Marker-assisted enhancement of bacterial blight (Xanthomonas oryzae pv. oryzae) resistance in a salt-tolerant rice variety for sustaining rice production of tropical islands.

Introduction: Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae is a major disease of rice, specially in the tropical regions of the world. Developing rice varieties with host resistance against the disease is the most effective and economical solution for managing the disease. Methods: Pyramiding resistance genes (Xa4, xa5, xa13,and Xa21) in popular rice varieties using marker-assisted backcross breeding (MABB) has been demonstrated as a cost-effective and sustainable approach for establishing durable BB resistance. Here, we report our successful efforts in introgressing four resistance genes (Xa4, xa5, xa13, and Xa21) from IRBB60 to CARI Dhan 5, a popular salt-tolerant variety developed from a somaclonal variant of Pokkali rice, through functional MABB. Results and discussion: Both BB and coastal salinity are among the major challenges for rice production in tropical island and coastal ecosystems. Plants with four, three, and two gene pyramids were generated, which displayed high levels of resistance to the BB pathogen at the BC3F2 stage. Under controlled salinity microplot environments, the line 131-2-175-1223 identified with the presence of three gene pyramid (Xa21+xa13+xa5) displayed notable resistance across locations and years as well as exhibited a salinity tolerance comparable to the recurrent parent, CARI Dhan 5. Among two BB gene combinations (Xa21+xa13), two lines, 17-1-69-334 and 46-3-95-659, demonstrated resistance across locations and years, as well as salt tolerance and grain production comparable to CARI Dhan 5. Besides salinity tolerance, five lines, 17-1-69-179, 46-3-95-655, 131-2-190-1197, 131-2-175-1209, and 131-2-175-1239, exhibited complete resistance to BB disease. Following multilocation testing, potential lines have been identified that can serve as a prospective candidate for producing varieties for the tropical Andaman and Nicobar Islands and other coastal locations, which are prone to BB and coastal salinity stresses.

Tumor and Nodal Disease Growth Rates in Patients with Oropharyngeal Squamous Cell Carcinoma.

Though specific growth rate (SGR) has potential prognostic value for oropharyngeal squamous cell carcinoma (OPSCC), there is sparse literature defining these rates. Our aims were to establish the SGRs of primary tumors (PTs) and lymph nodes (LNs) in OPSCC and to correlate SGR with oncologic outcome. A pilot study was designed with a retrospective analysis examining 54 patients from the University of California, Davis with OPSCC (diagnosed 2012-2019). Radiation oncology software and pretreatment serial CT scans were used to measure PT and LN volumes to calculate SGR and doubling time (DT). The mean PT-SGR was 1.2 ± 2.2%/day and the mean LN-SGR was 1.6 ± 1.9%/day. There was no statistically significant difference between slow-growing and fast-growing cohorts in terms of age, gender, smoking status, tumor subsite, HPV status (as determined with p16 staining), initial volume, or overall stage. SGR had no impact on 2-year overall survival, disease-free survival, or disease-specific survival. We found the average daily growth rates for OPSCC to be 1.2%/day and 1.6%/day. Our findings suggest PT- and LN-SGR are independent factors, not heavily influenced by known biomarkers and patient characteristics, without a statistical impact on prognosis. This information has value in patient counseling regarding tumor growth and in providing patients worried about fast-growing tumors the appropriate reassurance.

Impact of practicing internal benchmarking on continuous improvement of cataract surgery outcomes: a retrospective observational study at Aravind Eye Hospitals, India.

OBJECTIVE: We aim to assess the effectiveness of a cataract surgery outcome monitoring tool used for continuous quality improvement. The objectives are to study: (1) the quality parameters, (2) the monitoring process followed and (3) the impact on outcomes. DESIGN AND PROCEDURES: In this retrospective observational study we evaluated a quality improvement (QI) method which has been practiced at the focal institution since 2012: internal benchmarking of cataract surgery outcomes (CATQA). We evaluated quality parameters, procedures followed and clinical outcomes. We created tables and line charts to examine trends in key outcomes. SETTING: Aravind Eye Care System, India. PARTICIPANTS: Phacoemulsification surgeries performed on 718 120 eyes at 10 centres (five tertiary and five secondary eye centres) from 2012 to 2020 were included. INTERVENTIONS: An internal benchmarking of surgery outcome parameters, to assess variations among the hospitals and compare with the best hospital. OUTCOME MEASURES: Intraoperative complications, unaided visual acuity (VA) at postoperative follow-up visit and residual postoperative refractive error (within ±0.5D). RESULTS: Over the study period the intraoperative complication rate decreased from 1.2% to 0.6%, surgeries with uncorrected VA of 6/12 or better increased from 80.8% to 89.8%, and surgeries with postoperative refractive error within ±0.5D increased from 76.3% to 87.3%. Variability in outcome measures across hospitals declined. Additionally, benchmarking was associated with improvements in facilities, protocols and processes. CONCLUSION: Internal benchmarking was found to be an effective QI method that enabled the practice of evidence-based management and allowed for harnessing the available information. Continuous improvement in clinical outcomes requires systematic and regular review of results, identifying gaps between hospitals, comparisons with the best hospital and implementing lessons learnt from peers.

Harnessing intra-varietal variation for agro-morphological and nutritional traits in a popular rice landrace for sustainable food security in tropical islands.

Introduction: Rice crop meets the calorie and nutritional requirements of a larger segment of the global population. Here, we report the occurrence of intra-varietal variation in a popular rice landrace C14-8 traditionally grown under the geographical isolation of the Andaman Islands. Methods: Based on grain husk color, four groups were formed, wherein the extent of intra-varietal variation was studied by employing 22 agro-morphological and biochemical traits. Results: Among the traits studied, flavonoid and anthocyanin contents and grain yield exhibited a wider spectrum of variability due to more coefficients of variation (>25%). The first five principal components (PCs) of principal components analysis explained a significant proportion of the variation (91%) and the first two PCs explained 63.3% of the total variation, with PC1 and PC2 explaining 35.44 and 27.91%, respectively. A total of 50 highly variable SSR (HvSSR) markers spanning over 12 chromosomes produced 314 alleles, which ranged from 1 to 15 alleles per marker, with an average of 6.28. Of the 314 alleles, 64 alleles were found to be rare among the C14-8 selections. While 62% of HvSSR markers exhibited polymorphism among the C14-8 population, chromosomes 2, 7, 9, and 11 harbored the most polymorphic loci. The group clustering of the selections through HvSSR markers conformed to the grouping based on grain husk coloration. Discussion: Our studies on the existence and pertinence of intra-varietal variations are expected to be of significance in the realms of evolutionary biology and sustainable food and nutritional security under the changing climate.

Managing Outpatient Cycle Times in Hospitals Using Integrated Closed-Loop Approaches.

Long waiting times in outpatient clinics have multiple adverse effects on patients and their attendants, staff and hospital management. Several approaches practiced to manage the cycle time have been proposed. The purpose of this study was to evaluate the impact of implementing closed-loop based multiple approaches together. This study was conducted in Aravind Eye Hospital (AEH), Madurai, India where several approaches to manage cycle times have been implemented over the years. Scheduling system was introduced to manage COVID-19 specific norms. We compared the cycle times in general outpatient clinics in a regime in which multiple approaches were practiced together before and after introducing scheduling to regimes in which individual approaches were practiced. We analysed how the cycle time varied by patient load. Cycle time for all patient days when the combined approach was used was 19% lower than baseline, and better than under each of the individual approaches. The outcome sustained even during the COVID-19 pandemic that necessitated additional processes and procedures. Therefore, implementing multiple approaches can be more effective to reduce the cycle time than implementing individual approaches.

Barriers to cervical cancer and breast cancer screening uptake in low- and middle-income countries: a systematic review.

There is an alarmingly high growth in breast and cervical cancers in low- and middle-income countries. Due to late presentation to doctors, there is a lower cure rate. The screening programmes in low- and middle-income countries are not comprehensive. In this paper, we systematically analyse the barriers to screening through an accessibility framework. We performed a systematic literature search in PubMed, Mendeley and Google Scholar to retrieve all English language studies (quantitative, qualitative and mixed-methods) that contained information on breast and cervical cancer screening in low- and middle-income countries. We only considered publications published between 1 January 2016 and 31 May 2021. The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension (PRISMA-S), an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews. The search yielded a total of 67 articles from low- and middle-income countries in this review. We used a framework on accessibility known as the 5A framework, which distinguishes five aspects of access: approachability, acceptability, availability, affordability and appropriateness, to classify the screening barriers. We added two more aspects: awareness and angst, as they could explain other important barriers to screening. They confirmed how the lack of awareness, cost of the screening service and distance to the screening centre act as major impediments to screening. They also revealed how embarrassment and fear of screening and cultural factors such as lack of spousal or family support could be obstacles to screening. We conclude that more needs to be done by policymakers and governments to improve the confidence of the people in the health systems. Women should be made aware of the causes and risk factors of cancer through evidence-based strategies so that there is an increased adherence to screening.

Disparities in Decompressive Cranial Surgery Utilization in Severe Traumatic Brain Injury Patients without a Primary Extra-Axial Hematoma: A U.S. Nationwide Study.

OBJECTIVE: Decompressive craniectomy is recommended to reduce mortality in severe traumatic brain injury (TBI). Disparities exist in TBI treatment outcomes; however, data on disparities pertaining to decompressive craniectomy utilization is lacking. We investigated these disparities, focusing on race, insurance, sex, and age. METHODS: Hospitalizations (2004-2014) were retrospectively extracted from the Nationwide Inpatient Sample. The criteria included are as follows: age ≥18 years and indicators of severe TBI diagnosis. Poor outcomes were defined as discharge to institutional care and death. Multivariable logistic regression models were used to assess the effects of race, insurance, age, and sex, on craniectomy utilization and outcomes. RESULTS: Of 349,164 hospitalized patients, 6.8% (n = 23,743) underwent craniectomy. White (odds ratio [OR] = 0.50, 95% confidence interval [CI] = 0.44-0.57; P < 0.001) and Black (OR = 0.45, 95% CI = 0.32-0.64; P = 0.003) Medicare beneficiaries were less likely to undergo craniectomy. Medicare (P < 0.0001) and Medicaid beneficiaries (P < 0.0001) of all race categories had poorer outcomes than privately insured White patients. Black (OR = 1.2, 95% CI = 1.08-2.34; P = 0.001) patients with private insurance and Black (OR = 1.39, 95% CI = 1.22-1.58; P < 0.0001) Medicaid beneficiaries had poorer outcomes than privately insured White patients (P < 0.0001). Older patients (OR = 0.74, 95%, CI = 0.71-0.76; P < 0.001) were less likely to undergo craniectomy and were more likely to have poorer outcomes. Females (OR = 0.82, 95% CI = 0.76-0.88; P < 0.001) were less likely to undergo craniectomy. CONCLUSIONS: There are disparities in race, insurance status, sex, and age in craniectomy utilization and outcome. This data highlights the necessity to appropriately address these disparities, especially race and sex, and actively incorporate these factors in clinical trial design and enrollment.

Evaluating Automatic Segmentation for Swallowing-Related Organs for Head and Neck Cancer.

Purpose: To evaluate the accuracy of deep-learning-based auto-segmentation of the superior constrictor, middle constrictor, inferior constrictor, and larynx in comparison with a traditional multi-atlas-based method. Methods and Materials: One hundred and five computed tomography image datasets from 83 head and neck cancer patients were retrospectively collected and the superior constrictor, middle constrictor, inferior constrictor, and larynx were analyzed for deep-learning versus multi-atlas-based segmentation. Eighty-three computed tomography images (40 diagnostic computed tomography and 43 planning computed tomography) were used for training the convolutional neural network, and for atlas-based model training. The remaining 22 computed tomography datasets were used for validation of the atlas-based auto-segmentation versus deep-learning-based auto-segmentation contours, both of which were compared with the corresponding manual contours. Quantitative measures included Dice similarity coefficient, recall, precision, Hausdorff distance, 95th percentile of Hausdorff distance, and mean surface distance. Dosimetric differences between the auto-generated contours and manual contours were evaluated. Subjective evaluation was obtained from 3 clinical observers to blindly score the autosegmented structures based on the percentage of slices that require manual modification. Results: The deep-learning-based auto-segmentation versus atlas-based auto-segmentation results were compared for the superior constrictor, middle constrictor, inferior constrictor, and larynx. The mean Dice similarity coefficient values for the 4 structures were 0.67, 0.60, 0.65, and 0.84 for deep-learning-based auto-segmentation, whereas atlas-based auto-segmentation has Dice similarity coefficient results at 0.45, 0.36, 0.50, and 0.70, respectively. The mean 95th percentile of Hausdorff distance (cm) for the 4 structures were 0.41, 0.57, 0.59, and 0.54 for deep-learning-based auto-segmentation, but 0.78, 0.95, 0.96, and 1.23 for atlas-based auto-segmentation results, respectively. Similar mean dose differences were obtained from the 2 sets of autosegmented contours compared to manual contours. The dose-volume discrepancies and the average modification rates were higher with the atlas-based auto-segmentation contours. Conclusion: Swallowing-related structures are more accurately generated with DL-based versus atlas-based segmentation when compared with manual contours.

Polyamine Metabolites as Biomarkers in Head and Neck Cancer Biofluids.

Background: Novel, non-invasive diagnostic biomarkers that facilitate early intervention in head and neck cancer are urgently needed. Polyamine metabolites have been observed to be elevated in numerous cancer types and correlated with poor prognosis. The aim of this study was to assess the concentration of polyamines in the saliva and urine from head and neck cancer (HNC) patients, compared to healthy controls. Methods: Targeted metabolomic analysis was performed on saliva and urine from 39 HNC patient samples and compared to 89 healthy controls using a quantitative, targeted liquid chromatography mass spectrometry approach. Results: The metabolites N1-acetylspermine (ASP), N8-acetylspermidine (ASD) and N1,N12-diacetylspermine (DAS) were detected at significantly different concentrations in the urine of HNC patients as compared to healthy controls. Only ASP was detected at elevated levels in HNC saliva as compared to healthy controls. Conclusion: These data suggest that assessment of polyamine-based metabolite biomarkers within the saliva and urine warrants further investigation as a potential diagnostic in HNC patients.

Head and neck synthetic CT generated from ultra-low-dose cone-beam CT following Image Gently Protocol using deep neural network.

PURPOSE: Image guidance is used to improve the accuracy of radiation therapy delivery but results in increased dose to patients. This is of particular concern in children who need be treated per Pediatric Image Gently Protocols due to long-term risks from radiation exposure. The purpose of this study is to design a deep neural network architecture and loss function for improving soft-tissue contrast and preserving small anatomical features in ultra-low-dose cone-beam CTs (CBCT) of head and neck cancer (HNC) imaging. METHODS: A 2D compound U-Net architecture (modified U-Net++) with different depths was proposed to enhance the network capability of capturing small-volume structures. A mask weighted loss function (Mask-Loss) was applied to enhance soft-tissue contrast. Fifty-five paired CBCT and CT images of HNC patients were retrospectively collected for network training and testing. The output enhanced CBCT images from the present study were evaluated with quantitative metrics including mean absolute error (MAE), signal-to-noise ratio (SNR), and structural similarity (SSIM), and compared with those from the previously proposed network architectures (U-Net and wide U-Net) using MAE loss functions. A visual assessment of ten selected structures in the enhanced CBCT images of each patient was performed to evaluate image quality improvement, blindly scored by an experienced radiation oncologist specialized in HN cancer. RESULTS: All the enhanced CBCT images showed reduced artifactual distortion and image noise. U-Net++ outperformed the U-Net and wide U-Net in terms of MAE, contrast near structure boundaries, and small structures. The proposed Mask-Loss improved image contrast and accuracy of the soft-tissue regions. The enhanced CBCT images predicted by U-Net++ and Mask-Loss demonstrated improvement compared to the U-Net in terms of average MAE (52.41 vs 42.85 HU), SNR (14.14 vs 15.07 dB), and SSIM (0.84 vs 0.87), respectively ( p < 0.01 $p < 0.01$ , in all paired t-tests). The visual assessment showed that the proposed U-Net++ and Mask-Loss significantly improved original CBCTs ( p < 0.01 $p < 0.01$ ), compared to the U-Net and MAE loss. CONCLUSIONS: The proposed network architecture and loss function effectively improved image quality in soft-tissue contrast, organ boundary, and small structure preservation for ultra-low-dose CBCT following Image Gently Protocol. This method has potential to provide sufficient anatomical representation on the enhanced CBCT images for accurate treatment delivery and potentially fast online-adaptive re-planning for HN cancer patients.

Deep learning model using retinal vascular images for classifying schizophrenia.

Contemporary psychiatric diagnosis still relies on the subjective symptom report of the patient during a clinical interview by a psychiatrist. Given the significant variability in personal reporting and differences in the skill set of psychiatrists, it is desirable to have objective diagnostic markers that could help clinicians differentiate patients from healthy individuals. A few recent studies have reported retinal vascular abnormalities in patients with schizophrenia (SCZ) using retinal fundus images. The goal of this study was to use a trained convolution neural network (CNN) deep learning algorithm to detect SCZ using retinal fundus images. A total of 327 subjects [139 patients with Schizophrenia (SCZ) and 188 Healthy volunteers (HV)] were recruited, and retinal images were acquired using a fundus camera. The images were preprocessed and fed to a convolution neural network for the classification. The model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The CNN achieved an accuracy of 95% for classifying SCZ and HV with an AUC of 0.98. Findings from the current study suggest the potential utility of deep learning to classify patients with SCZ and assist clinicians in clinical settings. Future studies need to examine the utility of the deep learning model with retinal vascular images as biomarkers in schizophrenia with larger sample sizes.

Venous Thromboembolism Risk and Outcomes Following Decompressive Craniectomy in Severe Traumatic Brain Injury: An Analysis of the Nationwide Inpatient Sample Database.

OBJECTIVE: Traumatic brain injury (TBI) is a risk factor for venous thromboembolism (VTE). The risk of VTE after decompressive craniectomy (DC) and its effects on the outcomes are unknown. We assessed the incidence of VTE, associated risk factors, and effects on the outcomes. METHODS: Using the National Inpatient Sample database, the hospitalizations of patients aged ≥18 years with a severe TBI diagnosis from 2004 to 2014 were extracted. The outcome was discharge status without mortality. Multivariable logistic and linear regressions were used. RESULTS: Of the 349,165 TBI hospitalizations, 23,813 (6.82%) had undergone DC and 14,175 (4.06%) had developed VTE. The VTE incidence was higher after DC compared with no DC (6.14% vs. 3.91%; P < 0.0001). DC (odds ratio [OR], 1.29; P < 0.005) was an independent predictor for the development of VTE. Age (OR, 1.26; P < 0.005), chronic lung disease (OR, 1.58; P < 0.05), electrolyte imbalance (OR, 1.43; P < 0.05), liver disease (OR, 0.10; P < 0.05), urinary tract infection (OR, 1.56; P < 0.05), pneumonia (OR, 2.03; P < 0.0001), and sepsis (OR, 1.57; P < 0.05) were significantly associated with the development of VTE. Obesity (OR, 2.09; P > 0.05) and spine injury (OR, 2.03; P > 0.05) showed a trend toward significance. VTE was associated with worse discharge outcomes (OR, 1.40; P < 0.05), longer lengths of stay (OR, 1.01; P < 0.00001), and higher costs (P < 0.0001). CONCLUSIONS: Our study showed an independent association between DC and an increased risk of VTE for patients with severe TBI. The development of VTE after DC increased the proportion of poor outcomes, prolonged the length of stay, and increased the hospitalization costs. Older patients with obesity, an electrolyte imbalance, chronic lung disease, spine injury, and infections were at a greater risk of VTE after DC. These risk factors could help in considering VTE prophylaxis for these patients.

Association between retinal vascular measures and brain white matter lesions in schizophrenia.

OBJECTIVE: Recent studies have examined retinal vascular abnormalities in schizophrenia as retinal vascular imaging is a non-invasive proxy to cerebral microvasculature. However, relation between retinal vascular abnormalities and brain structure is not well examined in schizophrenia. Hence in this study, for the first time, we examined the relationship between retinal vascular measures and brain white matter lesions in schizophrenia. We examined brain white matter lesions as they are considered a predictive marker for future adverse cerebrovascular event. METHODS: We acquired retinal vascular images of both eyes using a non-mydriatic camera and calculated retinal vascular diameter, tortuosity, trajectory and fractal dimension using validated methods. All patients underwent Magnetic Resonance Imaging of bran and we computed white matter hypo-intensities using Freesurfer software. We performed a linear regression analysis to examine the relationship between white matter hypo-intensities and retinal vascular measures controlling for age, sex, fasting blood sugar, creatinine, whole-brain volume, and antipsychotic dose. RESULTS: The regression model was significant in Schizophrenia patients (R=0.983;R2 =0.966;-F=10.849;p = 0.008) but not in healthy volunteers (R=0.828;R2 =0.686;F=0.182; p = 0.963). Among the retinal vascular measures, arterial tortuosity (ß = 0.963;p-0.002), tortuosity (ß = -1.002;p = 0.001) and fractal dimension (ß = -0.688;p = 0.014) were significant predictors of white matter lesions. DISCUSSION: The current study's findings support the conclusion that retinal vascular fractal dimension and tortuosity are associated with changes in cerebral white matter and may be considered proxy markers for cerebral microvasculature in schizophrenia. Considering the relationship between white matter lesions and stroke, these observations could have important clinical implications to screen schizophrenia patients for risk of adverse cerebrovascular event.

Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Short- and long-term opioid use in survivors of subarachnoid hemorrhage.

OBJECTIVES: Opioids are frequently used for analgesia in patients with acute subarachnoid hemorrhage (SAH) due to a high prevalence of headache and neck pain. However, it is unclear if this practice may pose a risk for opioid dependence, as long-term opioid use in this population remains unknown. We sought to determine the prevalence of opioid use in SAH survivors, and to identify potential risk factors for opioid utilization. METHODS: We analyzed a cohort of consecutive patients admitted with non-traumatic and suspected aneurysmal SAH to an academic referral center. We included patients who survived hospitalization and excluded those who were not opioid-naïve. Potential risk factors for opioid prescription at discharge, 3 and 12 months post-discharge were assessed. RESULTS: Of 240 SAH patients who met our inclusion criteria (mean age 58.4 years [SD 14.8], 58% women), 233 (97%) received opioids during hospitalization and 152 (63%) received opioid prescription at discharge. Twenty-eight patients (12%) still continued to use opioids at 3 months post-discharge, and 13 patients (6%) at 12-month follow up. Although patients with poor Hunt and Hess grades (odds ratio 0.19, 95% CI 0.06-0.57) and those with intraventricular hemorrhage (odds ratio 0.38, 95% CI 0.18-0.87) were less likely to receive opioid prescriptions at discharge, we did not find significant differences between patients who had long-term opioid use and those who did not. CONCLUSION: Opioids are regularly used in both the acute SAH setting and immediately after discharge. A considerable number of patients also continue to use opioids in the long-term. Opioid-sparing pain control strategies should be explored in the future.

Association between retinal vascular caliber and brain structure in schizophrenia.

OBJECTIVE: Several lines of research in the last decade have indicated the potential utility of retina as a window to the brain. Emerging evidence suggests abnormalities in retinal vascular caliber in schizophrenia. However, the relationship between retinal vascular measures and brain structure has not been examined in schizophrenia to date. Hence, we examined the relationship between retinal vasculature measured using fundus photography and brain structure measured using magnetic resonance imaging. METHOD: We recruited 17 healthy volunteers and 20 patients with schizophrenia. Using a non-mydriatic camera, we captured the images for left and right eyes separately and retinal vascular calibers were calculated using a semi-automated software package. Whole-brain anatomical T1 MPRAGE images were acquired using a 3-Tesla MRI scanner. Whole-brain and regional volume and cortical thickness were calculated using the Freesurfer software package. We used FreeSurfer's QDEC interface to compute vertex-by-vertex for analysis of the volume and cortical thickness. The relation between brain volume, cortical thickness, and retinal vascular caliber was examined using partial correlation and regression analysis. RESULTS: There was a significant negative correlation between average CRVE and global cortical mean thickness in schizophrenia but not in healthy. In schizophrenia patients, there was a significant negative correlation between average CRVE and cortical thickness in frontal regions - left rostral middle frontal, left superior frontal, and right caudal middle frontal gyri and posterior brain regions - left lateral occipital gyrus and left posterior cingulate cortex. DISCUSSION: The findings of the study suggest potential utility of retinal venular diameter as a proxy marker to abnormal neurodevelopment in schizophrenia.

Association of Early White Blood Cell Trend with Outcomes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. METHODS: We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0-3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. RESULTS: We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17 × 109 cells/L, SD 6.4 vs. 13.5 × 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586-0.755) compared with each component alone. CONCLUSIONS: WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.

The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists.

Traumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

Common biomarkers of physiologic stress and associations with delirium in patients with intracerebral hemorrhage.

PURPOSE: To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury. MATERIALS AND METHODS: We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring <24 h ("early-onset") or > 24 h after presentation ("later-onset"). RESULTS: Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5-7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1-8.2]), and troponin (OR 3.0 [95% CI 1.2-7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients. CONCLUSIONS: Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.