Liver infarctions as the first manifestation of antiphospholipid antibody syndrome in pregnancy: a case report.

BACKGROUND: The differential diagnosis of abdominal pain in pregnant women is broad. Liver diseases as the origin of abdominal pain in pregnancy are rare, and severe forms occur in less than 0.1% of pregnancies. Some disorders, such as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome and preeclampsia, are unique to pregnancy, while others, such as antiphospholipid antibody syndrome, may manifest in pregnancy but have consequences beyond the current pregnancy. All of them require prompt identification and treatment. CASE PRESENTATION: A 27-year-old Caucasian woman who was 15+1 weeks pregnant reported to the emergency department twice due to stabbing right-upper-quadrant abdominal pain. Initial laboratory testing revealed mild leukocytosis and slightly elevated liver enzymes. On second presentation, the patient was febrile and had an increased C-reactive protein concentration. Over the course of the next days, nonhemolytic anemia and thrombocytopenia emerged with elevated liver enzymes. Coagulation studies also revealed a prolongation of activated partial thromboplastin time. Magnetic resonance imaging showed nonspecific alterations in the right liver lobe, possibly corresponding to infection or infarction. A hepatic viral infection was ruled out. At that time, the most likely diagnosis was cholangitis with liver abscess formation, and antibiotic therapy was started. Further worsening of the anemia and thrombocytopenia, development of proteinuria, together with a miscarriage on the fourth day of hospitalization resulted in the tentative diagnosis of (triple-positive) antiphospholipid antibody syndrome, which was confirmed 12 weeks after the initial investigation. Treatment consisted of prompt anticoagulation with heparin and later on with a vitamin K antagonist as well as high-dose glucocorticoid therapy. There was no need for intravenous immunoglobulin therapy or plasma exchange, although we suspected a catastrophic form of antiphospholipid antibody syndrome due to infarctions of the liver, placenta, and possibly kidneys (proteinuria). The outcome was favorable. CONCLUSION: We report a 27-year-old pregnant woman whose abdominal pain was caused by liver infarctions as the first manifestation of catastrophic antiphospholipid antibody syndrome. The antiphospholipid antibody syndrome was possibly secondary to hitherto clinically silent systemic lupus erythematosus since the antinuclear antibodies were increased later on. Hydroxychloroquine therapy was initiated to prevent antiphospholipid antibody syndrome recurrence in a future pregnancy.

Immune checkpoint inhibitor therapy-associated encephalitis: a case series and review of the literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause a wide spectrum of immune-related adverse events, including encephalitis. To date, no prospective randomised controlled trials examining the patient characteristics, treatment and outcomes of ICI-associated encephalitis have been published. Therefore, we aimed to review case reports and to provide recommendations for the management of ICI-associated encephalitis. METHODS: A literature search using Google Scholar and PubMed was performed in December 2019. Published case reports and case series of ICI-associated encephalitis were reviewed, and a case series from the Limmattal Hospital in Schlieren, Switzerland was added. The results are presented as numbers and medians (ranges). RESULTS: Five different ICIs caused encephalitis in the 47 patients included in this case series. Nivolumab was the most frequently involved drug (27/47, 57%). The median time between treatment and onset of symptoms was 65 (4–630) days. Patients presented with rapidly evolving confusion, reduced level of consciousness, headache, seizures and focal neurological deficits. A total of 19 out of the 44 (43%) magnetic resonance imaging (MRI) scans performed revealed findings suggestive of encephalitis. No specific electroencephalogram (EEG) pattern consistent with encephalitis was found, but epileptiform discharges were detected in 7/20 (35%) of all tested patients. Typical findings of cerebrospinal fluid (CSF) analysis were pleocytosis, elevated protein levels and normal glucose concentrations. Forty-four out of 47 (94%) patients received corticosteroids. Intravenous immunoglobulins (IVIG), rituximab and plasma exchange therapy were less frequently prescribed. Nine out of 47 (19%) patients died during the index hospitalisation. CONCLUSIONS: Encephalitis should be suspected in patients treated with ICIs who present with rapidly evolving confusion. Blood tests, CSF analysis, cerebral MRI and an EEG should be performed. Therapy with intravenous corticosteroids is recommended. Steroid unresponsiveness is rare and should lead to a review of the diagnosis. Alternative treatment options are IVIG, plasma exchange therapy and rituximab.  .

Carbon dioxide narcosis due to inappropriate oxygen delivery: a case report.

BACKGROUND: Oxygen delivery to patients with chronic obstructive pulmonary disease may be challenging because of their potential hypoxic ventilatory drive. However, some oxygen delivery systems such as non-rebreathing face masks with an oxygen reservoir bag require high oxygen flow for adequate oxygenation and to avoid carbon dioxide rebreathing. CASE PRESENTATION: A 72-year-old Caucasian man with severe chronic obstructive pulmonary disease was admitted to the emergency department because of worsening dyspnea and an oxygen saturation of 81% measured by pulse oximetry. Oxygen was administered using a non-rebreathing mask with an oxygen reservoir bag attached. For fear of removing the hypoxic stimulus to respiration the oxygen flow was inappropriately limited to 4L/minute. The patient developed carbon dioxide narcosis and had to be intubated and mechanically ventilated. CONCLUSIONS: Non-rebreathing masks with oxygen reservoir bags must be fed with an oxygen flow exceeding the patient's minute ventilation (>6-10 L/minute.). If not, the amount of oxygen delivered will be too small to effectively increase the arterial oxygen saturation. Moreover, the risk of carbon dioxide rebreathing dramatically increases if the flow of oxygen to a non-rebreathing mask is lower than the minute ventilation, especially in patients with chronic obstructive pulmonary disease and low tidal volumes. Non-rebreathing masks (with oxygen reservoir bags) must be used cautiously by experienced medical staff and with an appropriately high oxygen flow of 10-15 L/minute. Nevertheless, arterial blood gases must be analyzed regularly for early detection of a rise in partial pressure of carbon dioxide in arterial blood in patients with chronic obstructive pulmonary disease and a hypoxic ventilatory drive. These patients are more safely managed using a nasal cannula with an oxygen flow of 1-2L/minute or a simple face mask with an oxygen flow of 5L/minute.

Severe rhinovirus pneumonia in a young woman taking performance-enhancing drugs.

A 22-year-old woman presented to the emergency room of a local hospital with pleuritic chest pain. She regularly worked out and admitted to taking performance-enhancing drugs (PEDs). Clinical findings and further diagnostic work up revealed a diagnosis of perimyocarditis, and adequate therapy was initiated. During the course of the first day, the patient had to be intubated and mechanically ventilated. A diagnosis of bilateral pneumonia and acute respiratory distress syndrome (ARDS) due to an infection by rhinovirus spp was made. A smoking habit, the intense physical training and the use of PED's may have exacerbated the course of the viral pneumonia. After 12 days the patient could be extubated. The length of stay in the intensive care unit was 16 days. After hospital discharge, the patient went to a pulmonary rehabilitation facility for 2 weeks. The outcome was favourable and the patient resumed her strength and endurance training.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare "disease of the desmosome" with multiple clinical presentations.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a rare but increasingly recognized form of a cardiomyopathy, involving primarily the right ventricle. Mutations in seven candidate genes coding for five desmosomal proteins (plakoglobin, plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2), for the cardiac ryanodine receptor-2, for the transforming growth factor beta-3, and for the transmembrane protein 43, respectively, are pathogenetically important. A typical feature of the disease is the replacement of the right ventricular myocardium by fibrofatty infiltrates, leading to electrical instability including ventricular arrhythmias in the early stages, and reduced contractility and heart failure later on. The left ventricle may also be involved. Unfortunately, the disease is often diagnosed post mortem only, especially in young adults dying suddenly during exercise. Since the disease is inherited in up to 50% of cases, the screening of relatives is important. The implantable cardioverter defibrillator is an important therapeutic tool. Nevertheless, the mortality of the disease remains to be 2%-4% per year. Several clinical, electrocardiographic, and imaging parameters were identified as risk predictors for an adverse outcome. In this paper, we describe distinct clinical presentations of ARVC/D, review the genetic background of the disease, and discuss its diagnosis and treatment.

Identification of histone H2B as a regulated plasminogen receptor.

Tethering of plasminogen to cell surfaces controls plasmin formation and, thereby, influences pericellular proteolysis and cell migration. Modulation of cellular plasminogen binding sites provides a mechanism for regulation of these events. In this study, two distinct models, phorbol ester-stimulated adhesion of U937 monocytoid cells and culturing of peripheral blood neutrophils, treatments which modulate plasminogen binding sites, have been examined to determine the molecular basis for the upregulation of plasminogen receptors. Membranes were isolated from cell populations, with and without upregulated plasminogen binding capacities, and analyzed by [(125)I]plasminogen ligand blotting of gel transfers. Approximately 15 different [(125)I]plasminogen-binding proteins were discerned in the membrane fractions, and only relatively minor differences in the intensities of individual bands were noted in the different cell populations. The notable exception was the presence of a 17 kDa band, which was selectively and markedly enhanced in the membranes from cells with enhanced plasminogen binding capacities. The 17 kDa protein was isolated from both cell types, and amino acid sequencing of peptide fragments identified the same protein, histone H2B. Increased expression of histone H2B was observed on stimulated U937 cells and cultured neutrophils by confocal microscopy with an antibody raised to the carboxy-terminal octopeptide sequence of histone H2B. This antibody or its Fab fragments substantially decreased the level of binding of plasminogen to these cultured neutrophils and stimulated U937 cells that exhibited elevated levels of binding but not to nonstimulated cells. Thus, histone H2B represents a regulated plasminogen receptor, which contributes significantly to the plasminogen binding capacity of cells.

Headache as a manifestation of a life-threatening vascular disorder.

Headache is a common complaint among patients seeking medical assistance. The differentiation between a primary headache disorder versus headache as a symptom of a serious underlying disease is of crucial importance. Dissections of the carotid or vertebral arteries frequently present with headache and can result in ischemic stroke. Rarely, headache or neck pain is a presenting symptom in patients with spontaneous proximal aortic dissection. We report on a 53-year-old man with a history of migraine with aura, who was admitted to the hospital because of severe frontal headache and neck pain. An anterior chest pain lasting for 10 minutes the day before and a diastolic heart murmur suggested a proximal aortic dissection, which was confirmed by transesophageal echocardiography. Patients with proximal aortic dissection rarely have headache or neck pain, reflecting the low incidence of carotid artery involvement in this disease. However, differentiation between an isolated cervical artery dissection and a proximal aortic dissection extending to the carotid arteries is pivotal, since treatment options are vastly different.

Regulation of plasminogen receptors.

Many eukaryotic and prokaryotic cells bind plasminogen in a specific and saturable manner. When plasminogen is bound to cell-surface proteins with C-terminal lysines via its lysine binding sites, its activation to plasmin is accelerated, and cell-bound plasmin is protected from inactivation by natural inhibitors. Plasmin mediates direct or indirect degradation of the extracellular matrix, and bound plasmin is used by cells to facilitate migration through extracellular matrices. Since cell migration and tissue remodelling are the underpinnings of many physiological and pathological responses, the modulation of plasminogen receptors may serve as a primary regulatory mechanism for control of many cellular responses. Specific examples of cell types on which plasminogen receptors undergo modulation include: fibroblasts, where modulation may contribute to cartilage and bone destruction in rheumatoid arthritis; leukemic cells, where enhanced plasminogen binding may contribute to the heightened fibrinolytic state in the patients; other tumor cells, where up-regulation may support invasion and metastasis; bacteria, where enhanced plasminogen binding may facilitate tissue destruction and invasion; platelets, where up-regulation of plasminogen binding may play a role in regulating clot lysis; and adipocytes, where the modulation of plasminogen receptor expression may regulate cell differentiation and fat accumulation. Two pathways for modulation of plasminogen receptors have been characterized: A protease-dependent pathway can either up-regulate or down-regulate plasminogen binding to cells by changing the availability of plasminogen-binding proteins with C-terminal lysines. New receptors may be generated by trypsin-like proteases, including plasmin, which create new C-terminal lysines; other enzymes may expose existing membrane proteins by altering the cell surface; or receptor function may be lost by removal of C-terminal lysines. The basic carboxypeptidases of blood carboxypeptidase N and plasma carboxypeptidase B (TAFI) mediate such down-regulation. A non-protease dependent pathway for modulation of plasminogen receptors may be initiated by growth factors, chemokines or cytokines that alter the cell membrane and/or cytoskeleton architectures to expose plasminogen binding sites. Many examples of the modulation of plasminogen receptors have been demonstrated in vitro, and the development of knock-out mice may soon lead to incisive evaluations of the significance of the regulation of plasminogen receptors in vivo.