Effect of Serum Deprivation Stress on Signal Induction Regulatory Protein-Alpha (SIRP-Alpha)-Mediated Erythrophagocytosis by Macrophages.

BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that involves loss of macrophages' self-cells recognition resulting in auto-phagocytosis of erythrocytes, leukocytes, and platelets and leading to multi-system effects. The pathogenesis of HLH is unclear but can be explained by malfunction of the physiologic inhibitory pathway through interaction between macrophage SIRP-alpha and erythrocyte CD 47. The goal of the present study was to evaluate if erythrocytes phagocytosis occurs as a result of altered macrophage SIRP-alpha expression during inflammatory/stressful conditions as seen in HLH. MATERIAL AND METHODS RAW264.7 macrophages were cultured in serum-free media (SFM) and complete media (CM) to simulate stressful and physiologic conditions, respectively. CD47+ mouse erythrocytes were used to test interactions with macrophages at different stages. SIRP-alpha expressions and phagocytosis assays were measured and analyzed at different steps. The study was in vitro and used murine cells to simulate in vivo human interactions. RESULTS SIRP-alpha expressions and phagocytosis rates were higher in SFM compared to CM. Interestingly, after adding SIRP-alpha blocking antibodies (Ab), phagocytosis rates significantly decreased. CONCLUSIONS Serum deprivation and LPS/INF-Gamma induction resulted in increased SIRP-alpha expression and erythrophagocytosis. Using SIRP-alpha Ab during this condition decreased the rate of erythrophagocytosis, which indicates that SIRP-alpha receptor can have pro-phagocytic activity.

The Effect of Perioperative Bevacizumab on Disease-Free and Overall Survival in Locally Advanced HER-2 Negative Breast Cancer: A Meta-Analysis.

INTRODUCTION: Multiple trials demonstrated that adding Bevacizumab to the standard neoadjuvant chemotherapy in HER-2 negative breast cancer increases pathological complete response. We conducted this meta-analysis to evaluate that effect on survival. METHODS: We performed a systematic search for randomized trials measuring the effect of adding either neoadjuvant or adjuvant Bevacizumab to the standard chemotherapy on disease-free and overall survival in breast cancer surgical candidates. The Mantel-Haenszel method and random effect model were used to analyze the data. A total of 7 randomized controlled trials were included in the analysis with a mean follow-up of 45 months. RESULTS: No statistically significant difference in overall survival was found after adding Bevacizumab to the standard chemotherapy in the overall study population, HR=0.9, 95% CI (90.72-1.13), estrogen/ progesterone positive subgroup, HR=0.99, 95% CI (0.72-1.35), or in triple negative breast cancer, HR=0.88, 95% CI (0.77-1.01). However, there was a small but significant improvement in disease-free survival in triple negative breast cancer with a HR of 0.88, 95% CI (0.78-0.98), but not in estrogen/ progesterone receptor positive tumors, HR=1.01, 95% CI (0.81-1.26). CONCLUSIONS: The addition of Bevacizumab along with the standard chemotherapy would not improve overall survival in breast cancer surgical candidates, however, due to a small but significant improvement on disease-free survival in triple negative breast cancer, that would not eliminate the possibility of a certain subgroup of the latter who might benefit from adding Bevacizumab.

A Rare Case of Complete Heart Block in a Young Patient.

INTRODUCTION: Complete heart block (CHB) is considered as one of the dangerous rhythms since it can progress to lethal arrhythmias such as ventricular tachycardia. It can be congenital or acquired. Patients may present with frequent palpitations, presyncope, dyspnea, or chest pain but also may remain asymptomatic. Extensive work-up should be conducted to exclude secondary causes such as infections, cardiac ischemia or myopathies, autoimmune diseases, or endocrinological diseases. In our paper, we would like to present a case of CHB in the setting of aortic abdominal thrombus that nearly occluded both renal arteries. The CHB in this case is thought to be caused by hypertensive cardiomyopathy due to ongoing uncontrolled hypertension, which is caused by bilateral renal artery stenosis. CASE PRESENTATION: A 31-year-old male with history of active smoking was incidentally found to have high blood pressure, bradycardia, and CHB on electrocardiogram. The patient was admitted to a cardiology ward and extensive work-up revealed hypokinesia of the left ventricle with low ejection fraction and left ventricle concentric hypertrophy, large abdominal aortic thrombus with bilateral renal artery stenosis, and evidence of arterial collateral connections, which suggest chronicity. The patient then was placed on four antihypertensive medications but eventually, he underwent bilateral renal artery stenting and insertion of permanent pacemaker for his CHB. The patient's blood pressure then was under control with only one medication, and subsequent CT angiogram showed no evidence of stenosis of both renal arteries. CONCLUSION: Uncontrolled hypertension can lead to hypertensive cardiomyopathy, which in turn can cause conduction abnormalities such as CHB. Although hypertension can be secondary to a treatable underlying cause, permanent pacemaker is essential to treat CHB.

The role of hydroxychloroquine in catastrophic antiphospholipid syndrome case: Series of two case reports and review of literature.

Catastrophic antiphospholipid syndrome is a rare disorder that remains under-recognized causing a high mortality rate even with treatment. Factors such as infections and systemic lupus erythematosus flare play as an inciting event in the thrombotic crisis which underlies catastrophic antiphospholipid syndrome. The use of plasmapheresis has improved the outcome of such cases with a reduction in mortality rate from over 50% to less than 30%, according to some studies. However, the definitive treatment of this disabling and fatal condition remains an area warranting research. Case 1. A case of 32-year-old female with a background of epilepsy and recurrent abortions who presented with difficulty in breathing, dry cough, and bilateral lower limb swelling. The patient initially received treatment with cyclophosphamide and systemic corticosteroids after being diagnosed with systemic lupus erythematosus. She also underwent plasmapheresis for suspected pulmonary hemorrhage as her condition deteriorated rapidly requiring intensive care. The diagnosis was revised as catastrophic antiphospholipid syndrome given the typical multi-organ involvement, namely, cerebritis, Libman-Sacks endocarditis, and nephritis apart from the pulmonary involvement. Eventually, hydroxychloroquine was added to the regimen which led to a remarkable improvement in her condition after a few days. Case 2. A case of 28-year-old female with history of recurrent abortions presented with abdominal pain and was admitted as a case of pancreatitis. The patient received intravenous fluids and analgesics with no significant improvement. Later, she developed multi-organ failure requiring critical care. Given her history and clinical presentation along with the multi-organ involvement in an acute setting, she underwent extensive workup that favored catastrophic antiphospholipid syndrome and she was started on Aspirin initially, and then, hydroxychloroquine was administered. Few days after initiation, her condition improved markedly and with complete resolution of her abdominal symptoms. Hydroxychloroquine's antithrombotic effect in synergy with other therapies has been observed in our cases. Yet, its role in the early course of catastrophic antiphospholipid syndrome merits further investigation.

Segmental arterial mediolysis presenting as spontaneous bilateral renal artery dissection.

The commonest site of primary dissection involving the visceral vessels is renal arteries; however, spontaneous bilateral renal artery dissection is an extremely rare entity. Spontaneous renal artery dissection (SRAD) is rarely a cause of renovascular hypertension. Segmental arterial mediolysis is a rare arteriopathy of unknown etiology which is a nonatherosclerotic and noninflammatory condition. We report a case of a 51-year-old male patient with spontaneous dissection of bilateral renal arteries with clinical, laboratory, and angiographic findings consistent with segmental artery mediolysis. Early diagnosis and treatment of this condition will decrease morbidity and mortality.

Superior mesenteric venous thrombosis complicating acute appendicitis: A case report.

RATIONALE: Superior mesenteric venous thrombosis (SMVT) is a rare condition that carries high mortality. Very few cases have been reported of SMVT, complicating acute appendicitis. Early recognition requires a high index of suspicion and is crucial in successful treatment of such a life-threatening condition. PATIENT CONCERNS: A 33-year-old male presents with a 4-day history of right lower abdominal pain, nausea and subjective fever. CT scan showed acute appendicitis and a central filling defect in the superior mesenteric vein. DIAGNOSES: Acute appendicitis complicated by SMVT. INTERVENTIONS: Intravenous antibiotics, appendectomy, and anticoagulation. OUTCOMES: Repeat CT scan showed successful resolution of the SMVT at a 3-month follow up. LESSONS: Clinical awareness and high index of suspicion are essential to diagnose and manage SMVT, a serious complication of acute appendicitis.

Metformin-associated lactic acidosis mimicking ischaemic bowel.

Metformin-associated lactic acidosis (MALA) is a rare complication among patients who are diabetic, commonly presenting with non-specific findings, and developing mostly among those with other risk factors for lactic acidosis. We report the development of MALA in a 67-year-old man with diabetes who presented with progressive abdominal pain and bloody diarrhoea. On presentation the patient was in shock, with signs suggestive of peritonitis, and with severe lactic acidosis, renal failure and non-specific findings on abdominal CT. Neither the patient nor family could provide details of his home pharmaceuticals. Circulatory resuscitation with intravenous crystalloids and vasopressors was commenced, along with empiric broad-spectrum antibiotics. Emergent laparotomy did not show pathological findings. Emergent haemodialysis, initiated postoperatively, resulted in rapid resolution of shock and lactic acidosis. A list of patient's medications, provided afterwards by the family, included metformin. Microbiological studies remained negative and renal function normalised by the time of patient's hospital discharge after 9 days.

Vertebral Artery Thrombosis in Chronic Idiopathic Thrombocytopenic Purpura.

INTRODUCTION: Immune thrombocytopenic purpura (ITP) is an autoimmune hematological disorder that causes decreased production and destruction of platelets leading to thrombocytopenia. Although thrombocytopenia usually causes hemorrhagic problems, thrombotic events like strokes, although rare, can still occur. Management of thrombotic events in patients with ITP differs from that of patients with normal platelet count function and count. CASE DESCRIPTION: A 32-year-old female with a history of ITP presented with ischemic stroke. The patient was treated in the hospital with IV immunoglobulin, discharged to a rehabilitation facility, and had complete resolution of symptoms when examined at a follow-up visit 3 months later. CONCLUSION: Although stroke in patients with ITP is very rare due to thrombocytopenia, it has been reported in several other published cases and is likely associated with increased platelet microparticle levels, a byproduct of platelet destruction. While usage of antiplatelet therapy in such patients is debated, immunosuppression therapy has been the mainstay treatment in all published cases.

Hemophagocytic syndrome masquerading as septic shock: An approach to such dilemma.

INTRODUCTION: Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis is a rare condition characterized by excessive inflammation that is thought to be caused by the absence of normal downregulation of activated macrophages and lymphocytes. The treatment of hemophagocytic lymphohistiocytosis can depend on whether it is primary or secondary. In secondary hemophagocytic lymphohistiocytosis, the treatment can be directed according to the cause. In general, protocol HLH-94 (which consists of dexamethasone and etoposide in induction and maintenance) has been widely used as it has good outcomes. Hemophagocytic lymphohistiocytosis and septic shock largely overlap which can lead to refractory septic shock and death if not treated. Unfortunately, there is no clear approach for such dilemma. Thereby, we would like to present our case as it has a valuable approach to hemophagocytic lymphohistiocytosis in the setting of sepsis. CASE DESCRIPTION: A 60-year-old female, with history of hypertension, came with fever, productive cough, and dyspnea; she was admitted for acute exacerbation of chronic obstructive pulmonary disease and was transferred to intensive care unit for septic shock. The patient progressed to refractory septic shock with no focus of infection. After further investigations, detailed history raised the suspicion of hemophagocytic lymphohistiocytosis; a bone marrow biopsy was collected and confirmed the diagnosis. The patient was on methylprednisolone while waiting for other investigation results and improved markedly. After ruling out secondary causes of hemophagocytic lymphohistiocytosis, she was switched to protocol-94 and continued to improve. CONCLUSION: It should be emphasized that septic shock, with or without focus of infection, overlaps with hemophagocytic lymphohistiocytosis and can consequently lead to refractory septic shock and death. Thus, our aim of this case is to encourage further investigations, specifically for hemophagocytic lymphohistiocytosis in the setting of septic shock of unknown origin, to decrease mortality rate. More importantly, early initiation of immunosuppression therapy may be a crucial step before switching to hemophagocytic lymphohistiocytosis-specific treatment.

Rare Purulent Cardiac Tamponade Caused by Streptococcus Constellatus in a Young Immunocompetent Patient: Case Report and Review of the Literature.

BACKGROUND Purulent pericardial tamponade is a very rare occurrence in the current era of widespread antibiotic use. It is even rarer when caused by Streptococcus constellatus: a microorganism usually classified among the normal flora of the human body. It is occasionally diagnosed with certain predisposing factors. CASE REPORT We present the third case of Streptococcus constellatus cardiac tamponade reported in the current medical literature, occurring in a previously healthy young man who was initially admitted and treated for possible community-acquired pneumonia. The patient required immediate subxyphoid pericardiocentesis. He was also treated successfully with a lengthy course of both intravenous and oral antibiotics. Two months post-hospitalization, he was confirmed clinically stable with complete resolution of his purulent effusion. We also conducted a review of the literature for all Streptococcus milleri group purulent pericardial infections between 1984 and 2015. CONCLUSIONS Purulent cardiac tamponade caused by Streptococcus constellatus is extremely rare. It can be life threatening, however. Early appropriate diagnosis and therapeutic intervention are critical for a good outcome.

Idiopathic Bilateral External Jugular Vein Thrombosis.

BACKGROUND: Vein thrombosis is mainly determined by 3 factors, which constitute a triad called Virchow's triad: hypercoagulability, stasis, and endothelial injury. Venous thrombosis commonly occurs in the lower extremities since most of the blood resides there and flows against gravity. The veins of the lower extremities are dependent on intact valves and fully functional leg muscles. However, in case of valvular incompetency or muscular weakness, thrombosis and blood stasis will occur as a result. In contrast, the veins of the neck, specially the jugulars, have distensible walls which allow flexibility during respiration. In addition, the blood directly flows downward towards the heart. Nevertheless, many case reports mentioned the thrombosis of internal jugular veins and external jugular veins with identified risk factors. Jugular vein thrombosis has previously been associated in the literature with a variety of medical conditions, including malignancy. CASE REPORT: This report is of a case of idiopathic bilateral external jugular vein thrombosis in a 21 year-old male construction worker of Southeast Asian origin with no previous medical history who presented with bilateral facial puffiness of gradual onset over 1 month. Doppler ultrasound and computed tomography were used in the diagnosis. Further work-up showed no evidence of infection or neoplasia. The patient was eventually discharged on warfarin. The patient was assessed after 6 months and his symptoms had resolved completely. CONCLUSIONS: Bilateral idiopathic external jugular veins thrombosis is extremely rare and can be an indicator of early malignancy or hidden infection. While previous reports in the literature have associated jugular vein thrombosis with malignancy, the present case shows that external jugular vein thrombosis can also be found in persons without malignancy.