Predictors of non-obstructive coronary slow flow in poorly controlled type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Coronary slow flow (CSF) can occur due to various factors, such as inflammation, small vessel disease, endothelial dysfunction, and inadequate glucose control. However, the exact pathological mechanisms behind CSF remain incompletely understood. The objective of this study was to identify the risk factors associated with slow coronary flow in individuals with Type 2 Diabetes Mellitus (T2DM) who have non-obstructive coronary artery disease (CAD) and experience CSF. METHODS: We conducted a prospective cohort study involving 120 patients with T2DM who were referred for invasive coronary angiography due to typical chest pain or inconclusive results from non-invasive tests for myocardial ischemia. Using a 2 × 2 design, we categorized patients into groups based on their glycemic control (adequate or poor) and the presence of CSF (yes or no), defined by a TIMI frame count > 27. All patients had non-obstructive CAD, characterized by diameter stenosis of less than 40%. We identified many variables associated with CSF. RESULTS: Our investigation revealed no significant differences in age, sex, family history of coronary artery disease, ECG ischemia abnormalities, or echocardiographic (ECHO) data between the groups. In patients with adequate glycemic control, hypertension increased the risk of CSF by 5.33 times, smoking by 3.2 times, while dyslipidemia decreased the risk by 0.142. Additionally, hematocrit increased the risk by 2.3, and the platelet-to-lymphocyte ratio (PLR) increased the risk by 1.053. Among patients with poor glycemic control, hematocrit increased the risk by 2.63, and the Neutrophil-to-Lymphocyte Ratio (NLR) by 24.6. Notably, NLR was positively correlated with glycemic control parameters in T2DM patients with CSF. CONCLUSIONS: In T2DM patients with CSF, various factors strongly correlate with glycemic control parameters and can be employed to predict the likelihood of CSF. These factors encompass hypertension, smoking, increased body mass index (BMI), elevated platelet count, hematocrit, NLR, PLR, and C-reactive protein (CRP). TRIAL REGISTRATION: Registry: ZU-IRB (ZU-IRB#9419-3-4-2022), Registered on: 3 April 2022, Email: IRB_123@medicine.zu.edu.eg.

Unleashing the potential of vanillic acid: A new twist on nature's recipe to fight inflammation and circumvent azole-resistant fungal infections.

Vanillic acid (VA) - a naturally occurring phenolic compound in plants - is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson's alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a-1i, 2a-2i, 3, 3a-3i, 4a-4i, 5a-5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b-3d, 4a-4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.

Geochemical processes, salinity sources and utility characterization of groundwater in a semi-arid region of Iraq through geostatistical and isotopic techniques.

Identifying factors contributing to water salinity is paramount in efficiently managing limited water resources in arid environments. The primary objective of this study is to enhance understanding regarding the hydrochemistry, source, and mechanism of water salinity, as well as to assess the suitability of water for various uses in southern Iraq. The groundwater samples were collected from water wells and springs and analyzed for major cations and anions along with stable isotopes (δ18O and δ2H) to accomplish the objective. The analysis of major ion chemistry, hydrochemical techniques, principal component analysis (PCA), and isotope signatures were adopted to determine the primary factors contributing to water mineralization. The study inferred that evaporation and geological processes encompassing water-rock interactions, such as dissolution precipitation and ion exchange, were key processes. The stable isotope analysis revealed that the water originated from meteoric sources and underwent significant evaporation during or before infiltration. The utility assessment of water samples indicates that most samples are not appropriate for consumption and are significantly below the established standards for potable water. In contrast, a significant portion of the groundwater samples were found to meet the criteria for irrigation suitability by adopting Wilcox and the US Salinity Laboratory criteria. The groundwater could be considered for irrigation with proper salinity control management. Overall, this study has significantly improved the understanding of the hydrogeochemical regimes and acts as a first step toward the sustainable utilization of water resources.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

Relationship between inflammatory markers and coronary slow flow in type 2 diabetic patients.

BACKGROUND: Diabetes is a serious and quickly expanding global health problem. Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Coronary slow flow (CSF) is characterised by delayed distal perfusion during coronary angiography with normal coronary arteries. This study aimed to investigate the correlation between CSF and inflammatory markers regarding glycemic status in T2DM. METHODS: This cross-sectional study included 120 patients who were divided equally into 4 groups according to their glycemic control and presence or absence of coronary slow flow: Group I included patients with T2DM with good glycemic control without CSF; Group II included patients with T2DM with good glycemic control and CSF; Group III included patients with T2DM with poor glycemic control without CSF; and Group IV included patients with T2DM with poor glycemic control and CSF. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), platelets, hematocrit, and haemoglobin were also evaluated as risk factors for coronary slow flow. RESULTS: This study showed that body mass index (BMI), hematocrit level, NLR, and CRP demonstrated a moderate but significant correlation (r = 0.53) with CSF in poorly controlled T2DM. NLR cutoff > 2.1 could predict CSF in poorly controlled T2DM with a modest sensitivity and specificity. A 1.9 increase in HbA1c increases the likelihood of coronary slow flow. Dylipidemia increases the likelihood of coronary slow flow by 0.18 times. Other predictors for coronary slow flow include NLR, PLR, CRP, platelets, hematocrit, and hemoglobin. The effect of the predictors is still statistically significant after being adjusted for glycemic status, age, and sex (p < 0.001). CONCLUSIONS: Poor glycemic control increases the incidence of CSF. This supports the hypothesis that CSF is related to endothelial dysfunction as poor glycemic control causes endothelial dysfunction due to inflammation. TRIAL REGISTRATION: ZU-IRB#9419-3-4-2022 Registered 3 April 2022, email.  IRB_123@medicine.zu.edu.eg .

Factors associated with unexplained sudden deaths among adults aged 18-45 years in India - A multicentric matched case-control study.

BACKGROUND OBJECTIVES: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study. METHODS: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI). RESULTS: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not. INTERPRETATION CONCLUSIONS: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.

Mechanistic Evaluation of Diffusion Weighted Hyperintense Lesions After Large Spontaneous Intracerebral Hemorrhage: A Subgroup Analysis of MISTIE III.

BACKGROUND: Ischemic lesions on diffusion weighted imaging (DWI) are common after acute spontaneous intracerebral hemorrhage (ICH) but are poorly understood for large ICH volumes (> 30 mL). We hypothesized that large blood pressure drops and effect modification by cerebral small vessel disease markers on magnetic resonance imaging (MRI) are associated with DWI lesions. METHODS: This was an exploratory analysis of participants in the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial with protocolized brain MRI scans within 7 days from ICH. Multivariable logistic regression analysis was performed to assess biologically relevant factors associated with DWI lesions, and relationships between DWI lesions and favorable ICH outcomes (modified Rankin Scale 0-3). RESULTS: Of 499 enrolled patients, 300 had MRI at median 7.5 days (interquartile range 7-8), and 178 (59%) had DWI lesions. The incidence of DWI lesions was higher in patients with systolic blood pressure (SBP) reduction ≥ 80 mm Hg in first 24 h (76%). In adjusted models, factors associated with DWI lesions were as follows: admission intraventricular hematoma volume (p = 0.03), decrease in SBP ≥ 80 mm Hg from admission to day 1 (p = 0.03), and moderate-to-severe white matter disease (p = 0.01). Patients with DWI lesions had higher odds of severe disability at 1 month (p = 0.04), 6 months (p = 0.036), and 12 months (p < 0.01). No evidence of effect modification by cerebral small vessel disease on blood pressure was found. CONCLUSIONS: In patients with large hypertensive ICH, white matter disease, intraventricular hemorrhage volume, and large reductions in SBP over the first 24 h were independently associated with DWI lesions. Further investigation of potential hemodynamic mechanisms of ischemic injury after large ICH is warranted.

A Statistical Approach for the Integration of Multi-Temporal InSAR and GNSS-PPP Ground Deformation Measurements.

Determining and monitoring ground deformations is critical for hazard management studies, especially in megacities, and these studies might help prevent future disaster conditions and save many lives. In recent years, the Golden Horn, located in the southeast of the European part of Istanbul within a UNESCO-protected region, has experienced significant changes and regional deformations linked to rapid population growth, infrastructure work, and tramway construction. In this study, we used Interferometric Synthetic Aperture Radar (InSAR) and Global Navigation Satellite System (GNSS) techniques to investigate the ground deformations along the Golden Horn coastlines. The investigated periods are between 2015 and 2020 and 2017 and 2020 for InSAR and GNSS, respectively. For the InSAR analyses, we used sequences of multi-temporal synthetic aperture radar (SAR) images collected by the Sentinel-1 and ALOS-2 satellites. The ground displacement products (i.e., time series and velocity maps) were then cross-compared with those achievable using the Precise Point Positioning (PPP) technique for the GNSS solutions, which can provide precise positions with a single receiver. In the proposed analysis, we compared the ground displacement velocities obtained by both methods by computing the standard deviations of the difference between the relevant observations considering a weighted least square estimation procedure. Additionally, we identified five circle buffers with different radii ranging between 50 m and 250 m for selecting the most appropriate coherent points to conduct the cross-comparison analysis. Moreover, a vertical displacement rate map was produced. The comparison of the vertical ground velocities derived from PPP and InSAR demonstrates that the PPP technique is valuable. For the coherent stations, the vertical displacement rates vary between -4.86 mm/yr and -23.58 mm/yr and -9.50 and -27.77 mm/yr for InSAR and GNSS, respectively.

Effects Of Excessive Screen Time During Online Teaching On The Physical And Mental Health Of Medical And Dental Students.

To assess the effects of excessive screen time on the health of medical and dental students due to online teaching during the COVID-19 pandemic. It was a descriptive cross-sectional study, conducted in Bahria University of Health Sciences from June 2022 to September 2022 after getting ethical approval. A total of 200 students who attended online teaching modules for at least one year through online teaching Apps, were included. A structured questionnaire was distributed using google forms. The results revealed that factors including strain on the eyes, restlessness, declined academic performance and exercise during lockdown, along with feeling connected as a group had a significant association with increased screen time. Excessive screen time has various adverse effects on the physical and mental health of medical and dental students. For improving students' physical and mental health during online teaching we need to change teaching strategies and support the introduction of flipped classroom.

Virosome: An engineered virus for vaccine delivery.

The purpose of immunization is the effective cellular and humoral immune response against antigens. Several studies on novel vaccine delivery approaches such as micro-particles, liposomes & nanoparticles, etc. against infectious diseases have been investigated so far. In contrast to the conventional approaches in vaccine development, a virosomes-based vaccine represents the next generation in the field of immunization because of its balance between efficacy and tolerability by virtue of its mechanism of immune instigation. The versatility of virosomes as a vaccine adjuvant, and delivery vehicle of molecules of different nature, such as peptides, nucleic acids, and proteins, as well as provide an insight into the prospect of drug targeting using virosomes. This article focuses on the basics of virosomes, structure, composition formulation and development, advantages, interplay with the immune system, current clinical status, different patents highlighting the applications of virosomes and their status, recent advances, and research associated with virosomes, the efficacy, safety, and tolerability of virosomes based vaccines and the future prospective.

Repeat liver resection for recurrent intrahepatic cholangiocarcinoma: meta-analysis.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare malignancy. The aim of this meta-analysis was to evaluate outcomes of repeat liver resection and non-surgical approaches for treatment of recurrent ICC. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception until March 2021 for studies of patients with recurrent ICC. Studies not published in English were excluded. Two meta-analyses were performed: a single-arm meta-analysis of studies reporting pooled short- and long-term outcomes after repeat liver resection for recurrent ICC (meta-analysis A), and a meta-analysis of studies comparing 1-, 3-, and 5-year overall survival (OS) rates after repeat liver resection and non-surgical approaches for recurrent ICC (meta-analysis B). RESULTS: Of 543 articles retrieved in the search, 28 were eligible for inclusion. Twenty-four studies (390 patients) were included in meta-analysis A and nine studies (591 patients) in meta-analysis B. After repeat liver resection, 1-, 3-, and 5-year OS rates were 87 (95 per cent c.i. 81 to 91), 58 (48 to 68), and 39 (29 to 50) per cent respectively. The 1-, 3-, and 5-year OS rates were higher after repeat liver resection than without surgery: odds ratio 2.70 (95 per cent c.i. 1.28 to 5.68), 2.89 (1.15 to 7.27), and 5.91 (1.59, 21.90) respectively. CONCLUSION: Repeat liver resection is a suitable strategy for recurrent ICC in selected patients. It improves short- and long-term outcomes compared with non-surgical treatments.

Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. METHODS: PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44-0.63; p < 0.001). Moreover, Statins decreased the recurrence 1 year after surgery (OR: 0.27; 95% CI: 0.16-0.47; P < 0.001), 3 years after surgery (OR: 0.22; 95% CI: 0.15-0.33; P < 0.001), and 5 years after surgery (OR: 0.28; 95% CI: 0.19-0.42; P < 0.001). The certainty of evidence for the outcomes was moderate. CONCLUSION: Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

Renal Artery Repair with Kidney Autotransplantation for Renal Artery Aneurysms.

OBJECTIVE: Kidney autotransplantation (ATx) is a treatment option for distal renal artery aneurysm (RAA). This systematic review evaluated the indications, treatment strategy, and outcome of kidney ATx to verify the value of this procedure in treating RAA. DATA SOURCES: PubMed, Embase, and Web of Science. REVIEW METHODS: All study types were included, except study protocols and animal studies, without time or language restrictions. Data sources were reviewed until April 2021 to identify relevant articles evaluating operating time, cold and warm ischaemia time, total complications, length of hospital stay, and mortality rate in patients with RAA receiving kidney ATx. RESULTS: The literature search retrieved 644 articles. Of these, 55 clinical studies (including 37 case reports and 18 case series) investigating 199 patients were eligible for inclusion. Endovascular treatment had failed in 17% of 70 patients with RAA. Heterotopic kidney ATx was performed in 81% of patients, and 19% received orthotopic kidney ATx. Unplanned nephrectomy was reported in only one patient (0.1%). Post-operative complications were reported in 6.9% of patients, including urinary tract infection (2.0%), wound infection (1.3%), acute renal insufficiency (0.6%), graft thrombosis (0.6%), kidney hypoperfusion (0.6%), haematoma (0.6%), lymphocoele (0.6%), pseudoaneurysm (0.6%), and arterial occlusion (0.6%). None of the patients died peri-operatively, and organ loss was reported in only one patient (0.05%). No further organ loss or death was reported during follow up (median follow up duration 12 months). CONCLUSION: In patients with distal perihilar RAA, surgical repair with kidney ATx appears to be a suitable alternative when endovascular approaches are not appropriate. In these cases, kidney ATx saves the kidney and provides good clinical outcomes. However, these findings should be interpreted with caution, considering the lack of data regarding the adverse events, potential for favourable publication bias among included studies, and the absence of consecutive series and prospective trials.

Systematic review and meta-analysis of endoscopic ultrasound drainage for the management of fluid collections after pancreas surgery.

BACKGROUND: The outcomes of endoscopic ultrasonography-guided drainage (EUSD) in treatment of pancreas fluid collection (PFC) after pancreas surgeries have not been evaluated systematically. The current systematic review and meta-analysis aim to evaluate the outcomes of EUSD in patients with PFC after pancreas surgery and compare it with percutaneous drainage (PCD). METHODS: PubMed and Web of Science databases were searched for studies reporting outcomes EUSD in treatment of PFC after pancreas surgeries, from their inception until January 2022. Two meta-analyses were performed: (A) a systematic review and single-arm meta-analysis of EUSD (meta-analysis A) and (B) two-arm meta-analysis comparing the outcomes of EUSD and PCD (meta-analysis B). Pooled proportion of the outcomes in meta-analysis A as well as odds ratio (OR) and mean difference (MD) in meta-analysis B was calculated to determine the technical and clinical success rates, complications rate, hospital stay, and recurrence rate. ROBINS-I tool was used to assess the risk of bias. RESULTS: The literature search retrieved 610 articles, 25 of which were eligible for inclusion. Included clinical studies comprised reports on 695 patients. Twenty-five studies (477 patients) were included in meta-analysis A and eight studies (356 patients) were included in meta-analysis B. In meta-analysis A, the technical and clinical success rates of EUSD were 94% and 87%, respectively, with post-procedural complications of 14% and recurrence rates of 9%. Meta-analysis B showed comparable technical and clinical success rates as well as complications rates between EUSD and PCD. EUSD showed significantly shorter duration of hospital stay compared to that of patients treated with PCD. CONCLUSION: EUSD seems to be associated with high technical and clinical success rates, with low rates of procedure-related complications. Although EUSD leads to shorter hospital stay compared to PCD, the certainty of evidence was low in this regard.

Biochemical characterization of zebrafish Prss59.1.

Eleven genes, including prss59.1, were selected as candidate ovulation-inducing genes on the basis of microarray analysis and RNA sequencing in our previous study. To address the role of prss59.1, the prss59.1 gene knock-out zebrafish strain is currently being established by genome editing. In this study, for further phenotypic analysis of prss59.1, biochemical characterization of Prss59.1 was conducted using recombinant protein. A C-terminal histidine-tagged version of zebrafish Prss 59.1 was constructed. Although E. coli-produced recombinant Prss59.1 showed almost no activity, peptidase activities appeared after denaturation and renaturation. Zebrafish Prss59.1 showed the highest activity against Lys-MCA. The optimal temperature and pH of the activity toward Lys-MCA were 37 °C and pH 8.0, respectively. The Km value was 0.17 mM. Thus, zebrafish Prss59.1 possesses the closed character of trypsin, as expected from the DNA sequence.

Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation.

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.

Effectiveness of apixaban versus enoxaparin in preventing wound complications and deep venous thrombosis following total knee replacement surgery: A retrospective study.

BACKGROUND: Enoxaparin, a thromboprophylactic drug that is widely used for preventing deep venous thrombosis (DVT) and surgical wound complications after total knee replacement surgery, can only be administered subcutaneously. Apixaban, a novel factor Xa inhibitor that could be comparable to enoxaparin, is an oral formulation and thus would be easier to manage. OBJECTIVE: To compare the thromboprophylactic effectiveness of apixaban and enoxaparin in patients receiving total knee replacements. METHODS: In this retrospective, single-institution study, the records of 200 patients who underwent elective total knee replacement surgery were reviewed. Of those, 120 patients had received enoxaparin 4000 IU daily (initiated 6 hours before surgery), whereas 80 had received apixaban 2.5 mg twice daily (initiated 12 hours after surgery), for 21 days. All patients were examined for major and minor surgical wound complications and DVT incidence during their hospital stay and 7-21 days after surgery. RESULTS: No statistically significant differences (P ≥ .005) were found between the apixaban and enoxaparin groups with regard to minor and major surgical wound complications and DVT incidence. Patients in both groups were comparable in terms of age, hospital stay, and required blood transfusion units. Two enoxaparin-treated patients and one apixaban-treated patient developed DVT (1.5%) during the study period. CONCLUSION: Oral apixaban is an effective alternative to enoxaparin as a thromboprophylactic drug for patients undergoing elective total knee replacement surgery.

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

Comparison of Traumatic Intracranial Hemorrhage Expansion and Outcomes Among Patients on Direct Oral Anticoagulants Versus Vitamin k Antagonists.

BACKGROUND: With increasing use of direct oral anticoagulants (DOACs) and availability of new reversal agents, the risk of traumatic intracranial hemorrhage (tICH) requires better understanding. We compared hemorrhage expansion rates, mortality, and morbidity following tICH in patients treated with vitamin k antagonists (VKA: warfarin) and DOACs (apixaban, rivaroxaban, dabigatran). METHODS: Retrospective chart review of patients from 2010 to 2017 was performed to identify patients with imaging diagnosis of acute traumatic intraparenchymal, subdural, subarachnoid, and epidural hemorrhage with preadmission use of DOACs or VKAs. We identified 39 patients on DOACs and 97 patients on VKAs. Demographic information, comorbidities, hemorrhage size, and expansion over time, as well as discharge disposition and Glasgow Outcome Scale (GOS) were collected. Primary outcome was development of new or enlargement of tICH within the first 48 h of initial CT imaging. RESULTS: Of 136 patients with mean (SD) age 78.7 (13.2) years, most common tICH subtype was subdural hematoma (N = 102/136; 75%), and most common mechanism was a fall (N = 130/136; 95.6%). Majority of patients in the DOAC group did not receive reversal agents (66.7%). Hemorrhage expansion or new hemorrhage occurred in 11.1% in DOAC group vs. 14.6% in VKA group (p = 0.77) at a median of 8 and 11 h from initial ED admission, respectively (p = 0.82). Patients in the DOAC group compared to VKA group had higher median discharge GOS (4 vs. 3 respectively, p = 0.03), higher percentage of patients with good outcome (GOS 4-5, 66.7% vs. 40.2% respectively, p = 0.005), and higher rate of discharge to home or rehabilitation (p = 0.04). CONCLUSIONS: We report anticoagulation-associated tICH outcomes predominantly due to fall-related subdural hematomas. Patients on DOACs had lower tICH expansion rates although not statistically significantly different from VKA-treated patients. DOAC-treated patients had favorable outcomes versus VKA group following tICH despite low use of reversal strategies. DOAC use may be a safer alternative to VKA in patients at risk of traumatic brain hemorrhage.

Musculoskeletal tumours throughout history and beyond: Clinical features, imaging, staging and biopsy.

BACKGROUND: Over the last century, there has been a remarkable development in the study of bone and soft tissue sarcomas. This is primarily due to the improved knowledge of the nature of these lesions and the improved imaging technology. In literature there are many protocols that are being used and all of them have reported various advantages and disadvantages of each technique used. However, there is no set guideline and whatever has been proposed has been developed on the basis of the experience of different centres and different surgeons. OBJECTIVE: The current systematic review was planned to thoroughly evaluate the levels of evidence on which we base decisions for surgical management of lower extremity bone tumours. METHODS: The review included descriptive studies published in the English language. Studies included case reports, case series and experiences of different centres for the surgical management of lower extremity bone tumours. Articles reporting all levels of evidence - Level I to V - were included. PubMed, ERIC, MEDLINE, EMBASE and Cochrane Reviews databases from 2002 to 2012 were searched. RESULTS: Information was gathered and thoroughly studied from 63 articles. There were no Level I studies, 2(3.2%) Level II studies, 47(74.6%) Level III, and the remaining 14(22.2%) studies were Level IV and Level V. CONCLUSIONS: Sarcomas are rarely occurring neoplastic conditions which are present in all age groups but commonly affect young age population. Most are asymptomatic but can present with pain or pathological fracture. These lesions are commonly diagnosed with plain radiographs. CT scan and MRI may be used to delineate anatomy and to quantify the extent of soft tissue involvement. Various advantages and disadvantages associated with each aspect in the management of patients starting from the basic history-taking, physical examination, imaging, biopsy principles, peri-operative laboratory work-up and staging of the cancer were studied. Treatment ranges from conservative to en-block resection including extended curettage. Aggressive tumours should be closely followed up for recurrence and metastasis.