Assessment of Utility of Immunohistochemical Marker Prostein for Evaluation of Primary and Metastatic Prostatic Carcinomas

Background: To assess utility of immunohistochemical marker prostein for evaluation of primary and metastatic prostatic carcinomas.Methods:Fifty- six samples of clinically suspected carcinoma prostate was included. Immunohistochemistry (IHC) was performed for assessment of Prostein (P501S). The intensity of positivity was scored from 0 to 3 as follows: score 0 = non-stained; score 1 = weak; score 2 = moderate; and score 3 = strong. The percentage of positively stained cells for each staining intensity was estimated in the respective lesions.Results:Age group 18-28 years comprised of 6 patients, 28-38 years had 12, 38- 48 years had 16 and >48 years had 22 cases. Type of cases were normal prostatic epithelium in 11, benign prostate hyperplasia in 23, HGPIN in 10, primary prostatic adenocarcinoma in 7 and metastatic prostatic adenocarcinoma in 5 cases. Prostein expression was seen in 100% in normal prostatic epithelium with intensity score of 1.8-2.1, benign prostate hyperplasia having 2-2.7, HGPIN with 2-2.3, primary prostatic adenocarcinoma having 1-1.6 and metastatic prostatic adenocarcinoma with 0.8-1.4 intensity score. Conclusion:Prostein is a new prostate specific marker which showed 100% sensitivity and specificity to identify normal and prostatic lesions.

Headache provocation by nitric oxide in men who have never experienced a headache

Introduction In the general population 4% have never experienced a headache. Freedom from headache could be due to distinctive protective mechanisms or a lack of environmental risk factors for headache. Isosorbide-5-mononitrate is an organic nitrate which in the body is metabolised to nitric oxide. The nitric oxide pathway plays a crucial role in the primary headaches. We hypothesized that people who are free from headache are protected by distinctive mechanisms in the nitric oxide pathway. Methods We performed an observer blinded case-control study using nitric oxide to provoke a headache. 32 headache free male participants and 26 randomly selected male controls received 60 mg Isosorbide-5-mononitrate orally on the study day. Participants fill out a headache diary with headache intensity and characteristics until 12 hours after administration of Isosorbide-5-mononitrate. Primary endpoint were areas under the curve of headache intensity score. Results All 58 participants completed the study. There was no significant difference in headache incidence, headache intensity score or migraine-like attack between headache free participants and controls. Conclusion We show that men who have never experienced a headache develop a headache when provoked with Isosorbide-5-mononitrate. This indicates that freedom from headache in men is not related to the nitric oxide pathway which is involved in the primary headache disorders.

Association between MR-proADM concentration and treatment intensity of antihypertensive agents in chronic kidney disease patients with insufficient blood pressure control

Response to antihypertensive drugs in patients with chronic kidney disease (CKD) has great interindividual variability. Adrenomedullin (ADM) is produced abundantly in hypertension, but clearance is very rapid. Mid-regional proADM (MR-proADM) produced from an ADM precursor is considered a surrogate biomarker for quantification of ADM. We investigated the association of MR-proADM with antihypertensive resistance in CKD patients with poor blood pressure (BP) control. This cross-sectional study analyzed 33 CKD patients with poor BP control defined as failure to achieve target BP despite at least two classes of antihypertensive drugs. Treatment intensity score was calculated to facilitate comparability of antihypertensive regimens across subjects taking different drugs. Plasma MR-proADM concentration was measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Plasma MR-proADM concentration correlated with estimated glomerular filtration rate (eGFR) (r = − 0.777, p < 0.001). Treatment intensity score correlated positively with plasma MR-proADM concentration (r = 0.355, p = 0.043), and the correlation was further enhanced after correction by weight (r = 0.538, p = 0.001). Single and multiple regression analysis identified MR-proADM concentration (p = 0.005) as independently associated with weight-corrected treatment intensity score. MR-proADM may be useful as a biomarker to determine the therapeutic intensity of antihypertensive drugs in CKD patients with poor BP control.

Rho Kinase Expression in Giant Cell Arteritis Validating pERM Intensity Score as a Method of Increasing Sensitivity of Temporal Artery Biopsy

Background: Aberrant rho-kinase (ROCK) activity is implicated in pathogenesis of several vascular and immunologic disorders. We previously demonstrated evidence of increased ROCK activity in histopathologically negative temporal artery biopsies (TAB) of subjects with clinical Giant Cell Arteritis (GCA) compared to those without GCA. This study aimed to examine ROCK activity in a larger cohort of biopsy-negative GCA subjects and to validate the prior findings. Methods: Subjects were categorized into 2 groups based on clinical data 6-months after TAB: biopsy-negative GCA and controls without GCA. Paraffin-embedded TAB were stained for phosphorylated ezrin/radixin/moesin (pERM), a surrogate of ROCK activity, and scored by two pathologists blinded to clinical diagnosis using a previously derived scoring system. Three areas of the vessel (intima, adventitial and vasa vasorum) were scored for staining intensity on a scale of 0–2, with a maximum possible score of 6 for each TAB. As determined a priori, scores ³4 were considered a high pERM intensity score correlating with ROCK activity. TAB sections were also stained for unphosphorylated ERM, the inactive protein. Results: Thirty six subjects with biopsy-negative GCA and 43 controls were analyzed. There were no differences between groups in age, sex and corticosteroid dose. The mean pERM intensity score in non-GCA subjects was 3.9 ± 1.4 (compared to 5.0 ± 1.4 in those with GCA, p = 0.002). Using the predetermined cut-off of 4 to define high pERM intensity, subjects with GCA were significantly more likely to have a high pERM intensity score compared to non-GCA, OR 3.67, 95%CI :1.19,11.36; p= 0.019. The sensitivity of high pERM intensity score for diagnosis of GCA in histologically negative TAB was 86%, 95%CI: 70,95. Conclusions:. In this well characterized cohort, those with GCA and negative biopsies had significantly higher pERM intensity scores in TAB specimens compared to subjects without GCA. pERM staining has diagnostic significance in enhancing the sensitivity of TAB, and helps to define the clinically important group of biopsy-negative GCA. The ROCK pathway warrants further investigation in GCA and may be a potential therapeutic target

498 Improving Surgical and Non-Surgical Oncological Outcomes in Patients with Head and Neck Cancer

Introduction Treatment of head and neck cancer is complex and involves a multi-disciplinary approach between surgeons and oncologists. Radiotherapy often leaves patients with debilitating side effects such as mucositis, sialadenitis and dysphagia. Radiation induces double strand breaks (DSBs) in DNA within both normal squamous cells and squamous cell carcinomas (SCCs) that, if left unrepaired, initiates programmed cell death. Like normal squamous cells, SCC’s have an effective DNA repair pathway to protect against apoptosis by repairing DSBs through proteins such as FanD2-S331. This study aims to show that mild hyperthermia inhibits FancD2, therefore having the potential to increase the susceptibility of SCCs to radiotherapy and subsequently reducing the side effects. Method Head and neck cancer cell line UMSCC47 was cultured, then irradiated with 2 Gray before washing with an anti γH2AX antibody, used as a biomarker for DSBs. Fluorescent antibodies against FacD2-S331 were then used to assess the levels present within the nucleus of cells exposed to mild hyperthermia (39 °C) and then compared to untreated cells and cells exposed to radiation only. Results A γH2AX fluorophore intensity score of 58 following radiation compared to 20 in the control confirmed the presence of DSBs. A FancD2-s331 fluorophore intensity score of 76 was observed in cells exposed radiation. Cells exposed to heat prior to radiation showed a FancD2-s331 fluorophore score of 21. Conclusions Exposure of SCCs to mild hyperthermia before radiotherapy reduces activation of DNA repair protein FancD2-S2331. A reduction in DNA repair increases the susceptibility of SCCs to radiotherapy and apoptosis.

Immunohistochemical Expression of Retinoblastoma Gene Product and p53 Protein in Transitional Cell Carcinoma of the Urinary Bladder and its Relationship to Different Clinicopathological Parameters

BACKGROUND: Carcinoma of urinary bladder is one of the most common malignancies worldwide and constitutes a major health problem. Multiple risk factors are associated with this tumor and its prognosis will depend on different clinicopathological parameters. Over expression of P53 protein and mutant Rb gene is associated with more aggressive clinical and histopathological features of the tumor such as advanced stage and higher grade. AIM: The immunohistochemical expression of Rb gene and P53 gene will be assessed through their protein products in transitional cell carcinoma (TCC) of the urinary bladder and then will be correlated with other well-known risk factors and prognostic parameters of bladder TCC, such as grading, tumor size, smoking, alcohol drinking, and family history. METHODS: Patients were recruited from the uro-surgical department/Surgical Subspecialties Teaching Hospital during the period from November 2020 through April 2021. In this study, patients enrolled were those suspected to have bladder carcinoma. The work up included a full history and clinical examination. Surgical samples were taken from the patients for histopathological evaluation; the study’s samples represented either endoscopic cup biopsy, transurethral resection of the tumor, or radical cystectomy. Sections obtained from these samples were stained with the conventional hematoxylin and eosin stain. Then, immunohistochemical staining for P53 and pRB was applied only for patients diagnosed with TCC. RESULTS: The differences between low-grade and high-grade tumors regarding pRb percentage score were statistically significant (p = 0.026), but were not significant regarding the intensity score (p = 0.094). There were significant correlations between tumor stage and both pRb intensity and percentage scores (p = 0.044 and 0.042, respectively). Differences between low-grade and high-grade tumors regarding p53 intensity score were significant (p = 0.022). The differences between low-grade and high-grade tumors regarding p53 percentage score were significant (p = 0.049). The differences between different tumor stages regarding p53 intensity score were significant (p = 0.018). The differences between different tumor stages regarding P53 percentage score were significant (p = 0.019). CONCLUSIONS: Tumor’s grade was found to be correlated with the tumor stage with no correlation with the age, gender, smoking, family history of TCC, history of urinary tract infection, bladder stones, nor the recurrence of the tumor. The pRb intensity and the percentage scores were correlated to each other and to tumor’s grade and stage, except for the pRb intensity which showed no correlation with the tumor’s grade. The P53 intensity and percentage scores were correlated to each other and also to tumor’s grade and stage, so that P53 is over-expressed in tumors with higher grade and stage.

The Cough Reflex Intensity Score in Critically Ill Patients’ Airway Management: Study Protocol for a Multicenter, Prospective, Observational Trial

Background A patient’s ability to cough is important for assessing a patient’s airway condition and likely mechanical ventilation outcome,there is still a lack of data comparing patients’ initial cough ability and outcomes. Methods The study is a prospective, observational trial which includes 144 patients from Xinjiang Medical University. After a patients is assigned a cough strength score, the cough intensity assessments will be implemented every other day for a week. The primary endpoint is whether the patient requires endotracheal intubation (including tracheostomy). Secondary endpoints include time spent under mechanical ventilation (excluding noninvasive ventilation), ICU and hospital lengths of stay, hospital expenses and in-hospital 30-day mortality. Discussion Anecdotally in our practice, we found that patients with a high Cough Reflex Intensity Score don't require endotracheal intubation, while patients with a low score always need to be intubated. This trial will test to what degree cough intensity is correlated to patient’s outcomes. Trial registration: Chinese Clinical Trial Registry,ChiCTR1900028265. Registered 16 December 2019

Treatment Intensity of Psoriasis Decreases With Age

Background: Elderly patients have worse skin related quality of life regardless of psoriasis severity. Despite this, there may be risks to starting systemic immunosuppressant therapy, a mainstay for moderate to severe psoriasis, in elderly patients. Objective: We assessed how age relates to treatment intensity for psoriasis. We defined treatment intensity as a continuous scale with a value of 0 indicating no treatment, 1 indicating topical treatment only, and 2 through 4 indicating progressive degrees of systemic treatment. Methods: We assessed the National Ambulatory Medical Care Survey from 1997 to 2016 to determine if treatment intensity for psoriasis was related to a patient’s age. Results: Between 1997 to 2006, a 1-year increase in age was not associated with a change in treatment intensity score for the younger ( p = .4) and older ( p = .8) age groups. Between 2007 to 2016, a 1-year increase in age was associated with a .01 (95% confidence interval .005, .02) decrease in the treatment intensity score ( p = .003) for patients aged 52 or older. When controlling for sex and race, a 1-year increase in age was associated with a decrease of .01 (.02, .005) in the treatment intensity score ( p = .005). There was no association with those who were younger than 52 ( p = .5). Discussion: Physicians provide less intense treatments for elderly patients with psoriasis. This effect has appeared in the last decade. It remains unknown if physicians are being cautious with more intense treatments in elderly patients or if they are unintentionally undertreating this population.

Association between multi-component initiatives and physical activity-related behaviors: interim findings from the Healthy Schools Healthy Communities initiative

Background Although successful, assessment of multi-component initiatives (MCIs) prove to be very challenging. Further, rigorous evaluations may not be viable, especially when assessing the impact of MCIs on long-term population-level behavior change (e.g., physical activity (PA) and health outcomes (e.g., childhood obesity). The purpose of this study was to use intensity scoring, to assess whether higher intensity MCIs implemented as part of Healthy Schools Healthy Communities (HSHC) were associated with improved physical activity and reduced sedentary behaviors among youth (dependent variables). Methods PA-related interventions were assigned point values based on three characteristics: 1) purpose of initiative; 2) duration; and 3) reach. A MCI intensity score of all strategies was calculated for each school district and its respective community. Multivariate longitudinal regressions were applied, controlling for measurement period, Cohort, and student enrollment size. Results Strategy intensity scores ranged from 0.3 to 3.0 with 20% considered “higher-scoring” (score > 2.1) and 47% considered “lower-scoring” (< 1.2). Average MCI intensity scores more than tripled over the evaluation period, rising from 14.8 in the first grant year to 32.1 in year 2, 41.1 in year 3, and 48.1 in year 4. For each additional point increase in average MCI intensity score, the number of days per week that students reported PA for at least 60 min increased by 0.010 days (p < 0.01), and the number of hours per weekday that students reported engaging in screen time strategies decreased by 0.006 h (p < 0.05). An increase of 50 points in MCI intensity score was associated with an average 0.5 day increase in number of weekdays physically active and an increase of 55 points was associated with an average decrease of 20 min of sedentary time per weekday. Conclusions We found a correlation between intensity and PA and sedentary time; increased PA and reduced sedentary time was found with higher-intensity MCIs. While additional research is warranted, practitioners implementing MCIs, especially with limited resources (and access to population-level behavior data), may consider intensity scoring as a realistic and cost effective way to assess their initiatives. At a minimum, the use of intensity scoring as an evaluation method can provide justification for, or against, the inclusion of an individual strategy into an MCI, as well as ways to increase the likelihood of the MCI impacting population-health outcomes.