Association between rates of ischemic stroke and all-cause mortality with the Watchman device compared to warfarin and direct oral anticoagulants in patients with atrial fibrillation.

Introduction: The Watchman device is approved in the US, but little is known about Watchman's ischemic stroke reduction compared to the newer direct oral anticoagulants (DOACs). This study explored the differences in ischemic stroke reduction between the Watchman device, warfarin, and DOAC medication. Methods: Three patient cohorts, each containing 10,969 patients, were created using TriNetX. The primary and secondary endpoints were the ischemic stroke risk and all-cause mortality risk at 1 and 5 years. Results: At 1 year, the Watchman device's relative risk of ischemic stroke was 0.86 against warfarin but 1.27 against DOACs (P < 0.0001). The relative risk of ischemic stroke between the Watchman and DOACs was higher at 1 and 5 years (1.27 and 1.30, P < 0.0001). The relative risk of all-cause mortality at 1 and 5 years was 0.49 and 0.72 for the Watchman device compared to warfarin (P < 0.0001) and 0.66 and 0.92 between the Watchman and DOACs (P < 0.0001 and 0.01). Conclusion: While DOACs were associated with lower ischemic stroke rates, treatment with the Watchman device was associated with lower all-cause mortality. Patients placed on the Watchman device due to DOAC contraindications may benefit from its lower all-cause mortality risk.

Efficacy and risk of osteonecrosis of the jaw for pamidronate, zoledronic acid, and denosumab in comparison to alendronate in multiple myeloma patients.

Background: Approximately 70% of multiple myeloma patients develop pathologic fractures. Osteoclast inhibitors can provide reduction in vertebral fractures with an increased risk of osteonecrosis of the jaw (ONJ). ONJ associated with currently used osteoclast inhibitors causes significant morbidity, often from delayed diagnosis and ineffective treatment. Methods: The TriNetX Diamond Network was used to create patient cohorts for each medication: alendronate, pamidronate, zoledronic acid, and denosumab. All patients had a diagnosis of multiple myeloma as identified by International Classification of Disease-10 (ICD-10) code C90.0. Pamidronate, zoledronic acid, and denosumab were each compared to alendronate for 5-year incidence of pathologic vertebral fracture (ICD-10 M48.50XA) and development of ONJ. Results: The 5-year risk of pathologic vertebral fracture was not statistically different between alendronate versus pamidronate, zoledronic acid, and denosumab. However, the 5-year risk of ONJ was significantly higher for both zoledronic acid and denosumab (relative risk 4.85 and 2.9, respectively). Conclusion: This study shows that fracture reduction risk is comparable for all four treatments in multiple myeloma patients, but ONJ risk is lowest for alendronate and pamidronate. Overall, these data support the continued use of pamidronate and alendronate in multiple myeloma patients.

Denosumab versus pamidronate in the treatment of osteolytic bone metastases secondary to breast cancer: a multi-institutional analysis.

Background: Breast cancer is the most common cancer in women and most often metastasizes to the bone, resulting in skeletal-related events (SREs). Bone-modifying agents (BMAs) including denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappa-b ligand (RANKL), and pamidronate, a bisphosphonate, are used to prevent these adverse events. Methods: To analyze the efficacy of denosumab versus pamidronate, we used the TriNetX research platform and compared the outcomes of pathologic fracture, spinal cord compression, and overall 5-year survival rate between each pharmacotherapy. Results: There was no statistical difference for an increased risk in pathological fractures (2.7% vs. 2.8%, P = 0.88), spinal cord compression (2.6% vs. 2.7%, P = 0.88), or 5-year survival rate (45.5% vs. 52.4%, P = 0.78) for the denosumab cohort versus the pamidronate cohort. Conclusion: Since neither therapy showed an increased risk in the adverse effects measured in this study, factors such as patient preference, financial costs, and additional side effects of each medication should be taken into consideration when choosing a therapy for bone metastases in patients with breast cancer.

The effect of polycystic ovarian syndrome on fibrocystic breast changes in postmenopausal women.

Background: Fibrocystic breast changes (FCCs) are benign lesions thought to be caused by an increased estrogen-to-progesterone ratio. One of the most common endocrinopathies that increases this ratio is polycystic ovarian syndrome (PCOS). Although nonproliferative FCCs do not increase the risk of breast cancer, they can make mammographic detection of malignancy in postmenopausal women more difficult. The aim of this study was to investigate the effects of PCOS on the development of postmenopausal FCCs. Methods: This retrospective cohort study used the TriNetX research network to identify two cohorts of postmenopausal women (Z78.0) older than 45, without a prior diagnosis of FCCs (N60.1) or hormone replacement therapy (Z79.890). One cohort included a diagnosis of PCOS (E28.2). The cohorts were balanced for age, race, ethnicity, and hormonally relevant comorbidities. The cohorts were then evaluated for the development of FCCs after menopause. Results: Postmenopausal patients with PCOS were 52% more likely to develop FCCs than those without PCOS (2.2% vs. 1.4%, relative risk 1.52, 95% confidence interval 1.05, 2.22, P = 0.03). Conclusion: Postmenopausal women with PCOS have a higher risk of developing FCCs. Further studies are needed to improve the differentiation of benign FCCs from malignant lesions on imaging for postmenopausal women with PCOS who develop FCCs.

Statin Therapy and Pancreatitis: A Multi-Institutional Retrospective Analysis.

INTRODUCTION:  Acute pancreatitis is a serious condition that has numerous etiologies and often requires hospital admission due to its high mortality rates. Statins are used worldwide to reduce the risk of cardiovascular disease. Some studies have shown an association between long-term statin use and acute pancreatitis. However, other studies have shown no effect or even postulated a mild protective effect. Due to conflicting information in the medical literature, the relationship between statins and acute pancreatitis remains unclear. The current study uses the TriNetX global research database to further investigate the impact of statin use on the development of acute pancreatitis over a five-year period. METHODS:  Two cohorts were created using the TriNetX global research database. One group consisted of patients not taking statins, while the other group included patients taking any statins. Patients in both groups were required to be between the ages of 40 and 75 and had normal low-density lipoprotein cholesterol (LDL) (≤200 mg/dl) and triglyceride (≤150 mg/dl) levels. Patients were matched for age, gender, race, and comorbidities. The statin group was then compared to the no-statin group and measured for the outcome of the incidence of acute pancreatitis and the frequency of episodes within the first five years of statin use. Patients who experienced any acute pancreatitis episode before starting statin therapy or before meeting inclusion criteria were excluded from the study. RESULTS:  Patients on statin therapy were significantly more likely to develop acute pancreatitis compared to patients not taking statin therapy (risk ratio 1.332, 95% CI: 1.242-1.429, P<0.0001). However, the statin group had a lower mean number of pancreatitis episodes than the no-statin group (4.6 vs. 5.3, P=0.043). CONCLUSION:  The results from this large global dataset support the previously established idea that prolonged use of statins is associated with an increased risk of pancreatitis. Clinicians should strongly consider statin-induced pancreatitis when other common etiologies have been ruled out.

Distinguishing Fibroepithelial Lesions Requires Clinical, Imaging, and Pathology Correlation.

Phyllodes tumor (PT) is a rare tumor that can present as benign, borderline, or malignant. These tumors arise from the breast stroma, similar to fibroadenomas. Phyllodes tumors and fibroadenomas often have overlapping features in both radiological imaging and pathologic analysis. As a result, these two lesions are often difficult to differentiate and require the correlation of multiple modalities, including clinical context, radiologic imaging, and histological evaluation. This article presents a case of a borderline phyllodes tumor in a 51-year-old female, with the inclusion of its radiologic and pathologic images and performed treatment. The goal of this article is to provide a review of the clinical presentation, diagnostic imaging and pathology features, treatment, and management of a phyllodes tumor and compare and contrast this against the more common fibroadenomas, in order to provide aid for differentiating these two breast lesions.

An Interesting Imaging Presentation of a Common Benign Entity: Fibrocystic Changes in a Postmenopausal Patient.

Fibrocystic changes (FCCs) are common, often benign, breast lesions characterized by adenosis, fibrosis, and cyst formation. These changes are believed to be associated with fluctuating hormone levels and are predominantly found in premenopausal women due to higher levels of estrogen. Certain conditions that cause hormonal imbalances, such as polycystic ovarian syndrome, have also been associated with an increased risk of FCCs. FCCs can occur in postmenopausal women on hormonal replacement therapy but are otherwise extremely rare. Although this condition is primarily considered benign, complex cysts presenting in a rare demographic warrant further evaluation beyond screening mammograms to exclude the possibility of malignancy. In this paper, we present the case of new FCCs in a postmenopausal woman and explore the radiology, histology, carcinogenic potential, treatment options, and potential contributing factors of the condition.

Mucocele-Like Lesion of the Breast.

Mucocele-like lesions (MLLs) of the breast are rare neoplasms characterized by dilated, mucin-filled epithelial ducts or cysts that can rupture and expel their contents into the surrounding stroma. They are frequently associated with atypia, dysplastic change, and, more recently, pre-malignant and malignant conditions like atypical ductal hyperplasia, ductal carcinoma, invasive carcinoma, or mucinous carcinoma. The malignant potential of MLLs is often challenging to determine from the initial histologic evaluation of a core-needle biopsy due to copious mucin and low cellularity. Therefore, at initial presentation, MLLs should be surgically excised and thoroughly evaluated for malignancy. In this paper, we present a rare case of an MLL and explore the radiology, histology, carcinogenic potential, diagnostic evaluation, and suggested management of the condition.

The potential impact of computed tomography coronary calcium score screening on patients with dyslipidemia.

Background: Coronary artery calcium (CAC) scoring helps determine whether patients with known coronary artery disease (CAD) should initiate medical management by predicting future cardiac event risk. CAC scoring is underutilized because many insurance companies consider it experimental. This study aimed to determine whether CAC screening of patients at risk for CAD is associated with decreased risk of myocardial infarction and improved survival. Methods: The TriNetX research network was used for this study. Two cohorts of 86,574 patients aged 40 to 70 years were created. All patients were diagnosed with dyslipidemia and without CAD, and the cohorts were matched for demographics, comorbidities, and statin use. One cohort had been screened with CAC scoring while the other had not. The primary outcomes of this study were myocardial infarction and overall survival at 5 years. Results: Screened patients had 44% fewer myocardial infarction events at 5 years with a 76% lower risk of death. Conclusion: CAC scoring is associated with reduced risk of myocardial infarction and death in asymptomatic dyslipidemia patients and should be considered as a screening tool in these patients. The presumed mechanism for improved outcomes is that early identification of CAD results in earlier or more intensive treatment, reducing future cardiac event risk.

Rare Primary Malignant Melanoma of the Breast Presenting as a Solitary Breast Mass in a 43-Year-Old Male.

Primary malignant melanoma of the breast (PMMB) is an extremely rare lesion that carries a poor prognosis. Therefore, it is crucial to examine the patient's medical history, clinical presentation, and histopathology considering this diagnosis. The rarity of this lesion has made it difficult to identify classic presentations or specific treatment guidelines. Staining for specific biomarkers can be helpful for diagnosis in the absence of melanin pigment on histology. Additional molecular studies to determine gene status can also be useful for targeted immunotherapy and increased survival time for patients. In this paper, we introduce a rare case of PMMB without skin involvement presenting as a solitary breast mass in a male and explore the radiology, histology, evaluation, and treatment options.

Rare Paget's Disease Associated With Breast Cancer in a 70-Year-Old Male.

Male breast cancer is far less common compared to female breast cancer. Paget's disease of the breast (PDB) is a rare disease, making it even rarer in men. It often presents with eczematous patches over the nipple and areola region, mimics benign dermatological conditions, and can result in a greatly delayed diagnosis. This report presents a rare case of PDB in a 70-year-old male and includes a review of its clinical presentation, radiographic findings, histology, carcinogenic potential, and management.

Free Silicone With Giant Cell Reaction Can Enhance on Breast MRI.

Background Breast augmentation with silicone implants is commonplace, and such implants have a risk of rupture which increases over time. Most implant ruptures are asymptomatic, and magnetic resonance imaging (MRI) is a recommended imaging modality for surveillance to detect these events. If a silicone leak enhances on MRI, it is currently categorized according to the Breast Imaging Reporting and Data System (BI-RADS) as category 4, which results in a recommendation for biopsy even when free silicone leakage is the most likely diagnosis. In this article, we present a case series that illustrates this issue with the BI-RADS system and propose an algorithmic approach that may allow some patients to be placed into BI-RADS category 3 and avoid biopsy. Methodology Eight cases of silicone breast implant rupture were identified at the University of Texas Medical Branch at Galveston over a five-year period. Two cases were excluded because MRI was not performed. The remaining six cases were evaluated for history and physical findings as well as mammogram, ultrasound, and MRI. All identified cases had been categorized as BI-RADS 4 and underwent biopsy. Results The six cases in this series exhibited pre-biopsy radiographic findings that were most consistent with silicone implant rupture. The ruptures were proven by biopsy, and no evidence of malignancy was identified in any of the patients. Conclusions Free silicone from breast implant rupture can present with enhancement on MRI. The two main categories of breast MRI enhancement, namely, mass and non-mass, include malignancies in their differential diagnoses and result in a BI-RADS category 4 designation. By correlating the findings with other imaging modalities, some of these patients can be classified as BI-RADS category 3 and biopsy can safely be avoided.

Intracystic Papillary Carcinoma: A Case Report.

Intracystic papillary carcinoma (IPC) of the breast is a rare form of in-situ carcinoma, which is contained within a dilated duct. Mammography and ultrasound may provide clues to its presence, but formal diagnosis always requires histologic evidence. Although IPC is associated with an excellent prognosis, surgical resection is important in order to rule out the possibility of any invasive component, which would result in the need for more aggressive treatment. In this paper, we review the radiographic and histologic features of this interesting diagnosis, present a patient case, and explore the possible reason why IPC does not require the same treatment modalities as the more common ductal carcinoma in situ (DCIS).

The Impact of Elexacaftor/Ivacaftor/Tezacaftor on Cystic Fibrosis Patients Who Acquire COVID-19 Infection.

The combination of medication containing elexacaftor, ivacaftor, and tezacaftor (EIT) has dramatically impacted the treatment and prognosis for patients with cystic fibrosis (CF). Lung function, weight, and self-reported quality of life have improved for many of these patients, but little is known about whether this treatment will have a beneficial effect in preventing morbidity and/or mortality from respiratory infections such as COVID-19. EIT received Food and Drug Administration (FDA) approval shortly before the first cases of COVID-19 appeared in the United States. We performed an analysis using the TriNetX (Cambridge, MA, USA) research database to determine if patients being treated with EIT who became infected with COVID-19 experienced significantly different outcomes compared to patients who were not receiving it.

The Use of Neodymium-Doped Yttrium Aluminum Garnet Laser for Treatment of Hypertrophic Port-Wine Stain.

Port-wine stains (also called nevus flammeus) are congenital malformations of the capillaries and postcapillary venules. They occur in 0.1-2% of newborns without sex predilection. Although PWS lesions are flat early in life, with age, they become hypertrophic and darker. Pulsed dye laser therapy is the standard of care for treating these lesions, although other laser wavelengths have been utilized with varying degrees of success. We present the case of a gentleman with a hypertrophic PWS who had an excellent response to Nd:YAG laser treatment. The increased tissue penetration of longer laser wavelengths may be of benefit to patients with hypertrophic PWS, and further research into this concept is warranted.

Angioimmunoblastic T-Cell Lymphoma: A Case Report.

Previously believed to be an exaggerated immune response and not a lymphoma, angioimmunoblastic T-cell lymphoma (AITL) is now recognized as a rare variant of peripheral T-cell lymphoma with an aggressive clinical course and poor response to current therapies. There is no standard of care for treatment, but the identification of extranodal involvement is useful for prognostic purposes since the involvement of more than one extranodal site can escalate the patient's risk category on the International Prognostic Index (IPI). Here we present the case of a patient with AITL who initially presented with an extranodal disease in the form of a fluorodeoxyglucose (FDG)-avid subcutaneous nodule and probable involvement of the spleen. After two months of treatment, her lymphoma exhibited an escalation of grade and an extensive worsening of Epstein-Barr virus (EBV) positivity.

Elucidation of a lingual detection mechanism for high-viscosity solutions in humans.

While perception of high-viscosity solutions (η > 1000 cP) is speculated to be linked to filiform papillae deformation, this has not been demonstrated psychophysically. Presently, just-noticeable-viscosity-difference thresholds were determined using the forced-choice staircase method and high-viscosity solutions (η = 4798-12260 cP) with the hypotheses that the tongue would be chiefly responsible for viscosity perception in the oral cavity, and that individuals with more, longer, narrower filiform papillae would show a greater acuity for viscosity perception. Subjects (n = 59) evaluated solutions in a normal, "unblocked" condition as well as in a "palate blocked" condition which isolated the tongue so that only perceptual mechanisms on the lingual tissue were engaged. Optical profiling was used to characterize papillary length, diameter, and density in tongue biopsies of a subset (n = 45) of participants. Finally, psychophysical and anatomical data were used to generate a novel model of the tongue surface as porous media to predict papillary deformation as a strain-detector for viscosity perception. Results suggest that viscosity thresholds are governed by filiform papillae features. Indeed, anatomical characterization of filiform papillae suggests sensitivity to high-viscosity solutions is associated with filiform papillae length and density (r = 0.68, p < 0.00001), but not with diameter. Modelling indicated this is likely due to a reciprocal interaction between papillae diameter and fluid shear stress. Papillae with larger diameters would result in higher viscous shear stress due to a narrower gap and stronger fluid-structure interaction, but a larger-diameter papilla would also deform less easily.

Escalation to Barbiturate-Induced Coma for Refractory Seizures after Liver Transplantation.

Seizures after liver transplantation were previously thought to be a reliable harbinger of catastrophe, but more recent studies have found seizure activity to be relatively common, and most cases do not result in a poor outcome. Generalized seizures are the most common, and they typically occur de novo within the first two weeks after transplantation. The underlying cause for seizure activity in these patients may be complex, with potential etiologies including metabolic, infectious, cerebrovascular, and medication-induced causes. Identification of the underlying cause and the use of antiepileptic drugs (AEDs) is crucial for minimizing risk to the patient's neurologic and overall health. In this report, we present the case of a patient with refractory seizures unresponsive to conventional treatment, requiring prolonged barbiturate burst suppression with ventilator support. Seizure activity eventually ceased, and the patient made a full recovery.

Postmenopausal Tubular Adenoma of the Breast: A Case Report.

Tubular adenoma (TA) of the breast is a rare, benign proliferative breast lesion that is predominantly composed of closely compacted tubules with an inner layer of epithelial cells and an outer layer of myoepithelial cells. They are regarded as residing on the opposite end of a spectrum of proliferative breast lesions from fibroadenomas, which are predominantly stromal. The majority of TAs are found in premenopausal women and the reason for this demographic predilection is not yet known. It is generally not possible to distinguish between TA and other, higher-risk breast lesions prior to biopsy or resection because the clinical and radiographic findings overlap. In this article, we present the case of a TA in a postmenopausal patient and review the epidemiology, histology, carcinogenic potential, and management of such lesions.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Lung Cancer: History, Epidemiology, and Market Outlook.

Lung cancer is a leading cause of death for both men and women. The treatment of lung cancer has been stifled with pessimism for many years. However, molecularly targeted therapies directed at pathologic epidermal growth factor receptor tyrosine kinases have come to market and, with them, a new tone to an old diagnosis. Treatment of lung cancer is a complex science that requires not only anatomical knowledge of the patient but also an understanding of the patient's overall physiologic condition. When patients are treated appropriately, this drug can transform the natural progression of their disease and improve survival. Interestingly, the clinical solidarity of these first-generation tyrosine kinase inhibitors (TKIs) has become the prelude to a second wave of advances in molecular targeting that we can expect to further improve how we classify and treat lung cancers. Cancers that become resistant to epidermal growth factor receptor (EGFR)-specific TKIs through a secondary mutation are likely to be dependent on the activated kinase for their growth and survival. Therefore, discovering a secondary means of inhibiting EGFR T790M may be therapeutically necessary. This has prompted the preclinical and clinical development of second and third-generation kinase inhibitors. Tumor subtypes are also now being identified, potentially allowing patients to be treated with drugs that most benefit their tumor subtype. We used the TriNetX research platform to analyze the rate of patients being prescribed first, second, and third-generation EGFR TKIs and propose a rationale for the trends seen over time.