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Cerebral hemodynamic adaptation in fetal growth restriction (FGR) is primarily assessed using middle cerebral artery (MCA) Doppler and cerebroplacental (CPR) or umbilicocerebral ratio (UCR). The superior vena cava (SVC) blood flow may provide additional hemodynamic insights. Our objective was to evaluate fetal SVC blood flow velocities, pulsatility index for vein (PIV), volume blood flow (QSVC), and volume blood flow (Q)-based indices of fetal brain sparing in small-for-gestational-age (SGA) and FGR fetuses in the third trimester of pregnancy and compare with appropriately grown (AGA) fetuses. This was a prospective cohort study of 40 non-anomalous, singleton fetuses during 32 + 0 to 36 + 6 gestational weeks. Fetuses with abdominal circumference or estimated fetal weight below the 10th percentile were classified into SGA and FGR groups based on Delphi criteria. Doppler velocimetry of the umbilical artery (UA), umbilical vein (UV), fetal MCA and SVC was performed. UV and SVC diameters were measured, and their volume blood flows, i.e. QUV and QSVC were calculated. Both pulsatility index (PI)-based and Q-based indices of fetal brain sparing were calculated and compared to previously reported reference ranges for AGA fetuses using z-scores. In our study population, z-scores of SVC velocities (except the end-diastolic A-wave velocity) and PIV were significantly lower than the gestational age-specific mean values for AGA fetuses (p-values 0.005 to 0.018). Similarly, z-scores of SVC diameter ( p  < 0.001), QSVC normalized to fetal weight (QSVCw) ( p  < 0.001), blood flow volume-based QCPR ( p  < 0.001) were higher and QUCR ( p  < 0.001) was lower. However, z-scores of PI-based CPR ( p  = 0.195), UCR ( p  = 0.195), and the end-diastolic (A wave) velocity ( p  = 0.177) were not significantly different compared to AGA fetuses. Subgroup analysis demonstrated that the FGR fetuses ( n  = 21) had increased SVC diameter ( p  < 0.001), QSVCw ( p  < 0.001), QCPR ( p  < 0.001), UCR ( p  < 0.001), and decreased CPR ( p  < 0.001), QUCR ( p  < 0.001) and SVC PIV ( p  = 0.030), but no significant change in velocities was observed compared to AGA fetuses ( n  = 98) of similar gestational age. The SGA fetuses ( n  = 19) had decreased SVC S velocity ( p  = 0.013), D velocity ( p  = 0.005), TAMxV ( p  = 0.030), PIV ( p  = 0.005), QUCR ( p  = 0.014), and increased SVC diameter ( p  = 0.026), QSVCw ( p  = 0.034) and QCPR ( p  = 0.014) in comparison to AGA fetuses. When compared to SGA fetuses, the FGR fetuses had significantly lower QUVw (60.5 ± 19.7 vs. 80.1 ± 20.2 ml/min/kg, p  = 0.004), QUCR (0.79 ± 0.45 vs. 1.34 ± 0.52 p  < 0.001) and birthweight (2181 ± 577 vs. 2848 ± 330 g, p  < 0.001) but higher QSVCw (91.82 ± 39.56 vs. 65.53 ± 17.79 ml/min/kg, p  = 0.039) and QCPR (1.63 ± 0.74 vs. 0.90 ± 0.45, p  < 0.001). In conclusion, third-trimester fetuses < 10th percentile had significantly increased SVC diameter, resulting in increased QSVCw in SGA and FGR despite reduced or unchanged TAMxV. Significantly altered QCPR and QUCR confirmed circulatory redistribution with increased brain and upper body venous return both in FGR and SGA fetuses. However, as the magnitude of increase in QSVCw and QCPR was significantly larger in FGR compared to SGA fetuses, it could be potentially used as a quantifiable marker to differentiate FGR from SGA. The role of SVC Doppler in refining the diagnosis of late FGR should be further investigated.

Background Caregivers are invaluable sources of support for individuals recovering from head and neck cancer (HNC). Accordingly, minimizing caregiver distress is essential to promote the well-being of both caregivers and their patients. This study assessed if psychosocial distress (i.e., anxiety and depression) among HNC caregivers is associated with a difference in how caregivers and their patients perceive patients’ quality of life (QOL) after treatment completion. Methods Caregivers’ and patients’ perceptions of patient QOL were assessed using the University of Washington QOL Questionaire (UWQOL), a validated HNC-specific health-related QOL questionnaire. The survey is interpreted in terms of its two composite scores: a physical QOL score and a social-emotional QOL score with higher scores indicating better QOL. Caregiver anxiety was assessed using the Generalized Anxiety Questionaire-7 (GAD-7) and caregiver depression was assessed using the Patient Health Questionaire 8 (PHQ-8). Patients completed the UWQOL as part of clinic intake while caregivers were asked to complete the UWQOL for their patients in addition to the PHQ-8 and GAD-7 in private. Linear regression was used to analyze the association between differences in caregivers’ and patients’ QOL scores (both social-emotional and physical QOL subscale scores) and GAD-7 and PHQ-8 scores. Results Of 47 caregivers recruited, 42.6% ( n  = 20) viewed patients’ social-emotional QOL more negatively than patients themselves, while 31.9% viewed patients’ physical QOL more negatively. After controlling for covariates, differences in perception of social-emotional QOL ( p  = .01) and differences in perception of physical QOL ( p  = .007) were significantly associated with caregiver depression, but not anxiety. Caregivers who disagreed with patients regarding patients’ social-emotional QOL scored 6.80 points higher on the PHQ8 than agreeing caregivers. Caregivers who disagreed regarding patients’ physical QOL scored 6.09 points higher. Conclusion Caregivers commonly view patients’ QOL more negatively than patients themselves. These caregivers tend to have greater psychosocial distress than caregivers who agree with their patients. Interventions designed to identify and aid at-risk caregivers are critically needed. We propose screening for differences in perception of patient QOL as a way of identifying distressed caregivers as well as provider-facilitated communication between patients and caregivers as possible interventions that should be examined in future research.

Fine-needle aspiration (FNA) is useful in the evaluation of salivary gland tumors, but currently no standard terminology or risk stratification model exists. FNA smears were reviewed and categorized based on cytonuclear features, stromal characteristics, and background characteristics. Risk of malignancy was calculated for each category. Classifications as benign, neoplasm of uncertain malignant potential (NUMP), suspicious for malignancy, and positive for malignancy were used to aggregate categories into similar risk groups. Categorization of salivary gland aspirates into morphologic categories resulted in the expected risk stratification. Grouping of categories maintained risk stratification, providing classes with malignancy risk as follows: benign, 2%; NUMP, 18%; suspicious for malignancy, 76%; and positive for malignancy, 100%. Salivary gland FNA categorization into commonly encountered morphologic categories provides risk stratification, which translates to a simplified classification scheme of benign, NUMP, suspicious, and positive for malignancy similar to the paradigm in other organ systems.

Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal and perinatal morbidity worldwide, and current screening strategies have limited predictive value in low-risk populations especially for late-onset HDP. This study aimed to develop and internally validate an interpretable machine-learning model for predicting HDP using noninvasive parameters of maternal systemic hemodynamics, endothelial function, and utero-placental and feto-placental blood flow measured in mid-pregnancy. In this cross-sectional cohort, 577 normotensive women underwent impedance cardiography and Doppler ultrasonography at 22 + 0 to 23 + 6 weeks’ gestation. The incidence of HDP was 16.6% (96/577) most (87.5%) occurring at term (≥ 37 weeks), including 73 cases of gestational hypertension (12.6%) and 23 cases of pre-eclampsia (4.0%). An optimized predictive model with seven physiological features was developed using Extreme Gradient Boosting (XGBoost). Hyperparameters were optimized using stratified 10-fold cross-validation maximizing average Precision Recall Area Under the Curve (PR–AUC), and the decision threshold was selected by maximizing the geometric mean of sensitivity and specificity on a separate validation set. On an independent test set ( n  = 58; 10 HDP), the model achieved an Area Under the Receiver Operating Curve (ROC–AUC) of 0.82 (95% CI 0.65–0.95) and a PR–AUC of 0.57 (95% CI 0.26–0.84). At the optimized operating point, sensitivity was 70% (95% CI 0.40–1.00), specificity 79% (95% CI 0.67–0.90), precision 41% (95% CI 0.18–0.65), and negative predictive value 93% (95% CI 0.84–1.00). This interpretable, non-invasive mid-gestation model demonstrates strong discrimination and excellent negative predictive value, supporting its integration into routine second-trimester screening for risk stratification without reliance on biochemical markers.

We evaluated neoadjuvant ipilimumab in patients with surgically operable regionally advanced melanoma in order to define markers of activity in the blood and tumor as assessed at baseline (before ipilimumab) and early on-treatment. Patients were treated with ipilimumab (10 mg/kg intravenously every 3 weeks ×2 doses) bracketing surgery. Tumor and blood biospecimens were obtained at baseline and at surgery. Flow cytometry and immunohistochemistry for select biomarkers were performed. Thirty five patients were enrolled; IIIB (3; N2b), IIIC (32; N2c, N3), IV (2). Worst toxicities included Grade 3 diarrhea/colitis (5; 14%), hepatitis (2; 6%), rash (1; 3%), elevated lipase (3; 9%). Median follow up was 18 months: among 33 evaluable patients, median progression free survival (PFS) was 11 months, 95% CI (6.2-19.2). There was a significant decrease in circulating myeloid derived suppressor cells (MDSC). Greater decrease in circulating monocyte gate MDSC Lin1-/HLA-DR-/CD33⁺/CD11b⁺ was associated with improved PFS (p = 0.03). There was a significant increase in circulating regulatory T cells (Treg; CD4⁺CD25hi⁺Foxp3⁺) that, unexpectedly, was associated with improved PFS (HR = 0.57; p = 0.034). Baseline evidence of fully activated type I CD4⁺ and CD8⁺ antigen-specific T cell immunity against cancer-testis (NY-ESO-1) and melanocytic lineage (MART-1, gp100) antigens was detected and was significantly potentiated after ipilimumab. In tumor, there was a significant increase in CD8⁺ T cells after ipilimumab (p = 0.02). Ipilimumab induced increased tumor infiltration by fully activated (CD69⁺) CD3⁺/CD4⁺ and CD3⁺/CD8⁺ T cells with evidence of induction/potentiation of memory T cells (CD45RO⁺). The change in Treg observed within the tumor showed an inverse relationship with clinical benefit and greater decrease in tumor MDSC subset Lin1-/HLA-DR-/CD33⁺/CD11b⁺ was associated with improved PFS at one year. Neoadjuvant evaluation revealed a significant immunomodulating role for ipilimumab on Treg, MDSC and effector T cells in the circulation and tumor microenvironment that warrants further pursuit in the quest for optimizing melanoma immunotherapy.

Objectives: Patients with head and neck cancer (HNC) frequently present with weight loss secondary to dysphagia and malnutrition. We sought to determine the relationship between weight loss and in-hospital mortality, complications, length of hospitalization, and costs in HNC surgery. Methods: We analyzed discharge data from the Nationwide Inpatient Sample for 93,663 patients who underwent an ablative procedure for malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasms between 2003 and 2008. Results: Weight loss was significantly associated with dysphagia (relative risk ratio [RRR] = 3.0; p < 0.001), alcohol abuse (RRR = 2.0; p < 0.001), advanced comorbidity (RRR = 1.8; p < 0.001), Medicaid payor status (RRR = 1.6; p = 0.002), urgent or emergent admission (RRR = 1.7; p = 0.015), and major surgical procedures (RRR = 2.3; p < 0.001). Patients with weight loss had increased risks of acute cardiac events, pneumonia, renal failure, sepsis, pulmonary failure (RRR = 2.6; p < 0.001), and postoperative wound healing complications, including fistula, dehiscence, and surgical site infection (RRR = 2.0; p < 0.001). After we controlled for all other variables, weight loss was associated with significantly increased length of hospitalization and hospital-related costs. Conclusions: Weight loss is associated with increases in medical complications, surgical complications, length of hospitalization, and hospital-related costs in HNC surgical patients. Aggressive preoperative identification and treatment of underlying dysphagia and malnutrition may reduce the medical and surgical morbidity in this high-risk population.

Frailty and sarcopenia are known risk factors for adverse liver transplant outcomes and mortality. We hypothesized that frailty or sarcopenia could identify the risk for common serious transplant-related adverse respiratory events. For 107 patients (74 men, 33 women) transplanted over 1 year, we measured frailty with gait speed, chair stands, and Karnofsky Performance Scale (KPS) and sarcopenia with Skeletal Muscle Index on computed tomography at L3. We recorded the stress-tested cardiac double product as an index of cardiac work capacity. Outcomes included days of intubation, aspiration, clinical pneumonia, reintubation/tracheostomy, days to discharge, and survival. We modeled the outcomes using unadjusted regression and multivariable analyses controlled for (i) age, sex, and either Model for End-Stage Liver Disease-Na (MELDNa) or Child-Turcotte-Pugh scores, (ii) hepatocellular carcinoma status, and (iii) chronic obstructive pulmonary disease and smoking history. Subgroup analysis was performed for living donor liver transplant and deceased donor liver transplant recipients. Gait speed was negatively associated with aspiration and pulmonary infection, both in unadjusted and MELDNa-adjusted models (adjusted odds ratio for aspiration 0.10 [95% confidence interval [CI] 0.02-0.67] and adjusted odds ratio for pulmonary infection 0.12 [95% CI 0.02-0.75]). Unadjusted and MELDNa-adjusted models for gait speed (coefficient -1.47, 95% CI -2.39 to -0.56) and KPS (coefficient -3.17, 95% CI -5.02 to -1.32) were significantly associated with shorter intubation times. No test was associated with length of stay or need for either reintubation or tracheostomy. Slow gait speed, an index of general frailty, indicates significant risk for post-transplant respiratory complications. Intervention to arrest or reverse frailty merits exploration as a potentially modifiable risk factor for improving transplant respiratory outcomes.

Postoperative pulmonary complications (PPCs) are significant problems in patients undergoing radical head and neck cancer surgery with free flap reconstruction. The objective of the study was to identify the incidence, outcome, and risk factors for PPCs We hypothesized that preoperative pulmonary disease and amount of fluid administered during the surgery would be associated with PPCs. A retrospective clinical observational study. A large academic institution. A total of 110 patients who underwent head and neck cancer surgery with microvascular free flap reconstruction between January 1, 2005 and December 31, 2011. No study interventions were performed. PPCs including pulmonary edema, pneumonia, and acute respiratory distress syndrome were clinically diagnosed. Perioperative parameters and outcomes among patients with and without PPCs were compared. Factors predictive of PPCs were identified with univariate and multiple logistic regression analyses. The incidence of PPCs was 32.7% (36 patients): pulmonary edema in 23.6% (26) and pneumonia in 9.1% (10). No acute respiratory distress syndrome was found. Inhospital mortality was 1.8% (2). No difference was found in survival between the patients with PPCs and those without (1 year survival was 69.4% vs 78.4%; P=.85). The patients with PPCs required longer ventilation support (median, 4 vs 2days; P=.002) and more frequent intensive care unit readmissions (30.3% vs 5.7%; P=.001) and stayed longer in the hospital (median, 17 vs 12days; P=.014). None of the preoperative parameters or intraoperative parameters including pulmonary comorbidity or the amounts of intraoperative fluid/blood administration was found as the factor to predict postoperative pulmonary compilations. The incidence of PPCs in patients undergoing radical head and neck surgery was 32.7% in 110 patients. Preoperative pulmonary disease or the amount of fluid administered during the surgery was not associated with PPCs. •Postoperative pulmonary complications (PPCs) are significant problems in patients undergoing radical head and neck cancer surgery with free flap reconstruction.•The incidence of PPCs in 110 patients who underwent the procedure was 32.7% (36 patients) with pulmonary edema in 23.6% and pneumonia in 9.1%.•The patients with PPCs required longer ventilation support, frequent ICU readmissions, and stayed longer in the hospital.•None of the preoperative or intraoperative parameters including pulmonary comorbidity or the amounts of intraoperative fluid/blood administration was found as the factor to predict PPCs.

The notion of a constant relationship between resistance and capacitance (RC time) in the pulmonary circulation has been challenged by more recent research. The RC time can be obtained using either a simplified empirical approach or a semilogarithmic equation. Although direct curve-fit analysis is a feasible and ostensibly reference approach for RC analysis, it remains largely unexplored. We aimed to study the relationship between various RC methods in different states of pulmonary hemodynamics. Methods  In total, 182 patients underwent clinically indicated right heart catheterization. The pressure curves were exported and processed using the MATLAB software. We calculated the RC time using the empirical method (RC EST ), semilogarithmic approach (RC SL ), and direct measurement of curve fit (RC FIT ). Results  Among 182 patients, 137 had pulmonary hypertension due to left heart disease (PH-LHD), 35 had pulmonary arterial hypertension (PAH), and 10 demonstrated normal hemodynamics (non-PH). RC EST consistently overestimated the RC FIT and RC SL measurements by a mean of 75%. With all three methods, the RC values were longer in the PAH (RC FIT  = 0.36 ± 0.14 s) than in the PH-LHD (0.27 ± 0.1 s) and non-PH (0.27 ± 0.09 s) groups ( p  < 0.001). Although the RC SL and RC FIT values were similar among the three subgroups, they exhibited broad limits of agreement. Finally, the RC EST demonstrated a strong discriminatory ability (AUC = 0.86, p  < 0.001, CI = 0.79–0.93) in identifying PAH. Conclusion  RC time in PAH patients was substantially prolonged compared to that in PH-LHD and non-PH patients. The use of the empirical formula yielded systematic RC overestimation. In contrast, the semilogarithmic analysis provided reliable RC estimates, particularly for group comparisons.

Objective This study aims to compare the effectiveness of 2 artificial saliva substitutes (Biotène vs HydraSmile) in the symptomatic management of radiation‐induced xerostomia. Study Design Randomized double‐blind cross‐over study. Setting Single tertiary care academic institution. Methods Included adult patients ≥$ $ 6 months postradiotherapy (50‐70 gy) for squamous cell carcinoma of the oral cavity, oropharynx, or larynx. The primary endpoint was change in overall subjective xerostomia score from baseline, through use of HydraSmile versus Biotène. Scores were derived from a 100‐point visual analog scale, with higher scores indicating better symptomatic control. Analysis of covariance model was used to regress the difference in after‐treatment measurement between HydraSmile and Biotène, with respect to baseline differences. Results A total of 91 participants were included (mean age 63.0 years [SD 9.7]; 85.7% male; 97.8% White). Change in overall xerostomia score with respect to baseline was not significantly different between HydraSmile and Biotène (mean difference 1.24, 95% confidence interval [CI] −2.35 to 4.81). Compared to water alone, both HydraSmile (mean difference 7.45, 95% CI 3.61‐11.29) and Biotène (mean difference 7.24, 95% CI 3.06‐11.43) significantly improved overall xerostomia score. Forty (44%) patients reported a preference for Biotène, 46 (50.5%) preferred HydraSmile, and 5 (5.5%) had no preference. Patients who preferred Biotène did not significantly benefit from HydraSmile, whereas those who preferred HydraSmile did not significantly benefit from Biotène. Conclusion Biotène and HydraSmile significantly improved oral dryness among patients with radiation‐induced xerostomia. While neither product demonstrated treatment superiority, individual product preference was predictive of greatest treatment benefit.