The prevalence of bilateral and ipsilateral radiographic osteoarthritis is high in White, Asian and Native Hawaiian/Pacific Islanders presenting for unilateral knee or hip arthroplasty.

BACKGROUND: It is estimated that one-third of patients presenting with unilateral joint pain have contralateral osteoarthritis (OA) at first presentation. Most studies have primarily examined White patient cohorts. The purpose of this study was to determine the prevalence of contralateral joint OA for patients presenting for unilateral total knee (TKA), unicompartmental knee (UKA) or total hip arthroplasty (THA) among Asian, Native Hawaiian/Pacific Islander and White patients. METHODS: Bilateral radiographic reports at initial presentation of 2,312 subjects who underwent unilateral arthroplasties (332 UKAs, 933 TKAs and 1,047 THAs) were reviewed. The presence of contralateral OA was recorded and compared by racial group and type of arthroplasty performed. Parametric statistical analyses were performed to determine differences between groups. Multivariable analyses were completed for each arthroplasty group to determine the influence on the presence of contralateral OA, presented as odds ratios and 95% confidence intervals. RESULTS: Contralateral joint OA was present in 86.7%, 90.4% and 70.4% of UKA, TKA and THA patients, respectively. Concurrent hip OA was present in 41.6% and 59.5% of UKA and TKA patients. No racial differences in the prevalence of contralateral knee OA were found for knee arthroplasty patients. White patients (74.6%) had a greater prevalence of contralateral hip OA compared to Asians (66.5%, p = 0.037) amongst THA recipients. Increased age and body mass index were significantly associated with the presence of contralateral knee OA. Increased age, being male and being White were significant contributors for the presence of contralateral hip OA. CONCLUSION: The prevalence of contralateral joint OA and concurrent hip OA is high in all three racial groups. Due to the extensive prevalence of contralateral and concurrent knee and hip OA, bilateral radiographic evaluation should be considered for all patients presenting with unilateral hip or knee pain due to OA.

Sensitization of cancer cells to ferroptosis coincident with cell cycle arrest.

Ferroptosis is a non-apoptotic form of cell death that can be triggered by inhibiting the system xc- cystine/glutamate antiporter or the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). We have investigated how cell cycle arrest caused by stabilization of p53 or inhibition of cyclin-dependent kinase 4/6 (CDK4/6) impacts ferroptosis sensitivity. Here, we show that cell cycle arrest can enhance sensitivity to ferroptosis induced by covalent GPX4 inhibitors (GPX4i) but not system xc- inhibitors. Greater sensitivity to GPX4i is associated with increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids (PUFA-PLs). Higher PUFA-PL abundance upon cell cycle arrest involves reduced expression of membrane-bound O-acyltransferase domain-containing 1 (MBOAT1) and epithelial membrane protein 2 (EMP2). A candidate orally bioavailable GPX4 inhibitor increases lipid peroxidation and shrinks tumor volumes when combined with a CDK4/6 inhibitor. Thus, cell cycle arrest may make certain cancer cells more susceptible to ferroptosis in vivo.

Abnormal Temporal Slowing on EEG Findings in Preclinical Alzheimer's Disease Patients With the ApoE4 Allele: A Pilot Study.

INTRODUCTION: Currently, there are limited accessible and cost-effective biomarkers for preclinical Alzheimer's disease (AD) patients. However, the apolipoprotein E (ApoE) polymorphic alleles can predict if someone is at high (e4), neutral (e3), or low (e2) genetic risk for developing AD. This study analyzed electroencephalogram (EEG) reports from individuals with various ApoE genotypes, aiming to identify EEG changes and patterns that could potentially serve as predictive markers for preclinical AD progression. METHODS: Participants aged 64-78 were selected from the patient database at an outpatient neurology clinic. Genotype studies were performed to determine ApoE status, followed by EEG analysis to identify any apparent trends. A case-control design was used, categorizing participants into cases (e2e3, e2e4, e3e4, e4e4) and controls (e3e3). EEG recordings were compared between the groups to identify potential differences in EEG characteristics, including abnormal temporal slowing, frequency, and ApoE genotype association. RESULTS: Among 43 participants, 49% demonstrated evidence of abnormal temporal slowing on EEG. Of these, 48% displayed focal left temporal slowing, and 52% displayed bilateral temporal slowing. The right-sided temporal slowing was not observed. Among participants with abnormal slowing, 95% exhibited theta frequency (4-8 Hz) slowing, while only 4.8% displayed delta frequency (0-4 Hz) slowing. Among participants with the ApoE4 allele, 61.5% demonstrated evidence of abnormal slowing, compared to 43.3% without it. Furthermore, the presence of an ApoE4 allele was associated with a significantly higher proportion of males (54%) compared to those without it (13%) (p=0.009). CONCLUSIONS: Although we did not find a statistically significant difference in temporal EEG slowing among different ApoE genotypes, our findings suggest a potential association between temporal slowing on EEG and the presence of an ApoE4 allele in individuals with preclinical AD. These observations highlight the need for further exploration into the potential influence of the ApoE4 allele on EEG findings and the utility of EEG as a complementary diagnostic tool for AD. Longitudinal studies with large sample sizes are needed to establish the precise relationship between EEG patterns, ApoE genotypes, and AD progression.

Hippocampal sparing radiation therapy for brain metastases: treatment techniques and clinical implementation.

High doses of radiation to the hippocampus have been correlated with increased cognitive decline following radiation therapy for brain metastases. To mitigate these effects, a variety of hippocampal sparing techniques have been implemented for both whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). The goal of this review article is to provide a practical resource for the clinical implementation of hippocampal-sparing radiation therapy, starting with a brief background on the function and delineation of the hippocampal structure, as well as radiation effects on the hippocampus and the most widely recommended dose constraints. Considerations for treatment simulation are discussed, including options for cranial immobilization and optional head tilt. Hippocampal sparing has been demonstrated for WBRT using helical TomoTherapy, static intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) with a variety of patient setup positions, beam arrangements, and planning parameters. Tomotherapy has been shown to achieve slightly greater hippocampal sparing in some studies, while VMAT enables the most efficient treatment delivery. Hippocampal sparing has also been evaluated in a wide range of studies for both GammaKnife and linear accelerator (LINAC)-based SRS, with the proximity of metastases to the hippocampus being the most significant predictor of hippocampal dose. The methods and resulting hippocampal doses from these studies on both WBRT and SRS are discussed, as well as the role of automation in hippocampal sparing radiation therapy.

The Properties and Domain Requirements for Phase Separation of the Sup35 Prion Protein In Vivo.

The Sup35 prion protein of budding yeast has been reported to undergo phase separation to form liquid droplets both at low pH in vitro and when energy depletion decreases the intracellular pH in vivo. It also has been shown using purified proteins that this phase separation is driven by the prion domain of Sup35 and does not re-quire its C-terminal domain. In contrast, we now find that a Sup35 fragment consisting of only the N-terminal prion domain and the M-domain does not phase separate in vivo; this phase separation of Sup35 requires the C-terminal domain, which binds Sup45 to form the translation termination complex. The phase-separated Sup35 not only colocalizes with Sup45 but also with Pub1, a stress granule marker protein. In addition, like stress granules, phase separation of Sup35 appears to require mRNA since cycloheximide treatment, which inhibits mRNA release from ribosomes, prevents phase separation of Sup35. Finally, unlike Sup35 in vitro, Sup35 condensates do not disassemble in vivo when the intracellular pH is increased. These results suggest that, in energy-depleted cells, Sup35 forms supramolecular assemblies that differ from the Sup35 liquid droplets that form in vitro.

A Cell Cycle-Dependent Ferroptosis Sensitivity Switch Governed by EMP2.

Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. Ferroptosis can be induced by system xc- cystine/glutamate antiporter inhibition or by direct inhibition of the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). The regulation of ferroptosis in response to system xc- inhibition versus direct GPX4 inhibition may be distinct. Here, we show that cell cycle arrest enhances sensitivity to ferroptosis triggered by GPX4 inhibition but not system xc- inhibition. Arrested cells have increased levels of oxidizable polyunsaturated fatty acid-containing phospholipids, which drives sensitivity to GPX4 inhibition. Epithelial membrane protein 2 (EMP2) expression is reduced upon cell cycle arrest and is sufficient to enhance ferroptosis in response to direct GPX4 inhibition. An orally bioavailable GPX4 inhibitor increased markers of ferroptotic lipid peroxidation in vivo in combination with a cell cycle arresting agent. Thus, responses to different ferroptosis-inducing stimuli can be regulated by cell cycle state.

Overexpression of Hsp104 by Causing Dissolution of the Prion Seeds Cures the Yeast [PSI+] Prion.

The yeast Sup35 protein misfolds into the infectious [PSI+] prion, which is then propagated by the severing activity of the molecular chaperone, Hsp104. Unlike other yeast prions, this prion is unique in that it is efficiently cured by the overexpression as well as the inactivation of Hsp104. However, it is controversial whether curing by overexpression is due to the dissolution of the prion seeds by the trimming activity of Hsp104 or the asymmetric segregation of the prion seeds between mother and daughter cells which requires cell division. To answer this question, we conducted experiments and found no difference in the extent of curing between mother and daughter cells when half of the cells were cured by Hsp104 overexpression in one generation. Furthermore, curing was not affected by the lack of Sir2 expression, which was reported to be required for asymmetric segregation of the [PSI+] seeds. More importantly, when either hydroxyurea or ethanol were used to inhibit cell division, the extent of curing by Hsp104 overexpression was not significantly reduced. Therefore, the curing of [PSI+] by Hsp104 overexpression is not due to asymmetric segregation of the prion seeds, but rather their dissolution by Hsp104.

Household conditions, COVID-19, and equity: Insight from two nationally representative surveys.

Background: With people across the United States spending increased time at home since the emergence of COVID-19, housing characteristics may have an even greater impact on health. Therefore, we assessed associations between household conditions and COVID-19 experiences. Methods: We used data from two nationally representative surveys: the Tufts Equity Study (TES; n = 1449 in 2021; n = 1831 in 2022) and the Household Pulse Survey (HPS; n = 147,380 in 2021; n = 62,826 in 2022). In the TES, housing conditions were characterized by heating/cooling methods; smoking inside the home; visible water damage/mold; age of housing unit; and self-reported concern about various environmental factors. In TES and HPS, household size was assessed. Accounting for sampling weights, we examined associations between each housing exposure and COVID-19 outcomes (diagnosis, vaccination) using separate logistic regression models with covariates selected based on an evidence-based directed acyclic graph. Results: Having had COVID-19 was more likely among people who reported poor physical housing condition (odds ratio [OR] = 2.32; 95% confidence interval [CI] = 1.17-4.59; 2021), visible water damage or mold/musty smells (OR = 1.50; 95% CI = 1.10-2.03; 2022), and larger household size (5+ versus 1-2 people; OR = 1.53, 95% CI = 1.34-1.75, HPS 2022). COVID-19 vaccination was less likely among participants who reported smoke exposure inside the home (OR = 0.53; 95% CI = 0.31-0.90; 2022), poor water quality (OR = 0.42; 95% CI = 0.21-0.85; 2021), noise from industrial activity/construction (OR = 0.44; 95% CI = 0.19-0.99; 2022), and larger household size (OR = 0.57; 95% CI = 0.46-0.71; HPS 2022). Vaccination was also positively associated with poor indoor air quality (OR = 1.96; 95% CI = 1.02-3.72; 2022) and poor physical housing condition (OR = 2.27; 95% CI = 1.01-5.13; 2022). Certain heating/cooling sources were associated with COVID-19 outcomes. Conclusions: Our study found poor housing conditions associated with increased COVID-19 burden, which may be driven by systemic disparities in housing, healthcare, and financial access to resources during the COVID-19 pandemic.

Development of Highly Fluorogenic Styrene Probes for Visualizing RNA in Live Cells.

Styrene dyes are useful imaging probes and fluorescent sensors due to their strong fluorogenic responses to environmental changes or binding macromolecules. Previously, indole-containing styrene dyes have been reported to selectively bind RNA in the nucleolus and cytoplasm. However, the application of these indole-based dyes in cell imaging is limited by their moderate fluorescence enhancement and quantum yields, as well as relatively high background associated with these green-emitting dyes. In this work, we have investigated the positional and electronic effects of the electron donor by generating regioisomeric and isosteric analogues of the indole ring. Select probes exhibited large Stokes shifts, enhanced molar extinction coefficients, and bathochromic shifts in their absorption and fluorescence wavelengths. In particular, the indolizine analogues displayed high membrane permeability, strong fluorogenic responses upon binding RNA, compatibility with fluorescence lifetime imaging microscopy (FLIM), low cytotoxicity, and excellent photostability. These indolizine dyes not only give rise to rapid, sensitive, and intense staining of nucleoli in live cells but can also resolve subnucleolar structures enabling highly detailed studies of nucleolar morphology. Furthermore, our dyes can partition into RNA coacervates and resolve the formation of multiphase complex coacervate droplets. These indolizine-containing styrene probes offer the highest fluorescence enhancement among the RNA-selective dyes reported in the literature; thus, these new dyes are excellent alternatives to the commercially available RNA dye, SYTO RNASelect, for visualizing RNA in live cells and in vitro.

A deep learning approach for automatic delineation of clinical target volume in stereotactic partial breast irradiation (S-PBI).

Accurate and efficient delineation of the clinical target volume (CTV) is of utmost significance in post-operative breast cancer radiotherapy. However, CTV delineation is challenging as the exact extent of microscopic disease encompassed by CTV is not visualizable in radiological images and remains uncertain. We proposed to mimic physicians' contouring practice for CTV segmentation in stereotactic partial breast irradiation (S-PBI) where CTV is derived from tumor bed volume (TBV) via a margin expansion followed by correcting the extensions for anatomical barriers of tumor invasion (e.g. skin, chest wall). We proposed a deep-learning model, where CT images and the corresponding TBV masks formed a multi-channel input for a 3D U-Net based architecture. The design guided the model to encode the location-related image features and directed the network to focus on TBV to initiate CTV segmentation. Gradient weighted class activation map (Grad-CAM) visualizations of the model predictions revealed that the extension rules and geometric/anatomical boundaries were learnt during model training to assist the network to limit the expansion to a certain distance from the chest wall and the skin. We retrospectively collected 175 prone CT images from 35 post-operative breast cancer patients who received 5-fraction partial breast irradiation regimen on GammaPod. The 35 patients were randomly split into training (25), validation (5) and test (5) sets. Our model achieved mean (standard deviation) of 0.94 (±0.02), 2.46 (±0.5) mm, and 0.53 (±0.14) mm for Dice similarity coefficient, 95th percentile Hausdorff distance, and average symmetric surface distance respectively on the test set. The results are promising for improving the efficiency and accuracy of CTV delineation during on-line treatment planning procedure.

A Review of ST-Elevation Myocardial Infarction in Patients with COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

The Impact of Prematurity at Birth on Short-Term Postoperative Outcomes Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

Prematurity is associated with surgical complications. This study sought to determine the risk of prematurity on 30-day complications, reoperations, and readmissions following ≥7-level PSF for AIS which has not been established. Utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP)-Pediatric dataset, all AIS patients undergoing ≥7-level PSF from 2012-2016 were identified. Cases were 1:1 propensity score-matched to controls by age, sex, and number of spinal levels fused. Prematurity sub-classifications were also evaluated: extremely (<28 weeks), very (28-31 weeks), and moderate-to-late (32-36 weeks) premature. Univariate analysis with post hoc Bonferroni compared demographics, hospital parameters, and 30-day outcomes. Multivariate logistic regression identified independent predictors of adverse 30-day outcomes. 5531 patients (term = 5099; moderate-to-late premature = 250; very premature = 101; extremely premature = 81) were included. Premature patients had higher baseline rates of multiple individual comorbidities, longer mean length of stay, and higher 30-day readmissions and infections than the term cohort. Thirty-day readmissions increased with increasing prematurity. Very premature birth predicted UTIs, superficial SSI/wound dehiscence, and any infection, and moderate-to-late premature birth predicted renal insufficiency, deep space infections, and any infection. Prematurity of AIS patients differentially impacted rates of 30-day adverse outcomes following ≥7-level PSF. These results can guide preoperative optimization and postoperative expectations.

Stability and reproducibility comparisons between deep inspiration breath-hold techniques for left-sided breast cancer patients: A prospective study.

PURPOSE: Deep inspiration breath-hold (DIBH) is crucial in reducing the lung and cardiac dose for treatment of left-sided breast cancer. We compared the stability and reproducibility of two DIBH techniques: Active Breathing Coordinator (ABC) and VisionRT (VRT). MATERIALS AND METHODS: We examined intra- and inter-fraction positional variation of the left lung. Eight left-sided breast cancer patients were monitored with electronic portal imaging during breath-hold (BH) at every fraction. For each patient, half of the fractions were treated using ABC and the other half with VRT, with an equal amount starting with either ABC or VRT. The lung in each portal image was delineated, and the variation of its area was evaluated. Intrafraction stability was evaluated as the mean coefficient of variation (CV) of the lung area for the supraclavicular (SCV) and left lateral (LLat) field over the course of treatment. Reproducibility was the CV for the first image of each fraction. Daily session time and total imaging monitor units (MU) used in patient positioning were recorded. RESULTS: The mean intrafraction stability across all patients for the LLat field was 1.3 ± 0.7% and 1.5 ± 0.9% for VRT and ABC, respectively. Similarly, this was 1.5 ± 0.7% and 1.6 ± 0.8% for VRT and ABC, respectively, for the SCV field. The mean interfraction reproducibility for the LLat field was 11.0 ± 3.4% and 14.9 ± 6.0% for VRT and ABC, respectively. Similarly, this was 13.0 ± 2.5% and 14.8 ± 9% for VRT and ABC, respectively, for the SCV. No difference was observed in the number of verification images required for either technique. CONCLUSIONS: The stability and reproducibility were found to be comparable between ABC and VRT. ABC can have larger interfractional variation with less feedback to the treating therapist compared to VRT as shown in the increase in geometric misses at the matchline.

On the feasibility of improved target coverage without compromising organs at risk using online adaptive stereotactic partial breast irradiation (A-SPBI).

PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.

Opioid Use Disorder in Patients Undergoing Primary 1- to 2-Level Anterior Cervical Discectomy and Fusion Is Associated With Longer In-Hospital Lengths of Stay and Higher Rates of Readmissions, Complications, and Costs of Care.

STUDY DESIGN: Retrospective study. OBJECTIVE: To determine whether opioid use disorder (OUD) patients undergoing 1- to 2-level anterior cervical discectomy and fusion (1-2ACDF) have higher rates of: 1) in-hospital lengths of stay (LOS); 2) readmissions; 3) complications; and 4) costs. METHODS: OUD patients undergoing primary 1-2ACDF were identified within the Medicare database and matched to a control cohort in a 1:5 ratio by age, sex, and medical comorbidities. The query yielded 80,683 patients who underwent 1-2 ACDF with (n = 13,448) and without (n = 67,235) OUD. Outcomes analyzed included in-hospital LOS, 90-day readmission rates, 90-day medical complications, and costs. Multivariate logistic regression analyses were used to calculate odds-ratios (OR) for medical complications and readmissions. Welch's t-test was used to test for significance for LOS and cost between the cohorts. An alpha value less than 0.002 was considered statistically significant. RESULTS: OUD patients were found to have significantly longer in-hospital LOS compared to their counterparts (3.41 vs. 2.23-days, P < .0001), in addition to higher frequency and odds of requiring readmissions (21.62 vs. 11.57%; OR: 1.38, P < .0001). Study group patients were found to have higher frequency and odds of developing medical complications (0.88 vs. 0.19%, OR: 2.80, P < .0001) and incurred higher episode of care costs ($20,399.62 vs. $16,812.14, P < .0001). CONCLUSION: The study can help to push orthopaedic surgeons in better managing OUD patients pre-operatively in terms of safe discontinuation and education of opioid drugs and their effects on complications, leading to more satisfactory outcomes.

Sex dependent differences of temporomandibular condylar bone mineral density distribution.

OBJECTIVE: The objective of this study was to examine whether bone mineral density (BMD) distribution in the mandibular condyle and facial morphology are associated with temporomandibular joint osteoarthritis (TMJ OA) using clinical cone beam computed tomography (CBCT) images. METHODS: CBCT images of 35 adults (16 male and 19 female) were examined to obtain TMJ OA counts, cephalometric analyses, and histograms of gray values that are proportional to BMD. Mean, standard deviation (SD), and low and high gray values at the 5th and 95th percentiles (Low5 and High5) of the histograms were measured. RESULTS: The female group had significantly higher values of TMJ OA counts, mean, and SD on the right mandibular condyle, High5 on both sides, and all gray value parameters for total (right + left) than the male group. CONCLUSION: Comprehensive analysis of BMD distribution in the mandibular condyle can provide useful information for prognosis of TMJ OA.

The 5-factor modified frailty index (mFI-5) is predictive of 30-day postoperative complications and readmission in patients with adult spinal deformity (ASD).

BACKGROUND: There is limited research regarding the association between the mFI-5 and postoperative complications among adult spinal deformity (ASD) patients. METHODS: Using the National Surgical Quality Improvement Project (NSQIP) database, patients with Current Procedural Terminology (CPT) codes for > 7-level fusion or < 7-level fusion with International Classification of Diseases, Ninth Revision (ICD-9) codes for ASD were identified between 2008 and 2016. Univariate analyses with post-hoc Bonferroni correction for demographics and preoperative factors were performed. Logistic regression assessed associations between mFI-5 scores and 30-day post-operative outcomes. RESULTS: 2,120 patients met criteria. Patients with an mFI-5 score of 4 or 5 were excluded, given there were<20 patients with those scores. Patients with mFI-5 scores of 1 and 2 had increased 30-day rates of pneumonia (3.5 % and 4.3 % vs 1.6 %), unplanned postoperative ventilation for > 48 h (3.1 % and 4.3 % vs 0.9 %), and UTIs (4.4 % and 7.4 % vs 2.0 %) than patients with a score of 0 (all, p < 0.05). Logistic regression revealed that compared to an mFI-5 of 0, a score of 1 was an independent predictor of 30-day reoperations (OR = 1.4; 95 % CI 1.1-18). A score of 2 was an independent predictor of overall (OR = 2.4; 95 % CI 1.4-4.1) and related (OR = 2.2; 95 % CI 1.2-4.1) 30-day readmissions. A score of 3 was not predictive of any adverse outcome. CONCLUSION: The mFI-5 score predicted complications and postoperative events in the ASD population. The mFI-5 may effectively predict 30-day readmissions. Further research is needed to identify the benefits and predictive value of mFI-5 as a risk assessment tool.

An Interesting Case Report of Myasthenia Gravis Exacerbation Induced by Durvalumab.

Immune checkpoint inhibitors are novel therapy for a wide range of malignancies. They have been associated with numerous side effects resulting in pulmonary, dermatological, gastrointestinal, and neurological complications. There are few reported cases of myasthenia gravis exacerbation from immune checkpoint inhibitors. We present a case of an 82-year-old woman with a history of myasthenia gravis in remission and non-small cell lung cancer who presented with diplopia, dyspnea, and generalized weakness after three cycles of durvalumab. She was diagnosed with a myasthenic crisis and was treated with high-dose steroids and plasmapheresis.

A Review of ST-Elevation Myocardial Infarction in Patients with COVID-19.

The Coronavirus disease 2019 (COVID-19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes, stress-induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared with their age- and sex-matched STEMI patients without COVID-19. We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

Femur Strength is Similar Before and After Iatrogenic Fracture During Total Hip Arthroplasty: A Biomechanical Analysis.

Background: The purpose of this study was to compare the biomechanical strength of femurs before an iatrogenic periprosthetic fracture vs after an initial fracture with supporting cerclage fixation during cementless total hip arthroplasty. Material and methods: Nineteen composite femurs and 5 matched pairs of cadaveric femurs were implanted with a single-wedge or dual-wedge tapered femoral stem and tested for ultimate load to failure producing a periprosthetic fracture. Following initial fracture, each femur was cerclaged with Vitallium cables and retested for ultimate load to failure. The mean force eliciting iatrogenic fracture before cabling and that after cabling were compared with a two-sided paired Student's t-test. Results: All composite femurs developed periprosthetic fractures with an average length extension from the calcar of 75.17 mm. For the 19 composite femurs, the mean ultimate load to failure before cabling and that after cabling were not significantly different (2422.95 N vs 2505.14 N, P = .678). For the 10 cadaveric femurs, the mean ultimate load to failure for the initial fracture vs that after cabling was statistically comparable (5828.62 N vs 7002.63 N, P = .126). Subanalysis of the 5 cadaveric femurs with a double-wedge stem revealed a significantly higher mean load to failure following cabling (5007.38 N vs 7811.17 N, P = .011). Conclusion: Biomechanical strength was similar for femurs that sustained an initial iatrogenic periprosthetic fracture and the same femurs cabled with cerclage wires after being fractured. These data may assist in operative decision-making for treating iatrogenic fractures during total hip arthroplasty.