Drug-Coated Balloon Angioplasty for Axillary Artery Stenosis.

We present a case report of a patient with symptomatic bilateral severe axillary artery stenosis who underwent drug-coated balloon angioplasty. A 59-year-old female with a past medical history of peripheral artery disease presented with bilateral upper extremity claudication on exertion and episodes of syncope. Peripheral angiography showed significant bilateral upper extremity peripheral artery disease (PAD) including bilateral severe axillary artery stenosis. The patient underwent endovascular management with drug-coated balloon angioplasty of the axillary artery bilaterally. Symptoms completely resolved and the patient continues to be on follow-up. Arterial duplex studies on both upper extremities showed no evidence of high-grade stenosis six years after intervention. Drug coated balloon angioplasty can be a successful modality of endovascular management for patients with symptomatic severe axillary artery stenosis. However, more randomized controlled data is required before making any conclusion.

Clot in Transit: Therapy via Peripherally Inserted Central Catheter Line.

There are currently no definitive guidelines for the optimal management of clots in transit (CIT) due to a distinct lack of quality research to suggest a recommended therapy. The three main treatment modalities that are commonly utilized for pulmonary emboli (PE) (a sequela of CIT) are thrombolysis, pulmonary embolectomy, and anticoagulation alone. The current recommendation for severe PE with hemodynamic collapse is to consult cardiothoracic surgery for clot retrieval. One ongoing area of research involves the use of catheter-directed application of thrombolytic agents as it may have similar outcomes to the systemic application while minimizing the risk of bleeding events due to a lower dose of medication used. We report the case of a patient in whom, by taking advantage of an already placed peripherally inserted central catheter (PICC) line, tissue plasminogen activator (tPA) was successfully delivered at a localized site near the clot for active thrombolysis while only causing minimal adverse effects related to recent laminectomy/fasciectomy and foraminotomy compared to what may have been observed with systemic tPA administration.

ST Depression in the Setting of Subarachnoid Hemorrhage.

We present a case report of a patient presenting with subarachnoid hemorrhage whose electrocardiogram (ECG) mimicked non-ST-elevation myocardial infarction. A 36-year-old male with a past medical history of resistant hypertension, previous severe acute respiratory syndrome coronavirus 2 infection, and alcohol abuse presented to the hospital after cardiac arrest. He was taken to the catheterization lab upon arrival and was found to have an unremarkable coronary angiogram. After angiography, computerized tomography (CT) head was performed revealing an acute, large-volume, subarachnoid hemorrhage. Subsequent CT angiogram of the head confirmed this with source noted to be a ruptured aneurysm of the anterior communicating artery. ST depression on ECG has been reported in patients who have suffered a subarachnoid hemorrhage. Although the most common etiology of cardiac arrest is an acute coronary syndrome, other etiologies based on a patient's past medical history need to remain in the differential. Recognition of ECG changes may lead to earlier diagnosis and decreased mortality in subarachnoid patients.

Prolonged Use of an Impella Assist Device in a Sepsis-Induced Cardiomyopathy: A Case Report.

The inflammatory response triggered by sepsis can frequently cause reversible myocardial depression termed sepsis-induced cardiomyopathy. The resulting pathologic changes are often self-limiting and cardiac function returns to baseline following resolution of the underlying exacerbating factors. The following case examines a patient with septic shock and sepsis-induced cardiomyopathy that, despite maximal medical therapy, required mechanical support with an Impella assist device for seven days. To the best of our knowledge and research, this represents the longest documented use of an Impella heart pump in septic shock and associated sepsis-induced cardiomyopathy. Utilization of mechanical support in the setting of septic shock has seen growing interest in recent years, but more structured studies need to be conducted for better understanding of their overall effect on morbidity and mortality.

Isolated Abdominal Aortitis Following a Urinary Tract Infection.

A 49-year-old female with a history of sporadic episodes of scleritis was initially seen by her primary care physician (PCP) due to a two-day history of cramping abdominal pain, new elevated high blood pressure, increased urinary frequency, and urgency. The patient was diagnosed with an acute cystitis supported by a positive urine culture for a pan sensitive Escherichia coli; however, after two courses of antibiotics as an outpatient, her blood pressure (BP) remained markedly elevated, and her abdominal pain got worse which prompted a computed tomography (CT) abdomen and pelvis with contrast revealing inflammatory changes consistent with aortitis. The diagnosis was supported by a magnetic resonance angiography (MRA) which showed wall thickening and enhancement extending for approximately 4.8 cm involving the abdominal aortic wall just prior to the bifurcation. An extensive work up including CTA, US doppler of four-limbs, and fluorodeoxyglucose (FDG)-positron emission tomography (PET) confirmed the isolated abdominal aortitis. After infectious etiologies were ruled out, the patient was started on prednisone 60 mg daily which resulted in marked improvement of her symptoms. After a four-month taper of steroids, the patient had complete resolution of her symptoms, with no signs of recurrence.

Myasthenia Gravis as an Immune-Mediated Side Effect of Checkpoint Inhibitors.

This is a case report of new-onset myasthenia gravis (MG) as an immune-mediated adverse event (irAE) related to the use of pembrolizumab in a patient with undifferentiated adenocarcinoma of the pancreato-biliary tract. Up to this moment, only 52 cases of new-onset MG have been related to immune checkpoint inhibitors (ICIs). She was diagnosed with ocular MG nearly three months after starting the use of the anti-programmed death-ligand 1 (PD-1) inhibitor. The diagnosis was confirmed by the presence of serum antibodies against the acetylcholine receptor and the patient was started on pyridostigmine with subsequent clinical improvement. The use of pembrolizumab was discontinued due to concomitant progression of the subjacent malignant disease.

Modified fibrinolytic therapy as treatment of mechanical aortic valve thrombosis.

Prosthetic valve thrombosis is a rare phenomenon with limited treatment options. Current management choices include anticoagulation with or without fibrinolysis or surgical valve replacement for appropriate candidates. We report an alternative fibrinolytic and anticoagulation regimen resulting in successful treatment of a patient presenting with mechanical aortic valve thrombosis.

Rapid resolution of severe subcutaneous emphysema causing respiratory failure with subcutaneous drain.

This case reports on a critically ill patient (Male, 74) with severe subcutaneous emphysema which progressed to causing respiratory distress. We document both the severity of the condition we observed and then present a novel intervention. In this case, we decompressed the patient at the intensive care unit-bedside and resolved the condition. While subcutaneous emphysema is relatively common, the severity of the condition we observed, and the lack of definitive treatment guidance have prompted us to present this case as a plausible treatment guide.

Descending paralysis as an atypical presentation of Guillain-Barré Syndrome.

We herein report a case of a 55-year-old man with an unusual case of Guillain-Barré Syndrome. Its presentation is usually a progression of symmetric muscle weakness that is ascending from the lower extremities making its way more proximal and accompanied by absent or depressed tendon reflexes. Here, the patient exhibited a rare presentation of Guillain-Barré syndrome, where the weakness was ascending upper extremity and descending lower extremity paralysis. The objective of this clinical case report is to highlight this extremely rare descending paralysis presentation of Guillain-Barré Syndrome.

Real-Time Investigation of a Large Nosocomial Influenza A Outbreak Informed by Genomic Epidemiology.

BACKGROUND: Nosocomial respiratory virus outbreaks represent serious public health challenges. Rapid and precise identification of cases and tracing of transmission chains is critical to end outbreaks and to inform prevention measures. METHODS: We combined conventional surveillance with influenza A virus (IAV) genome sequencing to identify and contain a large IAV outbreak in a metropolitan healthcare system. A total of 381 individuals, including 91 inpatients and 290 healthcare workers (HCWs), were included in the investigation. RESULTS: During a 12-day period in early 2019, infection preventionists identified 89 HCWs and 18 inpatients as cases of influenza-like illness (ILI), using an amended definition without the requirement for fever. Sequencing of IAV genomes from available nasopharyngeal specimens identified 66 individuals infected with a nearly identical strain of influenza A H1N1pdm09 (43 HCWs, 17 inpatients, and 6 with unspecified affiliation). All HCWs infected with the outbreak strain had received the seasonal influenza virus vaccination. Characterization of 5 representative outbreak viral isolates did not show antigenic drift. In conjunction with IAV genome sequencing, mining of electronic records pinpointed the origin of the outbreak as a single patient and a few interactions in the emergency department that occurred 1 day prior to the index ILI cluster. CONCLUSIONS: We used precision surveillance to delineate a large nosocomial IAV outbreak, mapping the source of the outbreak to a single patient rather than HCWs as initially assumed based on conventional epidemiology. These findings have important ramifications for more-effective prevention strategies to curb nosocomial respiratory virus outbreaks.

Neonatal Kawasaki syndrome presenting as out of hospital cardiac arrest rescued by extracorporeal cardiopulmonary resuscitation.

A 7-week-old girl presented in severe shock to a local emergency department. During transfer to the quaternary pediatric hospital, the child had a cardiac arrest and cardiopulmonary resuscitation was commenced en route. Upon arrival to the pediatric intensive care unit, extracorporeal life support was initiated via trans-sternal cannulation. Chest CT performed after extracorporeal life support cannulation, demonstrated widespread aneurysms and a diagnosis of Kawasaki disease was made. Immunomodulatory therapy with immunoglobulin and glucocorticoid medication was commenced and the child was separated from extracorporeal life support after 48 hours. Our case highlights both an unusual presentation of Kawasaki disease and the role extracorporeal cardiopulmonary resuscitation can play in the treatment of this disease. It describes the youngest reported patient in the literature with Kawasaki disease rescued by extracorporeal cardiopulmonary resuscitation and highlights how extracorporeal life support therapy can facilitate appropriate investigations to resolve diagnostic uncertainty and treat the underlying condition.

Plumbagin Inhibits Prostate Carcinogenesis in Intact and Castrated PTEN Knockout Mice via Targeting PKCε, Stat3, and Epithelial-to-Mesenchymal Transition Markers.

Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4(+)) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.

Prospective study of incidence and predictors of peripheral intravenous catheter-induced complications.

BACKGROUND: Although intravenous therapy is one of the most commonly performed procedures in hospitalized patients, it remains susceptible to infectious and noninfectious complications. Previous studies investigated peripheral intravenous catheter (PIVC) complications mainly in pediatrics, but apparently none were investigated among Saudi adult populations. The aim of this study was to assess the pattern and complications of PIVCs at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. METHODS: An observational prospective cohort study investigated PIVCs pattern and complications among adults with PIVCs, admitted to various wards at KAMC. PIVCs-related clinical outcomes (pain, phlebitis, leaking, and others) were recorded in 12-hour intervals, using the Visual Inspection Phlebitis scale. Density incidence (DI) and cumulative incidence (CI) of complications and their relative risks (RRs) were calculated. Regression analyses were applied and significance limits were set at P<0.05. RESULTS: During the study period, 359 adults were included, mounting to 842 PIVCs and 2,505 catheter days. The majority of patients, 276 (76.9%), had medical, chief admission complaints, whereas 83 (23.1%) were trauma/surgical and infectious cases. Complicated catheters were found in 141 (39.3%) patients, with 273 complications (32.4/100 catheters), in 190 complicated catheters (CI =22.56/100 catheters and DI =75.84/1,000 catheter days). Phlebitis ranked first among complications, 148 (CI =17.6%), followed by pain 64 (CI =7.6%), leaking 33 (CI =3.9%), dislodgement 20 (CI =2.4%), and extravasations and occlusion 4 (CI =0.5% each). Phlebitis was predicted with female sex (P<0.001), insertion in fore/upper arm (P=0.024), and infusion of medication (P=0.02). Removal time for PIVCs insertion was not a significant predictor of phlebitis (RR =1.46, P=0.08). CONCLUSION: Incidence of complications in this study was significantly higher than rates in previous studies. Better insertion techniques may be sought to lower the incidences of PIVC complications, thus extending their onset beyond day 3. Changing catheters is recommended when clinically indicated rather than routinely post-72 hours.

α-Mangostin: a dietary antioxidant derived from the pericarp of Garcinia mangostana L. inhibits pancreatic tumor growth in xenograft mouse model.

AIMS: Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC. RESULTS: The chemotherapeutic effect of α-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). α-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. α-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, α-mangostin inhibited the expression levels of pNF-κB/p65Ser552, pStat3Ser727, and pStat3Tyr705. α-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-κB) and signal transducer and activator 3 (Stat3). α-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of α-mangostin (6 mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with α-mangostin. α-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues. INNOVATION: We present, for the first time, that dietary antioxidant α-mangostin inhibits the growth of PC cells in vitro and in vivo. CONCLUSION: These results suggest the potential therapeutic efficacy of α-mangostin against human PC.

Plumbagin, a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone, inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model.

We present here first time that Plumbagin (PL), a medicinal plant-derived 1,4-naphthoquinone, inhibits the growth and metastasis of human prostate cancer (PCa) cells in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2 × 10(6)) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt. i.p. five days in a week) for 8 weeks. Growth and metastasis of PC-3M-luciferase cells was examined weekly by bioluminescence imaging of live mice. PL-treatment significantly (p = 0.0008) inhibited the growth of orthotopic xenograft tumors. Results demonstrated a significant inhibition of metastasis into liver (p = 0.037), but inhibition of metastasis into the lungs (p = 0.60) and lymph nodes (p = 0.27) was not observed to be significant. These results were further confirmed by histopathology of these organs. Results of histopathology demonstrated a significant inhibition of metastasis into lymph nodes (p = 0.034) and lungs (p = 0.028), and a trend to significance in liver (p = 0.075). None of the mice in the PL-treatment group showed PCa metastasis into the liver, but these mice had small metastasis foci into the lymph nodes and lungs. However, control mice had large metastatic foci into the lymph nodes, lungs, and liver. PL-caused inhibition of the growth and metastasis of PC-3M cells accompanies inhibition of the expression of: 1) PKCε, pStat3Tyr705, and pStat3Ser727, 2) Stat3 downstream target genes (survivin and Bcl(xL)), 3) proliferative markers Ki-67 and PCNA, 4) metastatic marker MMP9, MMP2, and uPA, and 5) angiogenesis markers CD31 and VEGF. Taken together, these results suggest that PL inhibits tumor growth and metastasis of human PCa PC3-M-luciferase cells, which could be used as a therapeutic agent for the prevention and treatment of human PCa.

Plumbagin inhibits prostate cancer development in TRAMP mice via targeting PKCε, Stat3 and neuroendocrine markers.

Plumbagin (PL), 5-hydroxy-2-methyl-1,4-naphthoquinone, is a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L. (also known as chitrak). PL has also been found in Juglans regia (English Walnut), Juglans cinerea (whitenut) and Juglans nigra (blacknut). The roots of P. zeylanica have been used in Indian and Chinese systems of medicine for more than 2500 years for the treatment of various types of ailments. We were the first to report that PL inhibits the growth and invasion of hormone refractory prostate cancer (PCa) cells [Aziz,M.H. et al. (2008) Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res., 68, 9024-9032.]. Now, we present that PL inhibits in vivo PCa development in the transgenic adenocarcinoma of mouse prostate (TRAMP). PL treatment (2 mg/kg body weight i.p. in 0.2 ml phosphate-buffered saline, 5 days a week) to FVB-TRAMP resulted in a significant (P < 0.01) decrease in prostate tumor size and urogenital apparatus weights at 13 and 20 weeks. Histopathological analysis revealed that PL treatment inhibited progression of prostatic intraepithelial neoplasia (PIN) to poorly differentiated carcinoma (PDC). No animal exhibited diffuse tumor formation in PL-treated group at 13 weeks, whereas 75% of the vehicle-treated mice elicited diffuse PIN and large PDC at this stage. At 20 weeks, 25% of the PL-treated animals demonstrated diffuse PIN and 75% developed small PDC, whereas 100% of the vehicle-treated mice showed large PDC. PL treatment inhibited expression of protein kinase C epsilon (PKCε), signal transducers and activators of transcription 3 phosphorylation, proliferating cell nuclear antigen and neuroendocrine markers (synaptophysin and chromogranin-A) in excised prostate tumor tissues. Taken together, these results further suggest PL could be a novel chemopreventive agent against PCa.

Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways.

Pancreatic cancer (PC) is the most aggressive malignant disease, ranks as the fourth most leading cause of cancer-related death among men and women in the United States. We present here that plumbagin (PL), a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L, inhibits the growth of PC cells both in vitro and in vivo model systems. PL treatment induces apoptosis and inhibits cell viability of PC cells (PANC1, BxPC3 and ASPC1). In addition, i.p. administration of PL (2 mg/kg body weight, 5 days a week) in severe combined immunodeficiency (SCID) mice beginning 3 days after ectopic implantation of PANC1 cells resulted in a significant (P < 0.01) inhibition of both tumor weight and volume. PL treatment inhibited (1) constitutive expression of epidermal growth factor receptor (EGFR), pStat3Tyr705 and pStat3Ser727, (2) DNA binding of Stat3 and (3) physical interaction of EGFR with Stat3, in both cultured PANC1 cells and their xenograft tumors. PL treatment also inhibited phosphorylation and DNA-binding activity of NF-κB in both cultured PC cells (PANC1 and ASPC1) and in PANC1 cells xenograft tumors. Downstream target genes (cyclin D1, MMP9 and Survivin) of Stat3 and NF-κB were similarly inhibited. These results suggest that PL may be used as a novel therapeutic agent against human PC. Published 2012 Wiley-Liss, Inc. This article is a US Government work, and, as such, is in the public domain in the United States of America.