Acute kidney injury after robot-assisted laparoscopic prostatectomy: A meta-analysis.

BACKGROUND: We investigated the rates of acute kidney injury (AKI) post robot-assisted laparoscopic prostatectomy (RALP). METHODS: A comprehensive search was conducted to identify studies that reported the rates of AKI post-RALP. A random effects model was used, and the pooled rates of AKI were calculated. RESULTS: We identified 10 studies with 60,937 patients to be included. The mean age was 65.1 years. The mean anaesthesia time was 234.3 min (95% CI: 177.8-290.9). The mean operation time was 212.2 min (95% CI: 188.7-235.6). The mean estimated blood loss was 314.1 mL (95% CI: 153-475.3). The mean intraoperative IV fluids administered were 1985 mL (95% CI: 1516.3-2453.7). The pooled rate of AKI post RALP was 7.2% (95% CI 19-23.9). CONCLUSIONS: The rates of AKI after RALP are significant. Further studies are needed to detect the risk factors for AKI and to determine the rates of chronic kidney disease post-RALP.

Cardiac Magnetic Resonance Imaging Findings in Patients With Chronic Kidney Disease and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

In this systematic review and meta-analysis, we explored the utilization of cardiac magnetic resonance imaging (CMR) to detect fibrotic changes secondary to uremic cardiomyopathy during the early stages of chronic kidney disease (CKD) and in patients with end-stage kidney disease (ESKD). Uremic myocardial fibrosis can lead to arrhythmia and heart failure, and it is important to detect these changes. CMR offers a noninvasive way to characterize the severity of cardiac remodeling. A comprehensive search of multiple electronic databases was conducted. Studies were divided according to scanner field strength (1.5 or 3 Tesla). The random effects model was used to calculate the pooled mean, 95% confidence interval (CI), standard error, and standardized mean difference (SMD). The I2 statistic was used to assess the heterogeneity between study-specific estimates. The search retrieved 779 studies. From these, 20 studies met the inclusion criteria and had 642 CKD patients (mean age of 56.8 years; 65.2% males; mean estimated glomerular filtration rate (eGFR) of 33 mL/min/1.73 m2) and 658 ESKD patients on dialysis (mean age of 55.6 years; 63.3% males; mean dialysis duration of 3.47 years). CKD patients had an increased left ventricular mass index (LVMi) compared to controls, with an SMD of 0.37 (95% CI: 0.20-0.54; I2 0%; p-value <0.05). ESKD patients also had increased LVMi compared to controls, SMD 0.88 (95% CI: 0.35-1.41; I2 79.1%; p-value 0.001). Myocardial fibrosis assessment using T1 mapping showed elevated values; the SMD of native septal T1 values between CKD and controls was 1.099 (95% CI: 0.73-1.46; I2 33.6%; p-value <0.05), and the SMD of native septal T1 values between ESKD patients and controls was 1.12 (95% CI: 0.85-1.38; I2 33.69%; p-value <0.05). In conclusion, patients with CKD and ESKD with preserved left ventricular ejection fraction (LVEF) have higher LVMi and T1 values, indicating increased mass and fibrosis. T1 mapping can be used for the early detection of cardiomyopathy and as a risk stratification tool. Large, randomized trials are needed to confirm these findings and determine the effect of long-term dialysis on cardiac fibrosis.

Lemierre's Syndrome Due to Streptococcus anginosus: A Case Report and Review of the Literature.

Lemierre's syndrome, also known as anaerobic post-anginal septicemia, necrobacillosis, and the "forgotten disease," is a rare manifestation. It is often presented with sepsis, sore throat, fever, neck pain, internal jugular vein thrombophlebitis/thrombosis, and septic emboli. The bacteria that are usually associated with the disease are Fusobacterium species, but it is also associated with Staphylococcus, Streptococcus, and other bacterial species. The diagnosis of Lemierre's syndrome is made based on evidence of septic thrombophlebitis, preceding oropharyngeal infection, and positive culture. Treatment usually consists of antibiotics directed toward the causative organism. The use of anticoagulation, although controversial, is shown to be beneficial by several studies. We describe a middle-aged patient who presented with a sore throat, neck pain, and dysphagia. Imaging of the neck and chest revealed right jugular thrombosis along with septic emboli in the lungs. The culture of the blood and pus drained from the peritonsillar abscess grew Streptococcus anginosus. In this study, we have illustrated the effective management of Lemierre's syndrome with antibiotics, anticoagulants, and needle aspiration of abscess.

Surgical Aortic Valve Replacement to Treat Prosthetic Valve Endocarditis After Valve-in-Valve Transcatheter Aortic Valve Replacement.

Prosthetic valve endocarditis (PVE) is an uncommon complication after heart valve replacement surgery that can result in increased morbidity and mortality. Current guidelines for management of PVE recommend antibiotic therapy followed by surgical valve replacement. The number of aortic valve replacements is expected to rise in the coming years with the expanded indications for use of transcatheter aortic valve replacement (TAVR) in patients with low, intermediate, and high surgical risk, as well as in patients with a failed aortic bioprosthetic valve. Current guidelines do not address the use of valve-in-valve (ViV) TAVR for management of PVE in patients who are at high risk for surgical intervention. The authors present a case of a patient with aortic valve PVE after surgical aortic valve replacement (SAVR); he was treated with valve-in-valve (ViV) TAVR due to the high surgical risk. The patient was discharged, but he returned to the hospital with PVE and valve dehiscence 14 months after ViV TAVR, after which he successfully underwent re-operative SAVR.

Disparities in the management of non-ST-segment elevation myocardial infarction in the United States.

Guidelines recommend managing patients aged ≥75 with non-ST-segment elevation myocardial infarction (NSTEMI) similar to younger patients. We analyze disparities in NSTEMI management and compare those ≥80 years to those <80 years. This is a matched case-control study using the 2016 National Inpatient Sample data of adults with NSTEMI receiving percutaneous coronary intervention with drug-eluting stent (PCI-DES) - one artery or no intervention. We included the statistically significant variables in univariate analysis in exploratory multivariate logistic regression models. Total sample included 156,328 patients, out of which 43,265 were ≥ 80 years, and 113,048 were < 80 years. Patients ≥80 years were more likely to not have an intervention (73.3%) when compared to those <80 (44.1%), P < 0.0005. Regardless of age, PCI-DES-one artery improved survival compared to no intervention (Age < 80: OR 0.230, 95% CI 0.189-0.279, and ≥ 80: OR 0.265, 95% CI 0.195-0.361, P < 0.0005). Women (OR 0.785, 95% CI 0.766-0.804, P < 0.0005) and non-white race (OR 0.832, 95% CI 0.809-0.855, P < 0.0005) were less likely to receive an intervention. Non-Medicare/Medicaid insurance was associated with 40% lower likelihood of dying in <80 age group (OR 0.596, 95% CI 0.491-0.724, P < 0.0005), and 16% higher chance of intervention overall (OR 1.160, 95% CI 1.125-1.197, P < 0.0005). Patients aged ≥80 with NSTEMI were 29% less likely to receive an intervention compared to patients aged <80, even though patients >80 derived similar mortality benefits from the intervention. There were gender, payor, and race-based disparities in NSTEMI management in 2016.

Reactions of Ru(III)-drugs KP1019 and KP418 with guanine, 2'-deoxyguanosine and guanosine: a DFT study.

Ruthenium (Ru)-based anticancer drugs are considered to be novel alternatives of platinum-based drugs. They exhibit potent cytotoxicity against the cancer cells and hence are useful for the treatment of cancer. Herein, the density functional theory calculations in the gas phase and aqueous media are carried out to study the reactions of two Ru(III)-based drugs such as KP1019 and KP418 with the N7 site of guanine (G), 2'-deoxyguanosine (dGua), and guanosine (Gua) to understand their reactivity against the DNA and RNA. All the reactions are found to be exothermic. The activation free energies and rate constants of these reactions indicate that KP1019 and KP418 would react with the dGua more readily than Gua. Hence, the binding of these drugs with the DNA would be more preferred as compared to RNA. It is further found that among these drugs, KP1019 would be more reactive than KP418 in agreement with the experimental observation. Thus, this study is expected to aid in the future development of potent anticancer drugs.

C-Terminal Extended Hexapeptides as Potent Inhibitors of the NS2B-NS3 Protease of the ZIKA Virus.

The Zika virus (ZIKV) protease is an attractive drug target for the design of novel inhibitors to control the ZIKV infection. As the protease substrate-binding site contains acidic residues, inhibitors with basic residues can be beneficial for the inhibition of protease activities. Molecular dynamics (MD) simulation and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) techniques are employed herein to design potent peptide inhibitors and to understand the nature of the basic residues that can potentially stabilize the acidic residues of the protease substrate-binding site. It is found that the inclusion of K, R, and K at P1, P2, and P3 positions, respectively, and Y at the P4 position (YKRK) would generate a highly stable tetrapeptide-protease complex with a ΔGbind of ~ -80 kcal/mol. We have also shown that the C-terminal extension of this and the second most stable tetrapeptide (YRRR) with small polar residues, such as S and T would generate even more stable hexapeptide-protease complexes. The modes of interactions of these inhibitors are discussed in detail, which are in agreement with earlier experimental studies. Thus, this study is expected to aid in the design of novel antiviral drugs against the ZIKV.

Ciliated respiratory epithelium encapsulating Pseudomonas brain abscess due to prior trauma.

Bacterial brain abscesses are typically spread through a haematogenous route. Open head wounds and neurosurgical interventions are uncommon aetiologies. Ectopic tissue found in the cerebral cortex is usually ascribed almost entirely from carcinomas. Here, we describe a 57-year-old gentleman who, 22 years after a fireworks related traumatic injury to the left orbit, presented with headaches and altered behaviour. Imaging revealed an abscess immediately superior to the orbit, whose bacterial aetiology was identified to be Pseudomonas aeruginosa, encapsulated by ciliated respiratory epithelium. This represents a case in which tissue was displaced during the initial trauma or craniofacial reconstructive surgery from the frontal sinus.

Anticoagulation Management and Outcomes in Patients With Covid-19 With Propensity Score Matching: A Multicenter Retrospective Cohort Study.

BACKGROUND: Therapeutic doses of anticoagulation have been administered to patients with coronavirus-19 disease (Covid-19) without thromboembolism, although there is a lack of robust evidence supporting this practice. STUDY QUESTION: To compare outcomes between patients admitted to the hospital for Covid-19 who received full-dose anticoagulation purely for the indication of Covid-19 and patients who received prophylactic doses of anticoagulation. STUDY DESIGN: This is a multicenter retrospective cohort study, including 7 community hospitals in Michigan. Patients were >18 years of age, confirmed positive for Covid-19 by polymerase chain reaction, and admitted to the hospital between March 10 and May 3, 2020. Exposed group: Patients receiving therapeutic dose anticoagulation for Covid-19 for any duration excluding clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction; control group: Patients receiving prophylactic anticoagulation. Propensity score matching was used to adjust for the nonrandomized nature of the study. MEASURES AND OUTCOMES: The primary endpoint: 30-day in-hospital mortality. Secondary endpoints: intubation, length of hospital stay, and readmissions in survivors. RESULTS: A total of 115 exposed and 115 control patients were analyzed. Rates of 30-day in-hospital mortality were similar (exposed: 33.0% vs. control: 28.7%). Controlling for institution, there was no significant association between treatment and 30-day in-hospital mortality (hazard ratio: 0.63; 95% confidence interval: 0.37-1.06). Survivors had statistically similar length of hospital stay and readmission rates. CONCLUSIONS: We found no difference in mortality in patients with Covid-19 without clinically evident venous thromboembolism, atrial fibrillation, and myocardial infarction who received therapeutic versus prophylactic doses of anticoagulation.

Review of ultrasound contrast agents in current clinical practice with special focus on DEFINITY® in cardiac imaging.

Echocardiography is the most widely used noninvasive modality to evaluate the structure and function of the cardiac muscle in daily practice. However, up to 15-20% of echocardiograms are considered suboptimal. To enable accurate assessment of cardiac function and wall motion abnormality, the use of ultrasound microbubble contrast has shown substantial benefits in cases of salvaging nondiagnostic studies and enhancing the diagnostic accuracy in daily practice. DEFINITY® is a perflutren based, lipid shelled microbubble contrast agent, which is US FDA approved for left ventricular opacification. The basis of ultrasound microbubbles, its development, and the clinical role of DEFINITY (characteristics, indications and case examples, side effect profile and existing evidence) is the subject of discussion in this review.

Impending Paradoxical Embolism Traversing Three Cardiac Chambers Presenting With Stroke and Pulmonary Embolism.

A straddling thrombus within a patent foramen ovale (PFO), also known as an impending paradoxical embolism, is an infrequent event that is rarely encountered in clinical practice. This should be considered whenever there is an arterial embolism in the presence of right-sided thromboembolic disease. Symptoms are widely variable depending on the severity of thrombus and obstructive embolic events. We present a patient who arrived at the hospital with signs and symptoms consistent with a cerebrovascular disease that was ultimately diagnosed with small foci of acute ischemic cerebral infarcts, bilateral pulmonary emboli, and a straddling thrombus traversing three cardiac chambers. Treatment included PFO closure, inferior vena cava filter placement, and surgical thrombectomy with a successful outcome. Consensus for treatment of an impending paradoxical embolism in the medical literature is a subject of controversy and is our reason behind contributing this case presentation with our treatment strategy.

Successful Catheter-Directed Thrombolysis of Massive Bilateral Upper Extremity DVT Presenting as Superior Vena Cava Syndrome.

Superior vena cava syndrome (SVCS) is traditionally associated with malignancy. However, approximately one-third of SVCS cases are due to intravascular devices and pacemakers. No specific guidelines exist for managing catheter-associated SVCS. We present catheter-associated SVCS resistant to anticoagulation, angioplasty, and thrombectomy but resolved with ultrasound-assisted catheter directed thrombolysis. (Level of Difficulty: Intermediate.).

Does tautomerization of FapyG influence its mutagenicity?

Oxidative degradation of guanine to 2,6-diamino-4-oxo-5-formamidopyrimidine (FapyG) is believed to be mutagenic. It has been proposed recently that the enol tautomer of FapyG is mainly responsible for this effect leading to a guanine-to-thymine mutation (T. H. Gehrke, U. Lischke, K. L. Gasteiger, S. Schneider, S. Arnold, H. C. Muller, D. S. Stephenson, H. Zipse, T. Carell, Nat. Chem. Biol.- 2013, 9, 455-461). Here, density functional methods suggest that the enol tautomer of FapyG might not be responsible for the proposed guanine-to-thymine mutation. Instead, it might result in a guanine-to-adenine mutation.

Is FapyG mutagenic?: Evidence from the DFT study.

2,6-diamino-4-oxo-5-formamidopyrimidine (FapyG) is an oxidatively damaged product of guanine (G), which is mainly formed through metabolic processes that produce OH radicals. It has been proposed that in bacterial cells, FapyG retains the coding properties of G, and is, therefore, not mutagenic. However, in mammalian cells, FapyG induces G to thymine (T) mutation more dominantly than another ubiquitous oxidative lesion, that is, 8-oxoguanine (8-oxoG). The exact reasons for these coding properties of FapyG are not properly understood. In order to rationalize the cause of FapyG-mediated mutagenesis, all of the possible base-pair interactions of FapyG with cytosine (C), adenine (A), and T, in both anti- and syn- conformations, are studied in detail by using density functional theory (DFT). The effects of solvation on the coding properties of FapyG are also evaluated. We demonstrate that the anti-FapyG:C base pair has the highest binding energy, and that the base-pair alignment is similar to that of the normal G:C base pair. Therefore, insertion of C opposite anti-FapyG is preferred over the other DNA bases. This could be the reason for the non-mutagenic behavior of FapyG in bacterial cells. However, as the binding patterns and energies of anti-FpyG:A and syn-FapyG:A base pairs are similar, and these are also similar to those of the T:A base pair, mammalian polymerases may not distinguish between FapyG and T. As a result, A would be mistakenly inserted opposite either anti-FapyG or syn-FapyG, resulting in G to T transverse mutation.

Binding of BIS like and other ligands with the GSK-3ß kinase: a combined docking and MM-PBSA study.

Binding of several bisindolylmaleimide (BIS) like (BIS-3, BIS-8 and UCN1) and other ligands (H89, SB203580 and Y27632) with the glycogen synthase kinase-3 (GSK-3ß) has been studied using combined docking, molecular dynamics and Poisson-Boltzmann surface area analysis approaches. The study generated novel binding modes of these ligands that can rationalize why some ligands inhibit GSK-3ß while others do not. The relative binding free energies associated with these binding modes are in agreement with the corresponding measured specificities. This study further provides useful insight regarding possible existence of multiple conformations of some ligands like H89 and BIS-8. It is also found that binding modes of BIS-3, BIS-8 and UCN1 with GSK-3ß and PDK1 kinases are similar. These new insights are expected to be useful for future rational design of novel, more potent GSK-3ß-specific inhibitors as promising therapeutics.

A theoretical study of some new analogues of the anti-cancer drug camptothecin.

The enzyme topoisomerase I (topo I), which is essential for cell replication, transiently causes a DNA single strand break and makes a complex with it. The anti-cancer agent camptothecin (CPT) binds to the topo I-DNA complex and stabilizes it, preventing resealing of the broken DNA strand and cell growth. Considering the structural factors of CPT that are believed to be involved in stabilizing the topo I-DNA complex via hydrogen bonding and stacking interactions, designs of two new analogues of CPT (topo I inhibitors) have been suggested. The molecular geometries of CPT, two of its analogues and certain other related molecules included in the study were fully optimized in both gas phase and aqueous media at the B3LYP/6-311++G(d,p) level of density functional theory. Solvation effects of aqueous media were treated using the polarizable continuum model (PCM). Net CHelpG charges and surface molecular electrostatic potentials (MEP) near the atomic sites of the molecules were studied. Structural analogy and surface MEP values suggests that the two new CPT analogues studied here would be potent topoisomerase I inhibitors.