Clinical Morbidities Research Articles

Cypermethrin triggers oxidative stress, apoptosis, and inflammation in bovine mammary glands by disruption of mitogen-activated protein kinase (MAPK) pathways and calcium homeostasis.

Cyano-(3-phenoxyphenyl)methyl]3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate (cypermethrin) is a pyrethroid insecticide that is widely used to repel insects, such as cockroaches and ants. In addition to the target insects, its hazards have been outlined for carp; mice; and the nervous, reproductive, and gastrointestinal systems of humans. However, the effects of cypermethrin on the mammary tissue and milk production in dairy cattle remain unknown. Therefore, in the present study, we aimed to elucidate the impact of cypermethrin on dairy cattle using bovine mammary epithelial cells (MAC-T), which play key roles in milk yield and quality maintenance. First, we assessed the effects of cypermethrin on cell viability, proliferation, and cell cycle progression, followed by correlated gene expression analysis. Cypermethrin-treated cells exhibited G1 phase arrest and an increase in the sub G1 population. The population of MAC-T cells in both early and late apoptotic phases was increased following cypermethrin exposure. Moreover, cypermethrin caused mitochondrial calcium overload and diminished the mitochondrial membrane potential in MAC-T cells. We also observed the disruption of mitogen-activated protein kinase (MAPK) cascades and eventually, apoptotic cell death and excessive oxidative stress in cypermethrin-exposed MAC-T cells. In addition, cypermethrin affects the transcription levels related to apoptosis and inflammation, which may lead to the development of clinical morbidities, such as mastitis.

Evaluation of the relationship between day or night birth time and morbidities and mortality in premature infants less than 32 weeks in a Turkish NICU.

Staffing levels, fatigue, and intervention timing may vary based on working hours and potentially influence the clinical outcomes of newborns. It remains unclear how the birth time of premature infants throughout the day affects their clinical outcome. This study aimed to compare the clinical outcomes of premature infants born during and after work hours. In this single-center retrospective cohort study, infants born at <32 weeks of age were categorized into two groups based on birth time. The first group included infants born during daytime working hours on weekdays, whereas the second group included infants born during nighttime working hours on weekdays, weekends, and public holidays. Both groups were compared in terms of clinical outcomes. Data from 572 patients born at <32 weeks of age were analyzed, with 137 (24%) infants in the on-hours group and 435 (76%) in the off-hours group. No significant differences were observed between the groups in terms of gestational age (GA) (27.4 ± 2.8 weeks vs. 27.7 ± 2.7 weeks), birth weight (BW) (1132 ± 459 g vs. 1064 ± 450 g), and gender distribution (53.2% vs. 55.4% male) (P > .05). There were no significant differences in other clinical outcomes, morbidities, or mortality rates between the groups (P > .05). Despite potential fluctuations in neonatal intensive care unit (NICU) staffing levels during on- and off-duty hours, the morbidity and mortality of premature infants aged <32 weeks were not affected in our unit. Each NICU should assess whether delivery time influences clinical outcomes, based on unique care conditions. The change in clinical outcomes depending on the time of birth may be particularly important in low- and middle-income countries (LMIC). Negative results may be an indication that the staff is under excessive workload. In addition, by providing a solution to the cause of the detected problem, both clinical outcomes may be improved and patient care costs due to morbidity may be reduced. Our results may be particularly important for studies to be conducted on this subject in LMIC.

Infants Born at Late Preterm Gestation: Management During the Birth Hospitalization

To examine the admission practices, frequency of common clinical morbidities, and rates of medical intervention in infants born at 34-36weeks gestational age (GA, late preterm). This retrospective, single institution, cohort study analyzed electronic health records of infants born late preterm from 2019 through 2021. Infants with known congenital anomalies necessitating neonatal intensive care unit admission were excluded. Analysis included descriptive and inferential statistics. The study included 1022 infants: 209 (21%) 34weeksGA, 263 (26%) 35weeksGA, and 550 (54%) 36weeksGA. Sixty-three percent of infants at 35weeksGA and 78% of infants of 36weeksGA remained in well newborn care throughout the birth hospitalization; infants born at 34weeksGA were ineligible for well newborn care. The need for respiratory support was 32%, 18%, and 11% in infants of 34, 35, and 36weeksGA, respectively. Supplemental tube feeds were administered in 55%, 24%, and 8% of infants of 34, 35, and 36 weeksGA, respectively. Most infants born at 34weeksGA (91%) were placed in an incubator; this was less frequent in infants at 35 (37%) and 36weeks (16%). Tachypnea, hypoglycemia, and hypothermia were noted in 40%, 61%, and 57% of infants, respectively. A subset of these infants (30% with tachypnea, 23% with hypoglycemia, and 46% with hypothermia) required medical intervention for these abnormalities. This single-center study provides an outlook on the care of infants born late preterm. Multicenter studies can contextualize these findings in order to develop clinical benchmarks and quality markers for this large population of infants.

Acquired antithrombin deficiency in adult patients with postcardiotomy extracorporeal membrane oxygenation.

This study aimed to investigate the relationship between acquired antithrombin deficiency in patients undergoing postcardiotomy extracorporeal membrane oxygenation (PC-ECMO) and thromboembolic or haemorrhagic events such as bleeding, peripheral arterial thromboembolism, and ischemic cerebrovascular events. The study was designed as a single-center, prospective study and conducted at our hospital between November 2019 and June 2021. 50 patients who underwent ECMO due to postcardiotomy cardiogenic shock were included in the study. Antithrombin (AT) activity testing was performed immediately after ECMO placement and continued for 5 days. The total of haemorrhagic or thromboembolic events was defined as morbidity. The entire patient population was assessed daily for AT measurements according to morbidity status, and ROC analysis was applied to determine the cut-off point. The correlation between clinical outcomes and morbidities with antithrombin levels was analysed. In our study, we identified a cut-off for AT levels on the first postoperative day. The risk of both bleeding (p = .006) and thromboembolism (p = .012) was significantly higher in patients below the 48.9% cut-off value. AT levels were compared with data on separation from PC-ECMO. The rate of separation from ECMO was 7.969 times higher in cases with AT levels above 51.8 on the third postoperative day and 5.6 times higher in cases with AT levels above 47.5 on the fourth postoperative day. Acquired antithrombin deficiency may develop in adults undergoing PC-ECMO. In our study, we demonstrated that in patients with low antithrombin levels, the risk of bleeding and thromboembolism increased. Additionally, since AT levels were higher in survivors, this can be considered an indicator of severity. This study is the first prospective study related to determining target antithrombin levels in adult patients undergoing PC-ECMO.

Vellus hair follicle diseases

Abstract Human hair follicles are composed of vellus hair follicles (vHFs), sebaceous hair follicles, and terminal hair follicles (tHFs), which share histoanatomy, but differ in biophysiology, therefore are distinctive in clinical morbidities. vHFs are much less studied, and many issues remain to be clarified, such as the expression and regulation of androgen receptors, hair follicle stem cells, immune privilege, and microbiome. Hirsutism is an example of an endocrine disorder with the pathogenesis incompletely understood, especially in idiopathic hirsutism. Interactions between androgens and other hormones deserve special attention. Treatment is unstandardized, whereas combination of antiandrogens and laser shows promise. Keratosis pilaris, a keratinization disorder, lacks clarity in etiopathogenesis, impacting esthetics and therapeutic efficacy. Among the inflammatory disorders, perioral/periorbital dermatitis arises from vHFs irritation, categorized into papular, eczematous, and granulomatous forms. This necessitates varied differential diagnoses and therapeutic approaches. Follicular eczema, a variant of atopic dermatitis in children, is also associated with xerotic dermatitis and allergic contact dermatitis in adults. Bacterial infections rarely target vHFs, in contrast to tHFs. Trichodysplasia spinulosa (TdS) links to TdS-associated polyomavirus infection localized to the inner root sheath cells of vHFs, underdiagnosed in immunocompromised patients. The varying manifestation and pathogenic significance of Malassezia furfur in Malassezia (pityrosporum) folliculitis, pityriasis versicolor, and seborrheic dermatitis remain debated. Proliferative/neoplastic entities of vHFs include vellus hair cyst, pilomatrixoma, trichoepithelioma, and trichostasis spinulosa. Follicular spiny hyperkeratosis, lichen spinulosus, and lichen scrofulosorum are reactive conditions of vHFs. Recognizing vHF-associated diseases helps us to better understand the human hair follicles and to enhance daily dermatological practices.

Clinical Profile and Ocular Morbidities in Patients with Both Diabetic Retinopathy and Uveitis

PurposeTo describe the clinical profile and complications of diabetic retinopathy (DR) and uveitis in patients with co-existing conditions and to derive associations based on site of primary inflammation, stage of DR and complications of each. DesignSingle-center, cross-sectional observational study. Participants66 patients with co-existing diabetic retinopathy and uveitis. MethodsElectronic medical records of 66 such cases were evaluated. The demographic data, diabetic status, clinical characteristics and complications of DR and uveitis on the final follow-up were recorded. Main Outcome MeasuresAssociations between best corrected visual acuity, prevalence of various stages and complications of DR among eyes with and without uveitis. Also, correlation between the intensity and primary sites of inflammation among eyes with proliferative and non-proliferative changes. ResultsOf the 132 eyes, all had DR and 97 eyes had uveitis (35 unilateral and 31 bilateral cases). Mean age of patients was 53.4±8.7 years, duration of diabetes was 10.5±6.9 years and duration of uveitis was 61.3±68.8 months. 54.6% uveitis patients had anterior uveitis, 20.6% had intermediate, 10.3% posterior and 14.4% pan-uveitis. 49.5% eyes had proliferative diabetic retinopathy (PDR) changes. There was a higher proportion PDR cases among anterior (56.6%), posterior (70%), and pan uveitis (64.3%), with difference in anterior uveitis cases approaching statistical significance (p=0.067). Conversely, significant (p<0.001) intermediate uveitis cases had non-proliferative changes (80%). Final BCVA was significantly poorer in the group with uveitis (p=0.045). The proportion of fibrovascular proliferations, tractional detachments and iris neovascularisation among proliferative retinopathy eyes with uveitis (14.6%, 18.8% and 12.5% respectively) was higher than those without uveitis (5.3%, 10.5% and 5.3%). Among uveitis cases, 58.5% eyes developed cataracts, 44.3% had posterior synechiae, 12.3% developed secondary glaucoma, 4.1% had epiretinal membrane, 4.1% had band-shaped keratopathy and 1.0% developed macular neovascularisation. ConclusionsEyes with co-existing DR and uveitis have a higher prevalence of neovascular and uveitis complications along with a risk of poorer visual outcomes. Treatment should aim at limiting the duration and intensity of inflammation. Strict glycaemic control is essential for inflammation control and preventing the progression of DR to more advanced stages.

Induction chemotherapy plus concomitant oxaliplatin-based chemoradiotherapy for locally advanced rectal cancer: A real world experience at San Raffaele Hospital.

144 Background: The standard treatment of locally advanced rectal cancer (LARC) consists of giving preoperative chemoradiation therapy (CT/RT) followed by surgery. Recently, total neoadjuvant therapy (TNT) has shown greater efficacy in terms of increasing the rate of complete pathological response (pCR) and reducing local and systemic relapse. However, based on the proposed therapy scheme, the risk of overtreatment and side effects is not negligible. The objective of this study was to evaluate the efficacy and safety of neoadjuvant doublet with oxaliplatin-based CT and concomitant RT. Methods: Patients with clinically staged II-III rectal cancer were treated with preoperative CT/RT using up to 3 cycles of oxaliplatin and fluoropyrimidine plus pelvic radiation daily, for a total dose of 46.2 Gy in 18 fractions. The first cycle of mXELOX (oxaliplatin 85 mg/m2 D1 Q14 plus capecitabine 825 mg/m2 BID) was administrated before RT (as induction CT); the other 2 cycles of mXELOX were administrated concurrent with RT, with capecitabine continued until the end of RT. Radical resection was performed within median 11 weeks of the last dose of RT. Adjuvant CT with FOLFOX or XELOX was administered according to pathological report. Results: Between 2007 and 2022, a total of 186 patients were enrolled, mean age was 61 years. 19 (10.2%) patients were clinically stage II and 167 (89.8%) were clinically stage III. Any grade most common toxicities during neoadjuvant CT/RT included diarrhea (53.2%), proctitis (51.2%) and neutropenia (14.5%). The most common grade 3/4 toxicity was diarrhea (9.1%). A total of 146 (78.5%) patients achieved a downstaging after CT/RT and 174 (93.5%) patients underwent surgery with R0 resection. Clinical meaningful surgical morbidities included infections (10.7%), anastomotic fistula (10.2%) and anastomotic leakage (7.5%). The pathological complete response (pCR) rate was 25.3%. Adjuvant CT was administered in 122 (65.6%) patients. Local recurrences and distant metastases were confirmed in 6 (3.2%) and 54 (29%) cases respectively. Median observation time, calculated with reverse Kaplan-Meier estimator, was 84 months and median overall survival (OS) was not reached. The estimated probability of OS (Kaplan-Meier method) at 3-5 years were 92.8% and 85.5% respectively. The median disease-free survival (DFS) was not reached and the estimated probability of DFS at 3-5 years were 74.7% and 69% respectively. Conclusions: Considering the low rate of toxicities and the comparable efficacy in terms of downstaging, pCR, probability of DFS and OS to other TNT regimens proposed in recent studies, our schedule of neoadjuvant CT/RT may represent a potential alternative to standard CT/RT in selected patients with LARC.

Identifying and quantifying initial post-discharge needs for clinical review of sick, newborns in Kenya based on a large multi-site, retrospective cohort study.

Progress in neonatal care has resulted in a 51% decrease in global neonatal mortality rates from 1990 to 2017. Enhanced survival will put pressure on health care systems to provide appropriate post-discharge, follow-up care but the scale of need for such care is poorly defined. We conducted a retrospective cohort study of newborns discharged from 23 public hospital neonatal units (NBUs) in Kenya between January 2018 and June 2023 to identify initial follow-up needs. We first determined pragmatic follow-up categories based on survivors' clinical conditions and morbidities. We then used individual phenotypes of individual babies to assign them to needing one or more forms of specialized clinical follow-up. We use descriptive statistics to estimate proportions of those with specific needs and patterns of need. Among 136,249/159,792 (85.3%) neonates discharged, around one-third (33%) were low birth weight (<2,500 g), and a similar 33.4% were preterm (<37 weeks). We estimated 131,351 initial episodes of follow-up would be needed across nine distinct follow-up categories: general pediatrics, nutrition, growth & development (40.4%), auditory screening (38.8%), ophthalmology for retinopathy of prematurity (9.6%), neurology (8.0%), occupational therapy (1.3%), specialized nutrition (0.9%), surgery (0.8%), cardiology (0.2%), and pulmonary (<0.1%). Most neonates met the criteria for two (52.3%, 28,733), followed by three (39.6%, 21,738) and one follow-up episodes (5.6%, 3,098). In addition to prematurity and very low birth weight (≤1,500 g), severe infections with extended gentamicin treatment, severe jaundice managed with phototherapy, and hypoxic-ischemic encephalopathy (HIE) contributed substantially to the pattern of need for post-discharge follow-up. Almost half of surviving NBU infants have multiple specialty post-discharge follow-up needs. More urgent attention needs to be focused on healthcare planning now to guide strategies to address the varied medical and developmental needs that we outline in resource-constrained contexts like Kenya.

Bronchopulmonary Dysplasia: A Five-Year Retrospective Cohort Study on Differences in Clinical Characteristics and Morbidities According to Severity Grading.

Bronchopulmonary dysplasia (BPD) is the most common complication associated with extreme prematurity. Although several criteria defining severity were developed over time, there are a few studies describing the differences in BPD phenotype and neonatal morbidities and complications between severity groups. We aimed to describe these differences in BPD patients of a neonatal intensive care unit (NICU). We conducted an observational retrospective cohort study through a medical record review over a five-year period. Participants were newborns admitted to an NICU who were diagnosed with BPD. We performed a descriptive statistical analysis of gestational complications and the use of antenatal corticosteroid therapy, birth-related data, and complications throughout the NICU stay, as well as the respiratory support used. We also compared different severity groups across these variables. The patients were divided into severe and non-severe BPD using the severity criteria of the 2001 NICHD/NHLBI/ORD consensus workshop. A total of 101 newborns with BPD participated in the study and 73 had data on BPD severity. The median gestational age was 27 weeks, ranging from 23 to 32 weeks. Of these 73 newborns, 36 had mild BPD (49.3%), 10 had moderate BPD (13.7%), and 27 had severe BPD (37.0%). When comparing severe and non-severe BPD, we found that extreme prematurity, extremely low birth weight, and small size for gestational age were more frequent in the severe BPD group (p-value=0.012, p-value<0.001, and p-value=0.012, respectively). Infants with severe BPD had a longer duration of invasive ventilation than those with mild or moderate BPD (p-value<0.001). Late sepsis, necrotizing enterocolitis, severe brain injury, and retinopathy of prematurity were more frequent in severe BPD (p-value=0.017, p-value=0.045, p-value=0.033, p-value=0.003, respectively). Previously published evidence describing causal links between BPD development and comorbidities exists but data on their impact on BPD severity are scarce. In our study, severe BPD seemed to be associated with a higher frequency of comorbidities and complications. Further studies are needed to ascertain the impact of each morbidity on the severity of BPD and if measures to prevent them could lead to potentially milder BPD disease.

The psychological impact of Early Pregnancy Loss in Portugal: incidence and the effect on psychological morbidity.

Worldwide, up to a quarter of all recognized pregnancies result in Early Pregnancy Loss (EPL), also known as miscarriage. For many women, this is a traumatic experience that leads to persistent negative mental health responses. The most common morbidity reported in studies from different countries is complicated grief, usually comorbid with depression, anxiety, and Post-Traumatic Stress Disorder (PTSD). To our best knowledge, no studies characterizing the psychological impact of EPL have been made in Portugal. An online survey was conducted to evaluate clinical symptoms of perinatal grief, anxiety, depression, and PTSD in women who suffered a spontaneous loss within 20 weeks of gestation. Out of 1,015 women who answered this survey, 873 were considered eligible, and subsequently distributed in 7 groups according to the time passed between their loss and their participation in the study. The proportion of women showing symptoms of all comorbidities was greater in those whose loss had happened within a month, and there was a significant gradual decrease over time in scores and proportions of clinical perinatal grief and PTSD. In terms of depression symptoms, scores dropped significantly in the group whose loss occurred 13-24 months before their participation but proportions oscillated without great changes in the other groups. Regarding anxiety, there were small oscillations, but there was no significant decrease of symptoms over time. Overall, despite a general drop in scores for most morbidities over time, substantial proportions of women showed persistent symptoms of clinical morbidities 3 years or more after the loss. Therefore, it is essential to promote monitoring of possible complicated responses to the event, to provide appropriate and timely intervention to those women in need.

Prediction of Sudden Cardiac Death: Looking Beyond Ejection Fraction

Sudden cardiac death (SCD) is a major public health burden accounting for 15-20% of global mortality. Contemporary guidelines for SCD prevention are centered around the presence of low left ventricular ejection fraction, although the majority of SCD accrues in those not meeting contemporary criteria for SCD prevention. The goal of this review is to elaborate on the contemporary landscape of SCD prediction tools and further highlight gaps and opportunities in SCD prediction and prevention. There have been considerable advancements in both non-invasive and invasive measures for SCD risk prediction including clinical morbidities, electrocardiographic measures, cardiac imaging (nuclear, magnetic resonance, computed tomography), serum biomarkers, genetics, and invasively assessed electrophysiological characteristics. Novel methodological approaches including application of machine learning, incorporation of competing risk, and use of computational modeling have underscored a future of personalized risk prediction. SCD remains a vital public health challenge. Emerging methods highlight opportunities to improve SCD prediction in the majority of those at risk who do not meet contemporary criteria for SCD prevention therapies. Future efforts will need to focus on easily deployed, multi-parametric risk models that enrich for SCD risk and not for competing mortality.

Preterm Neonates Admitted in the Neonatal Intensive Care Unit at a Tertiary Care Centre: A Descriptive Cross-sectional Study

Preterm birth, one of the leading causes of admissions to the Neonatal intensive care unit, is a major contributor to neonatal morbidity and mortality in developing countries. This study aimed to find out the prevalence of premature neonates admitted to the Neonatal Intensive Care Unit of a tertiary care centre. This descriptive cross-sectional study was conducted from clinical records of preterm neonates (born before 37 completed weeks of gestation) admitted in the Neonatal Intensive Care Unit from 16 July 2020 to 14 July 2021. Following ethical approval from the Institutional Review Committee (Reference number: 077/78-018), the patient's clinical characteristics and systemic morbidities were recorded. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Among 646 admissions, the prevalence of preterm neonates was found to be 147 (22.75%) (19.52-25.98, 95% Confidence Interval). The male: female ratio was 1.53:1. The median gestational age and birth weight were 33 weeks (Range: 24-36 weeks) and 1680 g respectively. A total of 73 (49.65%) delivery was followed by premature rupture of membrane. The morbidity due to respiratory problems was highest at 127 (86.39%), followed by metabolic at 104 (70.74%) and sepsis at 91 (61.90%). The renal system was the least affected 5 (3.40%). The prevalence of preterm neonates in the neonatal intensive care unit was higher than in other studies done in similar settings. morbidity; neonatal; neonatal intensive care unit; premature birth.

Bovine colostrum as a fortifier to human milk in very preterm infants – A randomized controlled trial (FortiColos)

Human milk for very preterm infants need fortification for optimal growth and development but the optimal fortification product remains to be identified. To investigate feasibility, safety and preliminary efficacy on growth and blood biochemistry when using intact bovine colostrum (BC) as a fortifier to human milk in very preterm infants. In an open-label, multicenter, randomized controlled pilot trial (infants 26-31 weeks' gestation), mother's own milk or donor human milk was fortified with powdered BC (n=115) or a conventional fortifier (CF, bovine-milk-based, n=117) until 35 weeks' postmenstrual age. Fortifiers and additional micronutrients were added to human milk according to local guidelines to achieve optimal growth (additional protein up to+1.4g protein/100mL human milk). Anthropometry was recorded weekly. Clinical morbidities including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) were recorded. Clinical biochemistry included plasma amino acid (AA) levels to assess protein metabolic responses to the new fortifier. A total of 232 infants, gestational age (GA) 28.5±1.4 (weeks+days), fulfilled inclusion criteria. Birthweight, GA and delta Z scores from birth to end of intervention on weight, length or head circumference did not differ between groups, nor between the subgroups of small for gestational age infants. Likewise, incidence of NEC (BC: 3/115 vs. CF: 5/117, p=0.72, unadjusted values), LOS (BC: 23/113 vs. CF: 14/116, p=0.08) and other morbidities did not differ. BC infants received more protein than CF infants (+10%, p<0.05) and showed several elevated AA levels (+10-40%, p<0.05). Infants fortified with BC showed similar growth but received more protein and showed a moderate increase in plasma AA-levels, compared with CF. Adjustments in protein composition and micronutrients in BC-based fortifiers may be required to fully suit the needs for very preterm infants.

Clinical anatomy of coronoid foramina of mandible and review of its implications in maxillofacial surgery.

A foramen in the coronoid process of the human mandible is a recently identified anatomic variant. The authors in this script aim at presenting a detailed assessment of the coronoid foramen terming it as '''foramen of Nyer' (FN) based on the person first identifying it. Mandibular cone beam computed tomography scans from a total of 2168 patients were evaluated on a prospective and retrospective scale for confirmation of the coronoid foramen after first identification over a panoramic radiograph. The coronoid foramen was found and confirmed in 96 (4.4%) patients. This script identifying the coronoid foramina of mandible becomes requisite research as a foundation for further analysis due to the scarcity of literature on this recent find. This anatomical-radiological study aims to explore the variant foramina using cone beam computed tomography while determining its prevalence and evaluating its variability in terms of unilateral, bilateral, or gender predilection and propose the significance of this unique anatomic finding. The lack of information about the presence of such variant foramina may lead to emergence of clinical morbidities such as increased risk of intra osseous hemorrhage and tumor spread due to presence of accessory blood vessels.

Synergistic combination therapy delivered via layer-by-layer nanoparticles induces solid tumor regression of ovarian cancer.

The majority of patients with high grade serous ovarian cancer (HGSOC) develop recurrent disease and chemotherapy resistance. To identify drug combinations that would be effective in treatment of chemotherapy resistant disease, we examined the efficacy of drug combinations that target the three antiapoptotic proteins most commonly expressed in HGSOC-BCL2, BCL-XL, and MCL1. Co-inhibition of BCL2 and BCL-XL (ABT-263) with inhibition of MCL1 (S63845) induces potent synergistic cytotoxicity in multiple HGSOC models. Since this drug combination is predicted to be toxic to patients due to the known clinical morbidities of each drug, we developed layer-by-layer nanoparticles (LbL NPs) that co-encapsulate these inhibitors in order to target HGSOC tumor cells and reduce systemic toxicities. We show that the LbL NPs can be designed to have high association with specific ovarian tumor cell types targeted in these studies, thus enabling a more selective uptake when delivered via intraperitoneal injection. Treatment with these LbL NPs displayed better potency than free drugs in vitro and resulted in near-complete elimination of solid tumor metastases of ovarian cancer xenografts. Thus, these results support the exploration of LbL NPs as a strategy to deliver potent drug combinations to recurrent HGSOC. While these findings are described for co-encapsulation of a BCL2/XL and a MCL1 inhibitor, the modular nature of LbL assembly provides flexibility in the range of therapies that can be incorporated, making LbL NPs an adaptable vehicle for delivery of additional combinations of pathway inhibitors and other oncology drugs.

Sex Differences in the Correlation between Fatigue Perception and Regional Gray Matter Volume in Healthy Adults: A Large-Scale Study.

The relationship between fatigue perception and regional gray matter volume (rGMV) has seldom been studied in healthy adults. Therefore, this study aimed to analyze sex differences in the correlation between rGMV and fatigue perception using Chalder’s fatigue questionnaire (CFQ). The CFQ was used to analyze the sexual features of rGMV related to the degree of perceived fatigue in 2955 healthy adults (male = 1560, female = 1395) of various ages (20–89 years, median 56). A higher CFQ score denotes a higher perceived fatigue level by the participant. According to the CFQ scores in males, the volumes of the right orbital part of the inferior frontal gyrus and left precuneus were negatively correlated (i.e., smaller rGMV had a higher CFQ score), whereas the left angular gyrus was positively correlated. In females, the right inferior temporal gyrus was negative, whereas the left middle temporal gyrus and right putamen were positive (i.e., larger rGMV had a higher CFQ score). The lack of identified regions in this large-scale study between males and females might be related to sex differences in clinical or pathological fatigue morbidities. Additionally, the sex differences in the negative or positive correlations between rGMV and fatigue perception may contribute to a better understanding of the neuronal mechanism in the early stages of fatigue development.

Feasibility of treating pediatric intracranial germ cell tumors in a middle-income country: The Jordanian experience.

Pediatric intracranial germ cell tumors (iGCT) are rare, with limited data available from Arabic countries. We retrospectively reviewed the medical charts of children <18years diagnosed with iGCT at King Hussein Cancer Center/Jordan (January 2003 to December 2020) for clinical characteristics, treatment, and morbidities. Sixteen patients had germinoma; median age was 6.9years and median symptoms duration 8months. Nine tumors were suprasellar, five pineal, and two bifocal. Four were metastatic. Eight patients had slightly elevated beta subunit human chorionic gonadotropin and 11 patients had resection/biopsy. Fifteen patients received chemotherapy; mostly carboplatin (450mg/m2 )/etoposide, which had low toxicity. All patients received radiotherapy (different doses and fields). At median follow-up of 7.7years, one tumor recurred (progression-free survival: 91%±8%). Twelve patients who continued follow-up had stable visual and endocrine deficits to their initial presentation. Five finished or are finishing diploma and seven had poor school performance (four left school). Six patients were diagnosed with nongerminomatous germ cell tumor; median symptom duration was 1month. Three tumors were pineal, two suprasellar, and one at quadrigeminal plate. Three were metastatic. Five tested patients had high tumor markers and four had resection/biopsy. All patients received chemotherapy, and then five received craniospinal radiation. Two patients are alive, two died with tumor progression, one died in remission with electrolyte imbalance, and one developed leukemia and died with septic shock. We achieved excellent survival in treating germinoma using a feasible protocol for low middle-income countries. However, patients encountered significant morbidities exacerbated by delayed diagnosis and unnecessary surgical interventions despite abnormal tumor markers. Raising awareness on iGCT symptomatology and diagnosis may help limit these morbidities.

Trends in Health Service Utilization After Enrollment in an Interdisciplinary Primary Care Clinic for Veterans with Addiction, Social Determinants of Health, or Other Vulnerabilities.

BackgroundModels of interdisciplinary primary care (IPC) may improve upon traditional primary care approaches in addressing addiction and social determinants of health.ObjectiveTo compare the trends in health care utilization in the year before and after enrollment in an IPC clinic model, and explore the variations in temporal patterns for patients with histories of high emergency department (ED) use, homelessness, and/or substance use disorders (SUDs).Design and ParticipantsInterrupted time series study of utilization among IPC patients.Main MeasuresQuarterly ED, inpatient, primary care, and behavioral health visits were abstracted from administrative data before and after IPC enrollment. Negative binomial segmented regressions estimated changes in health care utilization over time. We used interactions to test for statistical differences in temporal patterns for IPC subgroups.ResultsAmong IPC patients (n=994), enrollment was associated with overall reductions in ED, inpatient, and behavioral health visits (p’s<0.001) and increases in primary care (p’s<0.001). Temporal patterns of ED visits, hospitalizations, and behavioral health differed across IPC subgroups (interaction p’s<0.001). For those with histories of high ED use (n=265), ED, inpatient, and behavioral health visits decreased after enrollment (level change incidence rate ratios [IRRs]=0.57–0.69) and continued to decline over time (post-enrollment IRRs=0.80–0.88). Among other patients with homeless experiences (n=123), there were initial declines in hospitalizations (IRR=0.33) and overall declines in behavioral health visits (level change and post-enrollment IRRs=0.46–0.94). Other patients with SUDs had initial declines in hospitalizations (IRR=0.46), and post-enrollment declines in rates of specialty SUD visits (IRR=0.92). For all patients, primary care visits initially increased (level change IIRs=2.47–1.34) then gradually declined (post-enrollment IRRs=0.92–0.92).ConclusionsAn IPC model of care reduces acute care and behavioral health service use, particularly for patients with historically high ED use. IPC models may improve patient and system outcomes of vulnerable patient populations with social, clinical, and addiction morbidities.

Growth of Very Preterm Infants in a Low-Resourced Rural Setting after Affiliation with a Human Milk Bank

The extrauterine growth restriction (EUGR) of very preterm infants has been associated with long-term complications and neurodevelopmental problems. EUGR has been reported at higher rates in low resource settings. There is limited research investigating how metropolitan human milk banks contribute to the growth outcomes of very preterm infants cared in rural areas. The setting of this study is located at a rural county in Taiwan and affiliated with the Taiwan Southern Human Milk Bank. Donor human milk was provided through a novel supplemental system. A renewal nutritional protocol was initiated as a quality improvement project after the affiliated program. This study aimed to compare the clinical morbidities and growth outcome at term equivalent age (TEA) of preterm infants less than 33 weeks of gestational age before (Epoch-I, July 2015–June 2018, n = 40) and after the new implementation (Epoch-II, July 2018–December 2020, n = 42). The Epoch-II group significantly increased in bodyweight z-score at TEA ((−0.02 ± 1.00) versus Epoch-I group (−0.84 ± 1.08), p = 0.002). In multivariate regression models, the statistical difference between two epochs in bodyweight z-score changes from birth to TEA was still noted. Modern human milk banks may facilitate the nutritional protocol renewal in rural areas and improve the growth outcomes of very preterm infants cared for. Establishing more distribution sites of milk banks should be encouraged.

Applying Intersectionality Framework to Explore the Development of Frailty in Older Adults

Dementia disproportionately impacts the health and financial security of women and certain minority groups. Long-standing inequities create distrust of the medical system, fewer treatment options, and reduced access to care. Research predicts that from 2020 to 2060, the number of African Americans and Latinx living with dementia will grow by nearly 200 percent and 440 percent, respectively, while prevalence among non-Hispanic Whites will increase by 69 percent. As the prevalence of dementia rises, so will the costs associated with dementia care. African Americans bear 1/3 of the costs associated with dementia. And the costs for Latinx living with Alzheimer’s disease are expected to exceed $100 billion by 2060. To mitigate these growing health and economic concerns, efforts to improve dementia care must put equity front and center. This presentation highlights five actionable recommendations to build health equity by reducing disparities in dementia prevention, detection, diagnosis, and care. These recommendations center around two overarching themes: (1) Strengthening the infrastructure among health-care, long-term care, and community-based organizations to achieve greater health equity for people living with dementia and their caregivers and (2) Expanding dementia-friendly networks and workplaces in racially and ethnically diverse communities. The recommendations discussed in this presentation will offer guidance for policymakers, health services researchers, businesses, health systems, and communities to reduce the inequitable impact of dementia on African Americans and Latinx, which is even more vital amid demographic trends showing a population growing older and more racially and ethnically diverse.