Unjumbling the TWIST score for testicular torsion: systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis of the studies evaluating the utility of the Testicular Work-up for Ischemia and Suspected Torsion (TWIST) score in establishing or excluding the diagnosis of testicular torsion (TT) is herewith presented in an attempt to quantify the available evidence. METHODS: The study protocol was outlined in advance. The review has been conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The PubMed, PUBMED Central, PMC databases & Scopus followed by Google (Scholar & search engine) were systematically interrogated with the keywords TWIST score, testis and testicular torsion. Fourteen sets of data (n = 1940) from 13 studies were included; data from 7 studies (giving a detailed score-wise break-up) (n = 1285) were dis-integrated and re-integrated to tweak the cut-offs for low and high risk. RESULTS: For every 4 patients presenting to the Emergency Department (ED) with acute scrotum, one patient will eventually be diagnosed with TT. The mean TWIST score was higher in patients with testicular torsion (5.13 ± 1.53 vs 1.50 ± 1.40 for those without TT). TWIST score can be used to predict testicular torsion at cut-off of 5 with a sensitivity, specificity, PPV, NPV, and accuracy of 0.71 (0.66, 0.75; 95%CI), 0.97 (0.97, 0.98; 95%CI), 90.2%, 91.0%, and 90.9% respectively. While the slider for cut-off was shifted from 4 to 7, there was a rise in specificity and PPV of the test with a corresponding decline in sensitivity, NPV, and accuracy. The sensitivity witnessed a sharp decline from 0.86 (0.81-0.90; 95%CI) @ cut-off 4 to 0.18 (0.14-0.23; 95%CI) @ cut-off 7. The area under the SROC curve for cut-off 5 was more than that for cut-offs 4, 6 & 7. TWIST cut-off of 2 may be used to predict the absence of testicular torsion with a sensitivity, specificity, PPV, NPV, and accuracy of 0.76 (0.74, 0.78; 95%CI), 0.95 (0.93, 0.97; 95%CI), 97.9%, 56.5%, and 80.7%, respectively. While the cut-off is lowered from 3 to 0, there is a corresponding rise in the specificity and PPV, while the sensitivity, NPV, and accuracy are compromised. The sensitivity witnesses a sharp decline from 91 to 35%. The area under the SROC curve for cut-off 2 was more than that for cut-off @ 0, 1 or 3. The sum of sensitivity and specificity of TWIST scoring system to ascertain the diagnosis of TT is more than 1.5 for cut-off values 4 & 5 only. The sum of sensitivity and specificity of TWIST scoring system to confirm the absence of TT is more than 1.5 for cut-off values 3 & 2 only. CONCLUSION: TWIST is a relatively simple, flexible, and objective tool which may be swiftly administered even by the para-medical personnel in the ED. The overlapping clinical presentation of diseases originating from the same organ may prevent TWIST from absolutely establishing or refuting the diagnosis of TT in all the patients with acute scrotum. The proposed cut-offs are a trade-off between sensitivity and specificity. Yet, the TWIST scoring system is immensely helpful in the clinical decision-making process and saves time-lag associated with investigations in a significant majority of patients.

An in vitro Study on the Role of Hepatitis B Virus X Protein C-Terminal Truncation in Liver Disease Development.

Hepatitis B virus X protein C-terminal 127 amino acid truncation is often found expressed in hepatocellular carcinoma (HCC) tissue samples. The present in vitro study tried to determine the role of this truncation mutant in the hepatitis B-related liver diseases such as fibrosis, cirrhosis, HCC, and metastasis. HBx gene and its 127 amino acid truncation mutant were cloned in mammalian expression vectors and transfected in human hepatoma cell line. Changes in cell growth/proliferation, cell cycle phase distribution, expression of cell cycle regulatory genes, mitochondrial depolarization, and intracellular reactive oxygen species (ROS) level were analyzed. Green fluorescent protein (GFP)-tagged version of HBx and the truncation mutant were also created and the effects of truncation on HBx intracellular expression pattern and localization were studied. Effect of time lapse on protein expression pattern was also analyzed. The truncation mutant of HBx is more efficient in inducing cell proliferation, and causes more ROS production and less mitochondrial depolarization as compared with wild type (wt) HBx. In addition, gene expression is altered in favor of carcinogenesis in the presence of the truncation mutant. Furthermore, mitochondrial perinuclear aggregation is achieved earlier in the presence of the truncation mutant. Therefore, HBx C-terminal 127 amino acid truncation might be playing important roles in the development of hepatitis B-related liver diseases by inducing cell proliferation, altering gene expression, altering mitochondrial potential, inducing mitochondrial clustering and oxidative stress, and changing HBx expression pattern.