Astrocyte-secreted lipocalin-2 elicits bioenergetic failure-induced neuronal death that is causally related to high fatality in a mouse model of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neurological complication arising from acute liver failure with poor prognosis and high mortality; the underlying cellular mechanisms are still wanting. We previously found that neuronal death caused by mitochondrial dysfunction in rostral ventrolateral medulla (RVLM), which leads to baroreflex dysregulation, is related to high fatality in an animal model of HE. Lipocalin-2 (Lcn2) is a secreted glycoprotein mainly released by astrocytes in the brain. We noted the presence of Lcn2 receptor (Lcn2R) in RVLM neurons and a parallel increase of Lcn2 gene in astrocytes purified from RVLM during experimental HE. Therefore, our guiding hypothesis is that Lcn2 secreted by reactive astrocytes in RVLM may underpin high fatality during HE by eliciting bioenergetic failure-induced neuronal death in this neural substrate. In this study, we first established the role of astrocyte-secreted Lcn2 in a liver toxin model of HE induced by azoxymethane (100 µg/g, ip) in C57BL/6 mice, followed by mechanistic studies in primary astrocyte and neuron cultures prepared from postnatal day 1 mouse pups. In animal study, immunoneutralization of Lcn2 reduced apoptotic cell death in RVLM, reversed defunct baroreflex-mediated vasomotor tone and prolonged survival during experimental HE. In our primary cell culture experiments, Lcn2 produced by cultured astrocytes and released into the astrocyte-conditioned medium significantly reduced cell viability of cultured neurons. Recombinant Lcn2 protein reduced cell viability, mitochondrial ATP (mitoATP) production, and pyruvate dehydrogenase (PDH) activity but enhanced the expression of pyruvate dehydrogenase kinase (PDK) 1, PDK3 and phospho-PDHA1 (inactive PDH) through MAPK/ERK pathway in cultured neurons, with all cellular actions reversed by Lcn2R knockdown. Our results suggest that astrocyte-secreted Lcn2 upregulates PDKs through MAPK/ERK pathway, which leads to reduced PDH activity and mitoATP production; the reinforced neuronal death in RVLM is causally related to baroreflex dysregulation that underlies high fatality associated with HE.

Kaposiform Lymphangiomatosis as a Cause of Vaginal Bleeding & Discharge: A Case Report.

BACKGROUND: Prepubertal vaginal bleeding is a common presentation for pediatric adolescent gynecologists with a broad differential diagnosis that historically may not have included complex lymphatic anomalies. However, given recent consensus criteria and imaging capabilities, this may be a condition that pediatric adolescent gynecologists see more frequently in the future. CASE: We present a case of a 5-year-old pre-pubertal girl whose only presenting symptoms of a rare complex lymphatic anomaly was copious vaginal bleeding. After three vaginoscopies, two hysteroscopies, two pelvic MRIs, and a percutaneous ultrasound guided core needle biopsy, this patient was eventually diagnosed with Kaposiform lymphangiomatosis at age 9 years-old, and she is now being treated medically with sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, with improvement in her symptoms. SUMMARY AND CONCLUSION: Complex lymphatic anomalies should be considered after initial and secondary workups for pre-pubertal vaginal bleeding or copious vaginal discharge are negative. Furthermore, this case illustrates the value of pelvic MRI in the setting of unknown cause of vaginal bleeding when typical workup is negative.

Achieving research impact in medical research through collaboration across organizational boundaries: Insights from a mixed methods study in the Netherlands.

BACKGROUND: In the Netherlands, university medical centres (UMCs) bear primary responsibility for conducting medical research and delivering highly specialized care. The TopCare program was a policy experiment lasting 4 years in which three non-academic hospitals received funding from the Dutch Ministry of Health to also conduct medical research and deliver highly specialized care in specific domains. This study investigates research collaboration outcomes for all Dutch UMCs and non-academic hospitals in general and, more specifically, for the domains in the non-academic hospitals participating in the TopCare program. Additionally, it explores the organizational boundary work employed by these hospitals to foster productive research collaborations. METHODS: A mixed method research design was employed combining quantitative bibliometric analysis of publications and citations across all Dutch UMCs and non-academic hospitals and the TopCare domains with geographical distances, document analysis and ethnographic interviews with actors in the TopCare program. RESULTS: Quantitative analysis shows that, over the period of study, international collaboration increased among all hospitals while national collaboration and single institution research declined slightly. Collaborative efforts correlated with higher impact scores, and international collaboration scored higher than national collaboration. A total of 60% of all non-academic hospitals' publications were produced in collaboration with UMCs, whereas almost 30% of the UMCs' publications were the result of such collaboration. Non-academic hospitals showed a higher rate of collaboration with the UMC that was nearest geographically, whereas TopCare hospitals prioritized expertise over geographical proximity within their specialized domains. Boundary work mechanisms adopted by TopCare hospitals included aligning research activities with organizational mindset (identity), bolstering research infrastructure (competence) and finding and mobilizing strategic partnerships with academic partners (power). These efforts aimed to establish credibility and attractiveness as collaboration partners. CONCLUSIONS: Research collaboration between non-academic hospitals and UMCs, particularly where this also involves international collaboration, pays off in terms of publications and impact. The TopCare hospitals used the program's resources to perform boundary work aimed at becoming an attractive and credible collaboration partner for academia. Local factors such as research history, strategic domain focus, in-house expertise, patient flows, infrastructure and network relationships influenced collaboration dynamics within TopCare hospitals and between them and UMCs.

Disease severity prognostication in primary sclerosing cholangitis: a validation of the Anali scores and comparison with the potential functional stricture.

OBJECTIVES: Our aim was twofold. First, to validate Anali scores with and without gadolinium (ANALIGd and ANALINoGd) in primary sclerosing cholangitis (PSC) patients. Second, to compare the ANALIs prognostic ability with the recently-proposed potential functional stricture (PFS). MATERIALS AND METHODS: This retrospective study included 123 patients with a mean age of 41.5 years, who underwent gadoxetic acid-enahnced MRI (GA-MRI). Five readers independently evaluated all images for calculation of ANALIGd and ANALINoGd scores based upon following criteria: intrahepatic bile duct change severity, hepatic dysmorphia, liver parenchymal heterogeneity, and portal hypertension. In addition, hepatobiliary contrast excretion into first-order bile ducts was evaluated on 20-minute hepatobiliary-phase (HBP) images to assess PFS. Inter- and intrareader agreement were calculated (Fleiss´and Cohen kappas). Kaplan-Meier curves were generated for survival analysis. ANALINoGd, ANALIGd, and PFS were correlated with clinical scores, labs and outcomes (Cox regression analysis). RESULTS: Inter-reader agreement was almost perfect (Ï° = 0.81) for PFS, but only moderate-(Ï° = 0.55) for binary ANALINoGd. For binary ANALIGd, the agreement was slightly better on HBP (Ï° = 0.64) than on arterial-phase (AP) (Ï° = 0.53). Univariate Cox regression showed that outcomes for decompensated cirrhosis, orthotopic liver transplantation or death significantly correlated with PFS (HR (hazard ratio) = 3.15, p < 0.001), ANALINoGd (HR = 6.42, p < 0.001), ANALIGdHBP (HR = 3.66, p < 0.001) and ANALIGdAP (HR = 3.79, p < 0.001). Multivariate analysis identified the PFS, all three ANALI scores, and Revised Mayo Risk Score as independent risk factors for outcomes (HR 3.12, p < 0.001; 6.12, p < 0.001; 3.56, p < 0.001;3.59, p < 0.001; and 4.13, p < 0.001, respectively). CONCLUSION: ANALINoGd and GA-MRI-derived ANALI scores and PFS could noninvasively predict outcomes in PSC patients. CLINICAL RELEVANCE STATEMENT: The combined use of Anali scores and the potential functional stricture (PFS), both derived from unenhanced-, and gadoxetic acid enhanced-MRI, could be applied as a diagnostic and prognostic imaging surrogate for counselling and monitoring primary sclerosing cholangitis patients. KEY POINTS: Primary sclerosing cholangitis patients require radiological monitoring to assess disease stability and for the presence and type of complications. A contrast-enhanced MRI algorithm based on potential functional stricture and ANALI scores risk-stratified these patients. Unenhanced ANALI score had a high negative predictive value, indicating some primary sclerosing cholangitis patients can undergo non-contrast MRI surveillance.

Carriage of Neisseria meningitidis (meningococci) in the sputum of people with cystic fibrosis (CF): occupational health risks and mitigating interventions for physiotherapists.

OBJECTIVES: To estimate the carriage of Neisseira meningitidis (meningococci) in expectorated sputum from people with cystic fibrosis (CF) and to evaluate potential ramifications of such carriage for the health and (NM) wellbeing of physiotherapists performing airway clearance techniques. DESIGN: Descriptive observational study. MAIN OUTCOME MEASURES: Meningococcal carriage rate, CFTR mutation type and time to first meningococcal culture were determined. RESULTS: Microbiological data was examined from 100 patients from birth to present (31/12/2021), equating to 2455 patient years. NM was isolated from 6/100 (6%) adult CF patients who had F508del/F508del (homozygous), F508del/other (heterozygous) and other mutations. The median and mean time to first isolation of NM was 213 months and 230 months (standard deviation = 27.6 months), respectively, shortest time was 209 months, longest time 278 months. CONCLUSIONS: Physiotherapists should be aware of the risks to themselves of acquiring Neisseria meningtidis from CF patients' respiratory aerosols, whilst performing airway clearance techniques. Physiotherapists with underlying medical conditions or with specific concerns about meningococcal disease should discuss their circumstances with their occupational health team, to ensure optimal protection.

Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons.

Mitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated with reduced cellular health. However, it is still unclear to what extent the decline of mitochondrial transport and function observed during ageing are coupled, and if somal and axonal mitochondria display compartment-specific features that make them more susceptible to the ageing process. It is also not known whether the biophysical state of the cytoplasm, thought to affect many cellular functions, changes with age to impact mitochondrial trafficking and homeostasis. Focusing on the mouse peripheral nervous system, we show that age-dependent decline in mitochondrial trafficking is accompanied by reduction of mitochondrial membrane potential and intramitochondrial viscosity, but not calcium buffering, in both somal and axonal mitochondria. Intriguingly, we observe a specific increase in cytoplasmic viscosity in the neuronal cell body, where mitochondria are most polarised, which correlates with decreased cytoplasmic diffusiveness. Increasing cytoplasmic crowding in the somatic compartment of DRG neurons grown in microfluidic chambers reduces mitochondrial axonal trafficking, suggesting a mechanistic link between the regulation of cytoplasmic viscosity and mitochondrial dynamics. Our work provides a reference for studying the relationship between neuronal mitochondrial homeostasis and the viscoelasticity of the cytoplasm in a compartment-dependent manner during ageing.

Case Report: The Conundrum of What to Pick? Antibiotic Susceptibility Variability in Burkholderia cenocepacia in Cystic Fibrosis: Implications for Antibiotic Susceptibility Testing and Treatment.

Within cystic fibrosis microbiology, there is often mismatch between the antibiotic susceptibility result of an isolated bacterial pathogen and the clinical outcome, when the patient is treated with the same antibiotic. The reasoning for this remains largely elusive. Antibiotic susceptibility to four antibiotics (ceftazidime, meropenem, minocycline and trimethoprim-sulfamethoxazole) was determined in consecutive isolates (n = 11) from an adult cystic fibrosis patient, over a 63 month period. Each isolate displayed its own unique resistotype. The first isolate was sensitive to all four antibiotics, in accordance with Clinical and Laboratory Standards Institute methodology and interpretative criteria. Resistance was first detected at four months, showing resistance to ceftazidime and meropenen and intermediate resistance to minocycline and trimethoprim-sulfamethoxazole. Pan resistance was first detected at 18 months (resistotype IV), with three resistotypes (I, II and III) preceding this complete resistotype. The bacterium continued to display further antibiotic susceptibility heterogeneity for the next 45 months, with the description of an additional seven resistotypes (resistotypes V-XI). The Relative Resistance Index of this bacterium over the 63 month period showed no relationship between the development of antibiotic resistance and time. Adoption of mathematical modelling employing multinomial distribution demonstrated that large numbers of individual colony picks (>40/sputum), would be required to be 78% confident of capturing all 11 resistotypes present. Such a requirement for large numbers of colony picks combined with antibiotic susceptibility-related methodological problems creates a conundrum in biomedical science practice, in providing a robust assay that will capture antibiotic susceptibility variation, be pragmatic and cost-effective to deliver as a pathology service, but have the reliability to help clinicians select appropriate antibiotics for their patients. This study represents an advance in biomedical science as it demonstrates potential variability in antibiotic susceptibility testing with Burkholderia cenocepacia. Respiratory physicians and paediatricians need to be made aware of such variation by biomedical scientists at the bench, so that clinicians can contextualise the significance of the reported susceptibility result, when selecting appropriate antibiotics for their cystic fibrosis patient. Furthermore, consideration needs to be given in providing additional guidance on the laboratory report to highlight this heterogeneity to emphasise the potential for misalignment between susceptibility result and clinical outcome.

Arabidopsis Transcriptomics Reveals the Role of Lipoxygenase2 (AtLOX2) in Wound-Induced Responses.

In wounded Arabidopsis thaliana leaves, four 13S-lipoxygenases (AtLOX2, AtLOX3, AtLOX4, AtLOX6) act in a hierarchical manner to contribute to the jasmonate burst. This leads to defense responses with LOX2 playing an important role in plant resistance against caterpillar herb-ivory. In this study, we sought to characterize the impact of AtLOX2 on wound-induced phytohormonal and transcriptional responses to foliar mechanical damage using wildtype (WT) and lox2 mutant plants. Compared with WT, the lox2 mutant had higher constitutive levels of the phytohormone salicylic acid (SA) and enhanced expression of SA-responsive genes. This suggests that AtLOX2 may be involved in the biosynthesis of jasmonates that are involved in the antagonism of SA biosynthesis. As expected, the jasmonate burst in response to wounding was dampened in lox2 plants. Generally, 1 h after wounding, genes linked to jasmonate biosynthesis, jasmonate signaling attenuation and abscisic acid-responsive genes, which are primarily involved in wound sealing and healing, were differentially regulated between WT and lox2 mutants. Twelve h after wounding, WT plants showed stronger expression of genes associated with plant protection against insect herbivory. This study highlights the dynamic nature of jasmonate-responsive gene expression and the contribution of AtLOX2 to this pathway and plant resistance against insects.

Real-World Treatment Patterns and Outcomes by Line of Therapy and Race in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated in the United States: Results From the Final Analysis of the Prospective, Observational, informCLL Registry.

BACKGROUND: informCLL is the largest US-based prospective, observational registry of patients with chronic lymphocytic leukemia (CLL) initiating FDA-approved treatment in the era of targeted therapy. PATIENTS AND METHODS: Patients were enrolled between October 2015 and June 2019. Data were collected for baseline characteristics, treatment patterns, outcomes, and safety. RESULTS: In total, 1459 eligible patients were enrolled (first line, n = 854; relapsed/refractory, n = 605). The most common index treatments were ibrutinib (first line, 45%; relapsed/refractory, 49%) and chemoimmunotherapy (first line, 43%; relapsed/refractory, 20%). With median follow-up of 31.8 and 30.9 months in first-line and relapsed/refractory cohorts, respectively, median time to next treatment (TTNT) in patients who received any index treatment was not reached (NR) and 48.6 months; estimated proportions without next-line therapy at 48 months were 64% and 50%. Median overall survival (OS) was NR for both cohorts; estimated 48-month OS rates were 81% and 64% in first-line and relapsed/refractory cohorts, respectively. In match-adjusted analyses, TTNT was improved with first-line ibrutinib versus chemoimmunotherapy (median NR vs. 56.5 months; hazard ratio, 0.74; 95% CI, 0.56-0.98). Exposure-adjusted rates of AEs leading to discontinuation and serious AEs were lower with ibrutinib versus chemoimmunotherapy. Estimated 36-month OS rates were similar in Black versus White patients who received any index treatment (first line, 87% vs. 83%; relapsed/refractory, 74% vs. 74%) or ibrutinib (first line, 97% vs. 85%; relapsed/refractory, 81% vs. 77%). CONCLUSION: In this prospective, large, real-world CLL registry, first-line ibrutinib was associated with longer TTNT than chemoimmunotherapy, with sustained benefit up to 4 years of follow-up.

A Longitudinal Study of the Use and Effects of Fall-Risk-Increasing Drugs in Residential Aged Care.

OBJECTIVES: Fall-risk-increasing drugs (FRIDs)-psychotropics and cardiovascular disease (CVD) drugs-may elevate the risk of falling, with strong evidence observed in psychotropic FRIDs, whereas findings from cardiovascular disease (CVD) FRIDs remain inconclusive. Existing studies on FRIDs and falls are often hampered by methodologic limitations. Leveraging longitudinal observational data, we aimed to determine the long-term patterns of FRID use and their association with falls in residential aged care (RAC) homes. DESIGN: A retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: A total of 4207 permanent residents newly admitted to 27 RAC homes in Sydney, Australia. METHOD: The outcomes were incidence of all and injurious falls. We measured exposure to each FRID over 60 months using the Proportion of Days Covered (PDC) metric. We used group-based multitrajectory modeling to determine concurrent usage patterns of psychotropics and CVD FRIDs and applied negative binomial regression to assess their associations with the outcomes. RESULTS: A total of 83.6% (n = 3516) and 77.3% (n = 3254) residents used psychotropic and CVD FRIDs, respectively. The PDC values ranged from 67.3% (opioids) to 86.9% (antidepressants) for specific psychotropics and 79.0% (α-adrenoceptor antagonists) to 89.6% (ß blockers) for CVD FRIDs. We identified 4 groups: group 1, low psychotropics-low CVDs use (16.7%, n = 701); group 2, low psychotropics-high CVDs (25.0%, n = 1054); group 3, high psychotropics-high CVDs (41.0%, n = 1723); and group 4, high psychotropics-low CVDs (17.3%, n = 729). Group 4 had a significantly higher rate of falls than the other groups for both outcomes, including relative to group 3, in which exposure to both FRID classes was high. CONCLUSIONS AND IMPLICATIONS: Our findings reveal concerningly high FRID use in RAC homes and highlight a critical difference in the impact of the 2 major FRID classes on falls. Psychotropics were strongly associated with falls, whereas the studied CVD FRIDs did not elevate risk of falling.

Endobronchial Phenylephrine in Airway Bleeding During Bronchoscopy Does not Cause Hypertension: A Retrospective Observational Study.

BACKGROUND: Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. METHODS: In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. RESULTS: There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29 mm Hg (IQR 19 to 41) compared with 31.8 mm Hg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. CONCLUSIONS: We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.

Stakeholder-engaged development of a rapid test for detection of acute HIV infection.

Background/Objective: The utilization of rapid HIV tests has been effective at reducing transmission rates in high-risk populations by allowing individuals to receive diagnosis in as little as one minute and begin treatment. However, no current rapid tests can detect HIV immediately after infection in the acute HIV infection (AHI) phase, when the virus is at its most infectious, and instead require a waiting period of up to 90 days after exposure. Rapid HIV tests to detect AHI are currently under development. Investigation of stakeholder perspectives and context-specific needs are critical to ensure successful translation of novel AHI tests. The objectives of this study were to 1) understand context-specific factors such as barriers to HIV testing in Indiana, a state with one of 48 prioritized counties for HIV elimination; 2) assess the acceptability of a novel rapid AHI test, and 3) identify key implementation considerations for such a device, including ideal end-users. Methods: Semi-structured in-depth interviews were conducted with staff (n = 14) and clients (n = 5) of Indiana-based organizations that conduct HIV testing, including syringe service programs. Utilizing human-centered design frameworks, interview guides were developed and tailored to each participant group to understand their experiences with HIV testing, perspectives on a novel rapid AHI test in development, and preferences for self-testing versus testing by a community health worker (CHW) or a peer recovery coach. Thematic analysis was conducted to identify major themes, including barriers to HIV testing and perceived benefits and concerns of the proposed AHI test. Results: Overall acceptability for a novel AHI rapid test was high with a greater preference for CHW/Peerled testing. While self-testing was not a preferred modality, it was still seen as a potential tool to reach and address key barriers among high-risk individuals. Key considerations for implementation emphasized accuracy, cost-effectiveness, ease of use, ensuring access to counseling, education, and navigation to care while maintaining a human element to self-testing. Conclusion: Stakeholder engagement is meaningfully informing the design, development, and implementation of rapid AHI testing in order to facilitate adoption among populations at high-risk for HIV.

The Effect of Knee Height Asymmetry on Gait Biomechanics.

BACKGROUND: Though the primary goal for limb length discrepancy (LLD) management is to equalize the leg lengths, symmetry between corresponding long bones is usually not achieved, leading to knee height asymmetry (KHA). To date, there is minimal information on what effect KHA has on gait biomechanics and joint loading. Thus, the purpose of this study is to determine the impact of KHA on gait biomechanics. METHODS: Seventeen subjects with KHA after limb equalizing surgery and 10 healthy controls were enrolled. Subjects participated in 3D gait analysis collected using self-selected speed. Lower extremity kinematics, kinetics, work generated/absorbed, and total work were calculated. Standing lower limb x-rays and scanograms were used to measure LLD and calculate the tibia-to-femur (TF) ratio for each limb. Two sample t tests were used to compare differences in standing LLD, TF ratio, and work between groups. Bivariate correlation using Pearson correlation coefficients was conducted between TF ratio and total mechanical work, as well as between knee height asymmetry indices and total work asymmetry (α=0.05). RESULTS: Among participants, there were no differences between LLD; however, there were differences between TF ratio and knee height asymmetry. We found a nonsignificant relationship between TF ratio and total mechanical work for individual lower extremities. Therefore, the length of individual bones (TF ratio) relative to each other within the individual lower extremity was not associated with the amount of work produced. However, when a difference exists between sides (asymmetry, ie, TF ratio asymmetry), there were associated differences in work (work asymmetry) produced between sides (r=0.54, P=0.003). In other words, greater knee height asymmetry between limbs resulted in more asymmetrical mechanical work during walking. CONCLUSIONS: These findings may have implications for the management of LLD. Asymmetrical total mechanical work could lead to atypical joint loading during gait. Surgeons may want to consider prioritizing achieving knee height symmetry as a postoperative goal when correcting limb length discrepancy. LEVEL OF EVIDENCE: Level III, Case Control Study.

Uterus and cervix anatomical changes and cervix stiffness evolution throughout pregnancy.

The coordinated biomechanical performance, such as uterine stretch and cervical barrier function, within maternal reproductive tissues facilitates healthy human pregnancy and birth. Quantifying normal biomechanical function and detecting potentially detrimental biomechanical dysfunction (e.g., cervical insufficiency, uterine overdistention, premature rupture of membranes) is difficult, largely due to minimal data on the shape and size of maternal anatomy and material properties of tissue across gestation. This study quantitates key structural features of human pregnancy to fill this knowledge gap and facilitate three-dimensional modeling for biomechanical pregnancy simulations to deeply explore pregnancy and childbirth. These measurements include the longitudinal assessment of uterine and cervical dimensions, fetal weight, and cervical stiffness in 47 low-risk pregnancies at four time points during gestation (late first, middle second, late second, and middle third trimesters). The uterine and cervical size were measured via 2-dimensional ultrasound, and cervical stiffness was measured via cervical aspiration. Trends in uterine and cervical measurements were assessed as time-course slopes across pregnancy and between gestational time points, accounting for specific participants. Patient-specific computational solid models of the uterus and cervix, generated from the ultrasonic measurements, were used to estimate deformed uterocervical volume. Results show that for this low-risk cohort, the uterus grows fastest in the inferior-superior direction from the late first to middle second trimester and fastest in the anterior-posterior and left-right direction between the middle and late second trimester. Contemporaneously, the cervix softens and shortens. It softens fastest from the late first to the middle second trimester and shortens fastest between the late second and middle third trimester. Alongside the fetal weight estimated from ultrasonic measurements, this work presents holistic maternal and fetal patient-specific biomechanical measurements across gestation.

Screening for Breast Cancer Risk: An Analysis of Under-recognized Risk Factors and Comparison of Interventions.

Recognition of patients at high risk (HR) for breast cancer allows earlier screening and opportunities for risk reduction. We compare patients referred to our breast clinic as HR vs referrals for other reason (ROR) and found to be HR. We evaluate under-recognized factors and treatment differences. A retrospective chart review of patients found to be HR but referred for any reason to our breast clinic from July 2012 to December 2022 was performed. Referral reason, demographics, hormonal history, family history, and other risk factors were evaluated and compared (HR vs ROR). While other risk models were used for screening, Gail and Tyrer-Cuzick version 7 (TCv7) were used for comparison. Breast imaging received, hormonal therapy, and genetics referral evaluations were compared. 195 patients were referred to our breast team, 113 (58%) were referred as HR while 82 (42%) were ROR. Average age was 47 years old. 175 (91%) were Caucasian. 74 (65.5%) were referred for genetic testing, and 32 (26%) tested positive for a genetic mutation (n = 10, 12% ROR). 67 (35%) were recommended chemoprevention (n = 32, 16.4% took chemoprevention). 6 (3.1%) underwent prophylactic mastectomies and 163 (85%) had supplemental breast imaging. Comparison of HR vs ROR did not show significant differences in hormonal factors or treatments received; however, TCv7 was higher in the group referred as HR (P < .001). Our study showed that HR patients are more commonly referred secondary to family history but undergo similar treatments as those ROR. Accessibility to screening tools and education of risk factors, especially in minorities and those not otherwise being screened, may help better recognize HR.

Comparing demographics, treatments, and outcomes of patients with COVID-19 lesions versus hospital-acquired pressure ulcers/injuries during the first year of COVID-19.

BACKGROUND: As COVID-19 has emerged as a pandemic virus, multiple reports have surfaced to describe skin lesions that occur either associated with the virus or due to treatment. OBJECTIVE: To compare patient demographics, treatments, and outcomes in COVID-19 symptomatic patients who developed skin lesions (COVID-19 or hospital-acquired pressure ulcer/injury [HAPU/I]) during the first year of the pandemic. METHODS: A retrospective chart review was conducted on COVID-positive symptomatic patients admitted from March 1, 2020, through March 1, 2021. The authors analyzed the difference in patient demographics, patient skin tones, treatments, hospital length of stay (LOS), intensive care unit (ICU) LOS, death, and discharge disposition for those with COVID-19 lesions compared to those who developed HAPU/Is. RESULTS: Of those who developed lesions, 2.3% developed COVID-19 lesions and 7.2% developed HAPU/Is. Patients with COVID-19 lesions were more likely to be male (64%), younger (median age 60), and had a higher BMI (30) than patients with no wounds and patients with HAPU/I. CONCLUSION: This study advances the knowledge of the patient demographics and treatments that may contribute to identifying the new phenomenon of COVID lesions and how they differ from HAPU/Is.

Assessing Attitudes and Understanding After Ovarian Tissue Cryopreservation: A Follow-Up Telephone Interview Survey.

Purpose: Assessing patient and guardian experiences regarding their history of ovarian tissue cryopreservation (OTC) years after initial procedure. Methods: Cross-sectional follow-up telephone survey. A questionnaire developed by The Pediatric Initiative Network of the Oncofertility Consortium, modified to assess intent and attitudes regarding OTC, tissue access knowledge, financial burden of tissue storage, and intent to use tissue, was utilized. Interviews were conducted for those who underwent OTC at a metropolitan children's hospital between 2013 and 2022. Results: Of 60 eligible patients, 39 interviews were completed. Contacted patients were 3-28 years old, with minors accompanied by guardians. Average age at OTC was 8.5 years old, and 5.1% (2/39) were deceased at the time of contact. All interviewees underwent OTC for fertility preservation before gonadotoxic treatment. Seventy percent of patients (7/10) and 48.1% (13/27) of guardians stated they would use frozen tissue for pregnancy, with 50% (5/10) of patients and 59.3% (16/27) of guardians not understanding tissue access. Regret occurred in 10% (1/10) of patients and 3.4% (1/29) of guardians. It was associated with 10.8% (4/37) of tissue discard due to failed storage payments. Financial concerns occurred in 29.7% (11/37) of interviewees. Overall, 92.3% (36/39) would recommend OTC, and 94.9% (37/39) would repeat their choice to undergo OTC. Conclusion: Follow-up after OTC is essential to patient understanding of tissue status, access, and payments. Most do not regret OTC, except in cases of financial burden leading to tissue discard. Follow-up should be sequentially scheduled and include counseling on financial assistance programs.

Attitudes to cross infection, nebuliser hygiene and antimicrobial resistance in people with cystic fibrosis: Results of an international survey.

BACKGROUND: Respiratory infection is a major cause of disease severity in people with cystic fibrosis (PwCF). This project aimed to establish the CF community's opinion regarding cross infection (CI), nebuliser hygiene, antimicrobial resistance, personal impact of microbiological findings and the role of the microbiology laboratory. METHODS: A questionnaire was completed anonymously (n = 280; PwCF (n = 128), parents (n = 123); friends/family/carers/charity personnel (n = 29)) from 13 countries. Readability scores (Flesch Reading Ease (FRE), Flesch Kincaid Grade Level (FKGL)) were determined for CI/IP&C information from six national CF charities and 21 scientific abstracts. RESULTS: Respondents (72.5%) indicated knowledge of laboratory aspects of CF microbiology was important, however implications of microbiological findings on personal health/well-being were of higher importance (p < 0.0001). Cross infection/infection prevention & control (CI/IP&C) was of highest importance (95.6% respondents) with 27.3% indicating they were not given adequate information, particularly in older respondents (50 y+) (p = 0.006) versus young adults (16-29 y) and respondents from the Middle East versus N. America (p = 0.022) and Europe (p = 0.045). Responses highlighted how CI/IP&C health literacy could be enhanced. Respondents (77.3%), particularly females (p < 0.0001), indicated they would increase the frequency of nebuliser disinfection following guidance on infection risks/best practice, therefore an educational video was prepared. CI/IP&C readability scores (mean ± sd) from CF charities (FRE 52.5 ± 10.8; FKGL 9.7 ± 2.3) were more readable (p < 0.0001) than scientific abstracts (FRE 13.3 ± 11.1; FKGL 16.9 ± 2.3), however not meeting the targets (FRE≥60 and FKGL≤8). CONCLUSION: There is a requirement for further CI/IP&C evidence-based guidance, policies/guidelines, education awareness, best practice in the home environment and multi-modal communication, enabling the CF community to make informed choices on lifestyle behaviours.