Examining Barriers to Early Hearing Diagnosis.

PURPOSE: Many factors create barriers for early hearing detection and intervention (EHDI), especially those related to unfavorable social determinants of health (SDOH). The primary aim of this study was to evaluate diagnostic timing of infants at risk for congenital hearing loss in consideration of known barriers. Understanding the specific barriers to early diagnosis can inform interventions to improve timeliness of diagnosis and subsequent habilitation. METHOD: A retrospective chart review was completed for infants referred for diagnostic audiologic testing at a tertiary urban-setting Children's Hospital from 2018 to 2021. After exclusion criteria were applied, 1,488 infants were included in the analysis. Various factors were recorded from electronic medical records including those specific to SDOH. Time to diagnosis was derived and compared across five factors of interest that have previously been shown to impact diagnostic timeline, including (a) insurance type, (b) race/ethnicity, (c) presence of middle ear dysfunction at first auditory brainstem response (ABR), (d) proximity to diagnostic center, and (e) diagnostic timing before and during/after the COVID-19 pandemic. RESULTS: Across the study time period, 77% of infants referred for diagnostic testing had confirmed diagnosis by the EHDI benchmark of 3 months. Analysis of time to diagnosis across factors of interest revealed no clinically significant differences for insurance type, race/ethnicity, proximity to diagnostic center, or timing in reference to the COVID-19 pandemic. Presence of middle ear dysfunction on first ABR was found to significantly protract final diagnostic timing. CONCLUSIONS: Although some known barriers for EHDI can be universal, other factors may have a differential impact on an infant's timeline to diagnosis based on their specific location, which can interact differently with additional known barriers. Understanding local challenges will serve to better guide programs in implementing facilitators that will address their specific needs for improved outcomes.

Evaluation of the Diversity, Equity, and Inclusion Curriculum of a Pediatrics Residency Program.

OBJECTIVES: Diversity, equity, and inclusion (DEI) training is essential to graduate medical education, but it lacks standardization. Although the impact of providers' biases and cultural competency on patient outcomes is well documented, the value of and satisfaction with DEI curricula in Pediatrics residency training programs is not well studied. This study aimed to complete a cross-sectional evaluation of the current DEI curriculum at a large Pediatrics-focused academic institution and identify areas of perceived deficiency among Pediatrics trainees. METHODS: Residents and residency program directors completed surveys in 2020. Respondents evaluated the DEI curriculum of the program and the competency of residents to complete patient care related to specific DEI-oriented actions. Our analysis used descriptive statistics. RESULTS: In total, 48 of 137 resident trainees (35%) and 7 of 9 program leaders (78%) completed the survey. Respondents were most dissatisfied with current education related to implicit bias, refugee/immigrant health, and lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other health topics. Respondents reported low resident competency in DEI-focused patient care tasks and did not view residents as competent to address the healthcare needs of patients and families experiencing racism. CONCLUSIONS: Pediatrics residents and program directors consider DEI topics important and express a need for more robust DEI curricula.

Chlorfenapyr Crystal Polymorphism and Insecticidal Activity.

Four crystalline polymorphs of the proinsecticide chlorfenapyr [4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3-carbonitrile] have been identified and characterized by polarized light optical microscopy, differential scanning calorimetry, Raman spectroscopy, X-ray diffraction, and electron diffraction. Three of the four structures were considered polytypic. Chlorfenapyr polymorphs show similar lethality against fruit flies (Drosophila melanogaster) and mosquitoes (Anopheles quadrimaculatus) with the least stable polymorph showing slightly higher lethality. Similar activities may be expected to be consistent with structural similarities. Knockdown kinetics, however, depend on an internal metabolic activating step, which further complicates polymorph-dependent bioavailability.

Fluid-attenuated inversion-recovery sequence with fat suppression as an alternative to contrast-enhanced MRI in pediatric synovitis.

BACKGROUND: Non-contrast magnetic resonance imaging (MRI) fluid-attenuated inversion-recovery sequence (FLAIR) with fat suppression (FS) has not been validated in children. OBJECTIVE: Compare FLAIR to T1-weighted post contrast (T1CE) in the detection of knee synovitis. METHODS AND MATERIALS: Institutional review board (IRB) waived consent. Children who underwent T1CE and FLAIR sequences of the knee on a 3-T magnet from April 2021 to December 2021 were included. Two pediatric radiologists assessed axial FLAIR and T1CE images for synovitis and synovial thickness. Reliability and agreement were assessed. Sensitivities, specificities, and accuracy were calculated for FLAIR using T1CE as reference standard. RESULTS: In total, 42 knees (39 patients) were assessed (median age 12.9 years (2.3-17.8 years); 62% male, 38% female). Readers judged 20/42 (48%) knees to have synovitis. Sensitivity of FLAIR for reader 1 was 79% (19/24; 95% CI 0.58, 0.93) and 84% (16/19; 95% CI 0.60, 0.97) for reader 2. Specificity of FLAIR for reader 1 was 94% (17/18; 95% CI 0.73, 1) and 83% (19/23; 95% CI 0.61, 0.95) for reader 2. Accuracy for readers 1 and 2 was 86% (36/42; 95% CI 0.71, 0.95) and 83% (35/42; 95% CI 0.69, 0.93), respectively. Inter-reader reliability was good (0.75-0.90) for synovial measurements for FLAIR (ICC = 0.80; 95% CI 0.71, 0.86) and moderate for T1 CE (ICC = 0.62 (95% CI 0.48, 0.73)). CONCLUSION: FLAIR FS depicts synovium in the pediatric knee with similar reliability to T1 CE and may be an acceptable alternative to contrast in the initial diagnosis of synovitis.

Incidence of postpartum depression in low-income cannabis users with and without a history of depression.

While past research has linked cannabis use in pregnancy with a history of depression, sparse literature exists on cannabis use during pregnancy and postpartum depression (PPD). In this study, we aimed to better understand the association between PPD and cannabis use during pregnancy in those with and without a history of depression. This was a retrospective cohort study of patients who received prenatal care at a single institution between January 2017 and December 2019. Patient demographics, obstetric history, depression history, substance use history, and Edinburgh Postnatal Depression Scale (EPDS) scores were extracted from patients' medical records. Modified Poisson Regression with robust standard errors was used to estimate the relative risk (RR) of screening positive for PPD, adjusting for age at delivery, race/ethnicity, insurance type, marital status, and smoking history. Among the 799 subjects meeting inclusion criteria, 15.9% used cannabis during pregnancy. There was an increased risk of screening positive for PPD among prenatal cannabis users compared to non-users (aRR = 1.60, 95% CI: (1.05, 2.45)). Among individuals with a history of depression, the adjusted relative risk of screening positive for symptoms of PPD at the postpartum visit was 1.62 times greater in cannabis users compared to non-users (95% CI: (1.02, 2.58)). Prenatal cannabis use is associated with screening positive for PPD, particularly in those individuals with a history of depression. These results should discourage women with depression from self-medicating with cannabis in pregnancy and provide additional support to the existing recommendations to abstain from prenatal cannabis use.

Development of a scalar-based geometric parameterization approach for the crystal structure landscape of dithienylethene-based crystalline solids.

Dithienylethenes (DTEs) are a promising class of organic photoswitches that can be used to create crystalline solids with properties controlled by light. However, the ability of DTEs to adopt multiple conformations, only one of which is photoactive, complicates the rational design of these materials. Herein, the synthesis and structural characterization of 19 crystalline solids containing a single DTE molecule are described. A novel D-D analysis of the molecular geometries obtained from rotational potential energy surface calculations and the ensemble of experimental structures were used to construct a crystal landscape for DTE. Of the 19 crystal structures, 17 contained photoinactive DTE rotamers and only 2 were photoactive. These results highlight the challenges associated with the design of these materials. Overall, the D-D analysis described herein provides rapid, effective and intuitive means of linking the molecular structure to photoactivity that could be applied more broadly to afford a general strategy for producing photoactive diarylethene-based crystalline solids.

The Effect of a Psychologically Informed Video Series to Treat Adolescents With Patellofemoral Pain: A Randomized Controlled Trial.

OBJECTIVE: To test whether a series of brief, psychologically informed educational videos added to physical therapy improved function among adolescents with patellofemoral pain. The secondary aims were to assess pain and psychological beliefs. DESIGN: A double-blinded randomized controlled trial. METHODS: Sixty-eight adolescents with patellofemoral pain were randomly assigned to view brief, psychologically informed videos (n = 34) or control videos (n = 34) in addition to usual care physical therapy. The psychologically informed videos targeted fear-avoidance beliefs, kinesiophobia, and pain catastrophizing. The control videos conveyed basic anatomy, biomedical factors, and lower extremity mechanics. Outcomes were assessed at baseline, 3 weeks, 6 weeks (primary end point), and 3 months. The primary outcome was change in the Anterior Knee Pain Scale. Secondary outcomes were changes in Numeric Pain-Rating Scale and psychological beliefs (Modified Fear-Avoidance Beliefs Questionnaire-Physical Activity, Tampa Kinesiophobia Scale-11, and Pain Catastrophizing Scale-Child). RESULTS: Adolescents in the psychologically informed group experienced significantly greater improvements in function (Anterior Knee Pain Scale mean difference = 8 points; 95% CI: 2.2, 13.2; P = .01) and pain (Numeric Pain-Rating Scale mean difference = 1.2 points; 95% CI: 0.1, 2.4; P = .04) at 6 weeks compared to the control group. The psychologically informed group had significantly greater reductions in psychological beliefs over time than the control group (P≤.001; partial η2 = 0.32). CONCLUSION: Incorporating psychologically informed education into physical therapy care improved function, pain, and psychological beliefs to a greater extent than the control group. J Orthop Sports Phys Ther 2023;53(10):1-9. Epub: 14 September 2023. doi:10.2519/jospt.2023.12041.

Photocrystallography of [Ru(bpy)2(dmso)2]2+ reveals an O-bonded metastable state.

We report the first instance of observing the phototriggered isomerization of dmso ligands on a bis sulfoxide complex, [Ru(bpy)2(dmso)2], in the crystalline solid state. The solid-state UV-vis spectrum of the crystal demonstrates an increase in optical density around 550 nm after irradiation, which is consistent with the solution isomerization results. Digital images of the crystal before and after irradiation display a notable color change (pale orange to red) and cleavage occurs along planes, (1̄01) and (100), during irradiation. Single crystal X-ray diffraction data also confirms that isomerization is occurring throughout the lattice and a structure that contains a mix of the S,S and O,O/S,O isomer was attained from a crystal irradiated ex situ. In situ irradiation XRD studies reveal that the percentage of the O-bonded isomer increases as a function of 405 nm exposure time.

Improving Access to Early Palliative Care Delivery for Patients With an Advanced Thoracic Malignancy Through an Embedded Oncopalliative Clinic Model.

PURPOSE: Early integration of palliative care (PC) with standard oncology care is driving the development of innovative PC delivery models. METHODS: This was a single-institution retrospective study of outpatient PC before and after the opening of an embedded thoracic oncology-palliative clinic at The Ohio State University. Patients included in the preintervention (October 2017-July 2018) and postintervention (October 2018-July 2019) cohorts had a diagnosis of any non-small-cell lung cancer (stages I-IV) or small-cell lung cancer (limited or extensive stage) and were newly established in the thoracic medical oncology clinic during the study time periods. All patients in the preintervention cohort had access to outpatient PC through a freestanding clinic, while the postintervention cohort had access to both freestanding and embedded clinics. Using time-to-event analyses, we evaluated differences in time intervals from first medical oncology visit to PC referral and first PC visit between cohorts. RESULTS: The majority of patients in both cohorts had metastatic disease at diagnosis. In the postintervention cohort, 20.9% of patients were referred to outpatient PC compared with 9.2% in the preintervention cohort (P < .01). PC referrals for patients outside of Franklin and adjacent counties increased from 4.0% to 14.2% after opening the embedded clinic (P < .01). Completion percentages of PC referrals increased from 57.6% to 76.0% in the preintervention versus postintervention cohorts (P = .048). Median time from palliative referral order to first PC visit decreased from 29 to 20 days (P = .047). Similarly, median time from the first oncology visit to PC referral completion decreased from 103 to 41 days (P = .08). CONCLUSION: Implementation of an embedded PC model was associated with increased access to early PC among patients with thoracic malignancies.

Maternal mood and anxiety effects on the fetal nonstress test.

BACKGROUND: Previous studies have suggested that acute mood states may influence levels of fetal activity. Because the fetal nonstress test relies on markers of fetal activity to suggest fetal wellbeing, its interpretation may be affected by maternal mood. OBJECTIVE: This study sought to determine if there are differences in nonstress test characteristics between pregnant individuals with and without symptoms of mood disorder. STUDY DESIGN: In this prospective cohort study, we recruited pregnant individuals undergoing nonstress test in the third trimester and compared the results of the nonstress test between pregnant individuals with scores above and below the cutoff values on validated screening questionnaires for depression and anxiety symptoms, the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic information was collected from each participant at the time of recruitment, and medical information was extracted from the electronic medical record. RESULTS: A total of 68 pregnant individuals were enrolled, 10 (15%) of which screened positive for perinatal mood disorders. There was no significant difference in means of time to reactivity (15.6 [4.8] minutes vs 15.0 [8.0] minutes, P=.77), number of accelerations (0.16/min [0.08] vs 0.16/min [0.10], P>.95), number of fetal movements (17.0 [14.7] vs 19.7 [20.4], P=.62), heart rate baseline (138.0 [7.5] bpm vs 139.2 [9.0] bpm, P=.67) or variability (8.5 [2.5] bpm vs 9.1 (4.3) bpm, P=.51) between pregnant individuals who screen positive for mood disorders and those who did not. CONCLUSION: Fetal heart rate patterns are similar in pregnant individuals with and without symptoms of mood disorder. The results provide reassurance that acute symptoms of anxiety and depression do not have significant effects on the fetal nonstress test.

Enhancing the Stability of Nicotine via Crystallization Using Enantiopure Tartaric Acid Salt Formers.

Crystallization of nicotine, an oil prone to degradation at room temperature, has been demonstrated to be an effective means of creating nicotine-based materials with tunable thermal properties and improved resistance to photo-induced degradation. Herein, we show that both isomers of enantiomerically pure tartaric acid are highly effective salt formers when combined with nicotine. Both salts exhibit enhanced photostability, and with a melting point of 143.1 °C, the salt prepared using d-(-)-tartaric acid possesses one of the highest melting points for a crystalline nicotine solid reported to date.

Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study.

BACKGROUND: Insulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA. METHODS: This was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations. RESULTS: RA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ = - 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03). CONCLUSIONS: Mitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.

Characterization of Patients with Frequent Utilization of the Obstetric Triage Unit: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to identify characteristics of patients with frequent obstetric triage visits ("superusers") compared to those with fewer visits and to evaluate the association of frequent obstetric triage visits with preterm birth and cesarean delivery. STUDY DESIGN: This retrospective cohort included patients presenting to the obstetric triage unit at a tertiary care center from March through April 2014. Superusers were defined as individuals having four or more triage visits. Participant characteristics, including demographic, clinical, visit acuity, and health care characteristics of superusers and nonsuperusers, were summarized and compared. In the subset of patients where data were available regarding prenatal care, prenatal visit patterns were analyzed and compared between the two groups. The outcomes of preterm birth and cesarean were compared between groups using modified Poisson regression to control for confounding. RESULTS: Of the 656 patients evaluated in the obstetric triage unit during the study period, 648 patients met the inclusion criteria. Factors associated with frequent triage use included race/ethnicity, multiparity, insurance status, high-risk pregnancy, and a prior preterm birth. Superusers were more likely to present at an earlier gestational age and had a higher proportion of visits for hypertensive disease. Patient acuity scores were not different between the groups. In the subset of patients receiving prenatal care at the institution, prenatal visit patterns were similar. The risk of preterm birth (adjusted risk ratio [aRR]: 1.06; 95% confidence interval [CI]: 0.66-1.70) did not differ between groups; however, the risk of a cesarean delivery was increased in superusers (aRR: 1.39; 95% CI: 1.01-1.92) when compared to nonsuperusers. CONCLUSION: Superusers, compared to nonsuperusers, have distinct clinical and demographic characteristics and are more likely to be seen in the triage unit at earlier gestational ages. Superusers tended to have a higher proportion of visits for hypertensive disease and had an increased risk of cesarean delivery. KEY POINTS: · Patients with frequent triage visits did not have an increased risk of preterm birth.. · Patients with frequent triage visits were more likely to undergo cesarean delivery.. · Acuity scales were similar for patients with frequent visits compared to those with few visits..

Separation of diarylethene-based photoswitchable isomeric compounds by high-performance liquid chromatography and supercritical fluid chromatography.

Diarylethene-based photoswitches have become very popular over the last few decades for potential applications in chemistry, materials science, and biotechnology due to their unique physical and chemical properties. We report the isomeric separation of a diarylethene-based photoswitchable compound using high-performance liquid chromatography. The separated isomers were characterized by ultraviolet-visible spectroscopy and mass spectrometry confirmed the isomeric nature of the compounds. The isomers were purified by preparative high-performance liquid chromatography, providing fractionated samples to study the isomers individually. A total amount of 13 mg of an isomer of interest was fractionated from a solution of 0.4 mg/ml of the isomeric mixture. Because the preparative high-performance liquid chromatographic method required large quantities of solvent, we explored the use of supercritical fluid chromatography as an alternative separation mode which, to the best of our knowledge, is the first time this technique is used to separate diarylethene-based photoswitchable compounds. Supercritical fluid chromatography provided faster analysis times while maintaining sufficient baseline resolution for the separated compounds and consuming less organic solvent in the mobile phase compared to high-performance liquid chromatography. It is proposed that the supercritical fluid chromatographic method be upscaled and used in future fractionation of the diarylethene isomeric compounds, becoming a more environmentally benign approach for compound purification.

The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits.

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits in kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities. Methods: Native kidney biopsies showing glomerular IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between 2010 and 2021. Detailed clinicopathologic features were assessed. One-year clinical follow-up on a subset of cases was obtained. Results: A total of 285 cases were identified, and these clustered into IgA nephropathy (IgAN, n = 108), Staphylococcus or other infection-associated GN/infection-related GN (SAGN/IRGN, n = 43), and antineutrophil cytoplasmic antibody-associated GN (ANCA-GN, n = 26) based on a constellation of clinicopathologic features, but 101 cases (group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinicopathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases) revealed that clinicians' working diagnosis was IgAN in 43%, SAGN/IRGN in 22%, ANCA-GN in 28%, and others in 7% of the cases, but treatment approach varied from supportive or antibiotics to immunosuppression in each subgroup. Comparing these cases as "received immunosuppression" versus "non-immunosuppression," only 2 features differed, namely C3-dominant staining, and possibility of recent infection (both higher in the no-immunosuppression group) (P < 0.05). Renal loss was higher in the non-immunosuppression subgroup, but not statistically significant (P = 0.11). Conclusion: Diagnostic overlap may remain unresolved in a substantial number of kidney biopsies with glomerular crescents and IgA deposits. A case-by-case approach, appropriate antibiotics if infection is ongoing, and consideration for cautious immunosuppressive treatment for progressive renal dysfunction may be needed for best chance of renal recovery.

Feasibility of an embedded palliative care clinic model for patients with an advanced thoracic malignancy.

PURPOSE: Early palliative care (PC) with standard oncology care has demonstrated improved patient outcomes, but multiple care delivery models are utilized. This study prospectively evaluated the feasibility of an embedded PC clinic model and collected patient-reported outcomes (PROs) and caregiver needs. METHODS: In this observational study of embedded outpatient PC for patients with advanced thoracic malignancies treated at The Ohio State University Thoracic Oncology clinic, patients received same-day coordinated oncology and palliative care visits at one clinic location. PC encounters included comprehensive symptom assessment and management, advanced care planning, and goals of care discussion. Multiple study assessments were utilized. We describe the feasibility of evaluating PROs and caregiver needs in an embedded PC model. RESULTS: Forty patients and 28 caregivers were enrolled. PROs were collected at baseline and follow-up visits. Over a 12-month follow-up, 36 patients discontinued study participation due to hospice enrollment, death, study withdrawal, or COVID restrictions. At baseline, 32 patients (80%) rated distress as moderate-severe with clinically significant depression (44%) and anxiety (36%). Survey completion rates significantly decreased over time: 3 months (24 eligible, 66% completed), 6 months (17 eligible; 41% completed), 9 months (9 eligible; 44% completed), and 12 months (4 eligible; 50% completed). CONCLUSION: We found that an embedded PC clinic was feasible, although there were challenges encountered in longitudinal collection of PROs due to high study attrition. Ongoing assessment and expansion of this embedded PC model will continue to identify strengths and challenges to improve patient and caregiver outcomes.

4,4'-(Ethene-1,2-diyl)dipyridinium bis(2-hy-droxy-3-meth-oxy-benzoate).

In the title double proton-transfer salt, C12H12N2 2+·2C8H7O4 -, consisting of a 1:2 ratio of 4,4'-(ethene-1,2-diyl)dipyridinium cations (trans bipyridinium ethyl-ene) to 2-hy-droxy-3-meth-oxy-benzoate anions (o-vanillate), the complete cation is generated by crystallographic inversion symmetry and it is linked to adjacent o-vanillate anions by N-H⋯O hydrogen bonds, forming trimolecular assemblies. The trimers are linked by C-H⋯O hydrogen bonds as well as aromatic π-π stacking inter-actions into a three-dimensional network. The anion features an intra-molecular O-H⋯O hydrogen bond.

1,2-Bis(pyridin-4-yl)ethene-4-hy-droxy-3-meth-oxy-benzoic acid (1/1).

In the title 1:1 co-crystal [alternatively called bi-pyridine ethyl-ene-p-vanillic acid (1/1)], C12H10N2·C8H8O4, the dihedral angle between the pyridine rings is 59.51 (5)°. In the crystal, the mol-ecules are linked by O-H⋯N hydrogen bonds, generating [401] chains of alternating C12H10N2 and C8H8O4 mol-ecules.

Enhancing the Photo and Thermal Stability of Nicotine through Crystal Engineering with Gentisic Acid.

The use of crystal engineering to convert liquids into crystalline solids remains a powerful method for inhibiting undesired degradation pathways. When nicotine, a liquid sensitive to both light and air, is combined with the GRAS-listed compound, gentisic acid, the resulting crystalline solid, exhibits enhanced photo and thermal stability. Despite a modest ΔTm of 42.7 °C, the melting point of 155.9 °C for the nicotinium gentisate salt is the highest reported for nicotine-containing crystalline solids. An analysis of the crystal packing and thermodynamic properties provides context for the observed properties.

Beyond mismatch repair deficiency? Pre-treatment neutrophil-to-lymphocyte ratio is associated with improved overall survival in patients with recurrent endometrial cancer treated with immunotherapy.

OBJECTIVE: To determine the association of pre-treatment neutrophil-to-lymphocyte ratio (NLR) with progression-free survival (PFS) and overall survival (OS) for patients with recurrent endometrial cancer (EC) treated with immunotherapy. METHODS: Recurrent EC patients treated with immunotherapy alone or in combination from 2016 to 2021 were included. Demographics, pre-treatment laboratory results, pathologic data, response at first radiographic assessment, and cancer outcomes were obtained from the medical record. Kaplan-Meier curves were generated to compare PFS and OS stratified by NLR. RESULTS: The 106 patients included in the study were stratified by NLR <6 (n = 77, 72.6%) or NLR ≥6 (n = 29, 27.3%). Most had endometrioid pathology (59%), widely metastatic disease, and 36.8% had received ≥2 treatment lines before initiating immunotherapy. Mismatch repair deficiency (dMMR) was noted in 52 (49.1%) tumors. Most dMMR patients (94.3%) were treated with single-agent pembrolizumab, and most MMR proficient patients (78.7%) were treated with lenvatinb plus pembrolizumab. In the overall cohort, 40.2% (partial response (PR) 29.9%, complete response (CR) 10.4%) of patients with a NLR <6 responded at first radiographic assessment, compared to 31% (PR 27.5%, CR 3.4%) of patients with NLR ≥6 (p 0.691). Kaplan-Meier curves stratified by NLR <6 vs. ≥6 showed no difference in PFS. However, NLR <6 was associated with improved OS (p < 0.05). In the NLR < 6 group, the probability of survival at one year was 69% (95% CI: 58%, 82%), compared to 41% (95% CI: 26%, 67%) for the NLR > 6 group. CONCLUSIONS: Pre-treatment NLR <6 was associated with improved OS for recurrent EC patients treated with immunotherapy. NLR holds promise as a predictive biomarker for survival after immunotherapy treatment for patients with recurrent EC.