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Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant, adult-onset disease that stems from point mutations in the TTR gene encoding the protein transthyretin. The disease is progressive and life-threatening and is associated with amyloid deposits in multiple organs including the heart, kidney, skin, eyes, nervous system, and gastrointestinal tract. Genotypic and phenotypic heterogeneity is a characteristic hallmark of hereditary transthyretin amyloidosis. Herein, we present a rare variant of hATTR cardiomyopathy secondary to Ser97Tyr mutation, having been documented only in a handful of families previously. This case serves as a valuable opportunity to elucidate the clinico-pathogenesis of this disease, highlight the aggressive nature of this genetic mutation (c.290C>A; p.Ser97Tyr), and document the response to the latest advances in treatment currently available.

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Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract. Recent research indicates a significant link between IBD and cardiovascular disease (CVD), the leading cause of global morbidity and mortality. This review examines the association between IBD and CVD, emphasizing the role of the gut microbiome in this relationship. IBD patients have a higher risk of cardiovascular events, such as coronary artery disease, heart failure, and cerebrovascular incidents, primarily due to chronic systemic inflammation, genetic factors, and gut microbiota imbalance (dysbiosis). Dysbiosis in IBD increases intestinal permeability, allowing bacterial products to enter the bloodstream, which promotes inflammation and endothelial dysfunction, contributing to CVD. Understanding the gut microbiome's role in IBD and CVD suggests new therapeutic interventions. Modulating the microbiome through diet, probiotics, and fecal microbiota transplantation (FMT) are promising research avenues. These interventions aim to restore a healthy gut microbiota balance, potentially reducing inflammation and improving cardiovascular outcomes. Additionally, the review emphasizes the importance of regular cardiovascular risk assessments and personalized preventive measures in managing IBD patients. Such measures include routine monitoring of cardiovascular health, tailored lifestyle modifications, and early intervention strategies to mitigate cardiovascular risk. By integrating current knowledge, this review aims to improve understanding and management of the interconnected pathophysiology of IBD and CVD. This approach will ultimately enhance patient outcomes and provide a foundation for future research and clinical practice guidelines in this area.

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Statin-intolerance (SI) has prevalence between 8.0 % and 10 %, and muscular complaints are the most common reason for discontinuation. Bempedoic acid (BA), an ATP citrate lyase inhibitor, decreases hepatic generation of cholesterol, upregulates low-density lipoprotein (LDL) receptor expression in the liver, and eventually clears circulating LDL-cholesterol from the blood. Multiple randomized clinical trials studying BA demonstrate a reduction in LDL levels by 17-28 % in SI. The CLEAR OUTCOME trial established significant cardiovascular benefits with BA. A dose of 180 mg/day of BA showed promising results. BA alone or in combination with ezetimibe is US Food and Drug Administration-approved for use in adults with heterozygous familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. BA reduced HbA1c by 0.12 % (p < 0.0001) in patients with diabetes. Adverse events of BA include myalgia (4.7 %), anemia (3.4 %), and increased aminotransferases (0.3 %). BA can cause up to four times higher risk of gout in those with a previous gout diagnosis or high serum uric acid levels. Reports of increased blood urea nitrogen and serum creatinine were noted. Current evidence does not demonstrate a reduction in deaths from cardiovascular causes. More studies that include a diverse population and patients with both high and low LDL levels should be conducted. We recommend that providers consider BA as an adjunct to statin therapy in patients with a maximally tolerated dosage to specifically target LDL levels.

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Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger known to orchestrate a myriad of cellular functions over a wide range of timescales. In the last 20 years, a variety of single-cell sensors have been developed to measure second messenger signals including cAMP, Ca2+, and the balance of kinase and phosphatase activities. These sensors utilize changes in fluorescence emission of an individual fluorophore or Förster resonance energy transfer (FRET) to detect changes in second messenger concentration. cAMP and kinase activity reporter probes have provided powerful tools for the study of localized signals. Studies relying on these and related probes have the potential to further revolutionize our understanding of G protein-coupled receptor signaling systems. Unfortunately, investigators have not been able to take full advantage of the potential of these probes due to the limited signal-to-noise ratio of the probes and the limited ability of standard epifluorescence and confocal microscope systems to simultaneously measure the distributions of multiple signals (e.g. cAMP, Ca2+, and changes in kinase activities) in real time. In this review, we focus on recently implemented strategies to overcome these limitations: hyperspectral imaging and adaptive thresholding approaches to track dynamic regions of interest (ROI). This combination of approaches increases signal-to-noise ratio and contrast, and allows identification of localized signals throughout cells. These in turn lead to the identification and quantification of intracellular signals with higher effective resolution. Hyperspectral imaging and dynamic ROI tracking approaches offer investigators additional tools with which to visualize and quantify multiplexed intracellular signaling systems.

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CASE: A 50-year-old man presented with chronic refractory symptoms of radiating leg pain with muscle cramps because of a retained bullet in the calf after being shot in 1990. Radiographs confirmed the bullet lodged in posterolateral aspect of calf abutting proximal fibula. An intraoperative point-of-care ultrasound aided in accurate localization of bullet, thereby facilitating precise planning of surgical incision and subsequent removal. CONCLUSIONS: Ultrasound can be used as an alternative tool for safe surgical extraction of deep-seated metallic object with minimal tissue dissection, obviating the need for C-arm.

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Infective endocarditis can be acute or subacute. It can be caused by viral, bacterial, fungal, and sometimes nonbacterial etiologies. It is an important cause of mortality and morbidity in children as well as adolescents, despite advances in management. A 59-year-old male with a past medical history of aortic valve (AV) replacement on warfarin presented to the Emergency Department with dull right flank pain and poor dentition on examination. Computerized tomography (CT) scans of the abdomen revealed the presence of splenic and renal infarcts. Warfarin was held after the international normalized ratio (INR) was noted to be elevated at 11. Following the activation of the sepsis bundle in the ER, he received intravenous fluids (30 cc/kg) and was started on vancomycin and ceftriaxone. On further evaluation, the transesophageal echocardiogram revealed mobile densities on the aortic surface concerning vegetation. Antibiotics were transitioned to cefazolin, gentamycin, and rifampin for the management of prosthetic valve endocarditis. The patient's INR improved to 3.5 on the third day of hospitalization, and heparin was initiated to maintain anticoagulation for the prosthetic valve. However, on the eighth day of hospitalization, the patient developed left-sided weakness and slurred speech. The CT head showed acute frontoparietal intracranial hemorrhage (ICH), with an INR noted to be 5. Heparin was reversed with protamine sulfate, and vitamin K was administered, following which the INR improved to 2.3. The patient was transferred to intensive care, but on the second day of the ICU stay, the INR again shot up to 6 with normal LFTS. The patient received vitamin K, but the INR only improved to 5. Subsequently, antibiotics were changed from cefazolin to nafcillin. INR thus fell to 1.6 in two days after changing the antibiotics. The patient was soon transferred to a higher center for aortic valve replacement. While few case reports have described severe coagulopathy induced by cefazolin, it is particularly seen with impaired renal function; however, our patient's renal function was completely normal. Coagulopathy is due to the drug's effect on intestinal flora and its structural methyl-thiadiazole side chain, which has similar effects as epoxide reductase inhibitors and results in INR elevation. Patients on cefazolin need to be closely monitored for INR levels every day, as there is a high likelihood of developing complications like ICH, as noted in this patient. While the monitoring of cefazolin levels is not necessarily indicated, it is necessary to place patients on fall precautions and monitor INR levels every day, as mentioned above.

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Currently, bio-natural injectable hydrogels are receiving a lot of attention due to their ability to control, adjust, and adapt to random bone defects, in addition, to their ability to mimic the composition of natural bones. From such a viewpoint, this study goal is to prepare and characterize the injectable hydrogels paste based on the natural alginate (Alg) derived from brown sea algae as a polysaccharide polymer, which coupled with nano biogenic-hydroxyapatite (n-HA) prepared from eggshells and enriched with valuable trace elements. The viscosity and mechanical properties of the paste were investigated. As well as the in-vitro study in terms of water absorption and biodegradability in the PBS, biocompatibility and the capability of the injectable Alginate/n-Hydroxyapatite (Alg/n-HA) to regenerate bone for the most suitable injectable form. The injectable hydrogel (BP -B sample) was chosen for the study as it had an appropriate setting time for injecting (13 mins), and suitable compressive strength reached 6.3 MPa. The in vivo study was also carried out including a post-surgery follow-up test of the newly formed bone (NB) in the defect area after 10 and 20 weeks using different techniques such as (SEM/EDX) and histological analysis, the density of the newly formed bone by Dual x-ray absorptiometry (DEXA), blood biochemistry and the radiology test. The results proved that the injectable hydrogels Alginate/n-Hydroxyapatite (Alg/n-HA) had an appreciated biodegradability and bioactivity, which allow the progress of angiogenesis, endochondral ossification, and osteogenesis throughout the defect area, which positively impacts the healing time and ensures the full restoration for the well-mature bone tissue that similar to the natural bone.

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Cardiac tamponade is considered a medical emergency because a patient can deteriorate easily and die of cardiac arrest if the fluid is not drained immediately. The most common etiologies are the same as pericarditis as fluid accumulates due to pericardial inflammation, including infection, malignancy, trauma, iatrogenic, autoimmune, post-myocardial infarction, radiation, and renal failure. Although the treatment is pericardiocentesis or pericardial window, finding the etiology responsible for the development of pericardial effusion is important. Here, we describe the case of a 40-year-old female who presented to the emergency department with a chief complaint of severe epigastric pain of a two-day duration that was associated with multiple episodes of nausea, vomiting, dysphagia, and severe shortness of breath (New York Heart Association III). The patient was eventually diagnosed with cardiac tamponade as a cause of her dyspnea, as a two-dimensional cardiac echocardiogram detected a large pericardial effusion (>2 cm) with echocardiographic indications for cardiac tamponade with severe pulmonary hypertension. The patient underwent a therapeutic pericardial window with drainage of 250 mL of pericardial fluid. Ultrasound of the abdomen focusing on the kidneys showed an atrophic and echogenic right kidney with a bidirectional flow in the hepatic veins, suggestive of right heart failure. Subsequently, she underwent a kidney biopsy that showed diffuse mesangial proliferative glomerulonephritis with segmental sclerosing features consistent with IgA nephropathy, associated with tubular atrophy, interstitial fibrosis, interstitial inflammation, and moderate arteriosclerosis. The patient was diagnosed with stage V chronic kidney disease secondary to IgA nephropathy. IgA nephropathy is usually common in Caucasian or Asian males in their teens and late 30s, with hematuria as a usual presentation. This case is unique as cardiac tamponade with renal failure is rarely the presenting symptom of IgA nephropathy.

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Hyperspectral imaging (HSI) technology has been applied in a range of fields for target detection and mixture analysis. While HSI was originally developed for remote sensing applications, modern uses include agriculture, historical document authentication, and medicine. HSI has also shown great utility in fluorescence microscopy. However, traditional fluorescence microscopy HSI systems have suffered from limited signal strength due to the need to filter or disperse the emitted light across many spectral bands. We have previously demonstrated that sampling the fluorescence excitation spectrum may provide an alternative approach with improved signal strength. Here, we report on the use of excitation-scanning HSI for dynamic cell signaling studies-in this case, the study of the second messenger Ca2+. Time-lapse excitation-scanning HSI data of Ca2+ signals in human airway smooth muscle cells (HASMCs) were acquired and analyzed using four spectral analysis algorithms: linear unmixing (LU), spectral angle mapper (SAM), constrained energy minimization (CEM), and matched filter (MF), and the performances were compared. Results indicate that LU and MF provided similar linear responses to increasing Ca2+ and could both be effectively used for excitation-scanning HSI. A theoretical sensitivity framework was used to enable the filtering of analyzed images to reject pixels with signals below a minimum detectable limit. The results indicated that subtle kinetic features might be revealed through pixel filtering. Overall, the results suggest that excitation-scanning HSI can be employed for kinetic measurements of cell signals or other dynamic cellular events and that the selection of an appropriate analysis algorithm and pixel filtering may aid in the extraction of quantitative signal traces. These approaches may be especially helpful for cases where the signal of interest is masked by strong cellular autofluorescence or other competing signals.

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BACKGROUND: Catheter ablation (CA) is an important curative treatment for non-valvular atrial fibrillation (NVAF), however, nationwide data on its utilization and disparities is limited. Coronary vasospasm is a rare, life-threatening, peri-operative complication of CA with limited literature in Caucasians. METHODS: We performed a retrospective study on adult hospitalizations in the USA from 2007 to 2017 by obtaining the data from National Inpatient Sample. The primary endpoints of our study were to identify the utilization rate of CA, disparities in utilization, and study the outcomes associated with CA. The secondary endpoints of the study were to identify the incidence of coronary vasospasm amongst patients who underwent CA, evaluate their association, and identify the predictors of coronary vasospasm. RESULTS: From 35,906,946 patients with NVAF, 343641 (0.96%) underwent CA. Its utilization decreased from 1% in 2007 to 0.71% in 2017. Patients who underwent CA, compared to those without CA, fared better in terms of hospital length of stay, mortality rate, disability rate, and discharge to the non-home facility. Patients in the 50-75 years age group, Native Americans, those with private insurance, and median household income of 76-100th percentile were associated with higher odds of CA utilization. Urban teaching hospitals and large-bedded hospitals performed more ablations, while the Mid-West region fared lower than the South, the West, and the Northeast. The prevalence of coronary vasospasm was higher amongst CA in comparison without CA, however, in regression analysis, no significant association was demonstrated between CA and coronary vasospasm. CONCLUSION: CA is an important treatment modality that is associated with improved clinical outcomes. Identification of factors associated with lower utilization of CA and its disparities will help to mitigate the burden associated with NVAF.

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Background: Cardiovascular diseases contribute to considerable morbidity and mortality in the USA. We sought to establish regional disparities across the nation contributing to cardiovascular disease (CVD) among non-elective young adult hospitalizations. Methods: The National Inpatient Sample (2019) was utilized to identify the incidence of non-elective hospitalizations among young adults (18-44 yrs) and analyze the burden of CVD risk factors and outcomes (MACCE; all-cause mortality, AMI, cardiac arrest and stroke) in different US regions. Results: A total of 5,833,930 (median age 32 [26-37] years) non-elective admissions were recorded; plurality from the south (39.6%). Most admissions were white (51.4%) and female (65.5%) amid all regions. The burden of CVD risk factors was significantly higher in the South followed by the Mid-west regions. The South had the highest and the Northeast had the lowest rates of MACE (2.9% vs 2.3%) and stroke (1.0% vs 0.8%). The risk of AMI was high for the south and Midwest regions (1.1%). All-cause mortality was highest in South and West regions (0.7%). Multivariate adjusted odds for these cardiovascular events were higher in the West (aOR 1.22; 95%CI 1.12-1.33) followed by South (aOR 1.16; 95%CI 1.07-1.26) regions. Conclusions: This population-based study assessing non-elective admissions in the young revealed a higher burden of CVD risk factors and rate of MACCE in the South compared to other areas of the USA. Regional policies should be tailored to the local CVD risk burden.

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Background: The Surviving Sepsis Campaign suggested preferential resuscitation with balanced crystalloids, such as Lactated Ringer's (LR), although the level of recommendation was weak, and the quality of evidence was low. Past studies reported an association of unbalanced solutions, such as normal saline (NS), with increased AKI risks, metabolic acidosis, and prolonged ICU stay, although some of the findings are conflicting. We have compared the outcomes with the preferential use of normal saline vs. ringer's lactate in a cohort of sepsis patients. Method: We performed a retrospective cohort analysis of patients visiting the ED of 19 different Mayo Clinic sites between August 2018 to November 2020 with sepsis and receiving at least 30 mL/kg fluid in the first 6 h. Patients were divided into two cohorts based on the type of resuscitation fluid (LR vs. NS) and propensity-matching was done based on clinical characteristics as well as fluid amount (with 5 ml/kg). Single variable logistic regression (categorical outcomes) and Cox proportional hazards regression models were used to compare the primary and secondary outcomes between the 2 groups. Results: Out of 2022 patients meeting our inclusion criteria; 1,428 (70.6%) received NS, and 594 (29.4%) received LR as the predominant fluid (>30 mL/kg). Patients receiving predominantly NS were more likely to be male and older in age. The LR cohort had a higher BMI, lactate level and incidence of septic shock. Propensity-matched analysis did not show a difference in 30-day and in-hospital mortality rate, mechanical ventilation, oxygen therapy, or CRRT requirement. We did observe longer hospital LOS in the LR group (median 5 vs. 4 days, p = 0.047 and higher requirement for ICU post-admission (OR: 0.70; 95% CI: 0.51-0.96; p = 0.026) in the NS group. However, these did not remain statistically significant after adjustment for multiple testing. Conclusion: In our matched cohort, we did not show any statistically significant difference in mortality rates, hospital LOS, ICU admission after diagnosis, mechanical ventilation, oxygen therapy and RRT between sepsis patients receiving lactated ringers and normal saline as predominant resuscitation fluid. Further large-scale prospective studies are needed to solidify the current guidelines on the use of balanced crystalloids.

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The incidence of cardiomyopathy in athletes contributes significantly to the public health burden in developing countries. Most effective management strategies primarily rely on the modification of risk factors, and it is less expensive compared to other advanced investigations. Moreover, limited data is available concerning the incidence of adverse events including cardiac arrest and the strategies to prevent them, especially in this population subset. Therefore, devising preventative strategies that can easily be implemented in athletes and provide a cost-effective approach is warranted. We aim to discuss the incidence of major adverse cardiac events in athletes with cardiomyopathies and their associated risk factors and to evaluate the various strategies proposed to prevent the progression of cardiomyopathy in this population, with the initial hypothesis that the treatment of these pathologies poses a substantial challenge in this population. With regard to methodology, this is a narrative review. Search terms were described using the Population, Exposure, and Outcome (PEO) framework. A comprehensive search strategy was used to screen and identify any relevant literature in the PubMed and Google Scholar databases. This was done in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. Four studies were identified in the final analysis. The incidence of sudden cardiac arrest varied between 0.3% and 0.33% among the athletes affected with cardiomyopathies. Routine and pre-participation screening has shown success in reducing the incidence of sudden cardiac death in athletes as a result of undiagnosed cardiomyopathies. Supervised exercise regimes have been proposed to reduce the incidence of cardiomyopathy in athletes. Beyond identification strategies, the prevention of cardiomyopathies revolves around the modification of risk factors. To conclude, the challenges athletes face, suffering from cardiomyopathy, have been an ongoing issue with unexpected cardiac arrest as the end result. Despite the decreased incidence of cardiomyopathies observed in athletes, the challenge in diagnosis can result in catastrophic outcomes, especially in developing countries. Therefore, adopting prevention strategies can have a profound impact on the identification and management of these pathologies.

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Background Obesity has been considered to be a risk factor for increased morbidity and mortality among patients with cardiopulmonary diseases. The burden of chronic obstructive pulmonary disease (COPD) and obesity is very high in the United States. We aimed to use the National Inpatient Sample (NIS) to evaluate the impact of obesity on the outcomes of patients hospitalized with COPD exacerbation. Materials & Methods This is a retrospective cohort study from the NIS database involving adult patients hospitalized for COPD exacerbation in the year 2019 obtained using the international classification of diseases, 10th revision coding system (ICD-10). Obese and morbidly obese subgroups were identified. Statistical analyses were done using the Stata software, and regression analysis was performed to calculate odds ratios. Adjusted odds ratios (aOR) were calculated after adjusting for potential confounders. Results Among patients hospitalized for COPD exacerbations, mortality rates were lower among obese and morbidly obese patients; aOR 0.72 [0.65, 0.80] and aOR 0.88 [0.77-0.99], respectively. Obese and morbidly obese were more likely to require non-invasive ventilation aOR 1.63 [1.55, 1.7] and aOR 1.93 [1.85-2.05], respectively, and were more likely to require mechanical ventilation aOR 1.25 [1.19, 1.31], and aOR 1.53 [1.44-1.62], respectively. The tracheostomy rate was 1.17%, 0.83%, and 0.38% among patients with morbid obesity, obesity, and nonobese patients, respectively. Obese (aOR 1.11 [1.07-1.14]) and morbidly obese patients (aOR 1.21 [1.16-1.26]) had higher odds of being discharged on home oxygen and to a skilled nursing facility (SNF), aOR 1.32[1.27-1.38] and aOR 1.37 [1.3-1.43], respectively. Average hospital charges and length of hospitalization were significantly higher for morbidly obese and obese patients as compared to non-obese patients (p < 0.01). Conclusions Among admissions for COPD exacerbation, the rates of non-invasive ventilation, mechanical ventilation, tracheostomy, discharge with supplemental oxygen, length of hospitalization, hospitalization charges, and discharge to an SNF were higher among obese patients representing a higher morbidity and healthcare utilization in this group. This, however, did not translate into increased mortality among obese patients admitted with COPD exacerbations, and further randomized controlled trials are required to confirm our findings.

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Significance: Hyperspectral imaging (HSI) technologies offer great potential in fluorescence microscopy for multiplexed imaging, autofluorescence removal, and analysis of autofluorescent molecules. However, there are also associated trade-offs when implementing HSI in fluorescence microscopy systems, such as decreased acquisition speed, resolution, or field-of-view due to the need to acquire spectral information in addition to spatial information. The vast majority of HSI fluorescence microscopy systems provide spectral discrimination by filtering or dispersing the fluorescence emission, which may result in loss of emitted fluorescence signal due to optical filters, dispersive optics, or supporting optics, such as slits and collimators. Technologies that scan the fluorescence excitation spectrum may offer an approach to mitigate some of these trade-offs by decreasing the complexity of the emission light path. Aim: We describe the development of an optical technique for hyperspectral imaging fluorescence excitation-scanning (HIFEX) on a microscope system. Approach: The approach is based on the design of an array of wavelength-dependent light emitting diodes (LEDs) and a unique beam combining system that uses a multifurcated mirror. The system was modeled and optimized using optical ray trace simulations, and a prototype was built and coupled to an inverted microscope platform. The prototype system was calibrated, and initial feasibility testing was performed by imaging multilabel slide preparations. Results: We present results from optical ray trace simulations, prototyping, calibration, and feasibility testing of the system. Results indicate that the system can discriminate between at least six fluorescent labels and autofluorescence and that the approach can provide decreased wavelength switching times, in comparison with mechanically tuned filters. Conclusions: We anticipate that LED-based HIFEX microscopy may provide improved performance for time-dependent and photosensitive assays.

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IMPORTANCE: Aggressive fluid resuscitation remains a cornerstone of the Surviving Sepsis Campaign (SSC) guidelines, but there is growing controversy regarding the recommended 30 mL/kg IV fluid dosage. It is contended that, in selected patients, this volume confers an increased risk of volume overload without either concomitant benefit or strong evidence in support of the recommended IV fluid dosage. OBJECTIVES: Assessment of practice patterns and their impact on patient outcomes following the surviving sepsis guidelines for fluid resuscitation. DESIGN: Large, multisite retrospective cohort study. SETTING AND PARTICIPANTS: The retrospective study included all adult patients who presented to the emergency department at one of 19 different Mayo Clinic sites throughout the Midwest, Southeast, and Southwest from August 2018 to November 2020 with suspected sepsis. MAIN OUTCOMES AND MEASURES: Eight-thousand four-hundred fourteen patients suspected to have sepsis were assessed regarding fluid resuscitation and outcomes among patients receiving 30 mL/kg IV fluid dosing compared with patients who did not. Patient demographics and clinical information were collected via electronic health records. Patients were divided into two cohorts: those who received 0-29.9 mL/kg of IV fluid and those who received 30.0+ mL/kg of IV fluid. Statistical analyses were performed to evaluate the impact of fluid dose on in-hospital death, 30-day mortality, ICU admission after diagnosis, dialysis initiation after diagnosis, ventilator use, vasopressor use, as well as ICU and hospital length of stay. RESULTS: We observed lower in-hospital mortality and 30-day mortality risk in the 30+ mL/kg dosing group. Increased fluid dosage did, however, carry a much greater chance of ICU admission. Most patients (72% after propensity score weighting) in our population received less than 30 mL/kg fluid (based on ideal body weight). CONCLUSIONS AND RELEVANCE: IV fluid dosing for sepsis resuscitation greater than 30 mL/kg was associated with decreased risk of in-hospital mortality, 30-day mortality, and reduced risk of requiring mechanical ventilation. Our data does ultimately seem to support the SSC recommendation.

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Iliotibial band traction syndrome (ITBTS) after total knee arthroplasty (TKA) has been well documented following first-generation guided motion bicruciate substituting (BCS) TKA. The incidence of ITBTS following second-generation BCS has been found to be rare, and surgical release of the IT band has not been reported. A 64-year old male was diagnosed with ITBTS following second-generation guided motion BCS TKA. After a three-month trial of non-surgical treatment, he underwent selective open release of the iliotibial band (ITB), which successfully relieved his symptoms. Orthopedic surgeons should keep ITBTS as a possible differential diagnosis when evaluating the lateral-sided knee pain following guided motion BCS TKA.

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Several subunits in the matrix domain of mitochondrial complex I (CI) have been posited to be redox sensors for CI, but how elevated levels of reactive oxygen species (ROS) impinge on CI assembly is unknown. We report that genetic disruption of the mitochondrial NADPH-generating enzyme, isocitrate dehydrogenase 2 (IDH2), in Drosophila flight muscles results in elevated ROS levels and impairment of assembly of the oxidative phosphorylation system (OXPHOS). Mechanistically, this begins with an inhibition of biosynthesis of the matrix domain of CI and progresses to involve multiple OXPHOS complexes. Despite activation of multiple compensatory mechanisms, including enhanced coenzyme Q biosynthesis and the mitochondrial unfolded protein response, ferroptotic cell death ensues. Disruption of enzymes that eliminate hydrogen peroxide, but not those that eliminate the superoxide radical, recapitulates the phenotype, thereby implicating hydrogen peroxide as the signaling molecule involved. Thus, IDH2 modulates the assembly of the matrix domain of CI and ultimately that of the entire OXPHOS.

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BACKGROUND: Ketamine, a dissociative anesthetic, induces improvement in depressive symptoms by antagonizing glutaminergic NMDA receptors. Ketamine has been used previously in outpatient setting for treatment-resistant depression, but we showcase its utility in depression management at the Intensive Care Unit (ICU). Research Question: Can ketamine be used for depression treatment in ICU patients? Study Design and Methods: A retrospective chart review of ICU patients was done at a tertiary center from 2018 to 2021, to assess the ketamine usage. Among the patients reviewed, ketamine was used for depression in 12, and for analgesia & sedation in 2322 patients. Ketamine was administered in doses of 0.5mg/kg & 0.75mg/kg for depression. Each course consisted of 3 doses of ketamine administered over 3 days, and 7 in 12 patients received a single course of ketamine. The rest received 3-4 courses 1 week apart. Results: Ketamine was found to improve mood and affect in most of the patients with depression. 11 in 12 patients had a positive response with better sleep. It has a major advantage over conventional anti-depressants since it takes only a few hours to induce clinical improvement. Patients who were observably withdrawn from care team and family, were administered ketamine. Conclusion: A major drawback of ketamine is that the duration of clinical improvement is short, with the response lasting only up to seven days after a single dose. Hence, all the patients in our study were weaned off ketamine with a supporting antidepressant. Ketamine has been documented to cause cardio-neurotoxicity; however, only one patient had worsening lethargy in our study. To conclude, ketamine has a marked benefit in treating depression in the ICU. Although our study was associated with positive outcomes, there is a need for prospective studies with long-term follow-up assessments.

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