Comparative study of immunohistochemical expression of ERG and MAGI2 in prostatic carcinoma.

Diagnosis of Prostatic adenocarcinoma (PAC) is still a problematic issue. The objective of this study was to evaluate the diagnostic and prognostic value of ERG immunohistochemical (IHC) expression compared to MAGI2. MATERIALS AND METHODS: This study was conducted on 56 cases of PAC and 29 cases of nodular prostatic hyperplasia (NPH). IHC staining for ERG and MAGI2 was applied to archival formalin-fixed paraffin-embedded blocks. Semi-quantitative scoring was compared and correlated with clinicopathologic parameters and the Ki-67 index. RESULTS: Revealed positive ERG in 51.8% of PAC while all NPH cases were negative. On the other hand, MAGI2 was detected in 91.1% of PAC versus 17.2% of NPH. Using ROC curve, the ERG showed 53.6% sensitivity, 100% specificity, 76.5% diagnostic accuracy (DA) and area under the ROC curve 0.768 in comparison to MAGI2 that showed (91.1%, 86.2%, 88.25% and 0.948 respectively). Analysis of the combined use of the two markers revealed 95% sensitivity, 100% specificity, and 94% DA when tested synchronously. Moreover, a statistically significant inverse relationship could be detected between ERG expression and the Gleason grading group (P = 0.01) and Ki-67 index (P < 0.001). In addition, high-grade prostatic intraepithelial neoplasia (HGPIN) adjacent to carcinoma; showed positive expressions in (1/11 cases, 9.11%) for ERG and (6/11 cases, 54%) for MAGI2. CONCLUSION: This study recommends using both ERG and MAGI2 in a cocktail for better diagnostic validity of PAC. Only ERG expression could be a good prognostic indicator.

Oxidative stress contributes to hemolysis in patients with hereditary spherocytosis and can be ameliorated by fermented papaya preparation.

In the present study, we questioned the role of oxidative stress in hereditary spherocytosis (HS), where red blood cells (RBC) have a shortened survival due to primary deficiency in membrane proteins. Using flow cytometry techniques, we showed that RBC derived from 17 HS patients of seven families generate more reactive oxygen species, membrane lipid peroxides, and less reduced glutathione than normal RBC. Following in vitro incubation of HS-RBC from seven patients with a fermentation bioproduct of Carica papaya (fermented papaya preparation (FPP)) with known antioxidative properties, oxidative stress markers were significantly reduced. Similar results were obtained following treatment with FPP for 3 months of 10 adult HS patients, as well as decreased tendency to undergo hemolysis. The hemoglobin levels increased by >1 g/dl, mean corpuscular hemoglobin concentration decreased by >1 g/dl, and the reticulocyte count decreased by 0.93%. Concomitantly, lactic dehydrogenase decreased by 17% and indirect bilirubin by 50%. A significant decrease in malonyldialdehyde was also detected. These data indicate that oxidative stress plays an important role in the pathophysiology of HS which can be ameliorated by an antioxidant such as FPP. Additional clinical trials with FPP and other antioxidants are warranted.

Evisceration of small bowel through spontaneous perforation of rectum: Case report and review of literature.

INTRODUCTION: Small bowel evisceration through spontaneous perforation of the rectum is an extremely rare condition in which the small bowel herniates mostly through a defect in the anterior rectal wall. CASE PRESENTATION: We present the case of a 25-year-old otherwise healthy lady who denied any history of rectal prolapse or trauma. DISCUSSION: Small bowel evisceration through rectum is a rare surgical emergency with a mortality rate as high as 42.3%. Apart from trauma, chronic constipation, rectal prolapse, presence of a deep Douglas pouch and a sliding hernia formed by the cul-de-sac have also been described as etiological factors. CONCLUSION: It is extremely difficult to find out the actual cause of "spontaneous" small bowel evisceration, especially in young adults.

Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial.

OBJECTIVE: Ketamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are limited on patient-centered outcomes. We designed this pilot trial to evaluate the feasibility of a large randomized controlled trial (RCT) testing the effect of ketamine as an adjunct analgosedative compared with standard of care alone as a control group (CG) in critically ill patients with mechanical ventilation (MV). We also provided preliminary evidence on clinically relevant outcomes to plan a larger trial. MATERIAL AND METHODS: Pilot, active-controlled, open-label RCT was conducted at medical, surgical, and transplant ICUs at a large tertiary and quaternary care medical institution (King Faisal Specialist Hospital and Research Center, Saudi Arabia). The study included adult patients who were intubated within 24 h, expected to require MV for the next calendar day, and had institutional pain and sedation protocol initiated. Patients were randomized in a 1:1 ratio to adjunct ketamine infusion 1-2 µg/kg/min for 48 h or CG alone. RESULTS: Of 437 patients screened from September 2019 through November 2020, 83 (18.9%) patients were included (43 in CG and 40 in ketamine) and 352 (80.5%) were excluded. Average enrollment rate was 3-4 patients/month. Consent and protocol adherence rates were adequate (89.24% and 76%, respectively). Demographics were balanced between groups. Median MV duration was 7 (interquartile range [IQR] 3-9.25 days) in ketamine and 5 (IQR 2-8 days) in CG. Median VFDs was 19 (IQR 0-24.75 days) in ketamine and 19 (IQR 0-24 days) in the CG (p = 0.70). More patients attained goal Richmond Agitation-Sedation Scale at 24 and 48 h in ketamine (67.5% and 73.5%, respectively) compared with CG (52.4% and 66.7%, respectively). Sedatives and vasopressors cumulative use, and hemodynamic changes were similar. ICU length-of-stay was 12.5 (IQR 6-21.2 days) in ketamine, compared with 12 (IQR 5.5-23 days) in CG. No serious adverse events were observed in either group. CONCLUSIONS: Ketamine as an adjunct analgosedative agent appeared to be feasible and safe with no negative impact on outcomes, including hemodynamics. This pilot RCT identified areas of improvement in study protocol before conducting a large, adequately powered, multicenter RCT which is likely justified to investigate ketamine association with patient-centered outcomes further. Trial registration ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

Relation Between Immunohistochemical Expression of Hippo Pathway Effectors and Chronic Hepatitis Induced Fibrosis in Egyptian Patients.

OBJECTIVE: Chronic hepatitis is a global health problem especially in Egypt. Hepatic fibrosis is a common end clinical manifestation of many chronic liver diseases. Although it is a wound-healing process, excessive accumulation of fibrillary collagen leads to architectural damage, cirrhosis and liver failure. Recently, a few studies have linked Hippo pathway effectors of yes-associated protein (YAP) and its paralog transcriptional coactivator with PDZ-binding motif (TAZ) to extracellular matrix deposition and ongoing fibrosis. MATERIAL AND METHOD: Immunohistochemical expression of YAP and TAZ were analyzed in 121 liver needle core biopsies (91 core biopsies of chronic viral hepatitis, 20 biopsies of autoimmune hepatitis and 10 normal liver cores). RESULTS: YAP and TAZ nuclear localization was absent in all normal liver cores. Autoimmune hepatitis cases showed higher nuclear expression of both YAP and TAZ in comparison to chronic viral cases. YAP and TAZ expression were correlated with severity of hepatocyte injury together with fibrosis in chronic viral cases but these correlations were absent in AIH cases despite the pronounced increase of YAP and TAZ nuclear localization. CONCLUSION: The correlation between Hippo effectors activation and fibrosis in chronic viral hepatitis patients emphasize their role in the development and advancement of hepatic scarring and highlight the use of both YAP and TAZ as novel targets to ameliorate liver fibrosis.

Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial.

BACKGROUND: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h. METHODS/DESIGN: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized post-intubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 µg/kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 µg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first. DISCUSSION: The first patient was enrolled on 1 September 2019. As of 10 October 2019, a total of 16 patients had been enrolled. We expect to complete the recruitment by 31 December 2020. The findings of this pilot trial will likely justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

The Predictive Ability of PV-ACO2 Gap and PV-ACO2/CA-VO2 Ratio in Shock: A Prospective, Cohort Study.

INTRODUCTION: Compromised tissue oxygenation leads to anaerobiosis, leading to organ failure and death. This study attempts to demonstrate the predictive abilities of the Pv-aCO2 gap and Pv-aCO2/Ca-vO2 ratio in shock patients undergoing resuscitation. METHODS: In a prospective study, consecutive patients with shock were included. Timed measurements of Pv-aCO2 gap, ScvO2, lactate, and Pv-aCO2/ Ca-vO2 ratio were obtained. The association between the mortality and each variable at all intervals was analyzed. Receiver operating characteristics curves were built. RESULTS: Fifty patients were enrolled. Intensive care unit survivors had a higher Pv-aCO2/ Ca-vO2 ratio at time 0 (0.21, interquartile range [IQR] 0.14 vs. 0.27, IQR 0.38, P = 0.032) and at 3 h (0.27, IQR 0.08 vs. 0.21, IQR 0.12, P = 0.035).Twenty-eight day survival was higher in patients with a low Pv-aCO2 gap at time 0 (7.5, IQR 7 vs. 4.8, IQR 5, P = 0.007).Baseline Pv-aCO2 gap and Pv-aCO2/Ca-vO2 ratio showed good ability to predict 28-day mortality as seen by AUC 0.728 (95% CI 0.578-0.877, P = 0.007) and 0.711 (95% CI 0.563-0.860, P = 0.013). A cut-off point of Pv-aCO2 gap ≥6 mm Hg identified 28-day mortality (75% vs. 45.5%, P = 0.034). The best cutoff values, at baseline, to predict 28-day mortality were 0.25 for the Pv-aCO2/Ca-vO2 ratio (sensitivity 58%, specificity 85%, LR+ 3.86, LR- 0.49) and 6.3 for the Pv-aCO2 gap (sensitivity 58%, specificity 79%, LR+ 2.76, LR- 0.53). CONCLUSION: This study suggests that Pv-aCO2 gap and Pv-aCO2/Ca-vO2 ratio are discriminating predictors of 28-day mortality and can be used to provide supplementary information during resuscitation in shock.

A 21-year-old woman with mediastinal mass and cardiac arrest.

Mediastinal mass syndrome (MMS) is a devastating respiratory and haemodynamic condition that might be encountered postintubation if special precautions are not carefully undertaken. We describe a case of MMS in a 21-year-old woman with a fatal outcome following emergency intubation for acute respiratory failure.

Live birth after hysteroscopic-guided embryo transfer: a case report.

OBJECTIVE: To report a case with successful pregnancy using hysteroscopic guided embryo transfer (ET). DESIGN: Case report. SETTING: The Farah Hospital (a private tertiary referral fertility center). PATIENT(S): A healthy woman with previous ICSI trial for male factor infertility underwent a repeat ICSI trial. INTERVENTION(S): Embryo transfer was done under hysteroscopic guidance and 3 embryos were transferred. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Delivery of a healthy female baby. CONCLUSION(S): Hysteroscopic guided ET is feasible and may be of value in cases of difficult transfer.