Myocardial Infarction Due to Paradoxical Thromboembolism Originating From Distal Lower Extremity Deep Vein Thrombosis (LEDVT).

Paradoxical embolism (PDE) originates in the venous system and ends up in the arterial circulation via cardiac or pulmonary shunts. Cases of PDE from venous thrombosis resulting in acute myocardial infarctions (MIs) are seldom reported in the literature. Diagnoses can often be missed if further workups are not pursued in patients without any underlying risk factors for coronary artery disease (CAD). Here, we report a case of a paradoxical embolus that crossed the patent foramen ovale (PFO), causing ST-elevation MI (STEMI) from an embolized venous thrombus originating in the left distal posterior tibial vein.

A Rare Case of Neural Epidermal Growth Factor-Like 1 Protein (NELL-1) Antigen-Associated Membranous Nephropathy.

Membranous nephropathy (MN) is an autoimmune disease resulting in nephrotic syndrome. Neural epidermal growth factor-like 1 protein (NELL-1) has been shown to cause a rare form of MN that is more likely to be associated with malignancy. We present a case of a 73-year-old female who was found to have a NELL-1-associated segmental MN. She presented complaining of generalized weakness, chills, and poor appetite, worsening over a one-week duration. Her kidney functions were noted to be markedly deranged, with a computed tomography scan of the abdomen showing evidence of chronic kidney disease. Further testing confirmed heavy proteinuria, although the etiology was still uncertain. A kidney biopsy revealed granular subepithelial immunoglobulin G deposits with subsequent immunohistochemical staining for NELL-1 antigen being positive. She improved with supportive care over the next few days. Despite an extensive workup, no underlying malignancy was found. NELL-1 is a rare yet recognized antigen target for the development of MN. Up to a third of patients with NELL-1-associated MN have associated cancer, thus requiring evaluation for underlying malignancy in this cohort.

Agranulocytosis Secondary to Cancer Chemotherapy Associated With Higher In-Hospital Mortality in Patients With Central Line Insertion During a Hospital Stay.

Background Agranulocytosis secondary to cancer chemotherapy (ASCC) remains a leading cause of morbidity and mortality. Central line-associated bloodstream infections (CLABSI) are also particularly prevalent in these populations and may portend a poorer outcome. Our study serves to investigate the relationship between patients with agranulocytosis secondary to cancer chemotherapy and the insertion of a central venous catheter (CVC) with respect to in-hospital mortality. Methods and results We utilized the National Inpatient Survey 2019 database. We utilized the International Classification of Diseases (ICD)-10 CM codes to identify ASCC and other medical comorbidities. We utilized ICD-10 PCS codes to identify CVC insertions. Multivariate logistic regression was utilized to study the effect of CVC insertion on in-hospital mortality. In patients with ASCC, CVC insertion was associated with a higher in-hospital mortality (unadjusted: 11.9% vs. 1%, p<0.001, adjusted OR 19.27, 95% CI 5.84 - 65.6, p<0.001) adjusted for baseline characteristics and other comorbidities. Patients in the study cohort who were older than 70 years of age also had a higher in-hospital mortality relative to younger age groups (adjusted OR 2.31, 95% CI 1.04-5.13, p<0.039). Conclusion In patients with ASCC, CVC insertion during hospitalization is associated with higher in-hospital mortality.

An Aggressive Case of Adrenocortical Carcinoma Complicated by Paraneoplastic Cushing's Syndrome.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Surgical resection may be curative if localized disease is identified, although recurrence is common. Research shows that the use of adjuvant therapeutic regimens such as EDP-M (combination of mitotane, etoposide, doxorubicin, and cisplatin) in high-risk patients has survival benefits. A 75-year-old female was incidentally found to have a right adrenal heterogeneous internal enhancement measuring 5.0 x 3.7cm. The workup confirmed autonomous adrenal production of corticosteroids and she was referred to surgery for an adrenalectomy. A T2 ACC with positive margins and lympho-vascular invasion was resected, following which she was started on external beam radiation followed by four cycles of carboplatin and etoposide. Despite initial treatments, she was diagnosed with refractory metastatic disease at subsequent follow-ups. Pembrolizumab immunotherapy was started, but disease progression continued, and she was eventually transitioned to mitotane 1g twice daily. She continued to worsen and was eventually transitioned to hospice care. The management of ACC remains diagnostically challenging, especially because most patients do not present until an advanced stage of disease. Surgery is commonly employed with a curative intent, and opinions regarding adjuvant cytotoxic therapy and/or radiotherapy remain mixed.

Gut-brain axis: Review on the association between Parkinson's disease and plant lectins.

Gastrointestinal (GI) involvement in the pathogenesis of Parkinson's Disease (PD) has been widely recognized and supported in recent literature. Prospective and retrospective studies found non-motor symptoms within the GI, specifically constipation, precede cardinal signs and cognitive decline by almost 20 years. In 2002, Braak et al. were the first to propose that PD is a six-stage propagating neuropathological process originating from the GI tract (GIT). Aggregated α-synuclein (α-syn) protein from the GIT is pathognomonic for the development of PD. This article reviews the current literature from the past 10 years as well as original research found in PubMed on the combined effects of enteric glial cells and lectins on the development of Parkinson's Disease. Studies have found that these aggregated and phosphorylated proteins gain access to the brain via retrograde transport through fast and slow fibers of intestinal neurons. Plant lectins, commonly found within plant-based diets, have been found to induce Leaky Gut Syndrome and can activate enteric glial cells, causing the release of pro-inflammatory cytokines. Oxidative stress on the enteric neurons, caused by a chronic neuro-inflammatory state, can cause a-syn aggregation and lead to Lewy Body formation, a hallmark finding in PD. Although the current literature provides a connection between the consumption of plant lectins and the pathophysiology of PD, further research is required to evaluate confounding variables such as food antigen mimicry and other harmful substances found in our diets.

The Novel ReNu Region of TAF12 Regulates Gcn5 Nucleosomal Acetylation.

The post-translational acetylation of the histone components of chromatin mediates numerous DNA-templated events, including transcriptional activation, DNA repair, and genomic replication. The conserved SAGA (Spt-Ada-Gcn5 Acetyltranferase) and SLIK (SAGA-Like) Histone Acetyltransferase (HAT) complexes are required for transcriptional activation of a subset of yeast genes and contain multiple subunits including the histone fold-containing TBP- Associated Factors (TAFs): 6, 9, 10, and 12. These TAFs are also components of the TFIID complex and are consequently involved in most RNA polymerase II-transcription in yeast. Here we identify a novel conserved region of TAF12, termed ReNu, outside of its histone fold, which is required for SAGA and SLIK-directed nucleosomal acetylation. We demonstrate that this region is not required for chromatin association, but show that this region plays an important role for histone H3 acetylation at specific SAGA and SLIK-regulated promoters. Our data suggests that the ReNu region of TAF12 regulates Gcn5 acetylation of specific substrates within the SAGA super-family of HAT complexes.