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(1) Background: COVID-19 caused the worst international public health crisis, accompanied by major global economic downturns and mass-scale job losses, which impacted the psychosocial wellbeing of the worldwide population, including Saudi Arabia. Evidence of the high-risk groups impacted by the pandemic has been non-existent in Saudi Arabia. Therefore, this study examined factors associated with psychosocial distress, fear of COVID-19 and coping strategies among the general population in Saudi Arabia. (2) Methods: A cross-sectional study was conducted in healthcare and community settings in the Saudi Arabia using an anonymous online questionnaire. The Kessler Psychological Distress Scale (K-10), Fear of COVID-19 Scale (FCV-19S) and Brief Resilient Coping Scale (BRCS) were used to assess psychological distress, fear and coping strategies, respectively. Multivariate logistic regressions were used, and an Adjusted Odds Ratio (AOR) with 95% Confidence Intervals (CIs) was reported. (3) Results: Among 803 participants, 70% (n = 556) were females, and the median age was 27 years; 35% (n = 278) were frontline or essential service workers; and 24% (n = 195) reported comorbid conditions including mental health illness. Of the respondents, 175 (21.8%) and 207 (25.8%) reported high and very high psychological distress, respectively. Factors associated with moderate to high levels of psychological distress were: youth, females, non-Saudi nationals, those experiencing a change in employment or a negative financial impact, having comorbidities, and current smoking. A high level of fear was reported by 89 participants (11.1%), and this was associated with being ex-smokers (3.72, 1.14–12.14, 0.029) and changes in employment (3.42, 1.91–6.11, 0.000). A high resilience was reported by 115 participants (14.3%), and 333 participants (41.5%) had medium resilience. Financial impact and contact with known/suspected cases (1.63, 1.12–2.38, 0.011) were associated with low, medium, to high resilient coping. (4) Conclusions: People in Saudi Arabia were at a higher risk of psychosocial distress along with medium-high resilience during the COVID-19 pandemic, warranting urgent attention from healthcare providers and policymakers to provide specific mental health support strategies for their current wellbeing and to avoid a post-pandemic mental health crisis.

Background Funding may impact the quality and findings of systematic reviews (SRs). We aimed to compare the methodological quality of funded and non-funded SRs that investigated the outcomes in ischemic stroke patients undergoing mechanical thrombectomy. Methods We conducted a comprehensive search strategy in different databases, including Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid Medline (including epub ahead of print, in-process & other non-indexed citations), PubMed, Scopus and Web of Science Core Collection to retrieve all relevant SRs. Random sequence generation matched each funded SR with a non-funded one. A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool was used to assess the bias and quality of the included SRs. We also used uni- and multivariate analysis to perform our analysis, and results were expressed in odds ratio (OR) and 95% confidence interval (CI). Results We retrieved 150 articles, which were randomized and matched into 100 SRs, including 50 funded and 50 non-funded studies. By multivariate analysis, we found that including randomized clinical trials (RCTs) (OR: 5.7; 95% CI: 1.8–17.8; p = 0.003) and reporting conflict of interests (OR: 5.2; 95 CI: 1.1–24; p = 0.036) were the only significant differences between funded and non-funded SRs. No significant differences were found regarding the overall confidence for low-quality (OR: 0.54; 95% CI: 0.09–3.2; p = 0.49) and moderate/high-quality SRs (OR: 0.17; 95% CI: 0.02–1.87; p = 0.14). Conclusion Funded studies tend to include RCTs more often and report conflict of interests with no significant impact on overall confidence.

Study Design: Prospective observational study, level of evidence 1 for prognostic investigations. Objectives: To evaluate the prevalence of sleep impairment and predictors of improved sleep quality 24 months postoperatively in cervical spondylotic myelopathy (CSM) using the quality outcomes database. Summary of Background Data: Sleep disturbances are a common yet understudied symptom in CSM. Materials and Methods: The quality outcomes database was queried for patients with CSM, and sleep quality was assessed through the neck disability index sleep component at baseline and 24 months postoperatively. Multivariable logistic regressions were performed to identify risk factors of failure to improve sleep impairment and symptoms causing lingering sleep dysfunction 24 months after surgery. Results: Among 1135 patients with CSM, 904 (79.5%) had some degree of sleep dysfunction at baseline. At 24 months postoperatively, 72.8% of the patients with baseline sleep symptoms experienced improvement, with 42.5% reporting complete resolution. Patients who did not improve were more like to be smokers [adjusted odds ratio (aOR): 1.85], have osteoarthritis (aOR: 1.72), report baseline radicular paresthesia (aOR: 1.51), and have neck pain of ≥4/10 on a numeric rating scale. Patients with improved sleep noted higher satisfaction with surgery (88.8% vs 72.9%, aOR: 1.66) independent of improvement in other functional areas. In a multivariable analysis including pain scores and several myelopathy-related symptoms, lingering sleep dysfunction at 24 months was associated with neck pain (aOR: 1.47) and upper (aOR: 1.45) and lower (aOR: 1.52) extremity paresthesias. Conclusion: The majority of patients presenting with CSM have associated sleep disturbances. Most patients experience sustained improvement after surgery, with almost half reporting complete resolution. Smoking, osteoarthritis, radicular paresthesia, and neck pain ≥4/10 numeric rating scale score are baseline risk factors of failure to improve sleep dysfunction. Improvement in sleep symptoms is a major driver of patient-reported satisfaction. Incomplete resolution of sleep impairment is likely due to neck pain and extremity paresthesia.

OBJECTIVE Patient-reported outcomes (PROs) have become the standard means to measure surgical outcomes. Insurers and policy makers are also increasingly utilizing PROs to assess the value of care and measure different aspects of a patient’s condition. For cervical myelopathy, it is currently unclear which outcome measure best reflects patient satisfaction. In this investigation, the authors evaluated patients treated for cervical myelopathy to determine which outcome questionnaires best correlate with patient satisfaction. METHODS The Quality Outcomes Database (QOD), a prospectively collected multi-institutional database, was used to retrospectively analyze patients undergoing surgery for cervical myelopathy. The North American Spine Society (NASS) satisfaction index, Neck Disability Index (NDI), numeric rating scales for neck pain (NP-NRS) and arm pain (AP-NRS), EQ-5D, and modified Japanese Orthopaedic Association (mJOA) scale were evaluated. RESULTS The analysis included 1141 patients diagnosed with myelopathy, of whom 1099 had an NASS satisfaction index recorded at any of the follow-up time points. Concomitant radiculopathy was an indication for surgery in 368 (33.5%) patients, and severe neck pain (NP-NRS ≥ 7) was present in 471 (42.8%) patients. At the 3-month follow-up, NASS patient satisfaction index scores were positively correlated with scores for the NP-NRS (r = 0.30), AP-NRS (r = 0.32), and NDI (r = 0.36) and negatively correlated with EQ-5D (r = −0.38) and mJOA (r = −0.29) scores (all p < 0.001). At the 12-month follow-up, scores for the NASS index were positively correlated with scores for the NP-NRS (r = 0.44), AP-NRS (r = 0.38), and NDI (r = 0.46) and negatively correlated with scores for the EQ-5D (r = −0.40) and mJOA (r = −0.36) (all p < 0.001). At the 24-month follow-up, NASS index scores were positively correlated with NP-NRS (r = 0.49), AP-NRS (r = 0.36), and NDI (r = 0.49) scores and negatively correlated with EQ-5D (r = −0.44) and mJOA (r = −0.38) scores (all p < 0.001). CONCLUSIONS Neck pain was highly prevalent in patients with myelopathy. Notably, improvement in neck pain–associated disability rather than improvement in myelopathy was the most prominent PRO factor for patients. This finding may reflect greater patient concern for active pain symptoms than for neurological symptoms caused by myelopathy. As commercial payers begin to examine novel remuneration strategies for surgical interventions, thoughtful analysis of PRO measurements will have increasing relevance.

Background: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Methods: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. Results: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70–11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower–middle versus high: odds ratio, 0.08 [95% CI, 0.04–0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07–5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84–4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70–9.42]) were significantly associated with increased odds of MTA. Conclusions: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country’s per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Abstract Background: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within biomarker subtypes defined by hormone-receptor (HR), HER2, and MammaPrint (MP) status to evaluate novel agents as neoadjuvant therapy for high-risk breast cancer. The primary endpoint is pathologic complete response (pCR). Cemiplimab (Cemi) is a PD-1 inhibitor approved for the treatment of NSCLC, cutaneous basal, and squamous cell cancer. Here, we report current efficacy rates of Cemi in combination with paclitaxel followed by AC. Methods: Women with tumors ≥ 2.5cm were eligible for screening. Only HER2 negative (HER2-) patients were eligible for this treatment; HR positive (HR+) patients had to be MP high risk. Treatment included paclitaxel 80 mg/m2 IV weekly x 12 and Cemi 350 mg IV given q3weeks x 4, followed by doxorubicin/cyclophosphamide (AC) every 2 weeks x 4. The control arm was weekly paclitaxel x 12 followed by AC every 2-3 weeks x 4. All patients undergo serial MRI imaging; and imaging response (at 3 weeks, 12 weeks and prior to surgery) were used along with accumulating pCR data to continuously update and estimate pCR rates for trial arms. Analysis was modified intent to treat. Patients who switched to non-protocol therapy count as non-pCR. The goal is to identify (graduate) regimens with ≥85% Bayesian predictive probability of success (i.e. demonstrating superiority to control) in a future 300-patient phase 3 neoadjuvant trial with a pCR endpoint within responsive signatures. Cemi was eligible to graduate in 3 pre-defined signatures: HER2-, HR-HER2-, and HR+HER2-. To adapt to changing standard of care, we constructed “dynamic controls” comprising ‘best’ alternative therapies using I-SPY 2 and external data and estimated the probability of Cemi being superior to the dynamic control. Results: 60 HER2- patients (28 HR+ and 32 HR-) received Cemi arm treatment. The control group included 357 patients with HER2- tumors (201 HR+ and 156 HR-) enrolled since March 2010. Cemi graduated in HR-/HER2- signature. Estimated pCR rates (as of June 2022) are summarized in the table. Immune-related endocrine disorders include: hypothyroid (14.5%), adrenal insufficiency (10%), hyperthyroid (4.8%),) and thyroiditis (3.2%). Only one grade 3 adrenal insufficiency was observed. All immune related AE’s were manageable. Additional biomarker analyses are ongoing and will be presented at the meeting. Response predictive subtypes (Immune+ vs Immune-) and additional predictive biomarkers were assessed. Associations with pCR will be presented at SABCS. Conclusion: The I-SPY 2 study aims to assess the probability that investigational regimens will be successful in a phase 3 neoadjuvant trial. Anti-PD-1 therapy with Cemi resulted in a higher predicted pCR rate in HR-/HER2- 55 rate% disease compared to control at 29%. Immune-mediated AE’s were observed. This data is consistent with previously published data using check point inhibitors in early-stage HR-/HER2- breast cancer. Estimated pCR rates Citation Format: Erica Stringer-Reasor, Rebecca A. Shatsky, Jo Chien, Anne Wallace, Judy C. Boughey, Kathy S. Albain, Hyo S. Han, Rita Nanda, Claudine Isaacs, Kevin Kalinsky, Zahi Mitri, Amy S. Clark, Christos Vaklavas, Alexandra Thomas, Meghna S. Trivedi, Janice Lu, Smita Asare, Ruixiao Lu, Maria Pitsouni, Amy Wilson, Jane Perlmutter, Hope Rugo, Richard Schwab, W. Fraser Symmans, Nola M. Hylton, Laura Van ’t Veer, Douglas Yee, Angela DeMichele, Donald Berry, Laura J. Esserman, I-SPY Investigators. PD11-01 Evaluation of the PD-1 Inhibitor Cemiplimab in early-stage, high-risk HER2-negative breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-01.

Abstract Through its classic ATP‐dependent ion‐pumping function, basolateral Na/K‐ATPase (NKA) generates the Na + gradient that drives apical Na + reabsorption in the renal proximal tubule (RPT), primarily through the Na + /H + exchanger (NHE3). Accordingly, activation of NKA‐mediated ion transport decreases natriuresis through activation of basolateral (NKA) and apical (NHE3) Na + reabsorption. In contrast, activation of the more recently discovered NKA signaling function triggers cellular redistribution of RPT NKA and NHE3 and decreases Na + reabsorption. We used gene targeting to test the respective contributions of NKA signaling and ion pumping to the overall regulation of RPT Na + reabsorption. Knockdown of RPT NKA in cells and mice increased membrane NHE3 and Na + /HCO 3 − cotransporter (NBCe1A). Urine output and absolute Na + excretion decreased by 65%, driven by increased RPT Na + reabsorption (as indicated by decreased lithium clearance and unchanged glomerular filtration rate), and accompanied by elevated blood pressure. This hyper reabsorptive phenotype was rescued upon crossing with RPT NHE3 −/− mice, confirming the importance of NKA/NHE3 coupling. Hence, NKA signaling exerts a tonic inhibition on Na + reabsorption by regulating key apical and basolateral Na + transporters. This action, lifted upon NKA genetic suppression, tonically counteracts NKA's ATP‐driven function of basolateral Na + reabsorption. Strikingly, NKA signaling is not only physiologically relevant but it also appears to be functionally dominant over NKA ion pumping in the control of RPT reabsorption.

Abstract Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. This study aimed to assess serum hTERT level and its relation to the progression of liver disease. Also, it aimed to assess the effect of HCV core protein on memory T-cells in HCV patients with or without HCC, and the correlation between memory cells phenotype and the progression of the disease in the same patients. hTERT level in serum was assessed through relative quantitative RT-PCR. Flow cytometric analysis was used to assess T-cells responsiveness (as IFN-γ secretion) before and after stimulation with HCV core protein, and memory CD8+ cells phenotype using several differentiation markers. hTERT was found to be increased in a stepwise manner upon comparing its level in controls, chronic hepatitis patients, cirrhotic patients, and HCC patients. T-cells showed a similar manner of stepwise decrease in response (decreased IFN-γ secretion) in HCC patients compared to HCV patients without HCC and controls. Also, late differentiated memory cells (CD8+ CD27- CD28- CD45RA+CCR7-) were depleted in HCC patients compared to HCV patients without HCC. In conclusion, these results suggest a negative correlation between hTERT and IFN-γ secretion by T- cells in HCV patients and that this relationship along with the depletion of late differentiated memory cells could help the progression of liver disease to HCC.

Spinal cord tumors constitute a diverse group of rare neoplasms associated with significant mortality and morbidity that pose unique clinical and surgical challenges. Diagnostic accuracy and outcome prediction are critical for informed decision making and can promote personalized medicine and facilitate optimal patient management. Machine learning has the ability to analyze and combine vast amounts of data, allowing the identification of patterns and the establishment of clinical associations, which can ultimately enhance patient care. Although artificial intelligence techniques have been explored in other areas of spine surgery, such as spinal deformity surgery, precise machine learning models for spinal tumors are lagging behind. Current applications of machine learning in spinal cord tumors include algorithms that improve diagnostic precision by predicting genetic, molecular, and histopathological profiles. Furthermore, artificial intelligence-based systems can assist surgeons with preoperative planning and surgical resection, potentially reducing the risk of recurrence and consequently improving clinical outcomes. Machine learning algorithms promote personalized medicine by enabling prognostication and risk stratification based on accurate predictions of treatment response, survival, and postoperative complications. Despite their promising potential, machine learning models require extensive validation processes and quality assessments to ensure safe and effective translation to clinical practice.