Impact of remote ischemic preconditioning preceding coronary artery bypass grafting on inducing neuroprotection.

BACKGROUND: Neurological complications after coronary artery bypass grafting (CABG) reduce quality of life, increase mortality, and inflate resource utilization. The risk of postoperative neurological complications parallels the increasing risk burden of the contemporary patient population. We evaluated the efficacy of remote ischemic preconditioning (RIPC) on inducing neuroprotection. METHODS: Seventy patients undergoing first-time CABG were randomly assigned to RIPC or a sham procedure. Structural brain magnetic resonance imaging (MRI) was complemented with functional connectivity MRI to gain a whole-brain global connectivity analysis. Paired neurocognitive and MRI data were acquired pre- and postoperatively. The primary end point was a composite of new ischemic brain lesions and neurocognitive impairment. Secondary end points included brain connectivity profiles, pooled ischemic volumes, and individual components of the primary outcome. The Shapiro-Wilk test was used to determine whether a data set followed a normal distribution. The Fisher exact test was used to calculate the measures of association for categorical variables, whereas continuous data were tested with either the Mann-Whitney U test or the Student t test. RESULTS: There was no between-group difference in the incidence of the primary end point (9 [27%] in the RIPC group vs 8 [24%] in the control group, odds ratio, 1.17 [95% confidence interval, 0.34-4.06]; P = 1.0). Although RIPC did not reduce the incidence of brain ischemia (8/33 [24%] vs 7/33 [21%]; P = 1.0), the pooled ischemic volume was lower in the RIPC group (157 [interquartile range, 125-231] vs 777 [interquartile range, 564-965] mm3; P = .004). Postoperative neurocognition was marginally superior in the RIPC group as evidenced by a lower absolute number of abnormal neurocognitive tests in the RIPC group (7/99 [7%] vs 16/99 [16%]; odds ratio, 0.40 [95% confidence interval, 0.14-1.09]; P = .074). Robust reductions of functional connectivity profiles for the associative thalamus were documented in both groups, irrespective of RIPC (RIPC group, t = 3.31; P < .01; and the control group, t = 3.52; P < .01). CONCLUSIONS: Silent brain ischemia occurs frequently after CABG. RIPC did not reduce the incidence of the primary outcome. However, RIPC significantly reduced the pooled volume of ischemic brain lesions. Surgery adversely affected global brain connectivity, with RIPC conferring no demonstrable protection. The association of RIPC with superior neurocognitive test scores failed to cross the threshold for significance.

Resolution of polyserositis after removal of appendix mucinous cystadenoma.

Mucinous cystadenoma is a rare benign neoplasm and is usually discovered incidentally. Pleuritis and pericarditis, inflammation of the pleura and pericardium, may represent manifestations of autoimmune disorders especially in female subjects. We report a patient with polyserositis that was resolved after removal of the mucinous cystadenoma. To the best of our knowledge, this is a first report describing pleuritis and pericarditis as an initial presentation of mucinous cystadenoma of an appendix. A forty-year-old Caucasian female patient with a history of pleuritis and recurrent pericarditis was admitted to the hospital due to acute abdomen. At that time she was taking indomethacin and colchicine due to pericarditis that was controlled only with the combination of these two drugs. The patient had elevated erythrocyte sedimentation rate (ESR), increased C-reactive protein (CRP) and normocytic anemia. Immunological tests, including antinuclear antibody, anti-neutrophil cytoplasmic antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies, were repeatedly negative. Emergency surgery revealed acute appendicitis with perforation and subsequent diffuse peritonitis. Histopathological examination showed acute appendicitis and mucinous cystadenoma. Following the surgery the patient did not take any drugs. Fourteen months later the patient was symptom free. Pleuritis and pericarditis in female patients are most often associated with autoimmune diseases. We assume that increased ESR and CRP with anemia detected in the patient may reflect the altered immunity that is due to mucinous cystadenoma. We believe that this report has a broader clinical impact, implying that benign tumor could alter immunity, which can lead to unusual presentation such as polyserositis.

Hematologic malignancies in the medical intensive care unit--Outcomes and prognostic factors.

Objectives To analyze clinical characteristics, treatment, outcomes of critically ill patients with hematologic malignancies (HM) admitted to the medical intensive care unit (ICU) and to identify predictors of adverse outcome. Methods We analyzed prospectively 170 patients. Data included: demographic characteristics, hematologic diagnosis, reasons for ICU admission, transplant status, the presence of neutropenia, acute physiology and chronic health evaluation-II and sequential organ failure assessment scores, and level of organ support. Predictors of ICU mortality were evaluated using univariate and multivariate analysis. Results In total, 73% of patients had high-grade malignancy, 47.6% received intensive chemotherapy before admission, and 30% underwent hematologic stem cell transplantation procedure. In total, 116 (68.2%) of patients were mechanically ventilated; 88 (51.8%) required invasive mechanical ventilation (MV). Non-invasive ventilation started in 28 (16.5%) patients and was successful in 11 (6.5%). The ICU mortality rate was 53.5%, and the mortality of MV patients was 75.9%. Need for vasopressors at admission and MV were identified as independent predictors of fatal outcome. Conclusion The ICU mortality of critically ill patients with HM is high, particularly in the group of MV. Need for vasopressors at admission and MV were independent predictors of ICU mortality. Majority of patients required invasive MV due to severe respiratory failure and non-invasive MV was sufficient only in small number of cases with favorable outcome.

Impact of remote ischemic preconditioning preceding coronary artery bypass grafting on inducing neuroprotection (RIPCAGE): study protocol for a randomized controlled trial.

BACKGROUND: Neurological complications after cardiac surgery have a profound impact on postoperative survival and quality of life. The increasing importance of strategies designed to improve neurological outcomes mirrors the growing risk burden of the contemporary cardiac surgical population. Remote ischemic preconditioning (RIPC) reduces adverse sequelae of ischemia in vulnerable organs by subjecting tissues with high ischemic tolerance to brief periods of hypoperfusion. This trial will evaluate the neuroprotective effect of RIPC in the cardiac surgical arena, by employing magnetic resonance imaging (MRI) and neurocognitive testing. METHODS: Patients scheduled for elective coronary artery bypass grafting with the use of cardiopulmonary bypass will be screened for the study. Eligible patients will be randomized to undergo either a validated RIPC protocol or a sham procedure. The RIPC will be induced by inflation of a blood pressure cuff to 200 mmHg for 5 minutes, followed by a 5-minute reperfusion period. Three sequences of interchanging cuff inflations and deflations will be employed. Neurocognitive testing and MRI imaging will be performed preoperatively and on postoperative day 7. Paired pre- and postoperative neurocognitive and neuroimaging data will then be compared. The primary composite outcome measure will consist of new ischemic lesions on brain MRI, postprocedural impairment in brain connectivity on resting-state functional MRI (rs-fMRI), and significant new declines in neurocognitive performance. The secondary endpoint measures will be the individual components of the primary endpoint measures, expressed as continuous variables, troponin T release on postoperative day 1 and the incidence of major adverse cardiovascular events at 3 months postoperatively. Major adverse cardiovascular events, including accumulating cardiovascular mortality, stroke, nonfatal myocardial infarction, and rehospitalization for ischemia, will form a composite endpoint measure. DISCUSSION: This trial will aim to assess whether RIPC in patients subjected to surgical myocardial revascularization employing cardiopulmonary bypass initiates a neuroprotective response. Should the results of this trial indicate that RIPC is effective in reducing the incidence of adverse neurological events in patients undergoing coronary artery bypass grafting, it could impact on the current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02177981.

Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2.

Aggressive natural killer-cell leukaemia (ANKL) is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV) and P-glycoprotein (P-gp) expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56(+) NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

Extramedullary plasmacytoma imitating neoplasm of the gallbladder fossa after cholecystectomy.

Extramedullary plasmacytomas are plasma cell tumors that arise outside of the bone marrow. They account for approximately 3% of plasma cell neoplasms and are most frequently located in the head and neck region. Five months after undergoing cholecystectomy, a 69-year-old patient presented with the pain under the right costal margin and a 12 kg weight loss. Computed tomography of the abdomen demonstrated irregular, vascular mass in the gallbladder fossa that dents towards the duodenum and the pylorus and lowers caudally to the hepatic flexure. His laboratory tests indicated normocytic anemia and showed elevated sedimentation rate. During operative procedure, a tumorous mass in the gallbladder fossa was found, inseparable of the peritoneum of the hepatoduodenal ligament and the IVb liver segment. Histopathological examination and immunohistochemical staining determined the diagnosis of the plasmacytoma. Total resection of the tumor was achieved and after 24-month follow-up patient showed no signs of local recurrence or dissemination of the disease.

Cholelithiasis and thrombosis of the central retinal vein in a renal transplant recipient treated with cyclosporin.

The use of cyclosporin has been associated with the development of cholelithiasis in transplant recipients. Cholelithiasis in turn enhances the effects of cyclosporin on increased platelet aggregation. In this report, a patient who had undergone a renal transplantation as a result of malignant hypertension, and who was on immunosuppressive therapy consisting of cyclosporin, prednisone and azathioprine, developed thrombosis of the central retinal vein 5 years following the transplantation. Seven years after the transplantation, cholelithiasis, cholecystitis, cholangitis and subsequently secondary chronic biliary sclerosis were detected. Latero-lateral anastomosis between the common bile duct and duodenum was performed during explorative laparotomy and ursodeoxycholic acid treatment was introduced. The possible inter-relationship of the cholestatis, central retinal vein thrombosis and immunosuppression are discussed.

Hemophagocytic syndrome--should we consider it more often?

Hemophagocytic syndrome (HPS) is a rare condition characterized by overactive histiocytes, hepatosplenomegaly, fever and cytopenia, with two major types: familial, autosomal recessive genetic disease and acquired that can occur during systemic infections, immunodeficiency or malignancy. Inappropriate activation of macrophages by cytokines is the major mechanism of the disease. We report a case of an adult patient with HPS. After thorough clinical investigation, we have not been able to establish the underlying disease, and corticosteroids therapy was initiated empirically. After 8 months follow-up the patient is well with normal laboratory findings.

Surgical resection in the treatment of primary gastrointestinal non-Hodgkin's lymphoma: retrospective study.

AIM: To evaluate the role of surgical resection in the treatment of patients with primary gastrointestinal non-Hodgkin s lymphoma in our institution. METHOD: The retrospective study included 79 patients with a histologically confirmed primary gastrointestinal lymphoma, who were diagnosed and treated for the disease in the 1978-1997 period. According to the treatment modality, the patients were divided into surgically treated and surgically non-treated group. Data were analyzed with Fisher s exact test, long-rank test, and Kaplan-Meier method. RESULTS: The stomach was the primary site of non-Hodgkin s lymphoma in 45 (57%) patients, small intestine in 19 (24%), and colon in 9 (11%) patients. Six patients (8%) had multifocal disease. There were 56 (71%) patients with stages IE and IIE, and 23 (29%) with stages III and IV. Aggressive histology was found in 51 cases (65%), and low grade mucosa-associated lymphoid tissue (MALT) lymphoma in 28 (35%). Helicobacter pylori infection was registered in 20 out of 45 patients with gastric lymphoma. Twenty-six (33%) patients underwent surgical resection followed by chemotherapy, 47 (59%) were treated with chemotherapy alone, and 6 (8%) received antibiotics plus chemotherapy. Fifteen patients needed urgent surgical intervention. The overall response rate was 77%. Complete remission was achieved in 54 (68%) patients and partial remission in 7 (9%). Eighteen patients (23%) experienced progressive disease. A 10-year overall survival (OS) was 63% and event-free survival (EFS) was 52% for all patients. Patients with gastric lymphoma had better OS and EFS than patients with primary lymphoma at other sites (65% vs 42%, and 62 vs 28%, respectively) (p=0.005). A 10-year EFS rates were 58% and 52% for surgically treated and non-treated group, respectively. There was no significant difference between patients with resected and non-resected tumors (p=0.855). Patients with early-stage disease had significantly better OS and PFS than patients with advanced-stage disease (p=0.048). CONCLUSION: Primary gastrointestinal lymphoma can be successfully treated with chemotherapy alone but surgery remains an important therapeutic option for emergency problems. The main prognostic factors were primary tumor site and extent of the disease.

Surgical excision of a hemangioendothelioma of the left ventricle.

Primary intracardiac neoplasms are most commonly histologically benign with only 30% exhibiting signs of malignancy. Metastatic tumors of the heart are 30 times more common than primary cardiac tumors. Patients with intracardiac masses may present with dyspnea on exertion, thromboembolic events, pericarditis, arrhythmias, or congestive heart failure. In many, however, the diagnosis is made upon discovering a murmur in an otherwise asymptomatic patient. Hemangioendotheliomas are very rare tumors of the heart characterized by capillary-sized vessels lined by rounded and often multilayered endothelial cells. Cardiac muscle cells are found compressed between proliferating vascular channels. We present a patient with this unusual cardiac tumor with no previous cardiac history and a new systolic murmur.