Impact of a pharmacist-led oral chemotherapy monitoring clinic at the South Texas Veterans Health Care System.

As cancer treatments shift from traditional intravenous chemotherapy to inclusion of oral oncolytics, there is a critical need for structured oral chemotherapy monitoring and follow-up programs. To provide continuous care and minimize clinical gaps to Veterans receiving oral chemotherapy, the hematology/oncology clinical pharmacy practitioners designed and initiated a pilot, pharmacist-driven, Oral Chemotherapy Monitoring Clinic at the South Texas Veterans Health Care System supported by an oral chemotherapy certified pharmacy technician. A retrospective evaluation of patients receiving oral chemotherapy at the South Texas Veterans Health Care System was performed before (Phase I) and after (Phase II) pilot implementation to assess the impact of an Oral Chemotherapy Monitoring Clinic on compliance with drug-specific lab and symptom monitoring. Complete monitoring was defined as 100% of recommended labs and symptoms assessed per cycle, partial monitoring was <100%, but >0%, and incomplete monitoring was defined as 0%. The primary outcome assessed the proportion of patients receiving complete monitoring in Phase II compared to Phase I. Most patients were male (94%), with a median age of 72 years. The most common oncolytic was abiraterone acetate. Overall, drug-specific baseline and follow-up laboratory and symptom monitoring was complete at a statistically significantly higher rate in Phase II compared with Phase I (p-value < 0.01). A significantly higher portion of patients in the Phase II cohort had a clinical pharmacy practitioner intervention (44% vs. 90%; p < 0.01). Monitoring for Veterans receiving oral chemotherapy was optimized with clinical pharmacy practitioner and certified pharmacy technician involvement while simultaneously alleviating Oncologist and nurse oral chemotherapy workload.

National practice patterns in the use of endoscopic ultrasound biopsy for resectable Pancreatic Neuroendocrine Tumors: Insights into the role of DOTATATE PET/CT in diagnosis.

INTRODUCTION: Pancreatic neuroendocrine tumors (PNETs) are typically diagnosed using endoscopic ultrasound-guided (EUS) biopsy, which can be associated with complications. Since 2016, DOTATATE PET/CT has emerged as an effective tool to localize and stage PNETs. METHODS: Patients with PNETs who underwent R0 resections were identified from the 2004-2019 National Cancer Database PUF. Joinpoint regression and multivariable logistic regression were used to analyze trends in the use of biopsy. RESULTS: Of 16,746 R0 resected PNET patients, 44 â€‹% underwent diagnostic biopsy. Joinpoint regression showed a significant increase in the use of biopsy from 2004 to 2019 (APC 1.80, p â€‹< â€‹0.001). A higher percentage of patients diagnosed after DOTATATE approval underwent biopsy compared to those diagnosed before (48 â€‹% vs. 42 â€‹%, p â€‹< â€‹0.001). Adjusted analysis showed diagnosis after 2016 was associated with increased odds of biopsy (OR â€‹= â€‹1.67, p â€‹< â€‹0.001). CONCLUSIONS: Despite technologic advancement with DOTATATE PET/CT, there has been a significant increase in the proportion of resectable PNETs undergoing preoperative biopsy.

Characterization of the Pristionchus pacificus "epigenetic toolkit" reveals the evolutionary loss of the histone methyltransferase complex PRC2.

Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation-or lack thereof-of developmental networks, the conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system of plasticity and epigenetic regulation as it exhibits a bacterivorous or omnivorous morph depending on its environment. Here, we determined the "epigenetic toolkit" available to P. pacificus as a resource for future functional work on plasticity, and as a comparison with Caenorhabditis elegans to investigate the conservation of epigenetic mechanisms. Broadly, we observed a similar cast of genes with putative epigenetic function between C. elegans and P. pacificus. However, we also found striking differences. Most notably, the histone methyltransferase complex PRC2 appears to be missing in P. pacificus. We described the deletion/pseudogenization of the PRC2 genes mes-2 and mes-6 and concluded that both were lost in the last common ancestor of P. pacificus and a related species P. arcanus. Interestingly, we observed the enzymatic product of PRC2 (H3K27me3) by mass spectrometry and immunofluorescence, suggesting that a currently unknown methyltransferase has been co-opted for heterochromatin silencing. Altogether, we have provided an inventory of epigenetic genes in P. pacificus to compare with C. elegans. This inventory will enable reverse-genetic experiments related to plasticity and has revealed the first loss of PRC2 in a multicellular organism.

An allelic series at the EDNRB2 locus controls diverse piebalding patterns in the domestic pigeon.

Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive success, and survival. The domestic pigeon (Columba livia) is an exceptional model for understanding the genetic changes that give rise to diverse pigment patterns, as selective breeding has given rise to hundreds of breeds with extensive variation in plumage color and pattern. Here, we map the genetic architecture of a suite of pigmentation phenotypes known as piebalding. Piebalding is characterized by patches of pigmented and non-pigmented feathers, and these plumage patterns are often breed-specific and stable across generations. Using a combination of quantitative trait locus mapping in F2 laboratory crosses and genome-wide association analysis, we identify a locus associated with piebalding across many pigeon breeds. This shared locus harbors a candidate gene, EDNRB2, that is a known regulator of pigment cell migration, proliferation, and survival. We discover multiple distinct haplotypes at the EDNRB2 locus in piebald pigeons, which include a mix of protein-coding, noncoding, and structural variants that are associated with depigmentation in specific plumage regions. These results identify a role for EDNRB2 in pigment patterning in the domestic pigeon, and highlight how repeated selection at a single locus can generate a diverse array of stable and heritable pigment patterns.

Virtual psychoeducation for improvement of pain catastrophizing in pediatric presurgical patients and caregivers: a proof-of-concept study.

PURPOSE: Pain catastrophizing (PC) is the tendency to magnify the threat value of pain sensations and is associated with greater postsurgical pain intensity, functional disability, and pain chronicity. Higher parental PC predicts higher chronic postsurgical pain in youth. Treating PC in caregivers and youth prior to surgery may improve recovery and surgical outcomes. We developed and evaluated a psychoeducational workshop addressing PC for presurgical youth and their parents/caregivers. We hypothesized that parent/caregiver and youth PC scores would decrease over time. We also explored preintervention levels of youth anxiety and depression as moderators of outcome. METHODS: Youth (n = 43) and caregivers (n = 41) attended a virtual, group-based single-session intervention (SSI). Single-session intervention content addressed pain neuroscience, PC, and adaptive coping strategies for managing pain and PC drawn from cognitive-behavioural, acceptance and commitment, and dialectical behaviour therapy approaches. Participants completed questionnaires assessing PC at preintervention, postintervention, and two weeks postsurgery. Youth mood and anxiety were assessed at preintervention. RESULTS: Caregiver PC scores decreased from pre- to postintervention (P = 0.006), and this was maintained at postsurgery (P = 0.002). Youth PC scores decreased from preintervention to postsurgery, but only for those with higher preintervention anxiety (P = 0.01). CONCLUSION: Our results provide proof-of-concept support for a virtual SSI targeting caregivers and youth PC during the perioperative period. The present findings highlight the possible need to screen presurgical candidates for symptoms of anxiety. Replication with larger and more diverse samples, and a more robust design are warranted.

RéSUMé: OBJECTIF: Le terme de dramatisation de la douleur décrit la tendance à amplifier la valeur de menace des sensations de douleur et est associée à une plus grande intensité de la douleur postopératoire, à une incapacité fonctionnelle et à une chronicité de la douleur. Une dramatisation parentale plus élevée de la douleur prédit une douleur postopératoire chronique plus élevée chez les jeunes. Le traitement de la dramatisation de la douleur chez les soignant·es et les jeunes avant la chirurgie peut améliorer le rétablissement et les devenirs chirurgicaux. Nous avons mis au point et évalué un atelier psychoéducatif sur la dramatisation de la douleur destiné aux jeunes en période préchirurgicale et à leurs parents/soignant·es. Nous avons émis l'hypothèse que les scores de dramatisation de la douleur des parents/soignant·es et des jeunes diminueraient avec le temps. Nous avons également exploré les niveaux d'anxiété et de dépression des jeunes avant l'intervention en tant qu'éléments modérateurs des résultats. MéTHODE: Des jeunes (n = 43) et les personnes en prenant soin (n = 41) ont participé à une seule intervention virtuelle en groupe. Le contenu de l'intervention unique portait sur les neurosciences de la douleur, la dramatisation de la douleur et les stratégies d'adaptation pour la prise en charge de la douleur et la dramatisation de la douleur tirées des approches cognitivo-comportementales, d'acceptation et d'engagement, et de thérapie comportementale dialectique. Les participant·es ont rempli des questionnaires évaluant la dramatisation de la douleur avant l'intervention, après l'intervention et deux semaines après la chirurgie. L'humeur et l'anxiété des jeunes ont été évaluées avant l'intervention. RéSULTATS: Les scores de dramatisation de la douleur des soignant·es ont diminué de la période précédant à la période suivant l'intervention (P = 0,006), et cela s'est maintenu après la chirurgie (P = 0,002). Les scores de dramatisation de la douleur des jeunes ont diminué de la période précédant l'intervention à la période postchirurgie, mais seulement chez les jeunes présentant une anxiété pré-intervention plus élevée (P = 0,01). CONCLUSION: Nos résultats appuient la preuve de concept pour une intervention virtuelle unique ciblant la dramatisation de la douleur chez les soignant·es et les jeunes en période périopératoire. Ces résultats soulignent la nécessité potentielle de dépister les symptômes d'anxiété chez les candidat·es avant la chirurgie. La réplication avec des échantillons plus grands et plus diversifiés et une conception plus robuste est justifiée.

Survival and quality-of-life outcomes in early-stage NSCLC patients: a literature review of real-world evidence.

Aim: Assess the long-term survival and quality-of-life outcomes in early-stage NSCLC (eNSCLC) patients. Methods: Review of long-term survival and quality-of-life after curative treatment in eNSCLC patients in observational studies. Results: Disease-free proportion decreased in stage III vs stage I patients. Recurrence-free proportion decreased with age and disease stage. Advanced stage and vascular invasion increased risk of late recurrence. Conditional 5-year relative survival rates did not exceed 87%, indicating higher mortality in eNSCLC survivors. Lower conditional survival rates and relative survival rates were associated with older age and advanced disease. Survivors of eNSCLC had poorer physical quality-of-life. Conclusion: Despite curative-intent therapy, survivors of eNSCLC still face significant risks of recurrence, excess mortality, and diminished quality-of-life.

Early-stage NSCLC (eNSCLC) encompassing stage I and II, and resectable stage III disease is initially managed with curative-intent surgery and adjuvant chemotherapy to reduce the risk of recurrence. However, understanding the true curative potential and long-term outcomes is crucial for optimal clinical management. A literature review was conducted to identify observational studies describing long-term survival and quality-of-life outcomes following curative intent therapy in patients with eNSCLC. The proportion of patients who remained disease-free over time (without recurrence or death) statistically significantly decreased in patients with stage III disease compared with stage I disease. Similarly, the proportion of patients who remained recurrence-free over time decreased with increasing age and disease stage. A considerable risk of late recurrence (recurrence five or more years following resection) remained, increasing with advanced stage and tumor characteristics such as vascular invasion. Conditional 5-year relative survival rates did not exceed 87% in any study, indicating higher rates of all-cause mortality in long-term survivors of eNSCLC compared with members of the general population of the same age. Lower conditional 5-year relative survival rates, and 5 and 10-year relative survival rates were associated with older age and higher pathologic stage. Compared with the general population, survivors of eNSCLC reported significantly poorer physical quality-of-life, suggesting that symptoms persist after treatment. Overall, real-world evidence suggests that after standard curative-intent therapy, survivors of eNSCLC may not be considered fully cured, indicating a need for more effective adjuvant treatment in addition to the current standard of care.

An allelic series at the EDNRB2 locus controls diverse piebalding patterns in the domestic pigeon.

Variation in pigment patterns within and among vertebrate species reflects underlying changes in cell migration and function that can impact health, reproductive success, and survival. The domestic pigeon (Columba livia) is an exceptional model for understanding the genetic changes that give rise to diverse pigment patterns, as selective breeding has given rise to hundreds of breeds with extensive variation in plumage color and pattern. Here, we map the genetic architecture of a suite of pigmentation phenotypes known as piebalding. Piebalding is characterized by patches of pigmented and non-pigmented feathers, and these plumage patterns are often breed-specific and stable across generations. Using a combination of quantitative trait locus mapping in F2 laboratory crosses and genome-wide association analysis, we identify a locus associated with piebalding across many pigeon breeds. This shared locus harbors a candidate gene, EDNRB2, that is a known regulator of pigment cell migration, proliferation, and survival. We discover multiple distinct haplotypes at the EDNRB2 locus in piebald pigeons, which include a mix of protein-coding, noncoding, and structural variants that are associated with depigmentation in specific plumage regions. These results identify a role for EDNRB2 in pigment patterning in the domestic pigeon, and highlight how repeated selection at a single locus can generate a diverse array of stable and heritable pigment patterns.

Nutrient Limitation Mimics Artemisinin Tolerance in Malaria.

Mounting evidence demonstrates that nutritional environment can alter pathogen drug sensitivity. While the rich media used for in vitro culture contains supraphysiological nutrient concentrations, pathogens encounter a relatively restrictive environment in vivo. We assessed the effect of nutrient limitation on the protozoan parasite that causes malaria and demonstrated that short-term growth under physiologically relevant mild nutrient stress (or "metabolic priming") triggers increased tolerance of a potent antimalarial drug. We observed beneficial effects using both short-term survival assays and longer-term proliferation studies, where metabolic priming increases parasite survival to a level previously defined as resistant (>1% survival). We performed these assessments by either decreasing single nutrients that have distinct roles in metabolism or using a media formulation that simulates the human plasma environment. We determined that priming-induced tolerance was restricted to parasites that had newly invaded the host red blood cell, but the effect was not dependent on genetic background. The molecular mechanisms of this intrinsic effect mimic aspects of genetic tolerance, including translational repression and protein export. This finding suggests that regardless of the impact on survival rates, environmental stress could stimulate changes that ultimately directly contribute to drug tolerance. Because metabolic stress is likely to occur more frequently in vivo compared to the stable in vitro environment, priming-induced drug tolerance has ramifications for how in vitro results translate to in vivo studies. Improving our understanding of how pathogens adjust their metabolism to impact survival of current and future drugs is an important avenue of research to slow the evolution of resistance. IMPORTANCE There is a dire need for effective treatments against microbial pathogens. Yet, the continuing emergence of drug resistance necessitates a deeper knowledge of how pathogens respond to treatments. We have long appreciated the contribution of genetic evolution to drug resistance, but transient metabolic changes that arise in response to environmental factors are less recognized. Here, we demonstrate that short-term growth of malaria parasites in a nutrient-limiting environment triggers cellular changes that lead to better survival of drug treatment. We found that these strategies are similar to those employed by drug-tolerant parasites, which suggests that starvation "primes" parasites to survive and potentially evolve resistance. Since the environment of the human host is relatively nutrient restrictive compared to growth conditions in standard laboratory culture, this discovery highlights the important connections among nutrient levels, protective cellular pathways, and resistance evolution.

Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation.

The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is unknown. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution-specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings.

Treatment patterns and survival of patients with locoregional recurrence in early-stage NSCLC: a literature review of real-world evidence.

Approximately 10-50% of patients treated for early-stage (I-III), resectable non-small cell lung cancer (eNSCLC) will develop locoregional recurrence. There is a lack of prospective trials evaluating optimal post-surgery follow-up for this patient population, and treatment guidelines recommend salvage therapies such as surgery, local ablative therapy, and (chemo)radiotherapy. A literature review was conducted according to pre-defined criteria to identify observational studies describing treatment patterns and survival outcomes in patients with eNSCLC who experienced locoregional recurrence. Results showed that, in real-world clinical practice, around 80% of patients with locoregional recurrence underwent any form of active treatment. The most frequently administered treatments were chemotherapy (35.7%), chemoradiotherapy (31.2%), radiotherapy (20.3%), and surgery alone (12.8%). Chemoradiotherapy was associated with improved PFS and OS compared with radiotherapy, while no statistically significant survival benefits were observed for patients receiving surgery in addition to these treatments. The overall survival of patients following treatment for locoregional recurrence was generally poor, and the proportion of patients who experienced any form of post-treatment re-recurrence ranged from 35 to 72%. These findings highlight the need to develop more effective treatment strategies for locoregional recurrence, including preventative treatments, and strategies to improve the survival outcomes of those who do develop locoregional recurrence.

Longitudinal Serological Surveillance for COVID-19 Antibodies after Infection and Vaccination.

The impact of COVID-19 is still felt around the world, and more information is needed regarding infection risk, vaccination responses, and the timing of booster vaccinations. We aimed to evaluate the association of vaccination with closely followed, longitudinal antibody titers and COVID-19 infection events. We conducted a natural history study in a convenience cohort in an ambulatory research unit. We measured anti-nucleocapsid and anti-spike antibody levels every 3 months for 1 year and captured weekly reports of medically confirmed COVID-19 infections. We analyzed the association of antibody titers with infection events as well as the association of the decision to receive vaccination with social, medical, and behavioral characteristics. 629 subjects were followed for 1 year, and 82.8% of them were vaccinated. 90 cases of medically confirmed COVID-19 infection were reported. Notable findings from our study include: an association of vaccination choice with social distancing, a qualitatively different anti-spike response in participants receiving the Ad26.COV2.S vaccine compared to those receiving mRNA vaccines, a muted anti-nucleocapsid response in breakthrough infections compared to unvaccinated infections, and the identification of a low antibody titer threshold associated with the risk of breakthrough infections. We conclude that, in a real-life setting, vaccination and social distancing behavior are positively correlated. The observed effect of vaccination in preventing COVID-19 may include both vaccine-mediated protection and the associated more cautious behavior exhibited by vaccinated individuals. In addition, we identified an antibody threshold associated with breakthrough infections in mRNA vaccinees, and this threshold may be used in medical decision-making regarding the timing of booster vaccinations. Therefore, our data may aid in the refinement of vaccination strategies during the COVID-19 pandemic. IMPORTANCE The COVID-19 pandemic continues to impact societies and health care systems worldwide and is continuously evolving. Immunity via vaccination or prior infection is the first and most important line of defense against COVID-19. We still do not have complete information on how vaccination-induced or infection-induced antibody titers change with time or on how this information can be used to guide decisions regarding booster vaccination. In a longitudinal observational study of a cohort of 629 subjects, 82% of breakthrough infections in vaccinees occurred when their anti-spike antibody titers were below 3,000 AU/mL. Our findings suggest that there may be an antibody threshold associated with breakthrough infections and that this threshold could possibly be used to aid decision-making regarding booster vaccinations. In addition, the use of anti-nucleocapsid antibody tiers may significantly underestimate the prevalence of breakthrough infections in vaccinated individuals.

Mapping odorant sensitivities reveals a sparse but structured representation of olfactory chemical space by sensory input to the mouse olfactory bulb.

In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive. Using high-throughput odorant delivery and ultrasensitive imaging of sensory inputs, we imaged responses to 185 odorants presented at concentrations determined to activate only one or a few glomeruli across the dorsal olfactory bulb. The resulting datasets defined the tuning properties of glomeruli - and, by inference, their cognate odorant receptors - in a low-concentration regime, and yielded consensus maps of glomerular sensitivity across a wide range of chemical space. Glomeruli were extremely narrowly tuned, with ~25% responding to only one odorant, and extremely sensitive, responding to their effective odorants at sub-picomolar to nanomolar concentrations. Such narrow tuning in this concentration regime allowed for reliable functional identification of many glomeruli based on a single diagnostic odorant. At the same time, the response spectra of glomeruli responding to multiple odorants was best predicted by straightforward odorant structural features, and glomeruli sensitive to distinct odorants with common structural features were spatially clustered. These results define an underlying structure to the primary representation of sensory space by the mouse olfactory system.

The Launch of A Girl's First Period Study: Demystifying Reproductive Hormone Profiles in Adolescent Girls.

Limited data exist on the reproductive hormone dynamics that govern the transition from menarche to the establishment of the mature ovulatory cycles of a fertile young woman. It is also unclear how environmental and lifestyle factors could modulate this transition in contemporary girls. Here, we introduce A Girl's First Period Study, an ambitious longitudinal study aimed at charting the early post-menarchal course of a cohort of healthy girls in the Triangle region of North Carolina.

Single-cell sequencing of the small and AT-skewed genome of malaria parasites.

Single-cell genomics is a rapidly advancing field; however, most techniques are designed for mammalian cells. We present a single-cell sequencing pipeline for an intracellular parasite, Plasmodium falciparum, with a small genome of extreme base content. Through optimization of a quasi-linear amplification method, we target the parasite genome over contaminants and generate coverage levels allowing detection of minor genetic variants. This work, as well as efforts that build on these findings, will enable detection of parasite heterogeneity contributing to P. falciparum adaptation. Furthermore, this study provides a framework for optimizing single-cell amplification and variant analysis in challenging genomes.

Self-aligned sequential lateral field non-uniformities over channel depth for high throughput dielectrophoretic cell deflection.

Dielectrophoresis (DEP) enables the separation of cells based on subtle subcellular phenotypic differences by controlling the frequency of the applied field. However, current electrode-based geometries extend over a limited depth of the sample channel, thereby reducing the throughput of the manipulated sample (sub-µL min-1 flow rates and <105 cells per mL). We present a flow through device with self-aligned sequential field non-uniformities extending laterally across the sample channel width (100 µm) that are created by metal patterned over the entire depth (50 µm) of the sample channel sidewall using a single lithography step. This enables single-cell streamlines to undergo progressive DEP deflection with minimal dependence on the cell starting position, its orientation versus the field and intercellular interactions. Phenotype-specific cell separation is validated (>µL min-1 flow and >106 cells per mL) using heterogeneous samples of healthy and glutaraldehyde-fixed red blood cells, with single-cell impedance cytometry showing that the DEP collected fractions are intact and exhibit electrical opacity differences consistent with their capacitance-based DEP crossover frequency. This geometry can address the vision of an "all electric" selective cell isolation and cytometry system for quantifying phenotypic heterogeneity of cellular systems.

Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality. AECOPD treatment remains limited. High molecular weight hyaluronan (HMW-HA) is a glycosaminoglycan sugar, which is a physiological constituent of the lung extracellular matrix and has notable anti-inflammatory and hydrating properties. RESEARCH QUESTION: We hypothesized that inhaled HMW-HA will improve outcomes in AECOPD. METHODS: We conducted a single center, randomized, placebo-controlled, double-blind study to investigate the effect of inhaled HMW-HA in patients with severe AECOPD necessitating non-invasive positive-pressure ventilation (NIPPV). Primary endpoint was time until liberation from NIPPV. RESULTS: Out of 44 screened patients, 41 were included in the study (21 for placebo and 20 for HMW-HA). Patients treated with HMW-HA had significantly shorter duration of NIPPV. HMW-HA treated patients also had lower measured peak airway pressures on the ventilator and lower systemic inflammation markers after liberation from NIPPV. In vitro testing showed that HMW-HA significantly improved mucociliary transport in air-liquid interface cultures of primary bronchial cells from COPD patients and healthy primary cells exposed to cigarette smoke extract. INTERPRETATION: Inhaled HMW-HA shortens the duration of respiratory failure and need for non-invasive ventilation in patients with AECOPD. Beneficial effects of HMW-HA on mucociliary clearance and inflammation may account for some of the effects (NCT02674880, www.clinicaltrials.gov ).

Postoperative Diaphragmatic Liver Herniation Diagnosed by Point-of-Care Ultrasound.

Point-of-care ultrasound (PoCUS) is a sensitive and specific tool in early identification of malignant pathologies in unstable patients leading to improved outcomes. Postoperative diaphragmatic rupture is rare, can be life-threatening, and is difficult to diagnose. This report describes a 62-year-old women undergoing thoracoscopic right hemidiaphragm plication with acute postoperative hemodynamic instability. Bedside PoCUS identified hepatic herniation into the thorax causing cardiac compression and lateral displacement, which lead to expedited imaging and surgical reexploration.

From Circulation to Cultivation: Plasmodium In Vivo versus In Vitro.

Research on Plasmodium parasites has driven breakthroughs in reducing malaria morbidity and mortality. Experimental analysis of in vivo/ex vivo versus in vitro samples serve unique roles in Plasmodium research. However, these distinctly different environments lead to discordant biology between parasites in host circulation and those under laboratory cultivation. Here, we review how in vitro factors, such as nutrient levels and physical forces, differ from those in the human host and the resulting implications for parasite growth, survival, and virulence. Additionally, we discuss the current utility of direct-from-host methodologies, which avoid the potentially confounding effects of in vitro cultivation. Finally, we make the case for methodological improvements that will drive research progress of physiologically relevant phenotypes.