Water Ligands Regulate the Redox Leveling Mechanism of the Oxygen-Evolving Complex of the Photosystem II.

Understanding how water ligands regulate the conformational changes and functionality of the oxygen-evolving complex (OEC) in photosystem II (PSII) throughout the catalytic cycle of oxygen evolution remains a highly intriguing and unresolved challenge. In this study, we investigate the effect of water insertion (WI) on the redox state of the OEC by using the molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) hybrid methods. We find that water binding significantly reduces the free energy change for proton-coupled electron transfer (PCET) from Mn to YZ•, underscoring the important regulatory role of water binding, which is essential for enabling the OEC redox-leveling mechanism along the catalytic cycle. We propose a water binding mechanism in which WI is thermodynamically favored by the closed-cubane form of the OEC, with water delivery mediated by Ca2+ ligand exchange. Isomerization from the closed- to open-cubane conformation at three post-WI states highlights the importance of the location of the MnIII center in the OEC and the orientation of its Jahn-Teller axis to conformational changes of the OEC, which might be critical for the formation of the O-O bond. These findings reveal a complex interplay between conformational changes in the OEC and the ligand environment during the activation of the OEC by YZ•. Analogous regulatory effects due to water ligand binding are expected to be important for a wide range of catalysts activated by redox state transitions in aqueous environments.

Higher-order functional brain networks and anterior cingulate glutamate + glutamine (Glx) in antipsychotic-naïve first episode psychosis patients.

Human connectome studies have provided abundant data consistent with the hypothesis that functional dysconnectivity is predominant in psychosis spectrum disorders. Converging lines of evidence also suggest an interaction between dorsal anterior cingulate cortex (dACC) cortical glutamate with higher-order functional brain networks (FC) such as the default mode (DMN), dorsal attention (DAN), and executive control networks (ECN) in healthy controls (HC) and this mechanism may be impaired in psychosis. Data from 70 antipsychotic-medication naïve first-episode psychosis (FEP) and 52 HC were analyzed. 3T Proton magnetic resonance spectroscopy (1H-MRS) data were acquired from a voxel in the dACC and assessed correlations (positive FC) and anticorrelations (negative FC) of the DMN, DAN, and ECN. We then performed regressions to assess associations between glutamate + glutamine (Glx) with positive and negative FC of these same networks and compared them between groups. We found alterations in positive and negative FC in all networks (HC > FEP). A relationship between dACC Glx and positive and negative FC was found in both groups, but when comparing these relationships between groups, we found contrasting associations between these variables in FEP patients compared to HC. We demonstrated that both positive and negative FC in three higher-order resting state networks are already altered in antipsychotic-naïve FEP, underscoring the importance of also considering anticorrelations for optimal characterization of large-scale functional brain networks as these represent biological processes as well. Our data also adds to the growing body of evidence supporting the role of dACC cortical Glx as a mechanism underlying alterations in functional brain network connectivity. Overall, the implications for these findings are imperative as this particular mechanism may differ in untreated or chronic psychotic patients; therefore, understanding this mechanism prior to treatment could better inform clinicians.Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101 . Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253 .

Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer.

PURPOSE: The optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. METHODS AND MATERIALS: A review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39-84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2-102 months). RESULTS: Re-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local-regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). CONCLUSION: Although re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.

Higher-Order Intrinsic Brain Network Trajectories After Antipsychotic Treatment in Medication-Naïve Patients With First-Episode Psychosis.

BACKGROUND: Intrinsic brain network connectivity is already altered in first-episode psychosis (FEP), but the longitudinal trajectories of network connectivity, especially in response to antipsychotic treatment, remain poorly understood. The goal of this study was to investigate how antipsychotic medications affect higher-order intrinsic brain network connectivity in FEP. METHODS: Data from 87 antipsychotic medication-naïve patients with FEP and 87 healthy control participants were used. Medication-naïve patients received antipsychotic treatment for 16 weeks. Resting-state functional connectivity (FC) of the default mode, salience, dorsal attention, and executive control networks were assessed prior to treatment and at 6 and 16 weeks after treatment. We evaluated baseline and FC changes using linear mixed models to test group × time interactions within each network. Associations between FC changes after 16 weeks and response to treatment were also evaluated. RESULTS: Prior to treatment, significant group differences in all networks were found. However, significant trajectory changes in FC were found only in the default mode and executive control networks. Changes in FC in these networks were associated with treatment response. Several sensitivity analyses showed a consistent normalization of executive control network FC in response to antipsychotic treatment. CONCLUSIONS: Here, we found that alterations in intrinsic brain network FC were not only alleviated with antipsychotic treatment, but the extent of this normalization was also associated with the degree of reduction in symptom severity. Taken together, our data suggest modulation of intrinsic brain network connectivity (mainly frontoparietal connectivity) as a mechanism underlying antipsychotic treatment response in FEP.

Refining Target Volume Coverage After Parotidectomy for Cutaneous Squamous Cell Carcinoma: Omission of the Cervical Neck From the Radiation Field.

Purpose: For patients without pathologic evidence of cervical disease after neck dissection for cutaneous squamous cell carcinoma involving the parotid region, inclusion of the ipsilateral cervical neck in the postparotidectomy radiation volume is routinely performed. We report our experience with selective avoidance of the ipsilateral neck for patients undergoing postoperative radiation to the parotid bed. Methods and Materials: From January 2014 to December 2023, a total of 30 consecutive patients underwent postoperative radiation after parotidectomy for cutaneous squamous cell carcinoma involving the parotid area. All patients had previously had a neck dissection confirming pathologic N0 disease. Treatment was delivered using intensity modulated radiation therapy to a median dose of 60 Gy (range, 56-66 Gy). The radiation target volumes included the parotid bed only, with deliberate avoidance of the ipsilateral cervical neck. The median pathologic tumor size of the parotid tumor was 3.3 cm (range, 0.2-9.4 cm). Final pathologic evaluation showed positive microscopic margins in 8 patients (27%), perineural invasion in 17 patients (57%), and facial nerve involvement in 6 patients (20%). Results: There were no isolated nodal failures. One patient developed an ipsilateral neck recurrence approximately 8 months after completion of radiation therapy. This occurred 2 months subsequent to the development of local recurrence. The 5-year actuarial rates of local (parotid) control, neck control, and overall survival were 87%, 97%, and 76%, respectively. Conclusions: Omission of the ipsilateral neck from the parotid volume does not compromise disease control for pathologically N0 patients undergoing postoperative radiation for cutaneous squamous cell carcinoma involving the parotid region. Practical implications are discussed.

Racial disparities in the timely receipt of adjuvant radiotherapy for head and neck cancer.

PURPOSE: To evaluate the influence of socioeconomic and demographic factors which might predict for excessive delays in the receipt of adjuvant radiotherapy for head and neck cancer. METHODS AND MATERIALS: The medical records of 430 consecutive patients referred for adjuvant radiation after surgical resection for squamous cell carcinoma of the head and neck were reviewed. The number of days from surgery to initiation of radiation was recorded. To study the variability in which adjuvant radiation was delivered, descriptive statistics were used to determine the percentage of patients who deviated from starting treatment beyond the recommended benchmark of 42 days. The chi-square statistic was used to compare differences in proportion among subsets. A Cox proportional hazards model was constructed to perform a multi-variate analysis to identify factors which independently influenced the likelihood for non-adherence. RESULTS: The interval between surgery and the start of radiation therapy ranged from 5 to 128 days (mean, 36 days). The mean number of days from surgery to radiation therapy was 31 days, 35 days, 40 days, and 42 days for Caucasians, Asians, Latino, and Black patients (p = 0.01). In all, 359 of 430 patients (83 %) started adjuvant radiation within 42 days. The proportion of patients who initiated radiation therapy within 42 days of surgery was 91 %, 86 %, 71 %, 65 %, and 80 % for Caucasians, Asians, Latinos, Blacks, and Native Hawaiian/Pacific Islanders, respectively (p < 0.001). Patient characteristics associated with higher odds of non-adherence to the timely receipt of adjuvant radiation therapy within then 42-day benchmark from surgery to radiation included race ([OR] = 4.23 95 % CI (1.30-7.97), non-English speaking status ([OR] = 2.38, 95 % CI: 0.61-4.50), and low socioeconomic status ([OR] = 1.21, 95 % CI: 1.01-1.86). CONCLUSION: Underrepresented minorities are more likely to experience delays in the receipt of adjuvant radiation for head and neck cancer. The potential underlying reasons are discussed.

Posttreatment Surveillance Imaging After Radiation for Head and Neck Cancer.

Importance: The role of surveillance imaging after treatment for head and neck cancer is controversial and evidence to support decision-making is limited. Objective: To determine the use of surveillance imaging in asymptomatic patients with head and neck cancer in remission after completion of chemoradiation. Design, Setting, and Participants: This was a retrospective, comparative effectiveness research review of adult patients who had achieved a complete metabolic response to initial treatment for head and neck cancer as defined by having an unequivocally negative positron emission tomography (PET) scan using the PET response criteria in solid tumors (PERCIST) scale within the first 6 months of completing therapy. The medical records of 501 consecutive patients who completed definitive radiation therapy (with or without chemotherapy) for newly diagnosed squamous cell carcinoma of the head and neck between January 2014 and June 2022 were reviewed. Exposure: Surveillance imaging was defined as the acquisition of a PET with computed tomography (CT), magnetic resonance imaging (MRI), or CT of the head and neck region in the absence of any clinically suspicious symptoms and/or examination findings. For remaining patients, subsequent surveillance after the achievement of a complete metabolic response to initial therapy was performed on an observational basis in the setting of routine follow-up using history-taking and physical examination, including endoscopy. This expectant approach led to imaging only in the presence of clinically suspicious symptoms and/or physical examination findings. Main Outcome and Measures: Local-regional control, overall survival, and progression-free survival based on assignment to either the surveillance imaging or expectant management cohort. Results: This study included 340 patients (mean [SD] age, 59 [10] years; 201 males [59%]; 88 Latino patients [26%]; 145 White patients [43%]) who achieved a complete metabolic response during this period. There was no difference in 3-year local-regional control, overall survival, progression-free survival, or freedom from distant metastasis between patients treated with surveillance imaging vs those treated expectantly. Conclusions and Relevance: In this comparative effectiveness research, imaging-based surveillance failed to improve outcomes compared with expectant management for patients who were seemingly in remission after completion of primary radiation therapy for head and neck cancer.

The homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling.

The elimination of synapses during circuit remodeling is critical for brain maturation; however, the molecular mechanisms directing synapse elimination and its timing remain elusive. We show that the transcriptional regulator DVE-1, which shares homology with special AT-rich sequence-binding (SATB) family members previously implicated in human neurodevelopmental disorders, directs the elimination of juvenile synaptic inputs onto remodeling C. elegans GABAergic neurons. Juvenile acetylcholine receptor clusters and apposing presynaptic sites are eliminated during the maturation of wild-type GABAergic neurons but persist into adulthood in dve-1 mutants, producing heightened motor connectivity. DVE-1 localization to GABAergic nuclei is required for synapse elimination, consistent with DVE-1 regulation of transcription. Pathway analysis of putative DVE-1 target genes, proteasome inhibitor, and genetic experiments implicate the ubiquitin-proteasome system in synapse elimination. Together, our findings define a previously unappreciated role for a SATB family member in directing synapse elimination during circuit remodeling, likely through transcriptional regulation of protein degradation processes.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

Computed tomography assessment of pelvic bone density: Associations with age and pelvic fracture in motor vehicle crashes.

Motor vehicle crash (MVC) occupants routinely get a computed tomography (CT) scan to screen for internal injury, and this CT can be leveraged to opportunistically derive bone mineral density (BMD). This study aimed to develop and validate a method to measure pelvic BMD in CT scans without a phantom, and examine associations of pelvic BMD with age and pelvic fracture incidence in seriously injured MVC occupants from the Crash Injury Research and Engineering Network (CIREN) study. A phantom-less muscle-fat calibration technique to measure pelvic BMD was validated using 45 quantitative CT scans with a bone calibration phantom. The technique was then used to measure pelvic BMD from CT scans of 252 CIREN occupants (ages 16+) in frontal MVCs who had sustained either abdominal or pelvic injury. Pelvic BMD was analyzed in relation to age and pelvic fracture incidence. In the validation set, phantom-based calibration vs. phantom-less muscle-fat calibration yielded similar BMD values at the anterior superior iliac spine (ASIS; R2 = 0.95, p < 0.001) and iliac crest (R2 = 0.90, p < 0.001). Pelvic BMD was measured in 150 female and 102 male CIREN occupants aged 16-89, and 25% of these occupants sustained pelvic fracture. BMD at the ASIS and iliac crest declined with age (p < 0.001). For instance, iliac crest BMD decreased an average of 25 mg/cm3 per decade of age. The rate of iliac crest BMD decline was 7.6 mg/cm3 more per decade of age in occupants with pelvic fracture compared to those not sustaining pelvic fracture. Findings suggest pelvic BMD may be a contributing risk factor for pelvic fracture in MVCs.

Timing of chemotherapy and radiation delivery for patients receiving chemoradiation for head and neck cancer: When does "concurrent" mean concurrent?

PURPOSE: To analyze practice patterns focusing on variations in the timing of chemotherapy relative to radiation in patients treated with concurrent chemoradiation for head and neck cancer. METHODS AND MATERIALS: The medical records of 302 consecutive adult patients treated with concurrent chemoradiation for head and neck cancer between April 2014 and February 2022 were reviewed. After excluding 38 patients who received non-platinum-based regimens, induction chemotherapy, and/or had non-squamous cell histology, a total of 264 patients formed the primary population. To study the variability in which concurrent chemoradiation was delivered, descriptive statistics were used to determine the percentage of patients who deviated from starting chemotherapy and radiation on the same day. The chi-square statistic was used to compare differences in proportion among various subsets. A Cox proportional hazards model was then used to perform a multi-variate analysis to identify factors which independently influenced the likelihood for non-adeherence. RESULTS: Among the 264 patients, a total of 187 patients (70.8%) had chemotherapy and radiation started on the same day with 171 of these (91.4%) receiving chemotherapy prior to radiation delivery. On multivariate analysis, both non-Caucasian ethnicity (OR: 1.13, 95% C.I. 1.01-1.20) and being non-English speaking (OR: 1.39; 95% C.I. 1.18--1.51) was significantly associated with greater likelihood of the receipt of radiation and chemotherapy on different days. CONCLUSION: Significant variation exists in the timing of chemotherapy relative to radiation for concurrent chemoradiation in the clinical setting. The potential repercussions on outcome warrante further invesigtation and are discussed.

Artificial neural network prediction of post-thyroidectomy outcome.

OBJECTIVES: The goal of this study was to develop a deep neural network (DNN) for predicting surgical/medical complications and unplanned reoperations following thyroidectomy. DESIGN, SETTING, AND PARTICIPANTS: The 2005-2017 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to extract patients who underwent thyroidectomy. A DNN consisting of 10 layers was developed with an 80:20 breakdown for training and testing. MAIN OUTCOME MEASURES: Three primary outcomes of interest, including occurrence of surgical complications, medical complications, and unplanned reoperation were predicted. RESULTS: Of the 21 550 patients who underwent thyroidectomy, medical complications, surgical complications and reoperation occurred in 1723 (8.0%), 943 (4.38%) and 2448 (11.36%) patients, respectively. The DNN performed with an area under the curve of receiver operating characteristics of .783 (medical complications), .709 (surgical complications) and .703 (reoperations). Accuracy, specificity and negative predictive values of the model for all outcome variables ranged 78.2%-97.2%, while sensitivity and positive predictive values ranged 11.6%-62.5%. Variables with high permutation importance included sex, inpatient versus outpatient and American Society of Anesthesiologists class. CONCLUSIONS: We predicted surgical/medical complications and unplanned reoperation following thyroidectomy via development of a well-performing ML algorithm. We have also developed a web-based application available on mobile devices to demonstrate the predictive capacity of our models in real time.

Hippocampal Hyperconnectivity to the Visual Cortex Predicts Treatment Response.

BACKGROUND: Converging lines of evidence point to hippocampal dysfunction in psychosis spectrum disorders, including altered functional connectivity. Evidence also suggests that antipsychotic medications can modulate hippocampal dysfunction. The goal of this project was to identify patterns of hippocampal connectivity predictive of response to antipsychotic treatment in 2 cohorts of patients with a psychosis spectrum disorder, one medication-naïve and the other one unmedicated. HYPOTHESIS: We hypothesized that we would identify reliable patterns of hippocampal connectivity in the 2 cohorts that were predictive of treatment response and that medications would modulate abnormal hippocampal connectivity after 6 weeks of treatment. STUDY DESIGN: We used a prospective design to collect resting-state fMRI scans prior to antipsychotic treatment and after 6 weeks of treatment with risperidone, a commonly used antipsychotic medication, in both cohorts. We enrolled 44 medication-naïve first-episode psychosis patients (FEP) and 39 unmedicated patients with schizophrenia (SZ). STUDY RESULTS: In both patient cohorts, we observed a similar pattern where greater hippocampal connectivity to regions of the occipital cortex was predictive of treatment response. Lower hippocampal connectivity of the frontal pole, orbitofrontal cortex, subcallosal area, and medial prefrontal cortex was predictive of treatment response in unmedicated SZ, but not in the medication-naïve cohort. Furthermore, greater reduction in hippocampal connectivity to the visual cortex with treatment was associated with better clinical response. CONCLUSIONS: Our results suggest that greater connectivity between the hippocampus and occipital cortex is not only predictive of better treatment response, but that antipsychotic medications have a modulatory effect by reducing hyperconnectivity.

A comparative analysis of treatment efficacy in intermediate-risk thyroid cancer.

PURPOSE: This study aimed to evaluate the efficacy of different treatment combinations on patient survival in intermediate-risk differentiated thyroid cancer (DTC). METHODS: The 2004-2017 National Cancer Database was queried for intermediate-risk papillary (PTC), follicular (FTC), or Hurthle cell (HTC) thyroid cancer patients. Four treatments were analyzed using Kaplan Meier and multivariable Cox regression: surgery, surgery with adjuvant radioiodine ablation (S + RAI), surgery with adjuvant thyroid-stimulating hormone suppression therapy (S + THST), and S + RAI + THST. Kaplan-Meier and multivariable Cox proportional-hazards analyses evaluated treatment-associated overall survival (OS). RESULTS: Of 65,736 patients, 72.2% were female and the average age was 45.4 ± 15.4 years. The 10-year OS rates for PTC, FTC, and HTC were 93.2%, 85.2%, and 78.5%, respectively. S + RAI + THST exhibited higher OS than surgery alone and S + RAI (all p < 0.05). Compared to surgery alone, S + RAI + THST demonstrated reduced mortality in PTC (Hazard Ratio [HR]: 0.628, p < 0.001), FTC (HR: 0.490, p < 0.001), and HTC (HR: 0.520, p = 0.006). Similarly, adjuvant RAI + THST reduced mortality regardless of lymphovascular invasion (HR: 0.490, p < 0.001), N1a (HR: 0.570, p < 0.001) or N1b metastasis (HR: 0.621, p < 0.001), or positive margin status (HR: 0.572, p < 0.001). CONCLUSIONS: Treatment combinations demonstrated varying efficacies in intermediate-risk DTC depending on histology and tumor characteristics, with S + RAI + THST exhibiting the greatest treatment response.

Prognostic Utility of Tumor Stage versus American Thyroid Association Risk Class in Thyroid Cancer.

OBJECTIVE: To evaluate the prognostic strengths of American Joint Committee on Cancer (AJCC) staging and American Thyroid Association (ATA) risk classification in well-differentiated thyroid cancer (DTC), and their implications in guiding medical decision-making and epidemiological study designs. METHODS: The 2004-2017 National Cancer Database was queried for DTC patients. Cox proportional hazards (CPH) and Kaplan-Meier analyses modeled patient mortality and overall survival, respectively. Each CPH model was evaluated by its concordance index, measure of explained randomness (MER), Akaike information criterion (AIC), and area under receiver operating characteristic curve (AUC). RESULTS: Overall, 134,226 patients were analyzed, with an average age of 48.1 ± 15.1 years (76.9% female). Univariate CPH models using AJCC staging demonstrated higher concordance indices, MERs, and AUCs than those using ATA risk classification (all p < 0.001). Multivariable CPH models using AJCC staging demonstrated higher concordance indices (p = 0.049), MERs (p = 0.046), and AUCs (p = 0.002) than those using ATA risk classification. The AICs of multivariable AJCC staging and ATA risk models were 7.564 × 104 and 7.603 × 104 , respectively. AJCC stage I tumors were associated with greater overall survival than those classified as ATA low risk, whereas AJCC stages II-III and stage IV tumors demonstrated worse survival than ATA intermediate- and high-risk tumors, respectively (all p < 0.001). CONCLUSION: AJCC staging may be a more predictive system for patient survival than ATA risk. The prognostic utility of these two systems converges when additional demographic and clinical factors are considered. AJCC staging was found to classify patients across a wider range of survival patterns than the ATA risk stratification system. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:205-211, 2023.

Outcomes and Trends of Treatments in High-Risk Differentiated Thyroid Cancer.

OBJECTIVES: To analyze the variant-specific survival benefits and usage patterns of standardized treatment combinations of surgery (S), radioactive iodine ablation (RAI), and thyroid-stimulating hormone suppression therapy (THST) for high-risk differentiated thyroid cancer. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: The 2004-2017 National Cancer Database was queried for patients receiving definitive surgery for high-risk papillary, follicular, or Hurthle cell thyroid cancer. Cox proportional hazards and Kaplan-Meier analyses assessed for treatment-associated survival. RESULTS: Of 21,076 cases, 18,214 underwent survival analysis with a mean ± SD age of 50.6 ± 17.1 years (71.3% female). When compared with surgery alone, S + RAI was associated with reduced mortality in papillary (hazard ratio [HR], 0.574; P < .001) and follicular (HR, 0.489; P = .004) thyroid cancer. S + RAI + THST was associated with reduced mortality in papillary (HR, 0.514; P < .001), follicular (HR, 0.602; P = .016), and Hurthle cell (HR, 0.504; P = .021) thyroid cancer. In papillary thyroid cancer, S + RAI (91.3%), S + THST (89.2%), and S + RAI + THST (92.7%) were associated with higher 5-year overall survival rates than surgery (85.4%, all P < .001). Papillary thyroid cancer treatments involving THST were associated with higher 5-year overall survival rates than corresponding regimens without THST (all P < .001). In follicular thyroid cancer, S + RAI (73.9%) and S + RAI + THST (78.7%) were associated with higher 5-year overall survival rates than surgery (65.6%, all P < .05). In Hurthle cell thyroid cancer, S + RAI (66.5%) and S + RAI + THST (73.4%) were associated with higher 5-year overall survival rates than surgery (53.7%, all P < .05). On linear regression, THST usage increased by 77.5% (R2 = 0.944, P < .001), while RAI usage declined by 11.3% (R2 = 0.320, P = .035). CONCLUSIONS: High-risk differentiated thyroid cancer exhibited varying susceptibilities to different treatment combinations depending on histology, with greatest responses to regimens that included RAI. Physician practices have trended toward decreased RAI and increased THST usage.

Dorsal striatial hypoconnectivity predicts antipsychotic medication treatment response in first-episode psychosis and unmedicated patients with schizophrenia.

INTRODUCTION: The dorsal striatum, comprised of the caudate and putamen, is implicated in the pathophysiology of psychosis spectrum disorders. Given the high concentration of dopamine receptors in the striatum, striatal dopamine imbalance is a likely cause in cortico-striatal dysconnectivity. There is great interest in understanding the relationship between striatal abnormalities in psychosis and antipsychotic treatment response, but few studies have considered differential involvement of the caudate and putamen. This study's goals were twofold. First, identify patterns of dorsal striatal dysconnectivity for the caudate and putamen separately in patients with a psychosis spectrum disorder; second, determine if these dysconnectivity patterns were predictive of treatment response. METHODS: Using resting state functional connectivity, we evaluated dorsal striatal connectivity using separate bilateral caudate and putamen seed regions in two cohorts of subjects: a cohort of 71 medication-naïve first episode psychosis patients and a cohort of 42 unmedicated patients with schizophrenia (along with matched controls). Patient and control connectivity maps were contrasted for each cohort. After receiving 6 weeks of risperidone treatment, patients' clinical response was calculated. We used regression analyses to determine the relationship between baseline dysconnectivity and treatment response. RESULTS: This dysconnectivity was also predictive of treatment response in both cohorts. DISCUSSION: These findings suggest that the caudate may be more of a driving factor than the putamen in early cortico-striatal dysconnectivity.

Effects of muscle quantity and bone mineral density on injury and outcomes in older adult motor vehicle crash occupants.

Objectives: Quantify the independent and combined effects of abdominal muscle quantity and lumbar bone mineral density (BMD) on injury risk and in-hospital outcomes in severely injured motor vehicle crash (MVC) occupants ages 50 and older.Methods: Skeletal muscle area measurements of MVC occupants were obtained through semi-automated segmentation of an axial computed tomography (CT) slice at the L3 vertebra. An occupant height-normalized Skeletal Muscle Index (SMI) was calculated - a defining metric of sarcopenia and low muscle mass (sarcopenia thresholds: <38.5 cm2/m2 females; <52.4 cm2/m2 males). Lumbar BMD was obtained using a validated, phantomless CT calibration method (osteopenia threshold: <145 mg/cm3). SMI and BMD values were used to categorize occupants, and logistic regression was used to associate sarcopenia, osteopenia, and osteosarcopenia predictors to injury outcomes (e.g., Injury Severity Score (ISS), maximum Abbreviated Injury Scale (MAIS) score, fractures) and hospital outcomes (e.g., length of stay, ICU days).Results: Of the 336 occupants, 210 (63%) were female (mean ± SD: age 66.3 ± 10.6). SMI was 41.7 ± 8.0 cm2/m2 in females and 51.2 ± 10.8 cm2/m2 in males. Based on SMI, 40% of females and 55% of males were classified as sarcopenic. BMD was 163.2 ± 38.3 mg/cm3 in females and 164.1 ± 35.4 mg/cm3 in males, with 41% of females and 33% of males classified as osteopenic. Prevalence of both conditions (osteosarcopenia) was similar between females (21%) and males (22%). Incidence of low SMI and BMD increased with age. Sarcopenic individuals were less likely to sustain a MAIS 2+ thorax injury and had longer ICU stays. Osteopenic individuals were more likely to sustain upper extremity injuries and fractures, and were less likely to be discharged to a rehabilitation facility. Osteosarcopenic individuals were less likely to be ventilated or admitted to the ICU but tended to spend more time on the ventilator if placed on one.Conclusions: Osteosarcopenia was not associated with any injury outcomes, but sarcopenia was associated with thoracic injury and osteopenia was associated with upper extremity injury incidence. Sarcopenia was only associated with ICU length of stay, while osteopenia was only associated with discharge destination. Osteosarcopenia was associated with likelihood of being ventilated, being admitted to the ICU, and with increased length of ventilation.

Synthesis, crystal structure, EPR, and DFT studies of an unusually distorted vanadium(II) complex.

We report the synthesis and structure of the most highly distorted four-coordinate d3 ion known to date that also serves as the second known example of a bis(biphenolato) transition metal complex. We demonstrate the application of density functional theory to calculate the magnetic parameters derived from the experimental and simulated EPR spectra.