Positive Scores Research Articles

Programmed Death-Ligand 1 (PD-L1) and Ki-67 Labeling Index: Correlation with Tumor Grade and Recurrence

Background: Meningiomas are common primary brain tumors with variable clinical behavior. While most are benign, a subset exhibits aggressive characteristics and a high recurrence rate. This study aimed to investigate the association of Programmed Death-Ligand 1 (PD-L1) and Ki-67 labeling index with histopathological grade and recurrence in meningioma. Methods: A retrospective study was conducted on 139 cases of meningioma diagnosed between January 2020 and December 2023. PD-L1 expression was evaluated using immunohistochemistry (IHC) and scored using the combined positive score (CPS). Ki-67 labeling index was determined as the percentage of tumor cells with positive nuclear staining. The association of PD-L1 and Ki-67 with histopathological grade and recurrence was analyzed. Results: PD-L1 expression was positive in 66.7% of cases and was significantly associated with recurrence (p = 0.006). A higher Ki-67 labeling index (>4%) was observed in 68.9% of cases and was also significantly associated with recurrence (p = 0.013). No significant association was found between PD-L1 expression or Ki-67 labeling index and histopathological grade. Conclusion: PD-L1 expression and Ki-67 labeling index may serve as potential prognostic markers for predicting recurrence in meningioma. Further studies are needed to validate these findings and explore their potential therapeutic implications.

Undetected Cribriform and Intraductal Prostate Cancer at biopsy is associated with adverse outcomes.

Intraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are increasingly recognized as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens. The aim of our project is to assess the impact of false negative biopsies for these two characteristics on oncological outcomes. Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of Biochemical Failure were examined using a multivariate Cox proportional hazards model. Among the 836 patients who underwent RP, 233 (27.9%) had Crib, and 125 (15.0%) had IDC on prostate biopsy, with 71 (8.5%) patients having both IDC and Crib. Concerning IDC/Crib status at biopsy, 217 (26%) patients had a false-negative biopsy, 332 (39.7%) had a true-negative biopsy, 256 (30.6%) showed a true-positive biopsy, and 24 (3.7%) exhibited a false-positive biopsy, with respect to either pattern. When comparing false-negative, false-positive, true-negative and true-positive biopsies for IDC/Crib, we found that patients with a false-negative biopsy for IDC/Crib versus those with a true-negative biopsy for IDC/Crib disclosed a rate of advanced pathological stage (≥pT3) which was twice that of patients with a true-negative biopsy for IDC/Crib: 56.8% versus 28.1%, respectively (p < 0.001). On multivariate Cox analysis, log PSA before RP (hazard ratio [HR] 2.07, 95% CI 1.53-2.82; p < 0.001), a higher percentage of positive cores at biopsy ( ≥ 33%) (HR 1.68, 95% CI 1.07-2.63; p = 0.024), and false negative biopsy for IDC/Crib (HR 2.14, 95% CI 1.41-3.25; p < 0.001), were each significantly associated with an increased risk of BCR. A false-negative biopsy for IDC/Crib is independently associated with higher risk of BCR and advanced pathological stage compared to a true negative biopsy.

Association of novel dietary and lifestyle inflammation scores with incidence and progression of coronary artery calcification in middle-late adulthood: a longitudinal cohort study

BackgroundDietary patterns and lifestyle factors can influence the intensity of systemic inflammation and, consequently, the development and progression of coronary artery calcification (CAC). This study aimed to explore the relationship between the inflammatory potentials of diet and lifestyle, as captured by novel dietary and lifestyle inflammation scores (DIS and LIS), with CAC incidence and progression.MethodsWe analyzed data on 5949 Black and White men and women ≥ 45 years old participating in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Baseline data on diet and lifestyle factors were collected from 2000 to 2002 and used to construct the DIS and LIS, which reflect the overall inflammatory potential of diet and lifestyle. Cox proportional hazard regression was used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI) for CAC incidence and progression across quartiles of DIS and LIS, adjusting for potential confounders.ResultsOver a median follow-up of 8.0 years, among 2638 participants with zero CAC score at baseline, 977 individuals developed positive scores, and 1681 out of 2561 participants showed CAC progression. For individuals in the highest (more pro-inflammatory) compared to the lowest (more anti-inflammatory) quartiles of the LIS, the multivariable-adjusted HR for CAC incidence was 1.35 (95% CI, 1.10–1.65; P trend < 0.002). This association was stronger among younger adults aged < 60 years compared to those aged ≥ 60 years, with respective values of 1.76 (1.34–2.30) and 1.02 (0.78–1.35) (P interaction < 0.001). However, the LIS was not significantly associated with the progression of existing CAC. Among the components of the LIS, a body mas index (BMI) ≥ 25 kg/m2 and current smoking were significant predictors for the incidence and progression of CAC, respectively. No significant association was found between DIS and CAC incidence and progression.ConclusionsLifestyle factors, through their impact on systemic inflammation, may be associated with a higher risk of CAC incidence in middle and late adulthood.

Severe hypersensitivity reactions to 2 immunotherapy agents in a patient with cutaneous squamous cell carcinoma.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. There is currently limited data on cross-sensitivity between immunotherapy agents. In this case study, we report a case of severe anaphylaxis to both pembrolizumab and cemiplimab. Pembrolizumab (Keytruda) and cemiplimab (Libtayo) are both approved for the treatment of metastatic cutaneous squamous cell carcinoma. Infusion reactions occur rarely with immunotherapy agents. However, if infusion reactions are severe, the treatment should be discontinued, and there is no guidance as to whether another immunotherapy agent may be used. An 87-year-old-male was diagnosed with metastatic cutaneous squamous cell carcinoma expressing a PD-L1 combined positive score of 81%-90%. He was treated with pembrolizumab and, 15 minutes after completion of the first infusion, developed swelling of the eyelids, ears, and tongue in addition to a whole-body rash without pruritus. Due to the severity of the reaction, pembrolizumab was permanently discontinued and the patient was then started on cemiplimab. The patient received a high-dose corticosteroid as premedication before the first infusion of cemiplimab and tolerated the treatment without any adverse effects. However, when the corticosteroid premedication dose was decreased before the second cycle, the patient had a severe infusion reaction to cemiplimab requiring discontinuation. A patient with metastatic cutaneous squamous cell carcinoma developed a severe hypersensitivity reaction to pembrolizumab and subsequently to cemiplimab, despite premedication.

Synthesis, characterization, and in vitro-in ovo toxicological screening of silibinin fatty acids conjugates as prodrugs with potential biomedical applications.

Silibinin (SIL), the most active phytocompound from Silybum marianum (L.), exerts many biological effects but has low stability and bioavailability. To overcome these drawbacks, the current research proposed the synthesis of silibilin oleate (SIL-O) and silibilin linoleate (SIL-L) derivatives as prodrugs with potentially optimized properties for biomedical applications, and the establishment of their in vitro-in ovo safety profiles. The physicochemical characterization of the obtained compounds using density functional theory (DFT) calculations, and Raman and 1H liquid-state nuclear magnetic resonance (NMR) spectroscopy confirmed the formation of SIL-O and SIL-L complexes. Computational predictions revealed that these lipophilic derivatives present a lower drug-likeness score (-29.96 for SIL-O and -23.55 for SIL-L) compared to SIL, but an overall positive drug score (0.07) and no risk for severe adverse effects. SIL-O and SIL-L showed no cytotoxicity or impairment in cell migration at low concentrations, but at the highest concentration (100 μM), they displayed distinct toxicological profiles. SIL-L was more cytotoxic (on cardiomyoblasts - H9c2(2-1), hepatocytes - HepaRG, and keratinocytes - HaCaT) than SIL-O or SIL, significantly inhibiting cell viability (<60%), altering cellular morphology, reducing cell confluence (<70%), and inducing prominent apoptotic-like nuclear features. At the concentration of 100 μM, SIL-O presented an irritation score (IS) of 0.61, indicating a lack of irritant effect on the chorioallantoic membrane (CAM), while SIL-L was classified as a slight irritant with an IS of 1.99. These findings outline a more favorable in vitro and in ovo biocompatibility for SIL-O compared to SIL L, whose applications are dosage limited due to potential toxicity.

Predicting Metastasis and Mortality Risk in Prostate biopsy using genomics and biopsy related factors

Abstract Introduction/Objective Prostate cancer, the most prevalent cancer among men, is diagnosed through biopsy, yet its predictive accuracy for metastasis and mortality risk remains limited. An approach to stratifying this risk is by combining biopsy data and genetics. The Decipher genomic classifier aids in estimating such risks. This study investigates the correlation between Decipher, biopsy-related factors, and the risk of prostate cancer metastasis or mortality. Methods/Case Report 50 prostatic adenocarcinoma biopsies were analyzed. Patient age, average tumor volume in positive cores, PSA levels, and Gleason score were documented. Employing Tobit regression with maximum likelihood estimation, the study examined the link between various factors and metastasis/mortality risk of prostatic cancer. Dependent variables encompassed 5, 10, and 15-year risks, while the independent variable was patient age, positive to total core ratio, average tumor volume in positive cores, PSA level, and grade group of the prostate cancer. The model integrated three dummy variables-Grade Group 1, 3, and 4, with Grade Group 2 as reference. Coefficients gauged the distinct impact of Level 1, 3, and 4 diagnoses on outcomes relative to Level 2. Statistical significance was tested conventionally. Results (if a Case Study enter NA) Grade Group 1 (Gleason score: 3 + 3): 2.35 percentage point increase in the risk of metastasis within 10 years. 3.51 percentage point increase in the risk of mortality within 15 years. Grade Group 2 Base level for comparison with other grade groups. Grade Group 3 (Gleason score: 4 + 3): No statistically significant difference in the predicting 5 or 10 year risk of metastasis compared to Grade Group 2. No statistically significant difference in the predicting 15 year risk of mortality compared to Grade Group 2. Grade Group 4 (Gleason score: 4 + 4): 10.07 percentage point increase in the risk of metastasis within 5 years. 17.27 percentage point increase in the risk of metastasis within 10 years. 18.48 percentage point increase in the risk of mortality within 15 years. Conclusion The findings suggest combining genomics and grade group can help predict the risk of metastasis and mortality in prostate biopsy. Grade Group 4 diagnosis greatly impacts metastasis and mortality in all timeframes.While Grade Group 1 has a smaller but still significant impact on the 10 and 15 year risk of metastasis and mortality. However, Grade Group 3 diagnosis does not significantly impact the risk of metastasis in any of the timeframes considered.

Can multiplexing Immunohistochemistry for PD-L1, CD68, and CD3 improve scoring for “Keytruda®” Indication?

Abstract Introduction/Objective FDA-approved companion diagnostics immunohistochemistry scoring for PD-L1 is essential for Keytruda ® treatment in patients with NSCLC. The challenge with PD-L1 testing alone is false positive PD-L1 expression score due to alveolar macrophage infiltration. Multiplexing with PD-L1, CD68, and CD3 could help alleviate this issue. By viewing PD-L1 expression on tumor cells, CD68 expression on macrophages, and the presence of CD3+ T cells on a single slide, pathologists will be able to see the presence of an immune microenvironment (high PD-L1 expression with abundant macrophages) and the potential for response to other types of Immunotherapies (presence of T cells). Methods/Case Report Positive NSCLC FFPE blocks were sectioned and stained using Agilent Dako Omnis. Two combinations of multiplex staining were prepared for each block by staining PD-L1 (brown) alone first followed by CD3 and CD68. First slide: CD3(Vina Green), CD68(Magenta); Second slide: CD3(Magenta), CD68(Vina Green). To prevent wash out, dehydration and clearing occurred with two changes of 100% alcohol and three changes of xylene for manual cover slipping. Results (if a Case Study enter NA) Manual scoring of PD-L1 alone vs two different multiplex combinations was compared to Agilent Proscia digital AI scoring using a preliminary study set (9 positives, 2 negatives). CD68-green and CD3-magenta showed better discrimination than CD68-magenta and CD3-green at a glance. This could be due to the staining intensity and nonspecific background staining of CD68-magenta. Manual scoring was higher compared to digital scoring, which could be due to the human error of positive bias. Digital scoring was significantly lower for PD-L1 alone vs both multiplex stains. The digital scoring for the multiplex stains showed a higher scoring percentage by removing false positive macrophages. Conclusion Reflex scoring workflow is being developed to focus on difficult cases using the multiplex triple stain, i.e. clear negative and clear &amp;gt;50% with 3+ intensity. More cases will be collected and studied to further investigate the improved PD-L1 scoring with digital imaging assisted by artificial intelligence and to compare the multiplex color combinations.

Association of glutaminase expression with immune-suppressive tumor microenvironment, clinicopathologic features, and clinical outcomes in endometrial cancer

ObjectiveIncreased glutamine metabolism by cancer cells via upregulation of the drug-targetable enzyme glutaminase may contribute to an immune-suppressive tumor microenvironment. Inhibiting glutamine metabolism can not only suppress tumor growth, but...

Associations of diagnostic awareness with psychosocial symptoms and survival time in patients with advanced lung cancer.

Disclosing the diagnosis of lung cancer to patients is an issue, especially in the Middle East where cultural factors may prohibit disclosure from being done. The psychosocial consequences of diagnostic awareness and its impact on life expectancy of disclosure are an important issue that may influence this decision. The present study evaluated the effects of diagnostic awareness on psychosocial symptomatology and survival time in advanced lung cancer patients in Turkey. This prospective cohort study included 126 advanced lung cancer patients admitted to the oncology department between February 2021 and August 2021. A face-to-face survey included questions on age, gender, marital/employment statuses, comorbidities, and psychological symptoms (SCL-90-R). Diagnostic awareness was assessed by asking patients whether they knew their diagnosis. The correlation of diagnostic awareness with 2-year survival time was analyzed using Cox regression analysis. Of the 126 patients, 86 died at the time of follow-up. Survival time and scores on SCL-90-R symptom subscales were compared between diagnosis-aware (79.4%) and diagnosis-unaware groups (20.6%). Somatization (P = 0.04), depression (P = 0.01), hostility (P = 0.03), scores on additional symptom scales (P = 0.01), and Positive Symptom Total scores (P = 0.01) were significantly higher in the diagnosis-unaware group. No significant difference was found between diagnostic awareness and survival time (P = 0.24). Advanced lung cancer patients aware of their diagnosis experienced less psychosocial burden. However, no significant difference was found in survival time between diagnosis-aware and diagnosis-unaware patients. These findings suggest that the diagnosis should be disclosed to lung cancer patients after confirmation of diagnosis.

Intra-individual structural covariance network in schizophrenia patients with persistent auditory hallucinations

Neuroimaging studies have revealed that the mechanisms of auditory hallucinations are related to morphological changes in multiple cortical regions, but studies on brain network properties are lacking. This study aims to construct intra-individual structural covariance networks and reveal network changes related to auditory hallucinations. T1-weighted MRI images were acquired from 90 schizophrenia patients with persistent auditory hallucinations (pAH group), 55 schizophrenia patients without auditory hallucinations (non-pAH group), and 83 healthy controls (HC group). Networks were constructed using the voxel-based gray matter volume and the intra-individual structural covariance was based on the similarity between the morphological variations of any two regions. One-way ANCOVA was employed to compare global and local network metrics among the three groups, and edge analysis was conducted via network-based statistics. In the pAH group, Pearson correlation analysis between network metrics and clinical symptoms was conducted. Compared with the HC group, both the pAH group (p = 0.01) and the non-pAH group (p = 3.56 × 10−4) had lower nodal efficiency of the left medial superior frontal gyrus. Compared to the non-pAH group and HC group, the pAH group presented lower nodal efficiency of the temporal pole of the left superior temporal gyrus (p = 1.09 × 10−3; p = 7.67 × 10−4) and right insula (p = 0.02; p = 8.99 × 10−6), and lower degree centrality of the right insula (p = 0.04; p = 1.65 × 10−5). The pAH group had a subnetwork with reduced structural covariance centered by the left temporal pole of the superior temporal gyrus. In the pAH group, the normalized clustering coefficient (r = −0.36, p = 8.45 × 10−3) and small-worldness (r = −0.35, p = 9.89 × 10−3) were negatively correlated with the PANSS positive scale score. This study revealed network changes in schizophrenia patients with persistent auditory hallucinations, and provided new insights into the structural architecture related to auditory hallucinations at the network level.

A study of Lau v. Nichols’ legacy: Examining the relationship between language support program availability and student trajectories

ABSTRACT The Lau v. Nichols ruling shows the importance of tailoring programs for local multilingual learners. We used longitudinal data from one school district in California to assess the relationship between attending a school with a language support program and English language arts (ELA) achievement. We found that students labeled an English learner had positive and significant average score changes over time when they attended a school with an academic language acquisition or a two-way bilingual program. Findings highlight how emerging multilingual learner access to high-quality bilingual programs can be associated with positive ELA growth over time.

Resilience, Anger, and Insomnia in Nurses after the End of the Pandemic Crisis.

Nurses seem to be persistently experiencing intense psychological repercussions, even after the official conclusion of the COVID-19 pandemic. In this cross-sectional study conducted after the end of the pandemic crisis, from 1 June 2023 to 30 June 2023, we evaluated the levels and explored the associations between anger, insomnia, and resilience among Greek nurses. A total of 441 nurses participated in an online survey and were invited to state their work experience, gender, and age and to complete the self-report measures of the Dimensions of Anger Reactions-5 (DAR-5), the Athens Insomnia Scale (AIS), and the Brief Resilience Scale (BRS). Overall, 62.1% of the participants presented with positive scores on the AIS, and 41.5% displayed positive values on the DAR-5 scale, whereas 24.9% demonstrated scores indicative of low resilience on the BRS. A regression analysis revealed that 23.5% of the variance in the AIS scores can be attributed to the DAR-5 scores and 3% to the BRS scores. A mediation analysis confirmed the protective role of resilience, contributing as a negative mediator in the DAR-5 and AIS relationship. Screening for insomnia symptoms and anger issues among nurses after the end of the pandemic and implementing appropriate interventions is considered imperative to avoid long-term health consequences.

First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE‑048.

Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5years of follow-up. Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0months (range, 61.2-81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13-1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34-1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27-1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27-2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56-2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57-2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. After 5years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. NCT02358031.

Automated mental health screening in pediatric lupus: associations with disease features and treatment.

Patients with childhood-onset systemic lupus erythematosus (c-SLE) have higher rates of depression than their peers, which has been associated with worse medical outcomes. Therefore, it is imperative that their mental health be addressed. We utilized quality improvement (QI) methodology to automate mental health screening for patients with lupus within a pediatric rheumatology clinic. The retrospective cohort study aims to evaluate the association between mental health screening outcomes and demographics, medications, and disease activity measures in patients with childhood lupus. The mental health QI team at a quaternary pediatric rheumatology center implemented an automated process for mental health screening in patients with c-SLE. Patients seen between 2017 and June 2023 with a diagnosis of c-SLE were identified using International Classification of Disease -Clinical Modification (ICD-CM) codes. Disease activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K). Medications were identified on outpatient and inpatient orders for conventional synthetic and biologic disease-modifying anti-rheumatic drugs, hydroxychloroquine, corticosteroids, and aspirin. Mental health screening was accomplished with the Patient Health Questionnaire (PHQ). Descriptive statistics, univariate and multivariate linear regression were used. Between January 2017 and June 2023, 117 patients with c-SLE (41% with lupus nephritis) completed 534 total screenings. Each patient completed PHQ screenings, a median of 5 [interquartile range 2, 6] times. Screening increased when the screening process was automated. Those who were Black, female, or prescribed leflunomide, mycophenolate, and corticosteroids had higher PHQ scores. Mental health support is essential for patients with chronic rheumatologic diseases such as SLE. Sustainable processes for quickly identifying depression are needed for optimal care of patients with SLE. Our process of automated, streamlined mental health screening successfully increased the screening of patients with SLE at every visit and led to timely interventions for positive PHQ scores. Higher PHQ scores were correlated with patients on leflunomide, mycophenolate, and corticosteroids. Future research should identify modifiable risk factors for high PHQ scores that the medical team can target.

Positivity as a moderator of the association between enacted stigma and mental health among lesbian, gay, and bisexual individuals.

In this study, we investigated the association between enacted stigma and adverse mental health outcomes in Israeli lesbian, gay, and bisexual (LGB) individuals. Additionally, we explored the moderating effect of positivity, namely the inclination to perceive oneself, one's life, and one's future in a generally positive outlook, in this association. For this purpose, we surveyed 520 cisgender LGB Israelis (Mage = 33.20, SD = 8.68; 30.8% self-reported as lesbian women, 48.8% self-reported as gay men, 20.4% self-reported as bisexual individuals), and assessed enacted stigma, depressive symptoms, anxiety, negative affect, and positivity. The results of the hierarchical regressions and simple slope analyses indicated that enacted stigma was associated with higher depressive symptoms, anxiety, and negative affect. As hypothesized, positivity played a moderating role in the association between enacted stigma and adverse mental health indicators, whereby the association was weaker among participants with higher positivity scores and stronger among those with lower positivity scores. The findings contribute novel insights to the sexual minority literature within the field of mental health by unfolding the role played by positivity in mitigating the detrimental effects of enacted stigma. The results underscore that practitioners should not only be knowledgeable about the negative repercussions of enacted stigma, but they should also monitor positivity and integrate interventions aimed at enhancing positivity into their clinical work with sexual minority individuals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Application of mitoxantrone hydrochloride in lymph node imaging during radical thyroidectomy

Objective: To investigate the clinical application value of the new tracer mitoxantrone hydrochloride in imaging of cervical lymph nodes and identifying of parathyroid, recurrent laryngeal nerve during thyroid cancer radical surgery. Methods: A prospective controlled study was conducted between January 2022 and April 2024 at Tianjin First Central Hospital, recruiting 180 patients with thyroid cancer, including 54 males and 126 females, aged from 26 to 69 years. The patients were randomly divided into three groups: the mitoxantrone hydrochloride lymph node tracing group (MHI group), the nanocarbon lymph node tracing group (nanocarbon group), and the control group without lymph node tracers, with 60 cases in each group. All patients underwent total thyroid resection and regional lymph node dissection. The number of detected lymph nodes and positive metastatic lymph nodes and surgical field clarity scores and the identification rate of parathyroid glands and the instances of inadvertent excision were compared between the groups. Serum calcium and parathyroid hormone (PTH) levels at different perioperative time points and treatment-related complications were analyzed. One-way ANOVA, chi-square test and two independent sample non-parametric tests, were employed for statistical analyses. Results: The mean operation time, neck drainage volume and hospital stay in the MHI group and the nanocarbon group were respectively significantly lower than those in the control group (P<0.05). The mean staining intensity score, tracer success rate and surgical field clarity score in MHI group were respectively significantly higher than those in nanocarbon group (P<0.05). The mean numbers of dissected lymph nodes positive metastatic nodes and identification rates of parathyroid glands in MHI group were respectively significantly higher than those in both the nanocarbon and control groups (P<0.05). The rates of inadvertent parathyroid excision in both MHI group and nanocarbon group were significantly lower than those in control group (P<0.05). On postoperative day 1 and day 5, mean serum calcium and PTH levels in MHI group were respectively significantly higher than those in nanocarbon group and control groups. However, on postoperative day 1, there was no difference in mean serum calcium levels between the nanocarbon group and the control group (P>0.05), though PTH level in the nanocarbon group was higher than that in the control group. By postoperative day 5, both serum calcium and PTH levels were higher in the nanocarbon group compared to the control group (P<0.05). On postoperative days 30, there were no differences in serum calcium and PTH levels between the MHI group and the nanocarbon group (P>0.05). The risks of facial numbness, hand and foot tetany and choking during drinking were lower in both the MHI and nanocarbon groups compared to the control group (P<0.05). Conclusion: MHI demonstrates advantages in rapid targeted delivery and clear staining of the surgical field during regional lymph node dissection in radical thyroidectomy for thyroid cancer, effectively reducing the risk of collateral damage to the recurrent laryngeal nerve and parathyroid glands.

CORRELATION BETWEEN PSYCHOLOGICAL PARAMETERS SUCH AS DEPRESSION, ANXIETY, AND STRESS AND AFFECT SCORE AMONG MEDICAL STUDENTS

Objectives: In the modern era, internet use has turned out to be a significant arena for day-to-day life activities. Proper use of the internet is harmless, but misuse of this tool might lead to disruptions in psychological health and social relationships, yet available reports about the association between internet use and affect are inconsistent. Hence, the objective is to assess and correlate the psychological parameters with the affect score among medical college students using the depression anxiety stress scale (DASS)-21 questionnaire and positive and negative affect schedule (PANAS) scale. Methods: The present study was a cross-sectional study conducted on medical students in the age group of 17–22 years. 150 participants were recruited by random sampling. DASS-21 scale was used to assess depression, anxiety, and stress, consisting of 21 items designed to measure emotional states of depression, anxiety, and stress. PANAS is designed to assess individuals’ positive and negative moods. Results: Pearson’s correlation of these psychological parameters with affect scores had a significant negative correlation with the positive affect score (depression [p=0.003], anxiety [p=0.01], and stress [p&lt;0.04]) and a significant positive correlation with negative affect score (depression [p&lt;0.02], anxiety [p=0.0009], and stress [p=0.01]). Students should be closely monitored with regard to their use of the internet, and also, internet addiction and psychological behaviors can be reduced by providing early counseling and interventional therapy. Conclusion: Awareness about the harmful effects of excessive internet use should be provided so as to enhance the academic performance of students.

Surrogate Immunohistochemical Markers of Proliferation and Embryonic Stem Cells in Distinguishing Ameloblastoma from Ameloblastic Carcinoma

PurposeThe current study aimed to investigate the use of surrogate immunohistochemical (IHC) markers of proliferation and stem cells to distinguish ameloblastoma (AB) from ameloblastic carcinoma (AC).MethodsThe study assessed a total of 29 ACs, 6 ABs that transformed into ACs, and a control cohort of 20 ABs. The demographics and clinicopathologic details of the included cases of AC were recorded. The Ki-67 proliferation index was scored through automated methods with the QuPath open-source software platform. For SOX2, OCT4 and Glypican-3 IHC, each case was scored using a proportion of positivity score combined with an intensity score to produce a total score.ResultsAll cases of AC showed a relatively high median proliferation index of 41.7%, with statistically significant higher scores compared to ABs. ABs that transformed into ACs had similar median proliferation scores to the control cohort of ABs. Most cases of AC showed some degree of SOX2 expression, with 58.6% showing high expression. OCT4 expression was not seen in any case of AC. GPC-3 expression in ACs was limited, with high expression in 17.2% of ACs. Primary ACs showed higher median proliferation scores and degrees of SOX2 and GPC-3 expression than secondary cases. Regarding SOX2, OCT4 and GPC-3 IHC expression, no statistically significant differences existed between the cohort of ABs and ACs.ConclusionKi-67 IHC as a proliferation marker, particularly when assessed via automated methods, was helpful in distinguishing AC from AB cases. In contrast to other studies, surrogate IHC markers of embryonic stem cells, SOX2, OCT4 and GPC-3, were unreliable in distinguishing the two entities.

The reflux symptom score has good screening value for laryngopharyngeal reflux

ObjectiveTo investigate the consistency between the reflux symptom score (RSS) and the multitemporal salivary pepsin test in screening for laryngopharyngeal reflux (LPR) and the screening value of the RSS for LPR by simultaneously administering daytime multitemporal salivary pepsin test and RSS to patients.MethodsThis was a single-center prospective observational study. All included patients underwent simultaneous daytime multitemporal salivary pepsin testing and RSS. A participant was considered to have LPR when one or more positive salivary pepsin test results or RSS score > 13 were obtained. The consistency between the multitemporal salivary pepsin test and the RSS was compared by the weighted Cohen’s kappa statistic. The screening value of the RSS for LPR was investigated by receiver operating characteristic (ROC) analysis.ResultsA total of 67 patients were included. The positivity rate of LPR was 71.64% according to the results of the multitemporal salivary pepsin test. According to RSS, the positive rate of LPR was 70.15%. The weighted Kappa value between the multitemporal salivary pepsin test and the RSS was 0.675 (p < 0.001). The area under curve of RSS screening for LPR was 0.843 (p < 0.01), and the sensitivity, specificity, positive predictive value, and negative predictive value of RSS screening for LPR were 89.58%, 78.95%, 91.49%, and 75%, respectively.ConclusionThere is a good consistency between the RSS and the multitemporal salivary pepsin test, and the RSS has a good screening value for LPR, which can be applied to screen for LPR in otolaryngologic patients.

Protocol for Cancloz: multicentre randomised, placebo-controlled, double-blind, parallel-group adaptive trial of cannabidiol for clozapine-resistant schizophrenia.

Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia. To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia. This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability. Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.