Diagnostic Accuracy of Elastography and Liver Disease: A Meta-Analysis.

Background: Ultrasound-based transient elastography (TE) is a non-invasive alternative to liver biopsy for the staging of hepatic fibrosis due to various chronic liver diseases. This meta-analysis aims to assess the diagnostic accuracy of TE for detecting liver cirrhosis (F4) and severe fibrosis (F3) in patients with chronic liver diseases, in comparison to the gold standard liver biopsy. Methods: A systematic search was performed using PubMed search engine following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from inception to May 2021. The meta-analysis studies evaluating the diagnostic accuracy of TE for severe fibrosis and cirrhosis were identified. We conducted a meta-meta-analysis to generate pooled estimates of the sensitivity, specificity, and diagnostic odds ratios (ORs) for F3 and F4 fibrosis stage. Results: We included five studies with a total of 124 sub-studies and 20,341 patients in our analysis. Three studies have reported the diagnostic accuracy of TE in detecting F3/severe fibrosis stage and found 81.9% pooled sensitivity (95% confidence interval (CI): 79.9-83.7%; P < 0.001) (I2 = 0%), 84.7% pooled specificity (95% CI: 81.3-87.6%) (I2 = 81%; P = 0.02). All five studies reported the diagnostic accuracy of TE in detecting F4/liver cirrhosis stage. We found 84.8% pooled sensitivity (95% CI: 81.4-87.7%) (I2 = 86.4%; P < 0.001), 87.5% pooled specificity (95% CI: 85.4-89.3%) (I2 = 90%; P < 0.001) and pooled diagnostic OR (41.8; 95% CI: 3.9 - 56.5) (I2 = 87%; P < 0.001). Conclusions: Ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis and liver fibrosis stages 3. Future studies should focus on estimating the diagnostic accuracy of other fibrosis stages in chronic liver disease patients. This will eventually decrease the risk associated with invasive liver biopsy.

Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study.

BACKGROUND: Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. METHODS: We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient's medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon's rank test was used to look at the correlation between two subgroups upon admission and discharge. RESULTS: On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. CONCLUSIONS: Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission.

Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study.

Background: It is well known that traditional smoking causes various types of cancer, leading to the current decline in traditional smoking among US adults from 20.9% in 2005 to 14.0% in 2019. Electronic cigarettes (e-cigarettes) are commonly marketed as a safe alternative and gaining popularity especially among never-smokers and adolescents. However, there is limited evidence of effects of e-cigarette on cancer. Hence, we aim to find the prevalence and association of e-cigarette and traditional smoking among cancer respondents. Methods: We conducted a retrospective cross-sectional study using the NHANES database from 2015 to 2018. We assessed history of cancer (MCQ220), type of cancers (MCQ230a), and smoking status (e-cigarette: SMQ900 or SMQ905 and traditional smoking: SMQ020) using questionnaires. We performed multivariable logistic regression models to find the association of e-cigarette use, traditional smoking, and no smoking with cancer after adjusting for confounding variables. Results: A total of 154,856 participants were included, of whom 5% were e-cigarette users, 31.4% were traditional smokers, and 63.6% were nonsmokers. There is a higher prevalence of e-cigarette use among younger participants, females (49 vs. 38) in comparison to traditional smokers (P < 0.0001). The e-cigarette users have lower prevalence of cancer compared to traditional smoking (2.3% vs. 16.8%; P < 0.0001), but they were diagnosed with cancer at a younger age. Among cancer subtypes, cervical cancer (22 vs. 2.6), leukemia (8.5 vs. 1.1), skin cancer (non-melanoma) (15.6 vs. 12.3), skin (other) (28 vs. 10) and thyroid (10.6 vs. 2.4) had higher prevalence of e-cigarette use compared to traditional smokers (P < 0.0001). Our regression analysis showed that e-cigarette users have 2.2 times higher risk of having cancer compared to non-smokers (odds ratio (OR): 2.2; 95% confidence interval (CI): 2.2 - 2.3; P < 0.0001). Similarly, traditional smokers have 1.96 higher odds of having cancer compared to nonsmokers (OR: 1.96; 95% CI: 1.96 - 1.97; P < 0.0001). Conclusion: In our study, e-cigarette users had an early age of cancer onset and higher risk of cancer. Hence, this is stepping stone for future research to evaluate the safety and effects of e-cigarettes in patients with cancer.

Metagenomic analysis of bacterial communities during estrous cycle in Bos indicus.

The present study, using 16 s rRNA sequencing of the V3-V4 hypervariable region, was aimed to check diversity of vaginal microbiota throughout different stages of the estrous cycle in Bos indicus, with attention to changes in progesterone hormone and microorganism diversity. Metagenomic research was conducted on vaginal swabs obtained from nine healthy Indian Gir cows at estrus (day 0), metestrus (day 04), diestrus (day 12), and proestrus (day 16) phases of the estrous cycle. The findings revealed that the diestrus phase has a different bacterial diversity than the other three estrous cycle phases, implying that progesterone affects bacterial diversity. Proteobacteria and Firmicutes were the most abundant phyla at the phylum level, accounting for 94% of bacterial diversity. Actinobacteriota, Patescibacteria, Cyanobacteria, and Bacteroidota were among the less prevalent phyla observed in all samples. After statistical analysis, Bacillaceae, Alcaligenes, Enterobacteriaceae, and Morganellaceae families were more significant. The Enterobacteriaceae family was found to be lower in the diestrus phase than in the other three phases; in contrast, all statistically significant genera were high at the diestrus phase. The luteal stage had higher levels of Micrococcus, Stenotrophomonas, UGC-010, Massilia, and Methylobacillus than the follicular stage, and statistical analysis revealed substantial difference between the luteal and follicular stages. Lactobacillus genus was present in both the estrus and diestrus phases. This study represents an important step toward the understanding of microbial diversity within different stages of the estrous cycle of Indian cows.

The effect of oil pulling with coconut oil to improve dental hygiene and oral health: A systematic review.

OBJECTIVES: Coconut oil is a cheap and accessible oil for many people around the world. There are numerous advocates for the practice of oil pulling to prevent common oral diseases. Therefore determining the effectiveness of oil pulling with coconut oil could potentially have monumental benefits. This review aimed to assess the effect of oil pulling with coconut oil in improving oral health and dental hygiene. DATA: We included randomized controlled trials comparing the effect of oil pulling with coconut oil on improving oral health and dental hygiene.No meta-analysis was performed due to the clinical heterogeneity and differences in the reporting of data among the included studies. SOURCES: Six electronic databases were screened: PubMed, Medline, EMBASE, AMED, CENTRAL and CINAHL. STUDY SELECTION: Electronic searches yielded 42 eligible studies, of which four RCTs including 182 participants were included. The studies lasted between 7 and 14 days. Significant differences were demonstrated for a reduction in salivary bacterial colony count (p = 0.03) and plaque index score (p=<0.001). One study also demonstrated a significant difference in staining compared to using Chlorhexidine (p = 0.0002). However, data was insufficient for conclusive findings, the quality of studies was mixed and risk of bias was high. CONCLUSION: The limited evidence suggests that oil pulling with coconut oil may have a beneficial effect on improving oral health and dental hygiene. Future clinical trials are of merit considering the universal availability of the intervention. Prospective research should have a robust design with rigorous execution to provide a higher quality of evidence. CLINICAL SIGNIFICANCE: Oil pulling with coconut oil could be used as a adjunct to normal preventative regimes to improve oral health and dental hygiene although further studies are needed to determine the level of effectiveness.

Lidocaine tripotassium phosphate complex laden microemulsion for prolonged local anaesthesia: In vitro and in vivo studies.

Lidocaine is widely used as a local anaesthetic in the clinical practice to manage pre- and post-operative pain, skin burns, etc. However, the short duration of action (< 2 h) of marketed dosage forms limit their ability to meet clinical needs. Herein, we prepared a lidocaine-tPP(tri potassium phosphate)-complex loaded microemulsion to achieve greater penetration, followed by destabilization of microemulsion in the skin layer to precipitate oil-complex to produce a depot effect in the skin for prolonging the effects of anaesthesia. The lidocaine-tPP-complex-microemulsion was compared with lidocaine base loaded microemulsion, marketed ointment USP and lidocaine HCl. The pseudo ternary phase diagrams at three Smix ratios (1:2, 1:3 and 1:4; Pluronic F127: PEG 400) were constructed using Capmul MCM C8 EP as oil phase. The Smix at 1:4 ratio showed large microemulsion area in comparison to 1:2 and 1:6 ratio. The lidocaine base (LD-1:4-ME10O45SM and LD-1:4-ME20O45SM) and lidocaine-tPP-complex (LDC-1:4-ME10O45SM and LDC-1:4-ME20O45SM) loaded microemulsion batches (1:4 ratio) were thermodynamically stable. The ex vivo diffusion study showed sustained release up to 12 h with microemulsion batches, in comparison to lidocaine HCl (4 h) and ointment base (7 h). The selected LDC-1:4-ME20O45SM batch was non-irritating on the rabbit skin. In drug retention studies, LD-1:4-ME20O45SM and LDC-1:4-ME20O45SM batches showed 2.68- and 3.93-fold greater lidocaine retention in comparison to ointment USP. The radiant heat tail-flick test showed prolong local anaesthesia using LDC-1:4-ME20O45SM in comparison to ointment USP. The findings suggest that lidocaine-tPP-complex loaded microemulsion could be a potential strategy for providing prolong local anaesthesia.

Efficacy and Factors Associated with Treatment Response of Intravenous Immunoglobulin in Inpatients with Refractory Inflammatory Bowel Diseases.

BACKGROUND: The administration of intravenous immunoglobulin (IVIG) has demonstrated promise in the treatment of medically refractory inflammatory bowel diseases (IBD). We aimed to identify factors associated with IVIG failures in the treatment of refractory IBD. METHODS: Our historical cohort included patients with refractory IBD admitted to our inpatient service with an exacerbation and treated with at least 1 dose of IVIG (0.4 g/kg). Detailed clinical variables were recorded for subjects. Examined outcomes included changes in disease-specific severity indices, the duration of surgery-free survival after IVIG, infusion reactions, subsequent IBD-related emergency department visits, hospital readmissions, and mortality. RESULTS: Fifty-four subjects with refractory IBD (61% female, age 42 ± 16 yrs, 23 with Crohn's disease, 15 with ulcerative colitis, 16 with pouchitis) met the inclusion criteria. All disease severity scores were significantly improved after IVIG administration (Harvey-Bradshaw index P = 0.007, partial Mayo score P = 0.002, modified Pouchitis Disease Activity Index P = 0.008). Twenty-seven patients (50%) underwent surgery, with a mean surgery-free survival of 28.7 ± 3.7 months. In univariable analysis, patients with Clostridium difficile infection (CDI) had a 3-fold increased risk of bowel resection surgery after IVIG compared with those without (hazard ratio = 2.9, 95% confidence interval, 1.2-7.4; P = 0.023), and in subsequent multivariable analysis, CDI remained significant (hazard ratio = 3.0, 95% confidence interval, 1.2-7.6; P = 0.024). CDI was also associated with increased risk of hospital readmission (hazard ratio = 2.5, 95% confidence interval, 1.05-5.9; P = 0.038). CONCLUSIONS: Our study demonstrates that IVIG is beneficial in patients with medically refractory IBD, and that concomitant CDI is a risk factor for the treatment failure of IVIG for refractory disease.

Single 4.5 mg fixed-dose of rasburicase for hyperuricemia associated with tumor lysis syndrome.

Rasburicase is a recombinant urate oxidase enzyme administered for treatment of hyperuricemia associated with tumor lysis syndrome. Studies demonstrate effectiveness of single fixed-dose rasburicase as compared to the FDA-approved dose of 0.2 mg/kg intravenously daily for up to five days. Doses in these studies range from 1.5 mg to 7.5 mg. Our study evaluated outcomes in patients who received single 4.5 mg fixed-dose rasburicase. This retrospective, IRB-approved chart review evaluated adult oncology subjects who received fixed-dose rasburicase between January 2007 and April 2014. The primary outcome was percentage of patients with normalization of uric acid (level <8 mg/dL within 24 h) after a single 4.5 mg fixed-dose of rasburicase. Secondary objectives were incidence of initial failure of fixed-dose rasburicase and normalization of uric acid in overweight (body mass index ≥25 kg/m2) versus non-overweight patients. Initial failure was defined as need for additional doses or progression to dialysis within one week of the initial fixed-dose. In the 128 patients included, the mean baseline uric acid level was 14.84 mg/dL. Of the 112 patients with a follow-up uric acid level, 68% achieved normalization within 24 h of rasburicase administration. Thirty-eight patients received additional treatment: 10 received additional dose(s) and 28 underwent dialysis. Normalization of uric acid in overweight versus non-overweight patients was 66% and 73%, respectively. Overall, a single 4.5 mg fixed-dose of rasburicase effectively normalized uric acid in 68% of patients within 24 h. Further studies are needed to determine the optimal single fixed-dose necessary for treatment response across all patients.

Radial artery pseudoaneurysm: A rare complication after a single arterial puncture for blood-gas analysis.

With a reported incidence of 0.048%, radial artery pseudoaneurysm (PA) is a rare but serious complication of arterial cannulation. We report a case of PA developing after a single puncture of the right radial artery for arterial blood-gas analysis diagnosed by Doppler ultrasound in young male patient. The development of PA after puncture of radial artery for continuous blood pressure monitoring and serial blood-gas analysis has been reported in the past; however, to the best of our knowledge, there is only one case report of development of PA after a single arterial puncture for blood-gas analysis is reported in the past.

Rare Anatomical Variation of Dual IVC with Left Sided IVC Draining into Hemiazygous Vein- A Case Report.

Congenital anomalies of the Inferior Vena Cava (IVC) result from the persistence of the embryonic venous system. Knowledge of such anomaly is of great importance during abdominal surgery, liver and kidney transplantation, renal venous sampling and in the treatment of thromboembolic diseases. Here, we report a rare anatomical variation of dual IVC with normal course of right sided IVC and hemiazygous continuation of left sided IVC with interiliac communication in potential renal donor. Congenital abnormalities of the inferior vena cava are easily identified on Computed Tomography (CT) and should be considered when interpreting any CT of the abdomen or chest.

Role of 64 slice multidetector computed tomography and angiography to establish relationship between tumor size, aneurysm formation and spontaneous rupture of renal angiomyolipomas: Single center experience.

OBJECTIVE: To evaluate the role of computed tomography (CT) angiography using 64 slice multidetector CT scan to establish relationships among tumor size, aneurysm formation, and spontaneous rupture of renal angiomyolipomas (AML). MATERIALS AND METHODS: Total 27 patients were diagnosed as having renal angiomyolipoma (AML) at institute of kidney disease and research center from June 2008 to June 2015. All patients with renal AML underwent contrast-enhanced CT (CECT) with CT angiography with 64 slice multidetector CT scan. RESULTS: Total 34 kidneys were found to be affected by AML. Out of which 6 AML were ruptured and remaining 28 were unruptured. If tumor size of 4 cm or larger is used as predictor of rupture; sensitivity 20%, specificity 89%, positive predictive value 83.3%, and negative predictive value 28.5%; and If aneurysm size >5 mm is used as predictor of rupture; sensitivity 75%, specificity 90%, positive predictive value 50%, and negative predictive value 96.4% was found. CONCLUSION: Tumor size, aneurysm size and tumor multiplicity cannot use as a predictor of spontaneous rupture of the tumor.

Comparison between doppler ultrasound resistive index, serum creatinine, and histopathologic changes in patients with kidney transplant dysfunction in early posttransplantation period: A single center study with review of literature.

To determine the relationship between resistive index (RI) measured by Doppler ultrasound, serum creatinine (SCr), and histopathological changes on biopsy during kidney trans- plant dysfunction in early postoperative period, we studied 47 kidney transplant patients; 61% of the patients had acute transplant rejection, 19% had acute tubular necrosis, 4% had calcineurin inhibitor toxicity, 11% had normal morphology in biopsy, and 5% had changes compatible with pyelonephritis. None of the study patients had interstitial fibrosis or tubular atrophy on biopsy. We found that the sensitivity and specificity of RI in diagnosing transplant dysfunction was highly variable depending on the selected cutoff value. Sensitivity of RI decreased and its specificity increased with increasing the RI thresholds. Using an RI threshold of 0.7 resulted in a high sensitivity of 78% at a cost of very low specificity 40%, whereas using an RI threshold of 0.9 resulted in 100% specificity at a cost of very low sensitivity 16%. Acceptable specificity was only achieved at the expense of very low sensitivity, resulting in poor utility of RI as a screening tool for dysfunction. We found that there were no significant differences in the mean RI value between patients with and without biopsy-proven transplant dysfunction. However, we found a significant correlation between SCr value and RI of 0.383, P = 0.007.

Parry-romberg syndrome: a rare entity.

Parry-Romberg syndrome or progressive hemifacial atrophy is vary rare, uncommon, degenerative, poorly understood condition characterized by a slow and progressive atrophy affecting one side of the face. The incidence and the causes of this alteration are unknown. Possible factors that are involved in the pathogenesis include disturbance of fat metabolism, trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications are: trigeminal neuritis, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and become stable after certain time period. After stabilization of the disease multi specialty approach including physician, orthodontic treatment and reconstructive surgery with autogenous fat graft can be performed to correct the deformity. The objective of this article is to accomplish a literature review concerning general characteristics, etiology, physiopathology, differential diagnosis and treatment of progressive hemifacial atrophy.

Low utilization of circulating glucose after food withdrawal in Snell dwarf mice.

Glucose metabolism is altered in long-lived people and mice. Although it is clear that there is an association between altered glucose metabolism and longevity, it is not known whether this link is causal or not. Our current hypothesis is that decreased fasting glucose utilization may increase longevity by reducing oxygen radical production, a potential cause of aging. We observed that whole body fasting glucose utilization was lower in the Snell dwarf, a long-lived mutant mouse. Whole body fasting glucose utilization may be reduced by a decrease in the production of circulating glucose. Our isotope labeling analysis indicated both gluconeogenesis and glycogenolysis were suppressed in Snell dwarfs. Elevated circulating adiponectin may contribute to the reduction of glucose production in Snell dwarfs. Adiponectin lowered the appearance of glucose in the media over hepatoma cells by suppressing gluconeogenesis and glycogenolysis. The suppression of glucose production by adiponectin in vitro depended on AMP-activated protein kinase, a cell mediator of fatty acid oxidation. Elevated fatty acid oxidation was indicated in Snell dwarfs by increased utilization of circulating oleic acid, reduced intracellular triglyceride content, and increased phosphorylation of acetyl-CoA carboxylase. Finally, protein carbonyl content, a marker of oxygen radical damage, was decreased in Snell dwarfs. The correlation between high glucose utilization and elevated oxygen radical production was also observed in vitro by altering the concentrations of glucose and fatty acids in the media or pharmacologic inhibition of glucose and fatty acid oxidation with 4-hydroxycyanocinnamic acid and etomoxir, respectively.

Differential modulation of COX-2 expression in A549 airway epithelial cells by structurally distinct PPAR(gamma) agonists: evidence for disparate functional effects which are independent of NF-(kappa)B and PPAR(gamma).

Ligands of peroxisome proliferator-activated receptor-gamma (PPAR(gamma)) are thought to possess anti-inflammatory properties mediated via both PPAR(gamma) dependent and independent mechanisms. This work investigates the effects of PPAR(gamma) ligands on the regulation of cyclooxygenase-2 (COX-2) in the human lung epithelial cell line, A549. The synthetic ligand troglitazone activated the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase pathway (MAPK), whereas the endogenous ligand, 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), only activated the PI3K pathway. 15d-PGJ2 had no detectable effects on COX-2, mPGES expression, or PGE2 production. However, troglitazone induced time-dependent COX-2 expression, which was insensitive to PPAR(gamma) antagonists, but was abrogated by inhibitors of PI3K and the ERK MAP kinase pathway. Furthermore, troglitazone induced mPGES expression and PGE2 production. Neither troglitazone nor 15d-PGJ2 was able to convincingly activate NF-kappaB in A549 cells. Further heterogeneity in the responses to troglitazone and 15d-PGJ2 was observed in the regulation of gene expression as assessed by microarray analysis. In summary, this study provides compelling evidence that troglitazone (like 15d-PGJ2) can exert functional effects independently of actions via PPAR(gamma). Moreover, we have identified unique biochemical and functional actions of troglitazone that are not shared by 15d-PGJ2, which may influence the therapeutic potential of this compound in inflammatory settings.

Differential regulation of prostaglandin E biosynthesis by interferon-gamma in colonic epithelial cells.

1. Cyclooxygenase (COX)-2 expression and activity in response to pro-inflammatory cytokines TNF alpha and IFN gamma was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. 2. TNF alpha induced concentration- and time-dependent upregulation of COX-2 mRNA, protein and prostaglandin (PG)E(2) synthesis. 3. Co-stimulation of TNF alpha with IFN gamma resulted in reduced COX-2 mRNA and protein expression. 4. IFN gamma had no effect on the stability of TNF alpha-induced COX-2 mRNA. 5. TNF alpha-induced PGE(2) biosynthesis was significantly enhanced by the simultaneous addition of IFN gamma and was COX-2 dependent. 6. The combination of IFN gamma and TNF alpha induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE(2) synthesis. 7. These results suggest that, in terms of PGE(2) biosynthesis, IFN gamma plays a negative regulatory role at the level of COX-2 expression and a positive regulatory role at the level of mPGES expression. This may have important implications for the clinical use of IFN gamma in inflammatory diseases.