Therapeutic options in patients with lymphoma and severe liver dysfunction

OBJECTIVES: To determine the long-term outcome of patients presenting with synchronous lymphoma and severe liver dysfunction and to describe the outcome of patients treated with initial mechlorethamine-based therapy used as a bridge to more conventional chemotherapy. PATIENTS AND METHODS: We reviewed the clinical course of all patients diagnosed as having lymphoma who presented with severe liver dysfunction and received intravenous mechlorethamine between September 1988 and February 2003 at the Mayo Clinic in Rochester, Minn. RESULTS: Forty-one patients were identified, 33 (80%) of whom had newly diagnosed, previously untreated lymphoma. Thirty-seven (90%) had non-Hodgkin lymphoma, and 4 (10%) had Hodgkin disease. Thirty-four patients (83%) had stage IV disease, and 31 (84%) of 37 had an intermediate-high International Prognostic Index. The median total bilirubin level before therapy was 10.7 mg/dL (range, 2.5-30.2 mg/dL), and the median alkaline phosphatase level was 982 U/L (range, 233-3415 U/L). In addition to mechlorethamine, 34 patients (83%) received concomitant corticosteroids, and 12 (29%) received concomitant rituximab. Twenty-two patients (54%) had sufficient improvement in liver function to receive subsequent standard chemotherapy. Nine patients (22%) are alive and disease-free at a median of 31 months (range, 4 to > or = 87 months) after mechlorethamine treatment. Factors associated with improved overall survival included improvement in bilirubin levels (P < .001) and receiving subsequent standard chemotherapy (P = .001). CONCLUSION: Mechlorethamine, high-dose corticosteroids, and rituximab are useful therapeutic interventions for this unique group of patients with lymphoma and severe liver dysfunction. Substantial clinical improvement and long-term survival are possible.     

Pregnancy-associated osteoporosis

The clinical features, investigation and outcome in 24 patientswith pregnancy-associated osteoporosis, followed for up to 24years from the first pregnancy are described. Symptoms occurredmost often in the first pregnancy (17 patients) at a mean ageof 27 years (range 21–36); the most frequent was backpain in late pregnancy or post partum (n=18); less common waship (n= 5) or ankle (n= 1) pain. In most, symptoms improvedsoon after delivery. Four subjects had pre-existing disordersknown to reduce bone density (corticosteroid therapy, heparintreatment, mild osteogenesis imperfecta and previous anorexianervosa). Radiographs showed vertebral collapse or localizedosteoporosis of the hip, with MRI evidence of oedema. Forearmbone mineral density (BMD) was sometimes normal, but spinalBMD (measured by DXA) was low. Bone biopsies in eleven patientsshowed features compatible with osteoblast failure. Except forthe patient with mild osteogenesis imperfecta, cultured dermalfibroblasts synthesized and exported normal Type I collagen.In 14 subsequent pregnancies (10 patients) there was no recurrencein ten and mild symptoms in the remainder. Excluding one patientwho had repeated osteoporotic fractures and vertebral collapse,the long-term prognosis was good.     

多种损伤因子与重症胸腹损伤急性肝功能障碍相关性研究

目的探讨肿瘤坏死因子-α（tumornecrosisfactor-α,TNF-α）、白细胞介素-6（interleukin-6,IL-6）、磷脂酶A2（phospholipaseAz,PLA2）在重症胸腹损伤急性肝功能损害发生过程中的作用。方法胸腹创伤患者82例（观察组）,同期体检健康者46例（对照组）,检测2组谷丙转氨酶（glutamicpropylictransaminase,GPT）、谷草转氨酶（glutamicoxaolacetictransaminase,GOT）、TNF—α、IL-6和PLA2水平并进行比较。结果观察组就诊时GPT（（208．43±41．35）u／L）、GOT（（198．49±39．62）u／L）、TNF—α（（36．41±18．09）μg／L）、IL-6（（393．83±143．86）μg／L）、PLA2（（41．35±14．26）μg／L）均高于对照组（（17．25±4．48）u／L,（18．29±5．37）u／L,（1．28±0．59）μg／L,（63．93±41．49）μg／L,（7．47±5．27）μg／L）（P〈O．01）;观察组GPT、GOT分别与TNF-α、IL-6、PLA2呈显著正相关（P〈0．01）。结论TNF-α、IL-6、PLA2参与了胸腹损伤急性肝功能损害的发生、发展;对TNF—α、ID6、PLA2进行早期干预可抑制急性肝功能损害发生或减轻损害程度。     

Pregnancy-associated thrombosis

Venous thromboembolism (VTE) occurs infrequently but is a leading cause of illness and death during pregnancy and the puerperium. In the general population the incidence of pregnancy associated VTE is approximately 1 in 1500 deliveries The risk of VTE is five times higher in a pregnant than in a non-pregnant woman. Postpartum the VTE-risk is even higher. Women with congenital abnormalities or persistent presence of antiphospholipid antibodies have an increased risk of VTE during pregnancy and the puerperium. In individuals with well defined hereditary thrombosis risk factors, such as the factor V:R506Q mutation, the factor II:G20210A variation, antithrombin-deficiency or protein C-deficiency, a relative risk of pregnancy associated VTE between 3.4 and 15.2 has been found. Women with previous VTE have an approximately 3.5 fold increased risk of recurrent VTE during pregnancy compared to non-pregnant periods. Our ability to diagnose pregnancy-associated VTE clinically is generally poor, since dyspnea, tachypnea, swelling and discomfort in the legs are common. Objective diagnosis is essential for treatment decisions. Exposure to radiation of less than 50,000 microGy (5 rad) has not been associated with a significant risk of fetal injury Therefore, besides sonography, routine diagnostic procedures should be performed, if clinically necessary. Heparin does not cross the placenta and is therefore the anticoagulant of choice. In case of acute thrombosis during pregnancy, treatment is performed like in nonpregnant patients. There is ongoing debate, whether or not pregnant women with previous venous thrombosis should routinely receive prophylactic anticoagulation. In patients who have hereditary antithrombin deficiency, antiphospholipid antibodies, a combined abnormality or a history of a severe thrombotic event (pulmonary embolism, extended deep vein thrombosis) should be advised to use prophylactic heparin during pregnancy, starting during the first trimester. Post partum prophylaxis should be given in all women with an increased risk for VTE.     

Captopril-induced liver dysfunction

We have described a patient with captopril-induced cholestatic jaundice. Captopril was confirmed as the causative agent, because jaundice occurred after administration of captopril and resolved quickly after administration was stopped.     

Disopyramide-associated liver dysfunction

A case of disopyramide-associated cholestatic jaundice is presented, and all reported cases of disopyramide-associated liver dysfunction are reviewed. Manifestations of liver dysfunction usually appear during the first week of treatment. Discontinuing administration of the drug often results in prompt clinical resolution, although in rare instances, laboratory abnormalities persist up to 18 months. Physicians should be aware of this rare but serious complication of disopyramide therapy.     

Microvascular dysfunction as a cause of organ dysfunction in severe sepsis

Reduced microvascular perfusion has been implicated in organ dysfunction and multiple organ failure associated with severe sepsis. The precise mechanisms underlying microvascular dysfunction remain unclear, but there are considerable experimental data showing reduced microcirculatory flow, particularly of small vessels, and increased heterogeneity. With the development of newer imaging techniques, human studies have also been conducted and have given rise to similar findings. Importantly, the degree of microvascular disturbance and its persistence is associated with poorer outcomes. The ability to influence these changes may result in better outcomes and bedside systems, enabling direct visualization of the microcirculation, which will help in the assessment of ongoing microcirculatory dysfunction and its response to established and new therapeutic interventions.     

Renal dysfunction in liver cirrhosis

Liver cirrhosis is an escalating health problem attributed to numerous causes, including an increase in alcohol consumption, morbid obesity and chronic viral hepatitis. The circulatory disturbances seen in advanced cirrhosis lead to the development of ascites, which often lead to progressive renal impairment or the development of hepatorenal syndrome. Furthermore, cirrhotic patients commonly experience clinical situations that predispose them to the development of pre-renal failure, such as dehydration, hypovolaemia, septic shock, or exposure to nephrotoxic drugs. This article provides an overview of the main causes of acute renal failure in liver cirrhosis and describes the current medical and nursing management.     

Pregnancy-associated plasma protein-A and asthma

Pregnancy-associated plasma protein-A (PAPP-A) is potentially a proatherosclerotic metalloproteinase and a new inflammatory marker. Investigators sought to evaluate the significance of PAPP-A in patients with asthma. Blood samples were collected from 35 patients and 20 control subjects. Serum PAPP-A was determined by enzyme-linked immunosorbent assay. PAPP-A levels of patients with asthma (8.1±5.0 mU/L) were higher than those of the control group (4.9±2.1 mU/L) (P < .01). A significant correlation was noted between serum PAPP-A concentration and asthma severity (r=.581;P < .01). Investigators concluded that PAPP-A may contribute to airway smooth muscle hyperplasia as an insulin-like growth factor-dependent insulin-like growth factor-binding protein-4 protease in patients with asthma.     

Renal dysfunction in chronic liver disease

This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the series can be found online at . Further information about the Yearbook of Intensive Care and Emergency Medicine is available from .     

Chronic liver dysfunction in multitransfused hemophiliacs

Liver dysfunction and exposure to the hepatitis B antigen were assessed by serum transaminase (SGPT and SGOT) levels and HBsAg and anti-HBs during a three year period in a group of 118 patients with factor VIII or factor IX deficiency. The 107 HBsAg negative patients were divided into four groups according to their mode of therapy. Persistently abnormal transaminase values were present in 51 per cent of patients with a large exposure to factor VIII concentrates, in 43 per cent with a small factor VIII exposure and in 37 per cent exposed to prothrombin complexes. This was contrasted with abnormalities in 8 per cent of patients treated only with cryoprecipitate. The incidence and degree of serum transaminase abnormality appeared independent of a past history of jaundice. All patients without persistent antigenemia who had been treated with pooled plasma products showed antibodies to HBsAg. High titer anti-HBs prior to initial fraction therapy appeared protective against jaundice. The eleven patients with persistent antigenemia had significantly higher transaminase levels than the HBsAg negative group.     

Multiple organ dysfunction associated with severe acute pancreatitis

OBJECTIVE: To compare three different multiple organ dysfunction scores in predicting hospital mortality rates and to discover which one best assesses organ dysfunction/failure in patients with severe acute pancreatitis in a general intensive care unit. DESIGN: Retrospective, observational study. SETTING: Surgical department and a ten-bed general intensive care unit in a tertiary care hospital. PATIENTS: Among the 178 consecutive patients admitted to the surgical department with severe acute pancreatitis from 1994 to 1998, 113 patients treated in the general intensive care unit underwent study. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Clinical and laboratory data were collected during a period of 35 days. Acute Physiology and Chronic Health Evaluation (APACHE) II, Multiple Organ Dysfunction (MOD) score, Sequential Organ Failure Assessment (SOFA) score, and Logistic Organ Dysfunction (LOD) score were calculated and compared regarding hospital mortality rate. In addition, daily maximum score and a total maximum score (sum of the highest values for each organ dysfunction) were calculated for all three scores. The area under the receiver operating characteristic curve was used as a measure of accuracy of the scores. The highest accuracy was revealed with daily maximum scores with the area under the receiver operating characteristic curve 0.847 for SOFA, 0.844 for MOD, and 0.836 for LOD. According to the maximum SOFA score, the highest mortality rate was associated with liver (83%, p <.001) and renal (63%, p <.001) failures. The mortality ratio with two organ failures ranged from 50% to 91%. The highest mortality rate (91%) was for a combination of hepatic and renal failure. In multiple logistic regression analysis, only hepatic, renal, and cardiovascular failure and previous cardiovascular medication were independent risk factors for hospital mortality. CONCLUSION: In patients with severe acute pancreatitis, organ dysfunction scores (MOD, SOFA, LOD) show good accuracy, comparable with APACHE II in predicting hospital mortality. The maximum daily organ dysfunction scores were simple and useful in assessing multiple organ dysfunction and in predicting hospital mortality rates of patients with severe acute pancreatitis.     

Vocal cord dysfunction mimicking a severe asthma attack

Vocal cord dysfunction is a rare type of airway obstruction that may mimic an acute asthma attack. We present a case of a patient who arrived in the Emergency Department (ED) in acute respiratory distress, with a history of severe asthma requiring previous intubation, who was diagnosed with vocal cord dysfunction by bronchoscopy in the ED.     

Non-neurologic organ dysfunction in severe traumatic brain injury

OBJECTIVE: To describe the incidence of non-neurologic organ dysfunction and its association with outcome in patients with severe traumatic brain injury admitted to intensive care. DESIGN: Observational cohort study. SETTING: Foothills Medical Centre, which is the only neurosurgical service in southern Alberta (population approximately 1.3 million). PATIENTS: Patients were 209 consecutive patients with severe traumatic brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Non-neurologic organ dysfunction was measured by the maximum modified multiple organ dysfunction score. Organ system failure was defined as a component score of >/=3 on any day during the patient's intensive care unit stay. One hundred and eighty-five patients (89%) developed dysfunction of at least one non-neurologic organ system. Ninety-six organ system failures were identified in 74 patients (35%). Respiratory failure was the most common non-neurologic organ system failure, occurring in 23% of patients, whereas cardiovascular failure occurred in 18%. Eight patients (4%) had failure of the coagulation system. One patient had renal failure, whereas no patient developed hepatic failure. In a multivariate model, non-neurologic organ dysfunction was independently associated with hospital mortality (odds ratio for hospital mortality, 1.63; 95% confidence interval, 1.34, 1.98 for one maximum modified multiple organ dysfunction score point). Non-neurologic organ dysfunction was also independently associated with dichotomized Glasgow Outcome Score, as a measure of neurologic outcome (odds ratio for unfavorable neurologic outcome, 1.53; 95% confidence interval, 1.22, 1.98 for one maximum modified multiple organ dysfunction score point). The timing of the organ dysfunction did not appear to be important in the prediction of outcome. CONCLUSIONS: Non-neurologic organ dysfunction is common in patients with severe traumatic brain injury and is independently associated with worse outcome.     

Symptomatic arrhythmias due to syringomyelia-induced severe autonomic dysfunction

Syringomyelia is characterized by cavity formation in the spinal cord, most often at C2-Th9 level. Clinical manifestation reflects extent and localization of the spinal cord injury. Cases: 20-year old woman was admitted for recurrent rest-related presyncopes with sudden manifestation. Paroxysms of sinus bradycardia with SA and AV blocks were repeatedly documented during symptoms. There was normal echocardiographic finding, (para) infectious etiology was not proved. Character of the ECG findings raised suspicion on neurogenic cause. Autonomic nervous system testing demonstrated abnormalities reflecting predominant sympathetic dysfunction. Suspicion on incipient myelopathy was subsequently confirmed by MRI, which discovered syringomyelia at Th5 level as the only pathology. A 52-year old man with hypotrophic quadruparesis resulting from perinatal brain injury was sent for 2-years lasting symptoms (sudden palpitation, sweating, muscle tightness, shaking) with progressive worsening. Symptoms occurred in association with sudden increase of sinus rhythm rate and blood pressure that were provoked by minimal physical activity. Presence of significant autonomic dysregulation with baroreflex hyperreactivity in orthostatic test and symptomatic postural orthostatic tachycardia with verticalization-associated hypertension were proved. MRI revealed syringomyelia at C7 and Th7 level affecting sympathetic centers at these levels. Sympathetic fibers dysfunction at C-Th spinal level may cause significant autonomic dysfunction with arrhythmic manifestation.