Diagnostic accuracy of lever sign test in acute and chronic ACL injuries.

Introduction: The anterior cruciate ligament (ACL) is a commonly affected knee ligament prone to frequent injuries. Henceforth, we aimed to determine the diagnostic accuracy of lever sign test in Acute and chronic ACL injuries. Method: At the institution's initial outpatient visit, 150 consecutive patients (92 males and 58 females) were evaluated. Total 108 patients had injury in their right leg, whereas 42 had injury in their left leg. Based on time since injury, the patients were divided into Acute and chronic groups. Clinical examinations (lachman's test and lelli's test) of all patients were confirmed with arthroscopic findings and compared between the two groups. Results: In the acute ACL injury, the lever test had a kappa value 0.704. The accuracy and sensitivity of the Lachman, anterior drawer, pivot shift, and lever tests were calculated. We found that the lever test had the highest accuracy and sensitivity (85.48 %, 91.18 %) than the rest. In the chronic ACL injury, the kappa value for the results of the Lachman test evaluation was 0.723. The chronic ACL injuries accuracy and sensitivity values for the Lachman (86.36 %, 91.67 %), anterior drawer (76.14 %, 81.25 %), pivot shift (55.68 %, 58.49 %), and lever tests were determined. Conclusion: The lever sign test is more accurate and reliable in the acute ACL injuries, while the Lachman test is more accurate and reliable in the chronic ACL injuries.

Improved assay development of pharmaceutical modalities using feedback-controlled liquid chromatography optimization.

Development of meaningful and reliable analytical assays in the (bio)pharmaceutical industry can often be challenging, involving tedious trial and error experimentation. In this work, an automated analytical workflow using an AI-based algorithm for streamlined method development and optimization is presented. Chromatographic methods are developed and optimized from start to finish by a feedback-controlled modeling approach using readily available LC instrumentation and software technologies, bypassing manual user intervention. With the use of such tools, the time requirement of the analyst is drastically minimized in the development of a method. Herein key insights on chromatography system control, automatic optimization of mobile phase conditions, and final separation landscape for challenging multicomponent mixtures are presented (e.g., small molecules drug, peptides, proteins, and vaccine products) showcased by a detailed comparison of a chiral method development process. The work presented here illustrates the power of modern chromatography instrumentation and AI-based software to accelerate the development and deployment of new separation assays across (bio)pharmaceutical modalities while yielding substantial cost-savings, method robustness, and fast analytical turnaround.

Structure Based Machine Learning Prediction of Retention Times for LC Method Development of Pharmaceuticals.

PURPOSE: Significant resources are spent on developing robust liquid chromatography (LC) methods with optimum conditions for all project in the pipeline. Although, data-driven computer assisted modelling has been implemented to shorten the method development timelines, these modelling approaches require project-specific screening data to model retention time (RT) as function of method parameters. Sometimes method re-development is required, leading to additional investments and redundant laboratory work. Cheminformatics techniques have been successfully used to predict the RT of metabolites & other component mixtures for similar use cases. Here we will show that these techniques can be used to model structurally diverse molecules and predictions of these models trained on multiple LC conditions can be used for downstream data-driven modelling. METHODS: The Molecular Operating Environment (MOE) was used to calculate over 800 descriptors using the strucutres of the analytes. These descriptors were used to model the RT of the analytes under four chromatographic conditions. These models were then used to create data-driven models using LC-SIM. RESULTS: A structural-based Random Forest (RF) model outperformed other techniques in cross-validation studies and predicted the RTs of a randomized test set with a median percentage error less than 4% for all LC conditions. RTs predicted by this structure-based model were used to fit a data-driven model that identifies optimum LC conditions without any additional experimental work. CONCLUSIONS: These results show that small training sets yield pharmaceutically relevant models when used in a combination of structure-based and data-driven model.

An improved workflow for the development of MS-compatible liquid chromatography assay purity and purification methods by using automated LC Screening instrumentation and in silico modeling.

The development of liquid chromatography UV and mass spectrometry (LC-UV-MS) assays in pharmaceutical analysis is pivotal to improve quality control by providing critical information about drug purity, stability, and presence and identity of byproducts and impurities. Analytical method development of these assays is time-consuming, which often causes it to become a bottle neck in drug development and poses a challenge for process chemists to quickly improve the chemistry. In this study, a systematic and efficient workflow was designed to develop purity assay and purification methods for a wide range of compounds including peptides, proteins, and small molecules with MS-compatible mobile phases (MP) by using automated LC screening instrumentation and in silico modeling tools. Initial LC MPs and chromatography column screening experiments enabled quick identification of conditions which provided the best resolution in the vicinity of the target compounds, which is further optimized using computer-assisted modeling (LC Simulator from ACD/Labs). The experimental retention times were in good agreement with the predicted retention times from LC Simulator (ΔtR < 7%). This workflow presents a practical workflow to significantly expedite the time needed to develop optimized LC-UV-MS methods, allowing for a facile, automatic method optimization and reducing the amount of manual work involved in developing new methods during drug development.

Islatravir Dimer: Crystal Form Dependence of a Radiation-Induced Degradation Product.

A rare example of crystal form-dependent, gamma radiation-induced degradation is presented. Islatravir is known to exist in several polymorphic forms, but only one of these forms shows the generation of a specific dimer degradation product under gamma irradiation. Extended gamma irradiation studies demonstrated that only one of the known crystalline forms shows an appreciable rate of dimer formation. Additionally, this dimer is not observed to form under other forced stress conditions. We present the structural elucidation of this dimer impurity and rationalize its form-dependent generation based on the analysis of the underlying crystal structure.

Early and mid-term outcomes of double-chambered right ventricle repair: An 8-year experience.

BACKGROUND/AIM: Double-chambered right ventricle is a rare and progressive condition that is characterised by obstruction of the right ventricular tract. Double-chambered right ventricle is usually associated with ventricular septal defect. Early surgical intervention is recommended in patients with these defects. Based on this background, the present study aimed to review early and midterm outcomes of primary repair after double-chambered right ventricle. METHODS: Between January 2014 and June 2021, 64 patients with a mean age of 13.42 ± 12.31 years underwent surgical repair for double-chambered right ventricle. The clinical outcomes of these patients were reviewed and assessed retrospectively. RESULTS: An associated ventricular septal defect was present in all the recruited patients; 48 (75%) patients of sub-arterial type, 15 (23.4%) of perimembranous, and 1 (1.6%) patient of muscular type. The patients were followed up for a mean period of 46.73 ± 27.37 months. During their follow-up, a significant decrease in the mean pressure gradient from 62.33 ± 5.52 mmHg preoperatively to 15.73 ± 2.94 mmHg postoperatively was observed (p < 0.001). Notably, there were no hospital deaths. CONCLUSIONS: The development of double-chambered right ventricle in association with ventricular septal defect results in an increased pressure gradient within the right ventricle. The defect needs correction in a timely manner. In our experience, the surgical correction of double-chambered right ventricle is safe and shows excellent early and mid-term results.

Early and Mid-Term Outcomes of Primary Repair After Atrioventricular Canal Defect: A Single-Center Eight-Year Experience.

BACKGROUND/AIM: Surgical repair techniques and management of patients with atrioventricular septal defect (AVSD) have progressed over the last few decades. Early and definitive interventions have become the choice of treatment for these patients. Based on this background, we aimed to review the early and mid-term outcomes of primary AVSD repair. METHODS: A total of 53 patients with a mean age of 3.45 ± 5.67 years underwent definitive repair for AVSD between January 2014 and June 2021. The clinical data including age, type of defect, associated co-anomalies, symptoms, pulmonary hypertension, etc. were collected and assessed retrospectively. Mitral regurgitation (MR) as a clinical outcome was assessed at 0, 1, 2, and 5 years. RESULTS: Among the recruited patients, 35 (66.1%) were male and 18 (33.9%) were female. Of 53 patients, repair for the complete defect was done in 38 (71.69%) patients, repair for intermediate/partial defect was done in 15 (23.1%) patients, and one patient underwent repair for incomplete type. Other associated co-anomalies were anterior mitral leaflet (12 (22.6%)), atrial and ventricular septal defect (VSD) (30 (56.6%)), and patent ductus arteriosus (PDA) (11 (20.8%)). Different procedures for surgical repair included patch closure, cleft repair, and polytetrafluoroethylene (PTFE) VSD closure. After repair, the mean follow-up period was 46.73 ± 27.37 months. Overall mortality was 3.78% (2/53), and two patients underwent reintervention due to symptomatic severe MR. CONCLUSIONS: A definitive and timely correction of AVSD shows satisfactory early and mid-term results.

Surgical Outcomes of Post-myocardial Infarction Ventricular Septal Defect/Rupture: A Systematic Review and Meta-Analysis.

Ventricular septal defect (VSD) is a catastrophic acute myocardial infarction (MI) complication. Despite a significant reduction in the prevalence of post-MI VSD with the advancement of surgical techniques, it is still considered fatal with a high mortality rate. The trends in the clinical outcomes of patients with post-MI VSD show discretion due to the complexity of the disease. Therefore, the present analysis aimed to evaluate the surgical outcomes and associated risks in the patients of post-MI VSD. A thorough literature survey resulted in 40 studies of our interest. The pooled proportion of differential variables, including the incidence of cardiogenic shock, 30-day survival, and overall mortality, were estimated using Bayesian hierarchical models. The risk difference was estimated for the location of MI and VSD and mortality in patients with coronary artery bypass graft (CABG). In addition, the heterogeneity tests for inconsistency and publication biases using Egger's and Begg's tests were also estimated. The analysis revealed a significant risk difference of 0.23 and 0.27 for the anterior vs. posterior location of MI and VSD, respectively. Further, the pooled proportion of 30-day survival and mortality was found to be 54.43% (95% credible interval (CI): 52.88-55.98%) and 48.22% (95% CI: 4-12.3%), respectively. Moreover, the heterogeneity test revealed significant inconsistencies in all the datasets with an I2 index of >90% (p<0.0001). Lastly, the publication bias results suggested no evidence of asymmetry and small-study effects. Conclusively, the surgical management of post-MI VSD patients is considered beneficial; however, the outcomes signify its fatal behavior.

Portable capillary LC for in-line UV monitoring and MS detection: Comparable sensitivity and much lower solvent consumption.

Pharmaceutical development currently relies on quality separation methods from early discovery through to line-of-site manufacturing. There have been significant advancements made regarding the column particle packing, internal diameter, length connectivity, the understanding of the impact key parameters like void volume, flow rate, and temperature all that affects the resultant separation quality, that is, resolution, peak shape, peak width, run time, and signal-to-noise ratio. There is however a strong need to establish better alternatives to large bulky high-performance liquid chromatography racks either for process analytical reaction monitoring or mass spectrometry analysis in establishing product quality. Compact, portable high-pressure liquid chromatography can be a more efficient alternative to traditional ultra-high pressure liquid chromatography and traditional liquid chromatography. The compact versatile instrument evaluated here allows good separation control with either the on-board column with fixed ultra-violet wavelength cartridge or for use with a high-resolution mass spectrometry. Significant space reduction results in greener lab spaces with improved energy efficiency for smaller labs with lower energy demands. In addition, this compact liquid chromatography was used as a portable reaction monitoring solution to compare forced degradation kinetics and assess portable liquid chromatography-mass spectrometry capability for the analyses required for pharmaceutical drug product testing.

Simultaneous Cesarean Section and Maternal Cardiac Surgery: Outcomes and Feasibility from a Tertiary Care Hospital in India.

INTRODUCTION: Cardiovascular disease is the leading cause of pregnancy-related mortality, and it has gradually increased over time; this rise has been attributed to numerous reasons including the growing number of women with congenital heart disease who are surviving to childbearing age. Valve surgery during pregnancy is a high risk, with a fetal and maternal mortality rate of 35% and 9%, respectively. Prior knowledge about the cardiovascular disease opens up a host of options for the mother even during pregnancy, but presentation in the 3rd trimester puts both the mother and the baby at risk. Simultaneous caesarean section and maternal cardiac surgery is a suitable option for this subset of patients, and with this study we aim to assess its outcomes and feasibility. METHODS: This is a retrospective study of five pregnant patients who presented with predominant symptoms of heart failure in the 3rd trimester between June 2019 and June 2021. Intraoperative and postoperative intensive care unit charts of all the patients were reviewed. RESULTS: All five patients underwent simultaneous cesarean section and maternal cardiac surgery successfully with no fetal or maternal mortality and are doing well in the follow-up period. CONCLUSION: Cesarean section followed by definitive maternal cardiac surgery in the same sitting is a safe and feasible approach in the management of such patients. A well-prepared team is pivotal for a safe delivery with a cardiopulmonary bypass machine on standby. Specialized multidisciplinary care in the antepartum, peripartum, and postpartum period is essential to improve outcomes.

Pediatric ERCP: Factors for Success and Complication-A 17-Year, Multisite Experience.

OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) is an increasingly utilized procedure in pediatric populations. A lack of dedicated pediatric research has led endoscopists to extrapolate adult risk factors and preventative strategies to children. The aim of this multisite, retrospective study was to identify risks for adverse events, procedure failure, and prolonged courses in pediatric patients undergoing ERCP. METHODS: Pediatric patients who had an ERCP at one of our academic centers were identified by query of their electronic medical records. Pre-procedure and post-procedure data were collected with ERCP-related adverse events defined according to the consensus criteria developed by Cotton et al 2010. RESULTS: Between January 2004 and January 2021, 287 children had a total of 716 ERCPs. The procedure success rate was 95.5% with no mortality and an adverse event rate of 12.7%. Younger age was associated with increased case complexity, increased adverse events, and an increased rate of repeat ERCP. Case complexity score correlated with increased procedure time ( P < 0.001) and increased adverse events (tau 0.24, P < 0.01); stent removal and pancreatic stenting were more likely to precede an adverse event. Pancreatitis, pancreatic divisum, and pancreatic stricture/stenosis were associated with increased adverse events and rates of repeat ERCP. CONCLUSIONS: Pediatric ERCP adverse event rates are higher than adults. The complexity grading system proposed by the Cotton et al appears to have applicability to pediatric patients. Young age and interventions affecting the pancreatic duct are associated with adverse ERCP outcomes in pediatrics.

Surgical outcomes of double-orifice mitral valve repair in patients with atrioventricular canal defects: a systematic review and meta-analysis.

INTRODUCTION: Double-orifice mitral valve or left atrioventricular valve is a rare congenital cardiac anomaly that may be associated with an atrioventricular septal defect. The surgical management of double-orifice mitral valve/double-orifice left atrioventricular valve with atrioventricular septal defect is highly challenging with acceptable clinical outcomes. This meta-analysis is aimed to evaluate the surgical outcomes of double-orifice mitral valve/double-orifice left atrioventricular valve repair in patients with atrioventricular septal defect. METHODS AND RESULTS: A total of eight studies were retrieved from the literature by searching through PubMed, Google Scholar, Embase, and Cochrane databases. Using Bayesian hierarchical models, we estimated the pooled proportion of incidence of double-orifice mitral valve/double-orifice left atrioventricular valve with atrioventricular septal defect as 4.88% in patients who underwent surgical repair (7 studies; 3295 patients; 95% credible interval [CI] 4.2-5.7%). As compared to pre-operative regurgitation, the pooled proportions of post-operative regurgitation were significantly low in patients with moderate status: 5.1 versus 26.39% and severe status: 5.7 versus 29.38% [8 studies; 171 patients]. Moreover, the heterogeneity test revealed consistency in the data (p < 0.05). Lastly, the pooled estimated proportions of early and late mortality following surgical interventions were low, that is, 5 and 7.4%, respectively. CONCLUSION: The surgical management of moderate to severe regurgitation showed corrective benefits post-operatively and was associated with low incidence of early mortality and re-operation.

Early surgical outcomes of a modified infarct exclusion technique in acute post-myocardial infarction ventricular septal rupture: a single-centre experience.

Introduction: Operative mortality in an acute post-myocardial infarction (AMI) ventricular septal rupture (VSR) is high. In addition to ventricular dysfunction, friable myocardium adds to the technical difficulty of the operation. In a modified infarct exclusion technique, the right ventricle is left undisturbed and the free edge of the pericardial patch is incorporated in the sutures while closing the left ventriculotomy. This simplifies the procedure and decreases the chances of right ventricular dysfunction, any residual defect, and bleeding. Study design: A retrospective analysis of patients with VSR following AMI operated in our institute from January 2018 to June 2021 was done. Results: Over the last 3 years, 16 patients with AMI VSR were treated with a modified infarct exclusion technique. Eight patients presented in cardiogenic shock preoperatively and were put on intra-aortic balloon pump support. All patients could be weaned successfully from the cardiopulmonary bypass, no patient had any residual defect, and none of the patients required re-exploration for bleeding. Postoperatively, 5 patients died within the first week and 2 more patients subsequently died due to intractable arrhythmias over the next 30 days. Conclusions: In our centre, the mortality following repair of VSR after AMI was 43%. The modified infarct exclusion technique is a good technique with less chances of postoperative re-exploration and residual defect.

Outcome of Scaphoid Nonunion Using Open Reduction and Internal Fixation With Iliac Crest Bone Graft (Fisk-Fernandez Technique).

Introduction The scaphoid is the most common carpal bone to be fractured and has a high propensity for nonunion. Restoration of scaphoid length mitigates the chances of long-term complications. The aim of this study was to assess the functional outcome of the Fisk-Fernandez technique for the treatment of scaphoid nonunion by using open reduction and internal fixation with trapezoidal iliac crest bone graft.  Materials and methods Fisk-Fernandez technique was used to manage scaphoid nonunion in 31 patients at a tertiary care hospital with follow-up at six weeks, 12 weeks, and 24 weeks. An objective assessment of the outcome was done using a comparison of the pre- and postoperative scaphoid score, QuickDASH, and visual analog score. Discussion The scaphoid is one of the most common carpal bones to get fractured. Anatomical factors, late presentation, and delay in diagnosis render it to usually land in nonunion. A comparison of the preoperative scaphoid, QuickDASH, and VAS scores with six-week, 12-week, and 24-week postoperative scores was made and was found to be statistically significant (p<0.001). Ninety-three percent of patients subjectively reported satisfaction after treatment. Though revascularization was not assessed, the bony union was observed in all the patients. Conclusion The operative technique proposed by Fisk-Fernandez is effective in correcting deformity of the scaphoid as well as providing satisfactory functional outcomes in patients with scaphoid nonunion.

Main pulmonary artery continuing as right pulmonary artery with trifurcation at its origin and aberrant origin of left pulmonary artery from ascending aorta in a case of tetralogy of Fallot.

Anomalous origin of the left pulmonary artery from the ascending aorta is a rare cardiac malformation described with tetralogy of Fallot. Trifurcation of right pulmonary artery after origin from the main pulmonary artery has not been reported in literature yet.

Simultaneous Cesarean Section and Maternal Cardiac Surgery: Outcomes and Feasibility from a Tertiary Care Hospital in India

ABSTRACT Introduction: Cardiovascular disease is the leading cause of pregnancy-related mortality, and it has gradually increased over time; this rise has been attributed to numerous reasons including the growing number of women with congenital heart disease who are surviving to childbearing age. Valve surgery during pregnancy is a high risk, with a fetal and maternal mortality rate of 35% and 9%, respectively. Prior knowledge about the cardiovascular disease opens up a host of options for the mother even during pregnancy, but presentation in the 3rd trimester puts both the mother and the baby at risk. Simultaneous caesarean section and maternal cardiac surgery is a suitable option for this subset of patients, and with this study we aim to assess its outcomes and feasibility. Methods: This is a retrospective study of five pregnant patients who presented with predominant symptoms of heart failure in the 3rd trimester between June 2019 and June 2021. Intraoperative and postoperative intensive care unit charts of all the patients were reviewed. Results: All five patients underwent simultaneous cesarean section and maternal cardiac surgery successfully with no fetal or maternal mortality and are doing well in the follow-up period. Conclusion: Cesarean section followed by definitive maternal cardiac surgery in the same sitting is a safe and feasible approach in the management of such patients. A well-prepared team is pivotal for a safe delivery with a cardiopulmonary bypass machine on standby. Specialized multidisciplinary care in the antepartum, peripartum, and postpartum period is essential to improve outcomes.

Simple diagnostic algorithm identifying at-risk nonalcoholic fatty liver disease patients needing specialty referral within the United States.

BACKGROUND: There is an urgent need to risk stratify patients with suspected nonalcoholic fatty liver disease (NAFLD) and identify those with fibrotic nonalcoholic steatohepatitis. This study aims to apply a simple diagnostic algorithm to identify subjects with at-risk NAFLD in the general population. AIM: To apply a simple diagnostic algorithm to identify subjects with at-risk NAFLD in the general population. METHODS: Adult subjects were included from the National Health and Nutrition Examination Survey database (2017-2018) if they had elevated alanine aminotransferase (ALT) and excluded if they had evidence of viral hepatitis or significant alcohol consumption. A fibrosis-4 (FIB4) cutoff of 1.3 differentiated patients with low risk vs high risk disease. If patients had FIB4 > 1.3, a FAST score < 0.35 ruled out advanced fibrosis. Patients with FAST > 0.35 were referred to a specialist. The same algorithm was applied to subjects with type 2 diabetes mellitus (T2DM). RESULTS: Three thousand six hundred and sixty-nine patients were identified who met all inclusion and exclusion criteria. From this cohort, 911 (28.6%) patients had elevated ALT of which 236 (22.9%) patients had elevated FIB4 scores ≥ 1.3. Among patients with elevated FIB4 score, 75 (24.4%) had elevated FAST scores, ruling in advanced fibrosis. This accounts for 2.0% of the overall study population. Applying this algorithm to 737 patients with T2DM, 213 (35.4%) patients had elevated ALT, 85 (37.9%) had elevated FIB4, and 42 (46.1%) had elevated FAST scores. This accounts for 5.7% of the population with T2DM. CONCLUSION: The application of this algorithm to identify at-risk NAFLD patients in need for specialty care is feasible and demonstrates that the vast majority of patients do not need subspecialty referral for NAFLD.

Role of serum and synovial procalcitonin in differentiating septic from non-septic arthritis- a prospective study.

Introduction: Septic arthritis is a serious orthopaedic emergency that must be diagnosed and managed early to prevent devastating complications. The current gold standard for diagnosing septic arthritis is synovial fluid culture, but results are delayed by 48-72 h, and the sensitivity of the test is very low. Differentiating Septic from non-septic arthritis is vital to prevent unnecessary use of antibiotics and prevent complications. Serum Procalcitonin (PCT) is a useful marker in differentiating septic from non-septic arthritis but there are very few studies that have studied the role of synovial PCT for the same. Aim: To determine the role of serum and synovial PCT in differentiating acute Septic from non-septic arthritis. Materials and methods: Prospective clinical study in which 60 patients presenting with acute inflammatory arthritis (<2 weeks duration) were enrolled from May 2018 to May 2020. Serum and synovial fluid samples were drawn at presentation and routine blood investigations, synovial fluid culture sensitivity, and Procalcitonin levels were measured. Patients were divided into 3 groups, with group-1 having confirmed pyogenic, group-2 having presumed pyogenic, and group-3 having non -pyogenic patients, respectively. All data was tabulated and statistically analysed using appropriate tests. Results: Mean serum PCT values in groups 1, 2 and 3 were 1.06 ± 1.11, 0.85 ± 0.74, and 0.11 ± 0.24, respectively. Patients in the Pyogenic group (group1 and group 2) had significantly higher mean serum PCT as compared to group3 (p < 0.0001). Group 1 had higher serum PCT as compared to group 2, but the difference was not significant (p = 0.58). Mean synovial PCT in group 1, 2 and 3 were 2.42 ± 1.98, 1.89 ± 1.18, and 0.22 ± 0.40, respectively. Patients in the Pyogenic group (Group1 and Group2) had significantly higher mean synovial PCT as compared to Group 3 (p < 0.0001). Group 1 had higher mean synovial PCT as compared to group 2, but the difference was not significant (p = 0.54). The area under the ROC curve of the serum levels of PCT was 0.0.895, and the area under the ROC curve of the synovial fluid levels of PCT was 0.914, which was higher than the serum PCT level. Conclusion: Serum and synovial Procalcitonin may be used as a diagnostic marker in differentiating septic from inflammatory arthritis and can help in reducing unnecessary use of antibiotics and early diagnosis and management of septic arthritis, thereby preventing complications.