The associations of spirituality and Hispanic ethnicity with neuroendocrine biomarkers among patients with colorectal cancer.

OBJECTIVE: Dealing with cancer evokes not only physical and emotional distress, but may also promote resilience through spirituality. Patients with cancer are vulnerable to neuroendocrine dysregulation. This longitudinal observational study examined the degree to which spirituality was associated with neuroendocrine biomarkers and the moderating role of Hispanic ethnicity. METHODS: Participants were adults who were recently diagnosed with colorectal cancer (n = 81, 55 years old, 66% male, 63% Hispanic, 72% advanced cancer, 7 months post-diagnosis). The domains of spirituality (faith, meaning, and peace) and ethnicity (Hispanic vs. non-Hispanic) were self-reported. Cortisol and alpha amylase (sAA) were assayed from saliva samples collected at waking and bedtime on seven consecutive days. Mean levels at waking and bedtime, and diurnal slopes over seven days were calculated. Age and cancer stage were covariates. RESULTS: Overall, patients reported moderate to high levels of spirituality. General linear modeling revealed that greater faith was associated with higher levels of sAA at waking and bedtime as well as more blunted diurnal pattern of sAA only among Hispanic patients (p ≤ .045). Greater peace was associated with steeper diurnal pattern of sAA, regardless of ethnicity (B = 0.021, p = .005). Meaning and cortisol were not significantly associated with study variables. CONCLUSIONS: Findings indicate that presence of peace facing a cancer diagnosis associated with neuroendocrine regulation, whereas drawing on one's faith, particularly among Hispanic patients, associated with neuroendocrine dysregulation during the first months after the diagnosis. Further investigations of psychobiobehavioral moderators and mediators for healthy neuroendocrine functioning among patients with cancer are warranted.

Differential effects of desvenlafaxine on hot flashes in women with breast cancer taking tamoxifen: a randomized controlled trial.

Hot flashes (HF) are a common adverse event of prolonged tamoxifen use in women with estrogen receptor-positive breast cancer, impacting psychiatric health and quality of life. While desvenlafaxine does not interact with tamoxifen, its efficacy and safety in breast cancer patients remain unstudied. This phase 3, four-week, multi-center, three-arm, parallel-group, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of desvenlafaxine for treating HF in women with breast cancer taking tamoxifen, assessing potential differential effects in patients with psychiatric and inflammatory conditions. Between December 2017 and February 2019, 57 women aged 19 or older, regularly taking tamoxifen as adjuvant therapy, experiencing moderate-to-severe HFs for more than a month, were randomized to receive desvenlafaxine 50 mg/day (D-50), desvenlafaxine 100 mg/day (D-100), or placebo for four weeks. The primary endpoint was the change rate in HF scores over four weeks, with adverse events as a secondary endpoint. Both desvenlafaxine arms demonstrated greater HF score reductions compared to placebo: D-50 (2.20 points/week, 95% CI: 0.71, 3.68) and D-100 (2.34 points/week, 95% CI: 0.92, 3.76). Notably, D-50 arm showed significantly greater efficacy in patients with depression or elevated inflammation. Desvenlafaxine offers an effective and safe treatment regimen for HF in women with breast cancer taking tamoxifen. The presence of depression and inflammation may guide optimal desvenlafaxine dosing. (Trial Registration: ClinicalTrials.gov Identifier: NCT02819921).

Tenapanor: A Phosphate Absorption Inhibitor for the Management of Hyperphosphatemia in Patients With Kidney Failure.

Because of increased risks of cardiovascular disease and death, patients with hyperphosphatemia receiving maintenance dialysis are advised to limit phosphorus consumption and are prescribed phosphate binders in an effort to better control serum phosphate concentrations. Because of large pill size, pill burden, and tolerability issues, phosphate binder adherence is relatively poor. On ingestion, phosphate is absorbed from the intestine via transcellular or paracellular transport. Data show that inhibiting sodium-hydrogen exchanger 3 modulates paracellular phosphate absorption (the predominant pathway in humans). Tenapanor is a first-in-class, minimally absorbed, phosphate absorption inhibitor that selectively inhibits sodium-hydrogen exchanger 3, with a mechanism distinct from, and complementary to, that of phosphate binders. In phase 3 and postregistrational studies, tenapanor conferred statistically significant and clinically meaningful reductions in serum phosphate in patients receiving maintenance dialysis with hyperphosphatemia. Here, we review the available preclinical and clinical data on the effects of tenapanor on controlling intestinal phosphate absorption.

Effectiveness of tenapanor for treating hyperphosphatemia in patients receiving dialysis: a plain language summary of the OPTIMIZE study.

What is this summary about?This summary provides a review of the OPTIMIZE study, the results of which were published in Kidney360 in February 2024. The OPTIMIZE study looked at how well tenapanor tablets work to treat patients receiving dialysis who have high levels of phosphate in their blood, a condition called hyperphosphatemia. In the OPTIMIZE study, researchers wanted to understand if tenapanor would decrease phosphate levels in the blood to the target range. They also tested different ways of starting tenapanor treatment in patients.In the human body, kidneys are organs that filter blood and remove waste products. In chronic kidney disease, sometimes referred to as CKD, a patient's kidneys do not work as well at filtering their blood and removing waste products. This can allow phosphate to build up in the blood. Phosphate levels may remain high despite patients receiving treatment such as dialysis, using pills that keep phosphate in the intestines (called phosphate binders) to prevent phosphate from being absorbed into the blood, and eating a low-phosphate diet. Phosphate levels may remain high despite these treatments because they can be difficult to follow. Most people receiving dialysis take 7­8 phosphate binder pills every day, and over half of those people have reported skipping at least one dose in the past month. Additionally, low-phosphate diets can be difficult to follow and people often struggle to meet their other nutritional needs.What are the key takeaways?Tenapanor used in combination with phosphate binders led to lower phosphate levels in the blood with the use of fewer phosphate-lowering pills. Tenapanor also lowered phosphate levels in patients who were not previously on phosphate binders but needed phosphate-lowering treatment.What were the main conclusions reported by the researchers?Tenapanor can help patients receiving dialysis better control their hyperphosphatemia.[Box: see text]Link to original article here.

Hypnosis facilitates psychosomatic improvement in a patient with treatment-resistant idiopathic tinnitus.

Chronic tinnitus, also known as phantom sound perception, is a pervasive and often debilitating condition, affecting 15 to 20% of the population. Due to its idiopathic and persistent nature, chronic tinnitus is frequently associated with co-occurring psychiatric disorders as well as decreased sleep and quality of life. Additionally, heterogeneous presentations of tinnitus create challenges for treatment. In this paper, we present a case study of a 70-year-old female patient who presented with severe bilateral tinnitus over a period of 5 years. After failing multiple treatment trials such as transtympanic electric stimulation, acupuncture, Eye Movement Desensitization and Reprocessing, and medication, the patient found relief only through hypnotherapy. Results may be explained by alterations in interoceptive processing, increased cognitive flexibility, or somatosensory changes, with corresponding changes in functional neural structures. Given the results of this case study, we recommend hypnosis as an alternative or adjunct to current treatment modalities for tinnitus and further investigation in this area.

Bifunctional Molecules That Induce Both Targeted Degradation and Transcytosis of Extracellular Proteins in Brain Cells.

Targeted protein degradation (TPD) has emerged as an effective therapeutic strategy for a wide range of diseases; however, the blood-brain barrier (BBB) limits access of degraders into the central nervous system (CNS). Here, we present a new class of bifunctional small molecules, called TransMoDEs (Transcytosis-inducing molecular degraders of extracellular proteins), capable of both (1) removal of target protein via lysosomal proteolysis and (2) transcytosis of protein targets across brain endothelial cells. TransMoDEs are derived from Angiopep-2, a peptide motif previously employed as a covalent tag to facilitate receptor-mediated transcytosis across the BBB. We demonstrate that TransMoDEs containing either a biotin or chloroalkane ligand can trigger endocytosis of streptavidin or HaloTag protein, respectively. Interestingly, although low-density lipoprotein receptor-related protein 1 (LRP1) has been reported as the primary receptor for Angiopep-2, TransMoDE-mediated target uptake does not rely exclusively on this pathway. Furthermore, TransMoDE-mediated endocytosis of streptavidin in a bEnd.3 BBB model occurs in a clathrin-mediated mechanism and results in both lysosomal localization and transcytosis of the target protein. This study demonstrates that TransMoDEs can recruit, transcytose, and degrade proteins of interest in cells relevant to the CNS, supporting their further development for the removal of pathogenic neuroproteins.

Treatment of Refractory Bipolar Depression With Stereotactic Radiosurgery Targeting the Subgenual Cingulate Cortex.

Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.

Preliminary testing of "roadmap to parenthood" decision aid and planning tool for family building after cancer: Results of a single-arm pilot study.

OBJECTIVE: Many young adult female cancer survivors need to use reproductive medicine, surrogacy, or adoption to have a child. This study pilot tested Roadmap to Parenthood, a web-based, self-guided decision aid and planning tool for family building after cancer (disease agnostic). METHODS: A single-arm pilot study tested feasibility, acceptability, and obtained effect size estimates of the Roadmap tool. Participants, recruited via hospital-based and social media strategies, completed a baseline survey (T1), accessed the Roadmap tool (website), then completed surveys at one- and 3-months (T2 and T3, respectively). Feasibility and acceptability were evaluated with rates of eligibility, enrollment, and survey completion, and feedback. Pairwise t-tests and repeated measures ANOVA evaluated usage effects. Effect size estimates were calculated. RESULTS: Participants (N = 98) averaged 31 years old (SD = 5.61); 71% were nulliparous. Enrollment rate was 73%, T1-T2 completion rate was 80%, and 93% accessed the website. From T1-T2, participants reported improvements in decisional conflict (p < 0.001; Cohen's d = 0.85), unmet information needs (p < 0.001; Cohen's d = 0.70), self-efficacy (p = 0.003; Cohen's d = 0.40), and self-efficacy for managing negative emotions (p = 0.03; Cohen's d = 0.29); effects were sustained at T3. There was no change in reproductive distress (p = 0.22). By T3, 94% reported increased consideration of preparatory actions and 20%-61% completed such actions. CONCLUSIONS: The Roadmap intervention was feasible to conduct, acceptable to users, and led to improvements in key psychosocial outcomes. Future directions will test intervention efficacy in a randomized controlled trial with a larger sample and over a longer period. A web-based tool may help women make decisions about family building after cancer and prepare for potential challenges.

Dyadic Investigation of Posttraumatic Stress Symptoms and Daily Sleep Health in Patients With Cancer and Their Caregivers.

OBJECTIVE: Cancer can be a traumatic experience affecting multidimensional aspects of sleep among patients and caregivers. This study examined the differential associations of cancer-related posttraumatic stress symptoms (PTSS) with various sleep markers in this population. METHODS: Patients newly diagnosed with colorectal cancer ( n = 138, mean age = 56.93 years, 31.88% female, 60.14% Hispanic, 6.53 months after diagnosis) and their sleep-partner caregivers ( n = 138, mean age = 55.32 years, 68.12% female, 57.97% Hispanic) completed questionnaires assessing the four PTSS clusters (intrusion, avoidance, alterations in arousal and reactivity, negative alterations in cognitions and mood). Participants also completed daily sleep diaries for 14 consecutive days, from which sleep onset latency (SOL), wake after sleep onset (WASO), and sleep duration were derived. RESULTS: Actor-partner interdependence model revealed that caregivers' greater alterations in arousal and reactivity were associated with their own longer SOL ( b = 15.59, p < .001) and their patients' longer sleep duration ( b = 0.61, p = .014), whereas patients' arousal and reactivity were associated with their caregivers' shorter SOL ( b = -8.47, p = .050). Patients' and caregivers' greater negative alterations in cognitions and mood were associated with patients' longer SOL ( b = 9.15, p = .014) and shorter sleep duration ( b = -0.41, p = .050), respectively. Caregivers' greater intrusion was related to their own shorter SOL ( b = -10.14, p = .004). CONCLUSIONS: The four PTSS clusters, particularly arousal and reactivity and negative cognitions and mood, have distinct associations with sleep markers individually and dyadically in patients and caregivers affected by cancer. Investigations of psychosocial and biobehavioral pathways underlying these relations are warranted. Tailored trauma treatments and sleep interventions may improve the well-being of this population.

Should I stay or should I go: an assessment of criteria for safe day of surgery discharge of displaced supracondylar humerus fractures.

Immobilization type and in-hospital observation following surgical management of displaced supracondylar fractures are subject to surgeon preference and training. Our goal was to determine criteria for immediate discharge and optimal type of immobilization. Medical records of 661 patients with type III, IV or flexion-type displaced supracondylar humerus fractures treated at a level 1 pediatric trauma center from January 2013 to September 2019 were reviewed. Patients were separated into 'admission appropriate' (AA = 113) and 'discharge appropriate' (DA = 548) sub-cohorts. Neurovascular deficit at presentation (P < 0.001), post-operative physical exam deterioration (P < 0.001), age (P < 0.001) and post-operative immobilization modality (P = 0.02) were significantly different between AA and DA groups. When comparing patients who presented with neurologic deficit to those neurovascularly intact, there was a significant difference in whether circumferential immobilization was used post-operatively (P < 0.001), IV medication need (P < 0.001), discharge or admission (P < 0.001), neurologic decline (P < 0.001), return to ED (P = 0.008) and vascular compromise (P = 0.05). Twenty-four of the 56 (43%) patients who were AA and had no neurovascular finding on presentation had their immobilization adjusted (bivalved or loosened) to accommodate for swelling overnight. Only 1 was initially maintained in a splint or bivalved cast; the other 23 were initially maintained post-operatively in circumferential immobilization (P = 0.01). Our findings suggest that patients with intact neurovascular exams at presentation are candidates for early discharge, and splinting or bivalved casting may be preferable, especially in patients who are discharged.

Tranceformation: Digital dissemination of hypnosis.

Hypnosis is an underutilized tool despite evidence of efficacy from randomized clinical trials. In this NeuroView, I discuss potential mechanisms in the context of brain networks and propose the use of app-based instruction in self-hypnosis.

Rotation and Asymmetry of the Axial Plane Pelvis in Cerebral Palsy: A CT-Based Study.

Spinopelvic malignment is commonly seen with non-ambulatory cerebral palsy (CP). Axial plane deformation is not well described in the literature. The purpose of this study was to describe and quantify the axial plane deformity in CP using CT scans and compare it to normal controls. We retrospectively collected data using CT scans of the abdomen and pelvis of 40 patients with GMFCS IV/V CP and neuromuscular scoliosis (CPP) and normal controls (NP) matched by age and sex. Pre-operative Cobb angle was recorded for the CP patients. Pelvic anatomy was evaluated at the supra-acetabular region of bone using two angles-iliac wing angle and sacral ala angle, measured for each hemipelvis. The larger of each hemipelvis angle was considered externally rotated while the smaller angle was considered internally rotated, termed as follows-iliac wing external (IWE) and internal (IWI); sacral ala external (SAE), and internal (SAI). Differences were noted using an independent t-test while correlations with Cobb angle were performed using Pearson's correlation. Iliac wing measurements showed the externally rotated hemipelvis showed a significantly greater magnitude compared with normal controls at 47.3 ± 18.1 degrees vs. 26.4 ± 3.7 degrees in NP (p < 0.001) while no internal rotation was observed (p > 0.05). Sacral ala measurements showed greater magnitude in both external and internal rotation. SAE was 119.5 ± 9.5 degrees in CPP vs. 111.2 ± 7.7 degrees in NP (p < 0.001) while SAI was 114.1 ± 8.5 degrees in CPP vs. 107.9 ± 7.5 degrees in NP (p = 0.001). In the CP cohort, the mean Cobb angle was 61.54 degrees (n = 37/40). Cobb angle correlated with the degree of external iliac wing rotation-IWE (r = 0.457, p = 0.004) and degree of absolute difference in the rotation of the iliac wing (r = 0.506, p = 0.001). The pelvis in a patient with CP scoliosis is asymmetrically oriented exhibiting a greater external rotation of one hemipelvis relative to normal controls. The severity of neuromuscular scoliosis is related to the pelvic axial rotation in CP patients. Axial plane deformity exists in the CP pelvis and this deformity warrants consideration when considering spinopelvic instrumentation strategies and outcomes of supra-pelvic and infra-pelvic pathologies.

The Neural Separability of Emotion Reactivity and Regulation.

One foundational distinction in affective science is between emotion reactivity and regulation. This conceptual distinction has long been assumed to be instantiated in spatially separable brain systems (a typical example: amygdala/insula for reactivity and frontoparietal areas for regulation). In this research, we begin by reviewing previous findings that support and contradict the neural separability hypothesis concerning emotional reactivity and regulation. Further, we conduct a direct test of this hypothesis with empirical data. In five studies involving healthy and clinical samples (total n = 336), we assessed neural responses using fMRI while participants were asked to either react naturally or regulate their emotions (using reappraisal) while viewing emotionally evocative stimuli. Across five studies, we failed to find support for the neural separability hypothesis. In univariate analyses, both presumptive "reactivity" and "regulation" brain regions demonstrated equal or greater activation for the reactivity contrast than for the regulation contrast. In multivariate pattern analyses (MVPA), classifiers decoded reactivity (vs. neutral) trials more accurately than regulation (vs. reactivity) trials using multivoxel data in both presumptive "reactivity" and "regulation" regions. These findings suggest that emotion reactivity and regulation-as measured via fMRI-may not be as spatially separable in the brain as previously assumed. Our secondary whole-brain analyses revealed largely consistent results. We discuss the two theoretical possibilities regarding the neural separability hypothesis and offer thoughts for future research. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00227-9.