Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Introducing a novel respiratory function monitor for neonatal resuscitation training.

Background: A respiratory function monitor (RFM) gives immediate feedback, allowing clinicians to adjust face mask ventilation to correct leak or inappropriate tidal volumes. We audited the satisfaction of clinicians with a neonatal resuscitation training package, incorporating a novel RFM. Methods: This was a mixed-methods study conducted at The Royal Women's Hospital, Melbourne, Australia. Clinicians were approached to complete a neonatal resuscitation training session. Participants watched a training video, then provided ventilation to term and preterm manikins first without, and then with, the RFM. Clinicians completed a survey after the session and undertook a follow-up session three months later. The primary outcome was participant satisfaction with the RFM. Secondary outcomes included participants' self-assessment of face mask leak and tidal volumes when using the RFM. Results: Fifty clinicians completed both the initial and follow-up session. Participants reported high levels of satisfaction with the RFM for both term and preterm manikins: on a scale from 0, meaning "not at all", and 100, meaning "yes, for all resuscitations", the median response (interquartile range, IQR) was 82 (74-94) vs 81.5 (69-94.5). Levels of satisfaction were similar for less experienced and more experienced clinicians: median (IQR) 83 (77-93) vs 81 (71.5-95) respectively. When using the monitor, clinicians accurately self-assessed that they achieved leak below 30% and tidal volumes within the target range at least 80% of the time. Conclusion: Clinicians of all experience levels had a high level of satisfaction with a training package including a novel RFM.

One-year Thyroglobulin Levels as a Predictive Measure for Recurrence and Need for Continued Surveillance in Treated Differentiated Thyroid Cancer.

PURPOSE: Patients with differentiated thyroid cancer (DTC) undergo posttreatment surveillance for several years. We aim to better define an excellent response to therapy using thyroglobulin (TG) and thyroglobulin antibody (TGab) levels at 1-year to tailor appropriate length of surveillance. METHODS: Patients with DTC who underwent surgical treatment with or without adjuvant radioiodine therapy were followed with standard American Thyroid Association surveillance. TG and TGab levels at 1-year posttreatment were used to define 3 cohorts: undetectable TG (<0.5 ng/mL), detectable TG (≥0.5 ng/mL), and positive TGab (>1 IU/mL). The rates of structural recurrence and the trends of TG and TGab were compared. RESULTS: Of the 268 study patients at 1-year, 210 (78%) had undetectable TG, 29 (11%) had detectable TG, and 29 (11%) had positive TGab. The overall structural recurrence rate was 18/268 (7%): undetectable TG at 1 year, 3/210 (1%), detectable TG at 1-year, 11/29 (38%), and positive TGab at 1-year, 4/29 (13%). At the last follow-up, 196/210 (93%) patients with undetectable TG at 1-year continued to have undetectable TG levels. Regarding patients with detectable TG at 1-year, in 11/29 (38%), detectable TG was converted to undetectable TG at the last follow-up without additional treatments. Of those with positive TGab at 1 year, 6/29 (21%) had resolution of TGab and undetectable TG levels at the last follow-up without additional treatments. CONCLUSION: One year after treatment of DTC, TG levels <0.5 ng/mL, in the absence of TGab, are associated with an exceedingly low risk of recurrence suggesting that further surveillance may not be warranted.

The Impact of Bilateral Stone Disease on Patients' Disease Progression and Health-Related Quality of Life.

Purpose: Patients with recurring kidney stone events can expect significant morbidity and functional impairment. Few studies have evaluated the effect of bilateral kidney stones on disease progression and quality of life. We wanted to determine the association of bilateral stone disease on age of onset, and the impact on number of stone events and individual kidney stone disease-specific health-related quality of life (HRQOL) by analyzing the validated and prospectively collected Wisconsin Stone Quality of Life (WISQOL) database. Materials and Methods: We studied 2906 stone patients from 16 centers in North America after having completed the WISQOL questionnaire from 2014 to 2019. Kidney stone formers were assessed if kidney stones were bilateral or unilateral on imaging. Analysis with a chi-square test compared categorical variables. Bilateral kidney stone disease and its impact on HRQOL were evaluated through a multivariable linear regression model. Results: Of 2906 kidney stone formers, 1340 had unilateral kidney stones and 1566 had bilateral kidney stones. We observed more frequently that patients with bilateral stones had an increased number of depression/anxiety symptoms, renal tubular acidosis, and rheumatoid arthritis (all p < 0.05). Patients with bilateral stones had a younger mean (standard deviation [SD]) age of kidney stone disease onset (37.2 ± 15.8 vs 46.4 ± 15.9 years of age, p < 0.001). Bilateral kidney stone formers had a higher mean (SD) number of stone events (11.3 ± 21.8) than unilateral kidney stone formers (3.0 ± 5.1) (p < 0.001). Within our multivariable analysis, we found that HRQOL was negatively affected by the presence of bilateral stones for kidney stone patients (ß = -11.2 [confidence interval: -19.5 to -3.0] points, p < 0.05). Conclusions: Bilateral kidney stone formers had a younger age of kidney stone disease onset and a higher number of stone events compared with unilateral kidney stone disease formers. The presence of bilateral kidney stone disease negatively impacted HRQOL.

High-sensitivity electronic Stark spectrometer featuring a laser-driven light source.

We report developmental details of a high-sensitivity Stark absorption spectrometer featuring a laser-driven light source. The light source exhibits intensity fluctuations of ∼0.3% over timescales ranging from 1 min to 12 h, minimal drift (≤0.1%/h), and very little 1/f noise at frequencies greater than 200 Hz, which are comparable to or better than an arc-driven light source. Additional features of the spectrometer include balanced detection with multiplex sampling, which yielded lower noise in A, and constant wavelength or wavenumber (energy) spectral bandpass modes. We achieve noise amplitudes of ∼7 × 10-4 and ∼6 × 10-6 in measurements of single A and ΔA spectra (with 92 data points) taking ∼7 and ∼19 min, respectively.

High-'n'-dry? A comparison of cannabis and alcohol use in drivers presenting to hospital after a vehicular collision.

DESIGN: This was a prospective observational study. BACKGROUND AND AIMS: The characteristics of cannabis-involved motor vehicle collisions are poorly understood. This study of injured drivers identifies demographic and collision characteristics associated with high tetrahydrocannabinol (THC) concentrations. SETTING: The study was conducted in 15 Canadian trauma centres between January 2018 and December 2021. CASES: The cases (n = 6956) comprised injured drivers who required blood testing as part of routine trauma care. MEASUREMENTS: We quantified whole blood THC and blood alcohol concentration (BAC) and recorded driver sex, age and postal code, time of crash, crash type and injury severity. We defined three driver groups: high THC (THC ≥ 5 ng/ml and BAC = 0), high alcohol (BAC ≥ 0.08% and THC = 0) and THC/BAC-negative (THC = 0 = BAC). We used logistic regression techniques to identify factors associated with group membership. FINDINGS: Most injured drivers (70.2%) were THC/BAC-negative; 1274 (18.3%) had THC > 0, including 186 (2.7%) in the high THC group; 1161 (16.7%) had BAC > 0, including 606 (8.7%) in the high BAC group. Males and drivers aged less than 45 years had higher adjusted odds of being in the high THC group (versus the THC/BAC-negative group). Importantly, 4.6% of drivers aged less than 19 years had THC ≥ 5 ng/ml, and drivers aged less than 19 years had higher unadjusted odds of being in the high THC group than drivers aged 45-54 years. Males, drivers aged 19-44 years, rural drivers, seriously injured drivers and drivers injured in single-vehicle, night-time or weekend collisions had higher adjusted odds ratios (aORs) for being in the high alcohol group (versus THC/BAC-negative). Drivers aged less than 35 or more than 65 years and drivers involved in multi-vehicle, daytime or weekday collisions had higher adjusted odds for being in the high THC group (versus the high BAC group). CONCLUSIONS: In Canada, risk factors for cannabis-related motor vehicle collisions appear to differ from those for alcohol-related motor vehicle collisions. The collision factors associated with alcohol (single-vehicle, night-time, weekend, rural, serious injury) are not associated with cannabis-related collisions. Demographic factors (young drivers, male drivers) are associated with both alcohol and cannabis-related collisions, but are more strongly associated with cannabis-related collisions.

Heterogeneous melting near the Thwaites Glacier grounding line.

Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment1-3. Because it is grounded below sea level4,5, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean6,7. Recent ice-flow acceleration2,8 and retreat of the ice front8-10 and GL11,12 indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice-ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming.

Comparison of Cost and Perioperative Outcomes Among Patients Undergoing Simple Prostatectomy and Laser Enucleation of the Prostate.

Introduction: Simple prostatectomy (SP) and laser enucleation of the prostate (LEP) are treatments for symptomatic benign prostatic hyperplasia (BPH) in men with large glands (e.g., >80 g). The decision between the two operations is often dependent on surgeon preference/experience and equipment availability. As the use of minimally invasive techniques, such as robotic-assisted simple prostatectomy, has increased for the treatment of large gland BPH, studies comparing the outcomes and cost of these modalities in a contemporary cohort are lacking. Methods: All-payer data from Healthcare Cost and Utilization Project State Databases from Florida, New York, California, and Maryland from 2016 to 2018 were used to identify adults who underwent SP or LEP for BPH. Patient demographics, facility characteristics, revisit rates, and cost of the index hospitalization were examined. Multivariable logistic and gamma generalized linear regression models were utilized to compare predictors of the operation performed, 30-day revisits, and index hospitalization cost among the two operations. Results: Of the 2032 patients in the cohort, 1067 (46.4%) underwent LEP and 965 (41.9%) underwent SP. On multivariable logistic regression analysis, SP patients were younger, had higher comorbidity scores, and were more likely to be uninsured compared with LEP patients. Thirty-day revisit rates among the operations were equivalent (odds ratio 0.89, 95% confidence interval 0.63-1.27, p = 0.05). The mean adjusted cost of the index hospital stay for LEP was significantly greater than that of SP ($7291 vs $6442, p = 0.04). However, our sub-group analysis examining high-volume centers revealed no significant differences in cost ($6184 vs $5353, p = 0.1). Conclusions: Across the four states examined, SP and LEP were performed with comparable volume and had similar rates of 30-day revisits. The SP was less expensive than LEP overall; however, among high-volume facilities, the cost of both operations was reduced, such that they were equivalent.

Epidemiology and outcomes for level 1 and 2 traumas during the first wave of COVID19 in a Canadian centre.

To determine if lockdown measures imposed during the first wave of the COVID19 pandemic affected trauma patterns, volumes, and outcomes in a western Canadian level 1 trauma center, we performed a retrospective cohort study assessing level 1 and 2 trauma patients presenting to our center during the initial COVID19 "lockdown" period (March 15-June 14, 2020) compared to a similar cohort of patients presenting during a "control" period 1 year prior (March 15-June 14, 2019). Overall, we saw a 7.8% reduction in trauma volumes during the lockdown period, and this was associated with a shorter average ED length of stay (6.2 ± 4.7 h vs. 9.7 ± 11.8 h, p = 0.003), reduced time to computed tomography (88.5 ± 68.2 min vs. 105.1 ± 65.5 min, p < 0.001), a reduction in intensive care unit admissions (11.0 ± 4.9% vs. 20.0 ± 15.5%, p = 0.001), and higher injury severity score (6.5 ± 7.6 vs. 6.2 ± 9.5, p = 0.04). Our findings suggest that lockdown measures imposed during the first wave of the COVID19 pandemic had a significant impact on trauma patients.

Largest recent impact craters on Mars: Orbital imaging and surface seismic co-investigation.

Two >130-meter-diameter impact craters formed on Mars during the later half of 2021. These are the two largest fresh impact craters discovered by the Mars Reconnaissance Orbiter since operations started 16 years ago. The impacts created two of the largest seismic events (magnitudes greater than 4) recorded by InSight during its 3-year mission. The combination of orbital imagery and seismic ground motion enables the investigation of subsurface and atmospheric energy partitioning of the impact process on a planet with a thin atmosphere and the first direct test of martian deep-interior seismic models with known event distances. The impact at 35°N excavated blocks of water ice, which is the lowest latitude at which ice has been directly observed on Mars.

Surface waves and crustal structure on Mars.

We detected surface waves from two meteorite impacts on Mars. By measuring group velocity dispersion along the impact-lander path, we obtained a direct constraint on crustal structure away from the InSight lander. The crust north of the equatorial dichotomy had a shear wave velocity of approximately 3.2 kilometers per second in the 5- to 30-kilometer depth range, with little depth variation. This implies a higher crustal density than inferred beneath the lander, suggesting either compositional differences or reduced porosity in the volcanic areas traversed by the surface waves. The lower velocities and the crustal layering observed beneath the landing site down to a 10-kilometer depth are not a global feature. Structural variations revealed by surface waves hold implications for models of the formation and thickness of the martian crust.

A call for disability health curricula in medical schools.

People with disabilities encounter significant health and health-care inequities yet disability health training in medical education remains inadequate. This Scientific Life article examines the need to integrate disability health education into medical school curricula and shares successful training examples that can serve as a framework for how to accomplish this.

Unmet need in Sierra Leone: a national oral health survey of schoolchildren.

OBJECTIVE: Sierra Leone (SL), in West Africa, with a population of over 7.5 million people has suffered the effects of a civil war previously, and more recently Ebola & Covid-19. Dental care is very limited, mostly in the capital Freetown and the private sector. No dental education is available in the country. The objective of this research was to investigate the oral health needs of schoolchildren at key ages, to inform future action. MATERIALS AND METHODS: This first national oral health survey of schoolchildren at 6-, 12- and 15-years was conducted in urban and rural settings across all four regions using a multi-stage cluster sampling in line with the WHO guidelines, adapted according to contemporary survey methods to include 'International Caries Detection and Assessment System (ICDAS)'. Whilst parents were invited to complete a questionnaire for 6-year-old children, 12- and 15-year-olds self-completed a questionnaire. Data were weighted according to age and regional population and analysed using STATA v.15 and SPSS v.22. RESULTS: A total of 1174 children participated across 22 schools from all four regions. Dental caries was prevalent (over 80% of all age-groups having clinical decay; ICDAS score ≥ 2) and largely untreated. No children had fillings and only 4% had missing teeth. Amongst 6, 12 and 15-year-olds, average decay levels at ICDAS > 3 threshold was 3.47 (primary teeth), 2.94 and 4.30 respectively. Almost, 10% (n = 119) of all children reported experiencing pain in their teeth with 7% (n = 86) children having PUFA lesions present. At least one in five children required one or more dental extractions. 'Age' was a significant predictor of dental caries experience and the odds of having dental caries experience was higher in rural areas at D3-6MFT (p < 0.05). CONCLUSION: The findings demonstrate a vast unmet oral health need in the children of SL. Using ICDAS as an epidemiological tool in a low-income country provides valuable insight to the pattern of oral disease to inform health service planning. Urgent action is required to address this silent epidemic.

The Duration of Stone Disease and the Impact of a Stone Event on Patients' Quality of Life.

Introduction: With a 5-year stone recurrence rate of 30% to 50%, kidney stone formers are subject to significant morbidity that negatively impacts their health-related quality of life (HRQOL). We sought to determine the impact of age at kidney stone onset, duration of stone disease, and kidney stone event (surgery or stone passage) on HRQOL of individual patients by querying the validated and prospectively collected Wisconsin Stone Quality of Life (WISQOL) database. Patients and Methods: Cross-sectional data were obtained from a total of 2438 kidney stone formers from 14 institutions in North America who completed the WISQOL questionnaire during the period from 2014 to 2019. The 28-question survey has a 1- to 5-point scale for each item (total score range 0-140). Multivariable linear regression models assessed the impact of age at kidney stone onset, duration of stone disease, and time since most recent surgery or stone passage on HRQOL. Results: Of 2438 patients, older age at kidney stone onset and longer duration of disease were both independent predictors of better WISQOL scores (ß = 0.33 points/year; confidence interval [CI] 0.17-0.49; p < 0.001; and ß = 0.50 points/year; CI 0.32-0.68; p < 0.001, respectively). Of 1376 patients who underwent surgery between 2010 and 2019, longer time since most recent surgery was an independent predictor of better WISQOL scores (ß = 2.28 points/year; CI: 1.47-3.10; p = <0.001). Of 1027 patients with spontaneous stone passage occurring between 2010 and 2019, longer time since most recent stone passage was an independent predictor of better WISQOL scores (ß = 1.59 points/year; CI: 0.59-2.59; p = <0.05). Conclusions: Our study demonstrates that older age at onset, longer duration of disease, and longer time since most recent surgery or stone passage were independent predictors of better HRQOL in kidney stone formers. Results of future studies that focus on optimizing stone-related modifiable risk factors to decrease the number of recurrent stone episodes and thus the need for recurrent surgeries will be essential.

A human brain vascular atlas reveals diverse mediators of Alzheimer's risk.

The human brain vasculature is of great medical importance: its dysfunction causes disability and death1, and the specialized structure it forms-the blood-brain barrier-impedes the treatment of nearly all brain disorders2,3. Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer's disease and 8 individuals with no cognitive impairment. We identify brain-region- and species-enriched genes and pathways. We reveal molecular principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum. We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization; and define perivascular versus meningeal fibroblast specialization. In Alzheimer's disease, we observe selective vulnerability of ECM-maintaining pericytes and gene expression patterns that implicate dysregulated blood flow. With an expanded survey of brain cell types, we find that 30 of the top 45 genes that have been linked to Alzheimer's disease risk by genome-wide association studies (GWASs) are expressed in the human brain vasculature, and we confirm this by immunostaining. Vascular GWAS genes map to endothelial protein transport, adaptive immune and ECM pathways. Many are microglia-specific in mice, suggesting a partial evolutionary transfer of Alzheimer's disease risk. Our work uncovers the molecular basis of the human brain vasculature, which will inform our understanding of overall brain health, disease and therapy.

Predictors and Cost Comparison of Subsequent Urinary Stone Care at Index Versus Non-Index Hospitals.

OBJECTIVE: To examine the effects of care fragmentation, or the engagement of different health care systems along the continuum of care, on patients with urinary stone disease. METHODS: All-payer data from the 2016 Healthcare Cost and Utilization Project (HCUP) State Databases from Florida (FL) and New York (NY) were used to identify a cohort of adult patients with an emergency department visit for a diagnosis of urolithiasis, who subsequently re-presented to an index or non-index hospital for renal colic and/or urological intervention. Patient demographics, regional data, and procedural information were collected and 30-day episode-based costs were calculated. Multivariable logistic and gamma generalized linear regression were utilized to identify predictors of receiving subsequent care at an index hospital and associated costs, respectively. RESULTS: Of the 33,863 patients who experienced a subsequent encounter related to nephrolithiasis, 9593 (28.3%) received care at a non-index hospital. Receiving subsequent care at the index hospital was associated with fewer acute care encounters prior to surgery (2.5 vs 2.7; P <.001) and less days to surgery (29 vs 42; P < .001). Total episode-based costs were higher in the non-index setting, with a mean difference of $783 (Non-index: $13,672, 95% CI $13,292-$14,053; Index: $12,889, 95% CI $12,677 - $13,102; P < .001). CONCLUSION: Re-presentation to a unique healthcare facility following an initial diagnosis of urolithiasis is associated with a greater number of episode-related health encounters, longer time to definitive surgery, and increased costs.

Short-Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis.

Current guidelines recommend restricting acetaminophen (APAP) use in patients with cirrhosis, but evidence to support that recommendation is lacking. Prior studies focused on pharmacokinetics (PK) of APAP in cirrhosis but did not rigorously examine clinical outcomes, sensitive biomarkers of liver damage, or serum APAP-protein adducts, which are a specific marker of toxic bioactivation. Hence, the goal of this pilot study was to test the effects of regularly scheduled APAP dosing in a well-defined compensated cirrhosis group compared to control subjects without cirrhosis, using the abovementioned outcomes. After a 2-week washout, 12 subjects with and 12 subjects without cirrhosis received 650 mg APAP twice per day (1.3 g/day) for 4 days, followed by 650 mg on the morning of day 5. Patients were assessed in-person at study initiation (day 1) and on days 3 and 5. APAP-protein adducts and both conventional (alanine aminotransferase) and sensitive (glutamate dehydrogenase [GLDH], full-length keratin 18 [K18], and total high-mobility group box 1 protein) biomarkers of liver injury were measured in serum on the mornings of days 1, 3, and 5, with detailed PK analysis of APAP, metabolites, and APAP-protein adducts throughout day 5. No subject experienced adverse clinical outcomes. GLDH and K18 were significantly different at baseline but did not change in either group during APAP administration. In contrast, clearance of APAP-protein adducts was dramatically delayed in the cirrhosis group. Minor differences for other APAP metabolites were also detected. Conclusion: Short-term administration of low-dose APAP (650 mg twice per day, <1 week) is likely safe in patients with compensated cirrhosis. These data provide a foundation for future studies to test higher doses, longer treatment, and subjects who are decompensated, especially in light of the remarkably delayed adduct clearance in subjects with cirrhosis.

Phosphaturic Mesenchymal Tumors of the Sinonasal Area and Skull Base: Experience at a Single Institution.

OBJECTIVES: Phosphaturic mesenchymal tumor (PMT) is a rare, polymorphous neoplasm with a highly variable presentation and natural history and unpredictable clinical course. The primary objective was to describe our clinical experience with and management of 4 markedly different cases of sinonasal and skull base PMT. METHODS: A retrospective case series with chart review, and relevant literature review, was performed at a tertiary academic medical center between 1998 and 2020. Adult patients treated for PMTs of the sinonasal area and skull base were included. Our main outcome measures included postoperative laboratory findings and radiological evidence of disease remission. RESULTS: Four patients (2 Males, 2 Females; Mean Age: 63.5 years) with PMTs of the skull base have been managed at our institution since 1998. Patient presentations varied, ranging from severe phosphorus wasting and osteoporosis to symptoms secondary to mass effect, including nasal obstruction and rhinorrhea. All 4 patients were eventually found to have elevated levels of fibroblast growth factor 23. Tumors were located in the sinonasal area (right frontal sinus, right ethmoid sinus, and right nasal cavity, respectively) in 3 patients and in the lateral skull base (right jugular foramen) in 1 patient. All 4 patients underwent complete surgical resection of their tumors. PMT tissue pathology was confirmed in all cases. Gross total resection was achieved in all patients. There was no chemical or radiological evidence of disease recurrence in any patients at follow-up. CONCLUSIONS: The presentation of skull base PMT is variable, and it may mimic other mass pathologies of the head and neck. Complete surgical resection with negative margins is potentially curative.

Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective: To assess the safety of inulin and sinistrin use in France. Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.