Quality of Life and Real-time Patient Experience During Neoadjuvant Therapy: A Prospective Cohort Study.

OBJECTIVE: To use a customized smartphone application to prospectively measure QOL and the real-time patient experience during neoadjuvant therapy (NT). BACKGROUND: NT is increasingly used for patients with localized gastrointestinal (GI) cancers. There is little data assessing patient experience and quality of life (QOL) during NT for GI cancers. METHODS: Patients with GI cancers receiving NT were instructed on using a customized smartphone application through which the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, a validated measure of health-related QOL, was administered at baseline, every 30 days, and at the completion of NT. Participants also tracked their moods and symptoms and used free-text journaling functionalities in the application. Mean overall and subsection health-related QOL scores were calculated during NT. RESULTS: Among 104 enrolled patients, the mean age was 60.5 ± 11.5 years and 55% were males. Common cancer diagnoses were colorectal (40%), pancreatic (37%), and esophageal (15%). Mean overall FACT-G scores did not change during NT ( P = 0.987). While functional well-being scores were consistently the lowest and social well-being scores the highest, FACT subscores similarly did not change during NT (all P > 0.01). The most common symptoms reported during NT were fatigue, insomnia, and anxiety (39.3%, 34.5%, and 28.3% of patient entries, respectively). Qualitative analysis of free-text journaling entries identified anxiety, fear, and frustration as the most common themes, but also the importance of social support systems and confidence in health care providers. CONCLUSIONS: While patient symptom burden remains high, results of this prospective cohort study suggest QOL is maintained during NT for localized GI cancers.

Ventricular arrhythmias and sudden death events following acalabrutinib initiation.

Acalabrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), associates with dramatic efficacy against B-cell malignancies. Recently, unexplained ventricular arrhythmias (VAs) with next-generation BTKi-therapy have been reported. Yet, whether acalabrutinib associates with VAs in long-term follow-up is unknown. Leveraging a large-cohort of 290 consecutive B-cell malignancy patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence of VAs. The primary-endpoint was incident VA development (ventricular fibrillation, ventricular tachycardia, and symptomatic premature ventricular contractions). Probability-scores were assessed to determine likelihood of acalabrutinib-association. Incident rates as function of time-on-therapy were calculated. Weighted average observed incidence rates were compared with expected population rates using relative-risks. Absolute excess risk (AER) for acalabrutinib-associated VAs was estimated. Over 1063 person-years of follow-up, there were 8 cases of incident-VAs, including 6 in those without coronary disease (CAD) or heart failure (HF) and 1 sudden-death; median time-to-event 14.9 months. Among those without prior ibrutinib-use, CAD, or HF, the weighted average incidence was 394 per 100 000 person years compared with a reported incidence of 48.1 among similar-aged non-BTKi-treated subjects (relative risk, 8.2; P < .001; AER, 346). Outside of age, no cardiac or electrocardiographic variables associated with VA development. Collectively, these data suggest VAs may be a class-effect of BTKi therapies.

Characterizing treatment burden during neoadjuvant therapy for patients with gastrointestinal cancer: A mixed methods analysis.

INTRODUCTION: Neoadjuvant therapy (NT) is increasingly used before surgery for patients with gastrointestinal (GI) cancers. Treatment burden is a patient-centered measure defined as the work of being a patient and characterizes the impact of medical treatment on one's functioning and well-being. While treatment burden has previously been studied in chronic diseases and cancer survivorship, the treatment burden of undergoing NT is unknown. METHODS: All patients enrolled in a prospective cohort study evaluating the real-time experience of NT for GI cancers completed either the Patient Experience with Treatment and Self-management (PETS) survey, a 46-item validated measure of treatment burden, or the mini-PETS questionnaire. PETS subsections were scored on a 5-point Likert scale and then standardized on a 100-point scale (a higher number means more treatment burden). Semistructured interviews were conducted among a convenience sample of patients (n = 5); qualitative data were coded and then analyzed using an integrated approach. RESULTS: Among 126 participants, the mean age was 59 years old, 61% were male, and the mean number of comorbidities was 1.57. The most common cancers were colorectal (46%) and pancreatic (28%). The mean length of NT treatment was 3.7 months and 80.2% of patients underwent surgical resection following NT. The highest standardized treatment burden scores were observed in healthcare services (44 ± 15), social limitations (44 ± 26), exhaustion (41 ± 23), and medical expenses (40 ± 18) whereas the lowest scores were reported in medication use (19 ± 16) and interpersonal challenges (19 ± 17). Commonly experienced emotional symptoms were feeling worn out (43%) or frustrated (32%). No significant differences were observed in mean treatment burden subscores between patients who underwent surgery versus those who did not. Qualitative analysis of treatment burden during NT identified common themes of impact on normal life activities, challenges with healthcare access, impact on relationships, and significant physical and emotional symptoms. CONCLUSIONS: NT is associated with a significant treatment burden, particularly in the domains of accessing healthcare services, social limitations, and exhaustion. Given the increasing use of NT for GI cancers, novel patient-centered approaches are needed to improve quality of life and ensure the completion of multimodality therapy.

Fall Prevention With the Smart Socks System Reduces Hospital Fall Rates.

BACKGROUND: Falls of inpatients are common in hospitals. Existing fall prevention measures do not work consistently. PURPOSE: To determine whether Smart Socks reduce fall rates in fall risk patients at a major academic health center's neurological and neurosurgical based units. METHODS: A prospective study was conducted that provided fall risk patients with Smart Socks and no other fall prevention system. Data collected included duration of Smart Socks wearing, number of alarms, response times, and patient-days. RESULTS: A total of 569 fall risk patients were included for 2211.6 patient-days. There were 4999 Smart Socks alarms, but none of the patients fell. We observed a lower fall rate, of 0 per 1000 patient-days, for patients wearing Smart Socks than the historical fall rate of 4 per 1000 patient-days. The median nurse response time was 24 seconds. CONCLUSIONS: The Smart Socks reduced fall rates of fall risk patients included in the study.

Impact of a pharmacist-led tacrolimus management protocol in the outpatient setting.

BACKGROUND: Clinical pharmacists are often used to make recommendations regarding tacrolimus therapy in the post transplant setting.Therapeutic drug monitoring (TDM) of tacrolimus after transplant is based on trough levels in the setting of predetermined institutional immunosuppression goals. To evaluate time within therapeutic range (TTR) of tacrolimus the Rosendaal method can be utilized. OBJECTIVE: Our study aimed to compare objective therapeutic drug monitoring outcomes after the implementation of a pharmacist driven tacrolimus management protocol (postprotocol initiation) with previous management by providers (preprotocol initiation). PRACTICE DESCRIPTION: The Ohio State University Wexner Medical Center (OSUWMC) is a 700-bed academic medical center in Columbus, OH. On average, OSUWMC completes more than 300 kidney transplants each year. There are 6 abdominal transplant pharmacists (including one postgraduate year 2 transplant pharmacy resident) that rotate through the inpatient and outpatient setting. PRACTICE INNOVATION: A pharmacist-led tacrolimus management protocol in kidney transplant recipients was initiated in October 2018 at our institution, which enabled pharmacists to dose and adjust tacrolimus in the outpatient setting in accordance with prespecified goals. EVALUATION METHODS: This single-center retrospective analysis included adult kidney transplant recipients on de novo tacrolimus. Patient's tacrolimus levels were evaluated for 6 months after transplant. The mean tacrolimus percent TTR and the median coefficient of variation (CV) were calculated and compared in postprotocol initiation group (n = 85) with preprotocol initiation group (n = 39). TTR was calculated using the Rosendaal method. RESULTS: There was no statistically significant difference between the preprotocol initiation and postprotocol initiation group mean TTR (59.6% vs. 60.5%, P = 0.723), mean CV from 0-3 months after transplant (36.3 vs. 36.0, P = 0.900), and mean CV from at least 3-6 months after transplant (24.5 vs. 22.7, P = 0.351). Rejection rates, development of donor-specific antibodies, and renal function were similar between groups. CONCLUSION: Based on our findings, transplant pharmacists were equally as effective at maintaining tacrolimus percent TTR and CV in the designated kidney transplant recipients included in the management protocol compared with primary management by other transplant providers. The delegation of tacrolimus management to clinical pharmacists is a viable alternative to primary management by outpatient practitioners.

Patient preferences and adherence to adjuvant GnRH analogs among premenopausal women with hormone receptor positive breast cancer.

PURPOSE: Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa. METHODS: We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes. RESULTS: A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa. CONCLUSION: Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship.

Efficacy of different dosing schedules of capecitabine for metastatic breast cancer: a single-institution experience.

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1-14 on 21-day cycle) to biweekly dosing (Arm B: days 1-7 and 15-21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm's correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1-14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1-7 and 15-21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.

Assessment of outcomes and novel immune biomarkers in metaplastic breast cancer: a single institution retrospective study.

BACKGROUND: Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear. METHODS: We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples. RESULTS: Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1-19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02). CONCLUSIONS: Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

The effect of supplemental high Fidelity simulation training in medical students.

BACKGROUND: Simulation-based education (SBE) with high-fidelity simulation (HFS) offers medical students early exposure to the clinical environment, allowing development of clinical scenarios and management. We hypothesized that supplementation of standard pulmonary physiology curriculum with HFS would improve the performance of first-year medical students on written tests of pulmonary physiology. METHODS: This observational pilot study included SBE with three HFS scenarios of patient care that highlighted basic pulmonary physiology. First-year medical students' test scores of their cardio-pulmonary curriculum were compared between students who participated in SBE versus only lecture-based education (LBE). A survey was administered to the SBE group to assess their perception of the HFS. RESULTS: From a class of 188 first-year medical students, 89 (47%) participated in the SBE and the remaining 99 were considered as the LBE group. On their cardio-pulmonary curriculum test, the SBE group had a median score of 106 [IQR: 97,110] and LBE group of 99 [IQR: 89,105] (p < 0.001). For the pulmonary physiology subsection, scores were also significantly different between groups (p < 0.001). CONCLUSIONS: Implementation of supplemental SBE could be an adequate technique to improve learning enhancement and overall satisfaction in preclinical medical students.

Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.

BACKGROUND: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood. METHODS: We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer. RESULTS: Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for < 6 months vs ≥ 6 months showed significant enrichment of Notch signaling pathway genes, along with a trend for enrichment for luminal progenitor gene signature similar to what is observed in BRCA1 mutation carriers and basal-like breast tumors. CONCLUSIONS: We report here for the first time that forced or abrupt involution of the mammary glands following pregnancy and lack of breastfeeding results in expansion of luminal progenitor cells, higher inflammation, proliferation, and ductal hyperplasia, a known risk factor for developing breast cancer.

HTLV-1 CTCF-binding site is dispensable for in vitro immortalization and persistent infection in vivo.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The exact mechanism(s) through which latency and disease progression are regulated are not fully understood. CCCTC-binding factor (CTCF) is an 11-zinc finger, sequence-specific, DNA-binding protein with thousands of binding sites throughout mammalian genomes. CTCF has been shown to play a role in organization of higher-order chromatin structure, gene expression, genomic imprinting, and serve as a barrier to epigenetic modification. A viral CTCF-binding site (vCTCF-BS) was previously identified within the overlapping p12 (sense) and Hbz (antisense) genes of the HTLV-1 genome. Thus, upon integration, HTLV-1 randomly inserts a vCTCF-BS into the host genome. vCTCF-BS studies to date have focused primarily on HTLV-1 chronically infected or tumor-derived cell lines. In these studies, HTLV-1 was shown to alter the structure and transcription of the surrounding host chromatin through the newly inserted vCTCF-BS. However, the effects of CTCF binding in the early stages of HTLV-1 infection remains unexplored. This study examines the effects of the vCTCF-BS on HTLV-1-induced in vitro immortalization and in vivo viral persistence in infected rabbits. RESULTS: HTLV-1 and HTLV-1∆CTCF LTR-transactivation, viral particle production, and immortalization capacity were comparable in vitro. The total lymphocyte count, proviral load, and Hbz gene expression were not significantly different between HTLV-1 and HTLV-1∆CTCF-infected rabbits throughout a 12 week study. However, HTLV-1∆CTCF-infected rabbits displayed a significantly decreased HTLV-1-specific antibody response compared to HTLV-1-infected rabbits. CONCLUSIONS: Mutation of the HTLV-1 vCTCF-BS does not significantly alter T-lymphocyte transformation capacity or early in vivo virus persistence, but results in a decreased HTLV-1-specific antibody response during early infection in rabbits. Ultimately, understanding epigenetic regulation of HTLV-1 gene expression and pathogenesis could provide meaningful insights into mechanisms of immune evasion and novel therapeutic targets.

Muscle contractility dysfunction precedes loss of motor unit connectivity in SOD1(G93A) mice.

INTRODUCTION: Electrophysiological measurements are used in longitudinal clinical studies to provide insight into the progression of amyotrophic lateral sclerosis (ALS) and the relationship between muscle weakness and motor unit (MU) degeneration. Here, we used a similar longitudinal approach in the Cu/Zn superoxide dismutase (SOD1[G93A]) mouse model of ALS. METHODS: In vivo muscle contractility and MU connectivity assays were assessed longitudinally in SOD1(G93A) and wild type mice from postnatal days 35 to 119. RESULTS: In SOD1(G93A) males, muscle contractility was reduced by day 35 and preceded MU loss. Muscle contractility and motor unit reduction were delayed in SOD1(G93A) females compared with males, but, just as with males, muscle contractility reduction preceded MU loss. DISCUSSION: The longitudinal contractility and connectivity paradigm employed here provides additional insight into the SOD1(G93A) mouse model and suggests that loss of muscle contractility is an early finding that may precede loss of MUs and motor neuron death. Muscle Nerve 59:254-262, 2019.

Time to treatment failure of palbociclib and letrozole as second-line therapy or beyond in hormone receptor-positive advanced breast cancer.

PURPOSE: The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy. METHODS: This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond. RESULTS: Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1-7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9-8.3 months). CONCLUSIONS: Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.

An evaluation of veterinary allergen extract content and resultant canine intradermal threshold concentrations.

BACKGROUND: Limited information is available for dogs on threshold concentrations (TCs), and the protein composition of common allergenic extracts produced by different manufacturers. HYPOTHESIS/OBJECTIVES: To characterize the protein heterogeneity of tree, grass, weed and mite allergens from different lots of allergenic extracts, and to determine intradermal TCs for healthy dogs using extracts from two manufacturers. ANIMALS: Twenty five privately owned, clinically healthy dogs and ten purpose-bred beagle dogs. METHODS AND MATERIALS: Protein concentration and heterogeneity of 11 allergens from two manufacturers were evaluated using a Bradford-style assay and SDS-PAGE. Intradermal testing was performed with 11 allergens from each company at four dilutions. Immediate reactions were subjectively scored (0 to 4+), and objectively measured (mm) and their percentage concordance evaluated. Model-based TCs were determined by fitting positive reactions (≥2+) at 15 min to generalized estimating equations. RESULTS: Allergen extract protein quantity and composition varied within and between manufacturers despite sharing the same PNU/mL values. Model-based TCs of one weed, five trees, two grasses and a house dust mite were determined for extracts from Manufacturer 1 (M1), and for extracts of three weeds, three trees and two grasses from Manufacturer 2 (M2). Receiver operating characteristic curve analyses determined a percentage concordance of the objective and subjective measurements of 77.3% for M1 and 75% for M2 allergens. CONCLUSIONS AND CLINICAL IMPORTANCE: Veterinary allergen extracts labelled as the same species and PNU/mL are not standardized; they show heterogeneity in composition and potency within and between manufacturers. Variability in extract content may require adjustment of intradermal testing concentrations.

Fetal sex is associated with maternal stimulated cytokine production, but not serum cytokine levels, in human pregnancy.

Some studies suggest that fetal sex plays a role in maternal physiological processes during pregnancy including glycemic control, blood pressure, and cortisol regulation. However, data examining fetal sex-specific differences in maternal immune parameters is lacking. In the current study, serum levels of interleukin(IL)-6, IL-8, and tumor necrosis factor(TNF)-α as well as LPS-stimulated production of IL-6, IL-8, TNF-α, and IL-1ß by PBMCs incubated for 24h were assessed in early, mid, and late pregnancy among 80 women (46 with male and 34 with female fetuses). Linear mixed models showed that women carrying females versus males exhibited greater stimulated production of IL-6 at each timepoint (ps⩽0.03), TNF-α in early pregnancy (p=0.04), and IL-1ß in mid- and late pregnancy (ps⩽0.05). Despite changes in serum levels of IL-8 (p=0.002) and TNF-α (p<0.0001) across pregnancy, no differences in any serum cytokines were observed in relation to fetal sex (ps>0.85). In conclusion, in pregnant women, those carrying female versus male fetuses exhibited greater stimulated cytokine production across pregnancy. Differential inflammatory responses could affect maternal health and fetal development. Fetal sex should be considered as a factor in studies of maternal inflammation. These findings have relevance both clinically and conceptually. For example, maternal asthma is exacerbated among women carrying female versus male fetuses. In addition, data on associations between fetal sex and maternal immune function among women with health conditions (e.g., preeclampsia) and adverse pregnancy outcomes (e.g., preterm birth) would be informative.

Assessing the Influence of Intraoperative Core Body Temperature on Postoperative Venous Thromboembolism after Abdominal Wall Reconstruction.

Background: Venous thromboembolism (VTE) is a dangerous postoperative complication after abdominal wall reconstruction (AWR). Intraoperative core body temperature has been associated with thrombotic events in other surgical contexts. This study examines the effects of intraoperative temperature on VTE rate after AWR. Methods: A retrospective study was performed on AWR patients. Cohorts were defined by postoperative 30-day VTE. Intraoperative core body temperature was recorded as the minimum, maximum, and mean intraoperative temperatures. Study variables were analyzed with logistic regression and cutoff analysis to assess for association with VTE. Results: In total, 344 patients met inclusion criteria. Fourteen patients were diagnosed with 30-day VTE for an incidence of 4.1%. The VTE cohort had a longer median inpatient stay (8 days versus 5 days, P < 0.001) and greater intraoperative change in peak inspiratory pressure (3 mm H2O versus 1 mm H2O, P = 0.01) than the non-VTE cohort. Operative duration [odds ratio (OR) = 1.32, P = 0.01], length of stay (OR = 1.07, P = 0.001), and intraoperative PIP difference (OR = 1.18, P = 0.045) were significantly associated with 30-day VTE on univariable regression. Immunocompromised status (OR = 4.1, P = 0.023; OR = 4.0, P = 0.025) and length of stay (OR = 1.1, P < 0.001; OR = 1.1, P < 0.001) were significant predictors of 30-day VTE on two multivariable regression models. No significant associations were found between temperature metrics and 30-day VTE on cutoff point or regression analysis. Conclusions: Intraoperative core body temperature did not associate with 30-day VTE after AWR, though operative duration, length of stay, immunocompromised status, and intraoperative PIP difference did. Surgeons should remain mindful of VTE risk after AWR, and future research is warranted to elucidate all contributing factors.

Assessing the Relationship between Obesity and Trigger Point-specific Outcomes after Headache Surgery.

Background: Trigger point deactivation surgery is a safe and effective treatment for properly selected patients experiencing migraine, with 68.3%-100% experiencing symptom improvement postoperatively. However, it is still unknown why certain patients do not respond. Obesity has been shown to be associated with worsened migraine symptoms and a decreased response to select pharmacotherapies. This study aimed to determine whether obesity may also be associated with an attenuated response to surgery. Methods: A retrospective chart review was conducted to identify patients who had undergone trigger point deactivation surgery for migraine. Patients were split into obese and nonobese cohorts. Obesity was classified as a body mass index of 30 or higher per Centers for Disease Control and Prevention guidelines. Outcomes and follow-up periods were determined with respect to individual operations. Outcomes included migraine attack frequency, intensity, duration, and the migraine headache index. Differences in demographics, operative characteristics, and operative outcomes were compared. Results: A total of 62 patients were included in the study. The obese cohort comprised 31 patients who underwent 45 total operations, and the nonobese cohort comprised 31 patients who underwent 34 operations. Results from multivariable analysis showed no impact of obesity on the odds of achieving a more than 90% reduction in any individual outcome. The overall rates of improvement (≥50% reduction in any outcome) and elimination (100% reduction in all symptoms) across both cohorts were 89.9% and 65.8%, respectively. Conclusion: Obese patients have outcomes comparable to a nonobese cohort after trigger point deactivation surgery for migraine.

Patient Perceptions of Care Coordination during Neoadjuvant Therapy for Gastrointestinal Cancers: A Mixed Methods Analysis.

PURPOSE: Effective cancer care coordination (CCC) is an integral component of health care delivery and critical to achieving optimal oncologic outcomes. Neoadjuvant therapy (NT), the delivery of multimodality therapy prior to surgery, is inherently complex and multidisciplinary, but CCC during NT is poorly understood. The objective of this study was to characterize patient perceptions of CCC during NT using a mixed methods approach. METHODS: This study is a cross-sectional analysis of patients with gastrointestinal cancers receiving NT who participated in a prospective longitudinal cohort study evaluating their real-time experience using a customized smartphone application. Patients completed the Cancer Care Coordination Questionnaire for Patients (CCCQ-P), a 20-item validated measure of care coordination quality, six weeks after initiating NT. Items were scored on a 5-point Likert scale, and subsections on communication (13 questions) and navigation (7 questions) were calculated with higher scores signifying better CCC. Univariate linear regression was used to calculate the impact of fragmented care and other factors on perceived CCC. Semi-structured interviews were conducted among a convenience sample of patients (n = 5); transcribed interviews were then coded using an inductive approach. RESULTS: Among 82 participants, mean age was 61 years old, 68% were male, and mean number of comorbidities was 1.68. Overall (mean 76.6 out of 100), communication subsection (48.6 out of 65), and navigation subsection (28.0 out of 35) CCCQ-P scores suggested overall positive perceptions of care coordination. Qualitative analysis of patient interviews highlighted the need for coordination among physicians before communicating the plan to patients as well as the importance of providers communicating plans in verbal and written form. CONCLUSIONS: Successful completion of NT requires significant care coordination between patients and healthcare professionals. Yet, in this cross-sectional analysis of patients on a prospective cohort study, patient perceptions of CCC during NT were overall positive. Future research should focus on optimizing other aspects of care delivery in order to improve outcomes of NT.

The effect of hydrocortisone versus hydrocortisone plus fludrocortisone on duration of shock: A propensity score-weighted analysis.

Background: The 2021 Surviving Sepsis Campaign Guidelines recommend the use of hydrocortisone in patients who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. Fludrocortisone has been used concomitantly with hydrocortisone in some studies without a clearly defined role or known clinical benefit. The purpose of this study was to assess the impact of fludrocortisone added to hydrocortisone on shock-free days for septic shock. Methods: A single-center, retrospective propensity score-weighted study was conducted to compare hydrocortisone versus hydrocortisone plus fludrocortisone for septic shock. Adults admitted to the medical intensive care unit (ICU) from 2015 to 2020 were included in the study. All patients received ≥200 mg/day hydrocortisone for at least 24 h ± fludrocortisone initiated within 72 h of vasopressors. The primary outcome was shock-free days by day 14. The secondary outcomes included duration of shock, change in Sequential Organ Failure Assessment (SOFA) score, hospital and ICU length of stay, and all-cause inhospital mortality. Results: A total of 228 patients met inclusion criteria with 212 patients retained after propensity score weighting. There was no difference between groups in 14-day shock-free days (6.3 vs. 6.1 days; P = 0.781). Furthermore, no significant differences were observed for the secondary outcomes of ICU/hospital length of stay, duration of shock, change in SOFA score, and all-cause inhospital mortality. Conclusion: The addition of fludrocortisone to hydrocortisone in septic shock did not increase shock-free days by day 14. These results suggest that the use of hydrocortisone alone may be an adequate adjunctive therapy in septic shock. A prospective randomized controlled trial is needed to confirm results.

Severe obesity is associated with increased migraine severity and frequency: A retrospective cohort study.

Migraine headaches and obesity are both prevalent disorders, resulting in a high socioeconomic burden. To better understand the relationship between obesity and migraine, the aim of this study was to investigate the association between migraine severity, metabolic syndrome and estrogen-associated variables. A retrospective analysis of adult patients with refractory migraine seen by our senior author (J.E.J.) was performed. Patient demographics and migraine characteristics, including migraine intensity, duration, and number of headaches per month were collected from medical records. Migraine headache index (MHI) was calculated by multiplying frequency, intensity and duration of headaches. Weight and height were used to calculate body mass index (BMI) and these were divided per Center for Disease Control (CDC) classifications. Univariate linear regression models were used to evaluate associations. Patients (n = 223) were predominantly female (78%) with a mean age of 44 years at presentation. Patients with a BMI higher than 40 (class 3 obesity) had a higher MHI (p = 0.01) and experienced a higher number of migraines per month (p = 0.007), compared to patients with a healthy BMI, respectively. Migraine frequency was found to be significantly higher in post-menopausal women compared to pre-menopausal women (p = 0.02). No other significant associations were found. This study found that severe obesity (BMI > 40) is associated with increased migraine severity and frequency. Post-menopausal patients are also found to have increased migraine frequency, which could be explained by the estrogen-withdrawal hypothesis. Future studies are needed to evaluate the outcomes of individuals with obesity after nerve deactivation surgery.