Cardiogenic Shock - Differences Between Males and Females and Sex Specific Risks.

Cardiogenic Shock (CS) remains a high-mortality condition despite technological and therapeutic advances. One key to potentially improving CS prognosis is understanding patient heterogeneity and which patients may benefit most from different treatment options, a key element of which is sex differences. While cardiovascular diseases have historically been thought of as a male-dominant conditions, the field is increasingly aware that females are also a substantial portion of the patient population. While estrogen has been implicated in protective roles against CVD and tissue hypoxia, it's role in CS remains unclear. Clinically, female CS patients tend to be older and have more severe comorbidities and are more likely to have non-acute myocardial infarction etiologies with preserved ejection fractions. Female CS patients are more likely to receive pharmacotherapy while less likely to receive mechanical circulatory support. There is increased short-term mortality in females, although long-term mortality is similar between the sexes. More sex-specific and age-stratified research needs to be done to fully understand the pathophysiological differences that are relevant in CS, to better recognize and manage CS patients and reduce its mortality.

High output cardiac state: evaluating the incidence, plausible etiologies and outcomes.

INTRODUCTION: The high output cardiac state (HOCS) [cardiac index (CI) >4 L/min/m2 ], primarily driven by abnormally low systemic vascular resistance (SVR), is a relatively under-recognized condition. Although, majority of these patients meet criteria for heart failure (HF), their treatment should be aimed at the primary pathology, as the majority of guideline directed HF therapies can reduce SVR further. OBJECTIVES: To characterize patients with HOCS and provide valuable insight into the condition. METHODS: Patients investigated by right heart catheterization (RHC) at the St. Boniface Hospital, Winnipeg, Canada between January 2009 and November 2021 were reviewed. Two groups of patients were included: 1) HOCS [CI >4 L/min/m2], and 2) pre-HOCS [CI between 3.8-4.0 L/min/m2]. Their medical records were reviewed to identify plausible etiologies, relevant investigations, and outcomes. RESULTS: 177/2950 (6 %) patients met criteria for inclusion: 144/177 (81 %) with HOCS [mean age 51 years (range 19 - 82); 67/144 (47 %) female] and 33/177 (19 %) with pre-HOCS [mean age 55 years (range 30 - 83); 6/33 (18 %) female]. The most common plausible etiologies for the HOCS included anemia (36 %), obesity (34 %), cirrhosis (17 %), and lung disease (32 %). Trans-thoracic echocardiography and magnetic resonance imaging findings were non-specific and predominantly described preserved left ventricular ejection fraction, and pulmonary hypertension. The population experienced high rates of hospitalization, and significantly high mortality [36/144 (25 %) of HOCS at a median follow-up of 31.5 months, and 13/33 (39 %) of pre-HOCS at a median follow-up of 17 months]. CONCLUSIONS: HOCS is not an uncommon condition and is associated with high mortality. Current HF guideline should incorporate such evaluation into the diagnostic criteria.

Permanent Pacemaker-Mediated Exertional Hypoxemia in a Patient With Ebstein Anomaly.

Patients with Ebstein anomaly are known to have a higher incidence of interatrial communications and shunting of blood and its components through, mainly due to either streaming of tricuspid regurgitation or due to elevated right atrial pressure. Here we describe a case where permanent pacemaker lead kept a patent foramen ovale open leading to right-to-left shunting of blood and exertional hypoxemia. This is the first such case report in the published literature.

Long-Term Safety and Efficacy of Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results of the PIONEER-OLE Study.

BACKGROUND: The phase 2 PIONEER-HCM (Phase 2 Open-label Pilot Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction) study showed that mavacamten improved left ventricular outflow tract gradients, exercise capacity, and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), but the results of longer-term treatment are less well described. We report interim results from the PIONEER-OLE (PIONEER Open-Label Extension) study, the longest-term study of mavacamten in patients with symptomatic obstructive HCM. METHODS AND RESULTS: Patients who previously completed PIONEER-HCM (n=20) were eligible to enroll in PIONEER-OLE. Patients received oral mavacamten, 5 mg once daily (starting dose), with individualized dose titration at week 6. Evaluations included serial monitoring of safety, echocardiography, Kansas City Cardiomyopathy Questionnaire-Overall Summary Score, and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Thirteen patients enrolled and received mavacamten (median study duration at data cutoff, 201 weeks). Most patients (92.3%) received ß-blockers concomitantly. Treatment-emergent adverse events were predominantly mild/moderate. One patient had an isolated reduction in left ventricular ejection fraction to 47%, which recovered and remained normal with continued treatment at a reduced dose. At week 180, mavacamten was associated with New York Heart Association class improvements from baseline (class II to I, n=9; class III to II, n=1; and unchanged, n=2), sustained reductions in left ventricular outflow tract gradients (mean [SD] change from baseline: resting, -50 [55] mm Hg; Valsalva, -70 [41] mm Hg), and serum NT-proBNP levels (median [interquartile range] change from baseline: -498 [-2184 to -76] ng/L), and improved Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (mean [SD] change from baseline: +17 [16]). CONCLUSIONS: This long-term analysis supports the continued safety and effectiveness of mavacamten for >3 years in obstructive HCM. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03496168.

Minimally invasive keyhole approach for supramaximal frontal glioma resections: technical note.

OBJECTIVE: The authors aimed to review the frontal lobe's surgical anatomy, describe their keyhole frontal lobectomy technique, and analyze the surgical results. METHODS: Patients with newly diagnosed frontal gliomas treated using a keyhole approach with supramaximal resection (SMR) from 2016 to 2022 were retrospectively reviewed. Surgeries were performed on patients asleep and awake. A human donor head was dissected to demonstrate the surgical anatomy. Kaplan-Meier curves were used for survival analysis. RESULTS: Of the 790 craniotomies performed during the study period, those in 47 patients met our inclusion criteria. The minimally invasive approach involved four steps: 1) debulking the frontal pole; 2) subpial dissection identifying the sphenoid ridge, olfactory nerve, and optic nerve; 3) medial dissection to expose the falx cerebri and interhemispheric structures; and 4) posterior dissection guided by motor mapping, avoiding crossing the inferior plane defined by the corpus callosum. A fifth step could be added for nondominant lesions by resecting the inferior frontal gyrus. Perioperative complications were recorded in 5 cases (10.6%). The average hospital length of stay was 3.3 days. High-grade gliomas had a median progression-free survival of 14.8 months and overall survival of 23.9 months. CONCLUSIONS: Keyhole approaches enabled successful SMR of frontal gliomas without added risks. Robust anatomical knowledge and meticulous surgical technique are paramount for obtaining successful resections.

Acute cardiogenic shock secondary to blunt traumatic aortic valve injury.

Background: Blunt cardiac injuries rarely result in aortic valve cusp rupture, leading to acute aortic insufficiency and cardiogenic shock. This rare clinical entity carries a high mortality rate if left undiagnosed and not managed surgically, with few patients surviving beyond 24 h. It presents a diagnostic challenge in the polytrauma patient in shock, with multiple possible and complementary etiologies. Case presentation: We present a 56-year-old male with persistent hypotension, a wide pulse pressure, and elevated serum troponin levels suggesting blunt cardiac injury after a motor vehicle accident. Transthoracic and transesophageal echocardiography revealed normal biventricular function but severe aortic insufficiency due to prolapse of the left coronary cusp.He was taken emergently to surgery, where aortic valve exploration revealed complete left coronary cusp avulsion from the aortic annulus with a mid-cusp tear, requiring aortic valve replacement with a bioprosthetic valve. Postoperative echocardiography showed normal biventricular function with a well-seated bioprosthetic aortic valve with no insufficiency. Conclusions: Traumatic aortic valve injury can lead to torn or prolapsed cusps causing acute aortic insufficiency leading to cardiogenic shock, but early recognition with appropriate and targeted diagnostic imaging is vital to prevent rapid patient deterioration and demise.

Development of a Risk Score for Long-term Survival and MACCE After Coronary Artery Bypass Grafting Surgery.

OBJECTIVE: To develop risk scoring models predicting long-term survival and major adverse cardiovascular and cerebrovascular events (MACCE) including myocardial infarction and stroke after coronary artery bypass grafting (CABG). METHODS: All-consecutive 4,821 patients undergoing isolated CABG at Lankenau between 01/2005-07/2021 were included. MACCE was defined as all-cause mortality+myocardial infarction (MI)+stroke. Variable selection for both outcomes was obtained using a double selection logit Lasso with adaptive selection. Models performance was internally evaluated by calibration and accuracy using bootstrap cross-validation. Mortality and MACCE were compared among patients split into three groups based on the predicted risk scores for all-cause mortality and MACCE. An external validation of our database was performed with 665 patients from the University of Brescia, Italy. RESULTS: Pre-operative risk predictors were found to be predictors for all-cause mortality and MACCE. In addition, being of African American ethnicity is a significant predictor for MACCE after isolated CABG. The AUC which measures the discrimination of the models were 80.4%, 79.1%, 81.3%, and 79.2% for mortality at 1,2,3, and 5 years follow-up. The AUC for MACCE were 75%, 72.5%, 73,8%, and 72.7% at 1, 2, 3, and 5-years follow-up. For external validation, AUC for all-cause mortality and MACCE at 1, 2, 3, and 5 years was 73.7%, 70.8%, 68.7%, and 72.2% and 72.3%, 68.2%, 65.6%, 69.6%, respectively. CONCLUSIONS: The Advanced (AD) Coronary Risk Score for All-Cause Mortality and MACCE provide good discrimination of long-term mortality and MACCE after isolated CABG. External validation observed a more AUC's above 70%.

The Effect of the COVID-19 Pandemic on Pituitary Surgeries.

PURPOSE: As the COVID-19 pandemic spread to the United States in 2020, there was an impetus towards postponing or ceasing non-urgent transsphenoidal pituitary surgeries to prevent spread of the virus. Some centers encouraged transcranial approaches for patients with declining neurologic function. However, no large-scale data exists evaluating the effects this had on national pituitary practice patterns. METHODS: Pituitary surgeries in the National Inpatient Sample were identified from 2017-2020. Surgeries in 2020 were compared to the three years prior to determine any differences in demographics, surgical trends/approaches and perioperative outcomes. In 2020, there was a decline in overall pituitary surgeries (34.2 vs. 36.3%, odds ratio (OR) 0.88, p<0.001) yet transsphenoidal approaches represented a higher proportion of interventions (69.0 vs. 64.9%, p<0.001). Neurosurgical complications were higher (51.9 vs. 47.4%, OR 1.13, p<0.001) and patients were less likely to be discharged home (86.4 vs. 88.5%, OR 0.84, p<0.001). This was especially true in April 2020 during the first peak in COVID-19 cases when transcranial approaches and odds of mortality/complications were highest. CONCLUSIONS: In 2020, transsphenoidal surgery remained the preferred approach for pituitary tumor resection despite initial recommendations against the approach to prevent COVID-19 spread. Pituitary surgeries had a higher risk of periprocedural complications despite accounting for preoperative comorbidities, COVID-19 infection status, and surgical approach, suggesting that an overwhelmed hospital system can negatively influence surgical outcomes in non-infected patients.

Comparative analysis of bevacizumab and LITT for treating radiation necrosis in previously radiated CNS neoplasms: a systematic review and meta-analysis.

PURPOSE: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. METHODS: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. RESULTS: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). CONCLUSION: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.

The potential of liquorpheresis to treat leptomeningeal disease.

Leptomeningeal disease (LMD) is a devastating sequela of many cancers with an extremely poor prognosis. Barriers to improving outcomes are related to the inability for many traditional therapies to effectively reach the cerebrospinal fluid (CSF) space within the central nervous system (CNS). Liquorpheresis is an emerging treatment modality specific to CSF pathologies, whose primary mechanism of action is direct targeted filtration of CSF content by neurosurgical access. In this review, we highlight the principles of liquorpheresis, and detail how LMD can be amenable to this for treatment. Further, we summarize the current in vitro and in vivo evidence supporting liquorpheresis as a feasible method to treat LMD and other CNS diseases, as well as describe its conceivable limitations.

Thoraco-abdominal normothermic regional perfusion for thoracic transplantation in the United States: current state and future directions.

PURPOSE OF REVIEW: To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery. RECENT FINDINGS: taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels. SUMMARY: taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.

Infrasellar Nasopharyngeal Craniopharyngiomas: An Individual Participant Data Meta-Analysis and Review of the Literature.

BACKGROUND: Craniopharyngiomas are benign tumors of the anterior skull base arising from epithelial remnants of Rathke pouch. They mainly occur in the suprasellar space, can be incredibly debilitating, and remain difficult to resect as they frequently involve critical neurovascular structures. Although it is embryologically possible for craniopharyngiomas to arise extracranially along the entire migrational path of Rathke pouch, these remain exceedingly rare, especially among adults, and can be mistaken for nasopharyngeal cancer. As such, minimal data exist evaluating the management and outcomes of such lesions. We evaluated our institutional experience with purely infrasellar nasopharyngeal craniopharyngiomas and obtained individual patient data reported in the contemporary literature to better characterize the demographics, presentation, surgical management, and long-term outcomes of these lesions. METHODS: A systematic review of the literature was performed to identify previously published cases of purely infrasellar nasopharyngeal craniopharyngioma in 3 electronic databases: MEDLINE (PubMed), Embase, and Scopus. Search terms were "infrasellar craniopharyngioma" and "nasopharyngeal craniopharyngioma." RESULTS: We identified 25 cases, in which 72% of patients presented with symptoms of nasal obstruction, epistaxis, or headache. An endoscopic approach was performed in 40% of cases; 83.3% of all patients had gross total resection, with 60% having no recurrence at a median follow-up of 13 months. No postoperative complications were reported. Tumor location involving the cavernous sinus was associated with incomplete resection (100%) compared with tumors not involving the cavernous sinus (87%) (P = 0.033). CONCLUSIONS: While uncommon, infrasellar nasopharyngeal craniopharyngiomas appear to have better perioperative and long-term surgical outcomes than their suprasellar counterparts.

Impact of biological sex on valvular heart disease, interventions, and outcomes.

Valvular heart disease (VHD) is common, affecting >14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differences are being found between males and females with VHD. These sex differences can involve the epidemiology, pathophysiology, presentation, diagnosis, and outcomes of the disease. Females are often disadvantaged, and female sex has been shown to be associated with delayed diagnosis and inferior outcomes in various forms of VHD. In addition, the unique pathophysiologic state of pregnancy is associated with increased risk for maternal and fetal morbidity and mortality in many forms of VHD. Therefore, understanding and recognizing these sex differences, and familiarity with the attendant risks of pregnancy and management of pregnant females with VHD, is of great importance for any primary care or cardiovascular medicine practitioner caring for the female patient. This review will outline sex differences in aortic, mitral, pulmonic, and tricuspid VHD, with particular focus on differences in pathophysiology, clinical presentation, and outcomes. In addition, the pathophysiology and management implications of pregnancy will be discussed.

Evolution in Casting Techniques: A Narrative Review of Casting Methods, Techniques, and Innovation.

Orthopedic casting has seen a remarkable evolution from ancient practices to cutting-edge innovations. Beginning with ancient Egyptian methods employing bark, linen, and bandages, casting techniques have progressed through historical milestones, including the adoption of plaster of Paris in the 19th century and the introduction of synthetic materials like fiberglass and thermoplastics in the 20th century. Historical progressions transitioned from primitive materials to more sophisticated techniques, such as resin-soaked bandages and starch-based casts. While thermoplastics showcased benefits like adjustability and comfort, widespread adoption faced hurdles due to cost and water resistance limitations. The emergence of 3D printing introduced patient-specific casts with improved ventilation but faced challenges in accessibility, cost, and immediate immobilization. FlexiOH presents as a groundbreaking foam cast by Orthoheal, offering customizable fit, lightweight design, improved ventilation, and moisture resistance. Its potential to reduce ER visits, enhance patient comfort, and streamline application procedures positions it as a promising technology for the future. This paper discusses each casting generation's advantages and drawbacks, highlighting the potential of innovative technologies like FlexiOH to revolutionize orthopedic casting practices, promising improved outcomes, reduced costs, and enhanced efficiency.

An Escape Room to Teach First- and Second-Year Medical Students Nephrology.

An escape room is a team-based activity that requires players to solve a series of puzzles to complete a story and "break out" of a room. It has recently gained traction in medical education for its ability to interactively and effectively present learning objectives. This was a prospective educational study that describes the successful application of a nephrology themed escape room for first- and second-year medical students. Compared to pre-escape room participation, the 52 students demonstrated a statistically significant improvement in self-reported knowledge for renal physiology (p < 0.01), pharmacology (p < 0.01), pathology (p < 0.01), and relevant clinical practice guidelines (p < 0.01). A majority of the students also claimed that the escape room was "more effective" than traditional lectures (80.8%) and textbooks (73.1%) and "equally effective" as third-party board preparation resources (69.2%) and their institution's problem-based learning curriculum (51.9%). The escape room also facilitated a high-level peer-to-peer collaboration with 82.7% and 76.9% of students reporting that they worked with someone in their year and outside of their year for at least half of the game, respectively. Ninety-five percent of the first-years and 84.6% of the second-years believed that the escape room was effective at preparing them for their respective exams, and an overwhelming majority (90.4%) described the escape room as "very enjoyable." Overall, this nephrology themed escape room was an engaging and well received educational modality and may be an effective supplemental study resource for medical students. Further studies are needed to assess knowledge acquisition. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01917-6.

Chat-GPT on brain tumors: An examination of Artificial Intelligence/Machine Learning's ability to provide diagnoses and treatment plans for example neuro-oncology cases.

OBJECTIVE: Assess the capabilities of ChatGPT-3.5 and 4 to provide accurate diagnoses, treatment options, and treatment plans for brain tumors in example neuro-oncology cases. METHODS: ChatGPT-3.5 and 4 were provided with twenty example neuro-oncology cases of brain tumors, all selected from medical textbooks. The artificial intelligence programs were asked to give a diagnosis, treatment option, and treatment plan for each of these twenty example cases. Team members first determined in which cases ChatGPT-3.5 and 4 provided the correct diagnosis or treatment plan. Twenty neurosurgeons from the researchers' institution then independently rated the diagnoses, treatment options, and treatment plans provided by both artificial intelligence programs for each of the twenty example cases, on a scale of one to ten, with ten being the highest score. To determine whether the difference between the scores of ChatGPT-3.5 and 4 was statistically significant, a paired t-test was conducted for the average scores given to the programs for each example case. RESULTS: In the initial analysis of correct responses, ChatGPT-4 had an accuracy of 85% for its diagnoses of example brain tumors and an accuracy of 75% for its provided treatment plans, while ChatGPT-3.5 only had an accuracy of 65% and 10%, respectively. The average scores given by the twenty independent neurosurgeons to ChatGPT-4 for its accuracy of diagnosis, provided treatment options, and provided treatment plan were 8.3, 8.4, and 8.5 out of 10, respectively, while ChatGPT-3.5's average scores for these categories of assessment were 5.9, 5.7, and 5.7. These differences in average score are statistically significant on a paired t-test, with a p-value of less than 0.001 for each difference. CONCLUSIONS: ChatGPT-4 demonstrates great promise as a diagnostic tool for brain tumors in neuro-oncology, as attested to by the program's performance in this study and its assessment by surveyed neurosurgeon reviewers.

The use of advanced neuroimaging modalities in the evaluation of low-grade glioma in adults: a literature review.

Low-grade gliomas encompass a subgroup of cancerous glial cell growths within the central nervous system and are distinguished by their slow growth and relatively low malignant potential. Despite their less aggressive nature, these tumors can still cause significant neurological symptoms through the compression of surrounding neural and vascular structures and, in some instances, undergo malignant transformation. For these reasons, timely and appropriate evaluation and management of low-grade gliomas is critical. Medical imaging stands as a cornerstone for evaluating patients with low-grade gliomas because of its noninvasive nature and ability to provide a vast amount of information about the underlying lesion. With the growing number of neuroimaging techniques and their capabilities, there is a lack of clear guidance on which techniques to utilize for the assessment of low-grade gliomas and what their respective core use cases should be. In this literature review, the authors discuss in significant depth the available evidence pertaining to the use of advanced neuroimaging techniques in the evaluation and management of low-grade gliomas. Specifically, they review the specificity, sensitivity, accuracy, and use cases of magnetic resonance spectroscopy (MRS), perfusion MR imaging (perfusion MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), as well as other emerging imaging techniques. They conclude that most of the advanced neuroimaging techniques are reliable in differentiating low- from high-grade gliomas, whereas MRS and DTI may further support molecular subclassification of the tumor. PET has been best employed for the purpose of tumor biopsy, whereas fMRI and DTI can be particularly valuable in preoperative surgical planning, as they delineate the functionally eloquent brain regions that need to be preserved during tumor resection. MRS, PET, SPECT, and perfusion MRI are best suited to monitor tumor progression, as their respective metrics closely correlate with the underlying metabolic activity of the tumor. Together, these techniques offer a vast amount of information and serve as tools for neurologists and neurosurgeons managing patients with low-grade gliomas.

Discovery of novel anticancer flavonoids as potential HDAC2 inhibitors: virtual screening approach based on molecular docking, DFT and molecular dynamics simulations studies.

Virtual screening of a library of 329 flavonoids obtained from the NPACT database was performed to find out potential novel HDAC2 inhibitors. Eleven out of 329 selected flavonoids were screened based on molecular docking studies, as they have higher binding affinities than the standard drugs vorinostat and panobinostat. All screened compounds occupying the catalytic site of HDAC2 showed important molecular interaction with Zn2+ and other important amino acids in the binding pocket. The screened compounds were validated using ADMET filtration and bioactivity prediction from which we obtained six compounds, NPACT00270, NPACT00676, NPACT00700, NPACT001008, NPACT001054, and NPACT001407, which were analyzed using DFT studies. DFT studies were performed for all six screened flavonoids. In DFT studies, three flavonoids, NPACT00700, NPACT001008, and NPACT001407, were found to be better based on HOMO-LUMO and molecular electrostatic potential (MEP) analyses. Furthermore, MD simulations were performed for 100 ns for the three compounds. In the MD analysis, NPACT001407 was found to be more stable in the active site of HDAC2 as zinc formed a coordination bond with ASP181, HIS183, ASP269, and GLY305, along with two hydroxyl groups of the ligand. Our findings reveal that these flavonoids can interact as ligands with the active site of HDAC2. Because of the absence of a hydroxamate group in flavonoids, there are no possibilities for the formation of isocyanate. This suggests that the major drawback of current HDACs inhibitors may be solved. Further experimental validation is needed to understand the selectivity of flavonoids as HDAC2 inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03912-5.

Patient-Reported Outcomes Following Open Broström-Gould Procedure: Minimum 5-Year Follow-Up.

Background: Ankle sprains are a common musculoskeletal injury among the general population and often involve the lateral ligament complex. Although the majority of ankle sprains are treated successfully with nonsurgical conservative measures, an estimated 5% to 20% of ankle injuries ultimately develop chronic lateral ankle instability (CAI). Multiple surgical treatment modalities for the lateral ankle complex exist, such as anatomical and nonanatomical reconstruction. The current gold standard for primary surgical repair is the Broström-Gould procedure. This is the first article to provide PROMIS scores following BG and the largest study with 5-year outcomes for an open BG. Methods: This was a descriptive study of a retrospective cohort of patients undergoing a BG with a minimum follow-up of 5 years. Patient-reported outcome instruments collected postoperatively were PROMIS Pain, Physical Function, Depression, and FAAM. Further preoperative clinic characteristics were analyzed to correlate with the final outcome. The electronic medical record was queried for Current Procedural Terminology (CPT) code 27698 (Broström-Gould) from January 2010 to June 2017. Surveys were conducted in the clinic and through phone interviews. Patient charts were reviewed to obtain basic patient demographic information including sex, age, race, and body mass index (BMI). The following preoperative variables were recorded: history of prior CAI procedures, history of major trauma, duration of symptoms, number of diagnosed ankle sprains, other collagen pathologies, generalized ligament laxity, participation in sports/activity level, peroneal subluxation, clinically diagnosed peroneus longus or brevis tendinopathy, deltoid ligament injury, anterior ankle impingement, and posterior ankle impingement. The PROMIS and Foot and Ankle Ability Measure (FAAM) scores were obtained with a combination of clinic and phone interviews. Data were aggregated in Microsoft Excel and entered in R (version 4.2.0) for statistical analysis. Results: Our results show that the minimum 5-year patient-reported PROMIS scores for patients following a Broström-Gould procedure are as follows: PROMIS physical function, 50.5; PROMIS pain interference, 48.2; and PROMIS depression, 38.2. This indicates, at a minimum, that patients 5 years removed from the procedure are within 1 SD of the general population in regard to PROMIS physical function and pain. Our patient-reported FAAM, activities of daily living, and FAAM sports scores were 59.6 and 13.0 respectively. Preoperative magnetic resonance imaging (MRI) findings were recorded. Arthroscopic examination was performed before lateral ligaments reconstruction for patients with intra-articular pathologies confirmed on MRI. Conclusion: The findings from our study offer evidence supporting the effectiveness of the Broström-Gould procedure to be associated with normal physical function, even 5 years after surgery. Furthermore, our research identified specific factors such as tobacco use, diabetes, and sports participation that independently correlated with reported outcome measures. These insights enable physicians to better manage patient expectations and tailor treatment strategies accordingly. Our study establishes a foundation for future prospective research endeavors that aim to leverage the PROMIS system for comprehensive outcome assessments. Level of Evidence: Level III, retrospective cohort study.