence of DWP in 228 adult patients using needles of different gauge and tip sharpness. Most needles were length-optimized to the distance between the skin puncture site and the IJV mid-lumen for a selected angle of needle insertion by (1) using a nylon screw-on needle stop or (2) using a cannulating needle that already had the desired shaft length. Results: Standard central venous cannulation kit needles were long enough to reach or traverse the deepest portion of the IJV wall in nearly all patients. Use of extra-sharp, smaller-diameter needles in place of standard needles was associated with a 26.3% relative reduction in DWP rate. Use of needles length-optimized to reach only the IJV mid-lumen was associated with a 78.4% relative reduction in DWP rate. A 0% DWP rate was attained using length-optimized 21-gauge extra-sharp needles and length-optimized 20-gauge needles of intermediate sharpness. Conclusion: The 9.2% DWP rate achieved during this project was approximately half the rate reported at the time of project inception. Use of length-optimized, sharper, narrower-gauge cannulating needles may help avoid DWP during ultrasound-guided IJV cannulation.

The cycle of seagrass life: From flowers to new meadows.

Understanding sexual reproduction and recruitment in seagrasses is crucial to their conservation and restoration. Flowering, seed production, seed recruitment, and seedling establishment data for the seagrass Posidonia australis was collected annually between 2013 and 2018 in meadows at six locations around Rottnest Island, Western Australia. Variable annual rates of flowering and seed production were observed among meadows between northern and southern sides of the island and among years. Meadows on the northern shore consistently flowered more intensely and produced more seeds across the years of the survey. Inter-site variation in clonal diversity and size of clones, seed production, wind and surface currents during pollen and seed release, and the large, but variable, impact of seed predation are likely the principal drivers of successful recruitment into established meadows and in colonizing unvegetated sands. The prolific but variable annual reproductive investment increases the probability of low levels of continuous recruitment from seed in this seagrass, despite high rates of abiotic and biotic disturbance at seedling, shoot, and patch scales. This strategy also imparts a level of ecological resilience to this long-lived and persistent species.

Cerebrospinal fluid shunt malfunctions: A reflective review.

PURPOSE: Pediatric hydrocephalus is a common and challenging condition. To date, the ventriculoperitoneal shunt (VPS) is still the main lifesaving treatment option. Nonetheless, it remains imperfect and is associated with multiple short- and long-term complications. This paper is a reflective review of the current state of the VPS, our knowledge gaps, and the future state of shunts in neurosurgical practice. METHODS AND RESULTS: The authors' reflections are based on a review of shunts and shunt-related literature. CONCLUSION: Overall, there is still an urgent need for the neurosurgical community to actively improve current strategies for shunt failures and shunt-related morbidity. The authors emphasize the role of collaborative efforts amongst like-minded clinicians to establish pragmatic approaches to avoid shunt complications.

Cryptosporidium parvum hijacks a host's long noncoding RNA U90926 to evade intestinal epithelial cell-autonomous antiparasitic defense.

Cryptosporidium is a zoonotic apicomplexan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans. It is an important opportunistic pathogen in AIDS patients and a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. The intestinal epithelial cells provide the first line of defense against Cryptosporidium infection and play a central role in activating and regulating the host's antiparasitic response. Increasing evidence suggests that long noncoding RNAs (lncRNAs) participate in host-pathogen interactions and play a regulatory role in the pathogenesis of diseases but the underlying molecular mechanisms are not fully understood. We previously identified a panel of host lncRNAs that are upregulated in murine intestinal epithelial cells following Cryptosporidium infection, including U90926. We demonstrate here that U90926 is acting in a pro-parasitic manner in regulating intestinal epithelial cell-autonomous antiparasitic defense. Inhibition of U90926 resulted in a decreased infection burden of the parasite while overexpression of U90926 showed an increase in infection burden in cultured murine intestinal epithelial cells. Induction of U90926 suppressed transcription of epithelial defense genes involved in controlling Cryptosporidium infection through epigenetic mechanisms. Specifically, transcription of Aebp1, which encodes the Aebp1 protein, a potent modulator of inflammation and NF-κB signaling, was suppressed by U90926. Gain- or loss-of-function of Aebp1 in the host's epithelial cells caused reciprocal alterations in the infection burden of the parasite. Interestingly, Cryptosporidium carries the Cryptosporidium virus 1 (CSpV1), a double-stranded (ds) RNA virus coding two dsRNA fragments, CSpV1-dsRdRp and CSpV1-dsCA. Both CSpV1-dsRdRp and CSpV1-dsCA can be delivered into infected cells as previously reported. We found that cells transfected with in vitro transcribed CSpV1-dsCA or CSpV1-dsRdRp displayed an increased level of U90926, suggesting that CSpV1 is involved in the upregulation of U90926 during Cryptosporidium infection. Our study highlights a new strategy by Cryptosporidium to hijack a host lncRNA to suppress epithelial cell-autonomous antiparasitic defense and allow for a robust infection.

Remediation of Thirdhand Tobacco Smoke with Ozone: Probing Deep Reservoirs in Carpets.

We assessed the efficacy of ozonation as an indoor remediation strategy by evaluating how a carpet serves as a sink and long-term source of thirdhand tobacco smoke (THS) while protecting contaminants absorbed in deep reservoirs by scavenging ozone. Specimens from unused carpet that was exposed to smoke in the lab ("fresh THS") and contaminated carpets retrieved from smokers' homes ("aged THS") were treated with 1000 ppb ozone in bench-scale tests. Nicotine was partially removed from fresh THS specimens by volatilization and oxidation, but it was not significantly eliminated from aged THS samples. By contrast, most of the 24 polycyclic aromatic hydrocarbons detected in both samples were partially removed by ozone. One of the home-aged carpets was installed in an 18 m3 room-sized chamber, where its nicotine emission rate was 950 ng day-1 m-2. In a typical home, such daily emissions could amount to a non-negligible fraction of the nicotine released by smoking one cigarette. The operation of a commercial ozone generator for a total duration of 156 min, reaching concentrations up to 10,000 ppb, did not significantly reduce the carpet nicotine loading (26-122 mg m-2). Ozone reacted primarily with carpet fibers, rather than with THS, leading to short-term emissions of aldehydes and aerosol particles. Hence, by being absorbed deeply into carpet fibers, THS constituents can be partially shielded from ozonation.

The Complexity of Interferon Signaling in Host Defense against Protozoan Parasite Infection.

Protozoan parasites, such as Plasmodium, Leishmania, Toxoplasma, Cryptosporidium, and Trypanosoma, are causative agents of health-threatening diseases in both humans and animals, leading to significant health risks and socioeconomic losses globally. The development of effective therapeutic and prevention strategies for protozoan-caused diseases requires a full understanding of the pathogenesis and protective events occurring in infected hosts. Interferons (IFNs) are a family of cytokines with diverse biological effects in host antimicrobial defense and disease pathogenesis, including protozoan parasite infection. Type II IFN (IFN-γ) has been widely recognized as the essential defense cytokine in intracellular protozoan parasite infection, whereas recent studies also revealed the production and distinct function of type I and III IFNs in host defense against these parasites. Decoding the complex network of the IFN family in host-parasite interaction is critical for exploring potential new therapeutic strategies against intracellular protozoan parasite infection. Here, we review the complex effects of IFNs on the host defense against intracellular protozoan parasites and the crosstalk between distinct types of IFN signaling during infections.

TKIs beyond immunotherapy predict improved survival in advanced HCC.

PURPOSE: For patients with advanced HCC, predictors of immunotherapy response are scarce, and the benefits of tyrosine kinase inhibitor (TKI) treatment after immunotherapy are unclear. We explored whether clinical features, such as target lesion response, immune-mediated toxicity, or subsequent TKI therapy predict immunotherapy response. METHODS: We retrospectively studied 77 patients with advanced HCC receiving immunotherapy. Patient characteristics and outcomes were assessed using various statistical methods, including the log-rank test and Kaplan-Meier methods. Cox proportional hazard modeling was used for multivariable survival analysis. RESULTS: For all patients, median overall survival (mOS) was 13 months (95% CI 8-19), and median progression-free survival (mPFS) was 6 months (95% CI 4-10). Patients with partial response (PR) and stable disease (SD) compared to progressive disease (PD) had prolonged mPFS (27 vs. 5 vs. 1 month(s), p < 0.0001) and mOS (not met vs. 11 vs. 3 months, p < 0.0001). Patients with vs. without immune-mediated toxicities trended towards longer mPFS (9 vs. 4 months p = 0.133) and mOS (17 vs. 9 months; p = 0.095). Patients who did vs. did not receive a tyrosine kinase inhibitor (TKI) after immunotherapy had a significantly improved mOS (19 vs. 5 months, p = 0.0024)). Based on multivariate modeling, the hazard ratio (HR) of overall survival (OS) of patients receiving TKI vs. no TKI was 0.412 (p = 0.0043). CONCLUSION: We show that disease control predicts prolonged mOS and mPFS. Furthermore, TKI therapy administered after immunotherapy predicts prolonged mOS in patients with advanced HCC.

A hospital at home case report: Prolonged amphotericin B therapy via elastomeric pump.

PURPOSE: Hospital at home is an alternative means of providing inpatient care for a patient requiring prolonged liposomal amphotericin B therapy. SUMMARY: Hospital at home is a unique care model that allows patients to receive inpatient hospital care within the comfort of their home and can be seen as an alternative care site for patients with complex treatment regimens that may require prolonged hospitalization. Hospital systems have increasingly begun incorporating hospital at home programs into their inpatient service lines. We present the case of a patient with disseminated histoplasmosis requiring a prolonged course of intravenous liposomal amphotericin B therapy. Because of the complex administration and stability of this medication, care is often provided in an inpatient setting. The Vanderbilt University Medical Center Hospital at Home team was able to coordinate resources and services to allow for this patient to receive acute hospital care at home and continue to receive amphotericin B infusion. CONCLUSION: This experience spotlights how hospital at home can be considered for patients requiring ongoing inpatient care for prolonged intravenous treatment courses.

The Role of Immunotherapy in Pancreatic Cancer.

Pancreatic adenocarcinoma remains one of the most lethal cancers globally, with a significant need for improved therapeutic options. While the recent breakthroughs of immunotherapy through checkpoint inhibitors have dramatically changed treatment paradigms in other malignancies based on considerable survival benefits, this is not so for pancreatic cancer. Chemotherapies with modest benefits are still the cornerstone of advanced pancreatic cancer treatment. Pancreatic cancers are inherently immune-cold tumors and have been largely refractory to immunotherapies in clinical trials. Understanding and overcoming the current failures of immunotherapy through elucidating resistance mechanisms and developing novel therapeutic approaches are essential to harnessing the potential durable benefits of immune-modulating therapy in pancreatic cancer patients.

Soft collar for acute cervical spine injury immobilisation -patient experiences and outcomes: A single centre mixed methods study.

BACKGROUND: Cervical collars are used as standard care for neck immobilisation after cervical spine injury. Although evidence for the most effective type of collar is lacking, there is evidence regarding adverse patient outcomes when managed in a semi or rigid collar. In response to the evidence of complications and adverse effects when using a hard collar, a large Australian adult trauma hospital that specializes in spinal care, changed its policy from hard to soft collars when managing acute cervical spine injury. OBJECTIVE: The aim of this study was to investigate patients' experiences and outcomes when wearing a soft collar for acute cervical spine injury management in hospital. METHOD: A single centre mixed method sequential study design was used. RESULTS: Medical records from 136 patients were examined and no adverse events resulting from collar use were recorded. Interviews with 20 patients revealed that they understood the value of wearing a soft collar. The soft collars were considered supportive and well tolerated, with good adherence to recommendations for use. CONCLUSIONS: Understanding the patients' experiences informs better care management. This study suggests that soft collars are well tolerated, do not result in pressure injuries or other adverse events and are suitable for managing acute cervical spine injury.