Determining the Mechanism of Propofol-induced Neurotoxicity

Background and Hypothesis: Propofol is an IV anesthetic agent with many clinical applications, including general anesthesia, sedation, delirium, and palliative care. Despite its versatility and effectiveness, Propofol has been shown to have detrimental effects on the vascular interface between the brain and circulation. The Blood-Brain Barrier (BBB) acts as a selective interface that serves to protect the brain from its cerebrovascular network. BBB dysfunction can have lethal complications such as cerebral edema and stroke. Matrix Metalloproteinases (MMP’s), specifically MMP-2 and MMP-9 have been linked to BBB breakdown. Using human induced pluripotent stem cell (IPSC) derived brain microvascular endothelial cells (BMECs), we evaluated the impact of inhibiting MMP-2 on restoring BBB integrity following exposure to Propofol with the intent to reveal the mechanism by which Propofol disrupts the BBB. We hypothesized that inhibiting MMP-2 would lead to phenotype recovery after exposure to Propofol. Methods: IPSC-differentiated BMECs were treated with MMP inhibitors at varying time points and concentrations relative to exposure to Propofol for 3 hours. Trans-endothelial electrical resistance (TEER) and sodium fluorescein permeability was used to assess BBB structural integrity. A MTT assay was conducted to assess cell viability. Results: Inhibiting MMP-2 did not result in in recovery of BBB integrity following exposure to Propofol as no significant differences were observed in TEER and sodium fluorescein permeability between the Propofol control and Propofol + MMP-2 inhibitor groups. Conclusions & Future Directions: Propofol-induced disruption of BBB integrity does not appear to be through MMP-2 activity. High concentrations of MMP-inhibitor compounds result in increased disruption of BBB tightness and permeability. It is plausible to suspect that Propofol may act through other MMP’s to facilitate BBB break-down, thus future studies should investigate the effects of the other selective MMP inhibitors in their ability to achieve phenotype recovery following exposure to Propofol.

Oxidative Stress and Pathogenesis in Malaria

Malaria is a highly inflammatory and oxidative disease. The production of reactive oxygen species by host phagocytes is an essential component of the host response to Plasmodium infection. Moreover, host oxidative enzymes, such as xanthine oxidase, are upregulated in malaria patients. Although increased production of reactive oxygen species contributes to the clearance of the parasite, excessive amounts of these free radicals can mediate inflammation and cause extensive damage to host cells and tissues, probably contributing to severe pathologies. Plasmodium has a variety of antioxidant enzymes that allow it to survive amidst this oxidative onslaught. However, parasitic degradation of hemoglobin within the infected red blood cell generates free heme, which is released at the end of the replication cycle, further aggravating the oxidative burden on the host and possibly contributing to the severity of life-threatening malarial complications. Additionally, the highly inflammatory response to malaria contributes to exacerbate the oxidative response. In this review, we discuss host and parasite-derived sources of oxidative stress that may promote severe disease in P. falciparum infection. Therapeutics that restore and maintain oxidative balance in malaria patients may be useful in preventing lethal complications of this disease.

Skeleton binding protein-1-mediated parasite sequestration inhibits spontaneous resolution of malaria-associated acute respiratory distress syndrome

Malaria is a hazardous disease caused by Plasmodium parasites and often results in lethal complications, including malaria-associated acute respiratory distress syndrome (MA-ARDS). Parasite sequestration in the microvasculature is often observed, but its role in malaria pathogenesis and complications is still incompletely understood. We used skeleton binding protein-1 (SBP-1) KO parasites to study the role of sequestration in experimental MA-ARDS. The sequestration-deficiency of these SBP-1 KO parasites was confirmed with bioluminescence imaging and by measuring parasite accumulation in the lungs with RT-qPCR. The SBP-1 KO parasites induced similar lung pathology in the early stage of experimental MA-ARDS compared to wildtype (WT) parasites. Strikingly, the lung pathology resolved subsequently in more than 60% of the SBP-1 KO infected mice, resulting in prolonged survival despite the continuous presence of the parasite. This spontaneous disease resolution was associated with decreased inflammatory cytokine expression measured by RT-qPCR and lower expression of cytotoxic markers in pathogenic CD8+ T cells in the lungs of SBP-1 KO infected mice. These data suggest that SBP-1-mediated parasite sequestration and subsequent high parasite load are not essential for the development of experimental MA-ARDS but inhibit the resolution of the disease.

Case Report: Portal cavernoma related to multiple liver hydatidosis: A rare case of fatal cataclysmic haemorrhage.

Clinical presentation of liver hydatidosis can vary from asymptomatic forms to lethal complications. We report herein a rare case of a 27-year-old male from a rural Tunisian region who presented with large-abundance haematemesis, haemodynamic instability, and marked biological data of hypersplenism. Endoscopy showed bleeding esophageal varicose veins that were ligated. Abdominal ultrasound concluded the presence of three type CE2 hydatic liver cysts causing portal cavernoma with signs of portal hypertension. Despite resuscitation, the patient died of massive rebleeding leading to haemorrhagic shock. Hepatic hydatid cyst should be considered as an indirect cause of gastrointestinal bleeding in endemic countries. Early abdominal ultrasound in varicose haemorrhage is essential in orienting the diagnosis.

Case Report: Portal cavernoma secondary to multiple liver hydatidosis: A rare cause of cataclysmic haemorrhage in a young adult.

Clinical presentation of liver hydatidosis can vary from asymptomatic forms to lethal complications. We report a rare case of a 27-year-old male from a rural Tunisian region who presented with large-abundance haematemesis, haemodynamic instability, and marked biological signs of hypersplenism. Endoscopy showed bleeding esophageal varicose veins that were ligated. Abdominal ultrasound concluded the presence of three type CE2 hydatic liver cysts causing portal cavernoma with signs of portal hypertension. Despite resuscitation, the patient died of massive rebleeding leading to haemorrhagic shock. Hepatic hydatid cyst should be considered as an indirect cause of gastrointestinal bleeding in endemic countries. Early abdominal ultrasound in varicose haemorrhage is essential in orienting the diagnosis.

Push-Dose Pressors During Peri-intubation Hypotension in the Emergency Department: A Case Series

Introduction: Emergency physicians frequently encounter critically ill patients in circulatory shock requiring definitive airway procedures. Performing rapid sequence intubation in these patients without blood pressure correction has lethal complications. Questioning the efficacy and fearing side effects of push-dose pressors (PDP) has created an obstacle for their use in the emergency department (ED) setting. In this case series we describe the efficacy and side effects of PDP use during peri-intubation hypotension in the ED. Case series: We included 11 patients receiving PDPs in this case series. The mean increase in systolic blood pressure was 41.3%, in diastolic blood pressure 44.3%, and in mean arterial pressure 35.1%. No adverse events were documented in this case series. Conclusion: The use of push-dose pressors during peri-intubation hypotension may potentially improve hemodynamic status when used carefully in the ED.

A renal angiomyolipoma with a challenging presentation: a case report

Introduction Renal angiomyolipoma is considered a benign mesenchymal tumor composed of fat, smooth muscle, and blood vessels. It represents 1–3% of solid renal tumors. Despite this tumor’s benignity, it can be aggressive with a locoregional extension. Case report A 41-year-old north African caucasian woman consulted with chief complaints of right lower back pain with no hematuria and no urinal sign. Thoracic-abdominopelvic contrast-enhanced computed tomography showed a right inferior polar heterogeneous renal mass complicated with venous thrombus ascending to the right atrium level. The patient underwent radical nephrectomy under extracorporeal circulation and direct supervision of the fatty thrombus at the right atrium level. The postoperative period was uneventful. The final histologic examination was concordant with renal angiomyolipoma. Conclusion Renal angiomyolipoma is the most common benign kidney tumor. Despite its benignity, it can be associated with lethal complications such as hemorrhage, and it can also show signs of local extension mimicking malignant tumors. The cornerstone of the treatment remains surgery.

Immediate outcomes of simultaneous and step-by-step reconstruction of aortic dissection: a single-center study

The aim. To evaluate the immediate outcomes after complete single-stage or step-by-step reconstruction of the primary and secondary distal aortic dissection using implantation of bare metal stents in the thoracoabdominal aorta.Materials and methods. A prospective study was performed involving 21 patients (19 male) with aortic dissection: 8 had secondary distal dissection (group 1) and 13 had primary distal dissection (group 2). In all patients, indications for intervention were signs of malperfusion in one or more vascular regions. The following factors were evaluated: 30-day survival after surgery, causes of fatal outcomes, frequency and characteristics of non-fatal complications.Results. The average age in group 1 was 43.0 ± 3.1 years, in group 2: 56.0 ± 3.9 years (p < 0.05). The most common cause of dissection in group 1 was connective tissue dysplasia, in group 2 – atherosclerosis in combination with arterial hypertension (p < 0.05). In group 1, 1 (13%) lethal outcome was registered, in group 2 – 4 (31%), the difference between the groups was not significant. Lethal complications were: multiple organ failure, stent implantation in the false aortic canal, aortic rupture, and thrombosis of the superior mesenteric artery. Non-fatal complications developed in group 1 in 3 (38%), in group 2 – in 3 (23%) patients, the difference between the groups is not significant. Among the non-lethal complications, malperfusion of the upper and lower extremities was diagnosed, requiring stent placement, prosthetics or bypass surgery; cerebrospinal circulation disorder, acute cerebrovascular accident, multiple organ failure, conservatively treated.Conclusion. The survival rate for 30 days after a complete single-stage or step-by-step reconstruction of the primary and secondary distal aortic dissection using implantation of bare metal stents in the thoracoabdominal aorta is 76%, the frequency of non – fatal complications is 28%.

A 24-Year-Old Female Transplant Recipient with Type 2 Membranoproliferative Glomerulonephritis and Disseminated Shingles: A Cautionary Tale of Deferring to Primary Care

In this report, the case of a 24-year-old Caucasian female with type 2 membranoproliferative glomerulonephritis status post-living donor kidney transplant managed on triple regimen immunosuppressive therapy who developed shingles is discussed. With its onset, she promptly reached out to her nephrologist who deferred her to primary care. Prior to seeing her primary provider, she developed disseminated herpes zoster. She consulted emergency services where she was given inadequate care and again deferred to primary care. One day later, the dissemination included her entire torso, face, oral cavity, and all extremities. Fortunately, the patient had the insight to again reach out to her nephrologist who arranged for her to be admitted for appropriate care 6 days after her initial inquiry that carried 6 days of zoster progression. This case demonstrates how it is pertinent that specialists recognize potentially lethal complications associated with the conditions they follow. Although convenient to defer to primary care, if specialists were to take on the responsibility of providing a broader scope of care for their unique subsets of patients, it would likely result in a reduction in the 80% of serious medical errors that occur as a result of miscommunication, or lack thereof, between care providers.

Update on the role of Angiogenesis in Diabetes associated Nephropathy

Diabetic mellitus is common worldwide health problem which brings about different rigorous complications like retinopathy, nephropathy and numerous other lethal complications. Diabetic nephropathy is the major cause for blindness and renal failure in many of the developing countries. Hyperglycemia induced diabetic nephropathy gets elicited through improved development of reactive oxygen species in multiple cell types. The starting of organ damage or kidney failure shows some symptomatic effect or morphological changes as in one or both the kidneys like expansion or enlargement of kidneys from their original size and this enlargement process is known as nephromegaly. Microalbuminuria is the best possible predictable condition proceeding towards renal failure. This review briefly discussed about the diabetic nephropathy with regard to progression, angiogenic and non-angiogenic factors involved in pathogenesis and treatment of angiogenesis in diabetic nephropathy.