Test Your Skills with a New Interactive Medical Case

Posted by Karen Buckley • June 16th, 2014

The latest Interactive Medical Case presents a 64-year-old man with gait instability, visual changes, diffuse weakness, headaches, and worsening shortness of breath with activity. Test your diagnostic and therapeutic skills at NEJM.org.

Interactive Medical Cases are online simulations based on a real patient’s experience of illness. You follow interactive steps through an evolving patient’s history, diagnosis, and management, from presentation to outcome. During the presentation of the case, you access videos, lab results and brief commentary that explain concepts important for diagnosis and treatment.

Browse the list of previous Interactive Medical Cases. Try one or all 30 cases and earn CME credit or MOC points now!

The Child or Adolescent with Elevated Blood Pressure

Posted by Sara Fazio • June 13th, 2014

Evaluation of children and adolescents with hypertension can detect evidence of the secondary systemic effects of hypertension (in particular, renal disease). Initial therapy is usually nonpharmacologic, but pharmacotherapy is used if other methods fail, hypertension is severe, or there are coexisting conditions such as diabetes mellitus.  NEJM Deputy Editor and Massachusetts General Hospital pediatrician Dr. Julie Ingelfinger is the author of this new Clinical Practice review article.

The prevalence of elevated blood pressure among children and adolescents has been increasing worldwide in concert with the marked increase in the prevalence of obesity among the young.

Clinical Pearls

How is hypertension defined in a child or adolescent?

Hypertension is diagnosed in a young person if the mean systolic blood pressure or diastolic blood pressure is above the 95th percentile for sex, age, and height on three or more occasions. Stage 1 hypertension is defined as blood pressure between the 95th and 99th percentile plus 5 mm Hg, and stage 2 hypertension is defined as blood pressure above the 99th percentile plus 5 mm Hg. Prehypertension is defined as a mean systolic or diastolic blood pressure at or above the 90th percentile but below the 95th percentile or blood pressure of 120/80 mm Hg or greater, even if the blood pressure is at or below the 90th percentile (and up to the 95th percentile).

Table 2. Classifications of Blood Pressure and Therapeutic Approaches.

In addition to a history and physical examination, what evaluation is recommended in children or adolescents with hypertension?

Evaluation of hypertension in children and adolescents is generally phased. In addition to a careful history taking and physical examination, a phase 1 evaluation to identify common secondary causes is recommended in patients with blood pressure that is persistently at or above the 95th percentile and in patients with diabetes, cardiac disease, and other chronic conditions if the blood pressure is above the 90th percentile. This evaluation includes basic laboratory tests (measurement of levels of blood urea nitrogen, creatinine, and electrolytes; a complete blood count; and a urinalysis and urine culture) and renal ultrasonography to assess for renal scarring, disparate kidney size, and congenital anomalies. About 80% of cases of secondary hypertension in children are attributed to renal disease, and another 10% are attributed to renovascular disease. Left ventricular mass should also be assessed; the interpretation must consider the patient’s height, body-surface area, and level of fitness.

Table 3. Continued Evaluation for Pediatric Hypertension.

Morning Report Questions

Q: What are the principles of nonpharmacologic therapy in childhood hypertension?

A: Lifestyle changes are recommended for children with prehypertension or stage 1 hypertension. These approaches include a program of dynamic exercise (i.e., exercise that involves substantial and recurrent body movement, such as bicycling or running); a balanced diet with a high intake of fruits, vegetables, and low-fat dairy products, as well as a reduction in dietary sodium; a weight-reduction program in patients who are overweight; and reinforcement of adherence to these practices. Several studies involving children and adolescents have suggested that successful weight loss is effective in decreasing blood-pressure levels. However, effecting such changes is often difficult. The inclusion of family participation appears to be useful, if not essential, particularly if the child needs to lose weight.

Q: When should medication be started in a child with hypertension and what is the best choice of agent?

A: If blood pressure does not improve with lifestyle changes, or if concerted efforts to encourage lifestyle modification are not successful, medication may be indicated. Medication should be initiated if there are symptoms or coexisting conditions or if there is an identified secondary cause of hypertension or evidence of end-organ damage in children or adolescents with stage 1 hypertension. In addition, drug therapy should be initiated routinely in young people with stage 2 hypertension. There is no consensus regarding the best initial therapy for hypertension in children and adolescents; comparative trials are lacking in the pediatric population. A survey of pediatric nephrologists indicated that 47% considered ACE inhibitors to be first-line therapy, 37% chose calcium-channel blockers, 15.3% chose diuretics, and 6.6% chose beta-blockers (some chose more than one medication as a first-line agent).

Table 4. Selected Oral Medications for Hypertension in Children and Adolescents.

Rash, Myalgia, and Weakness

Posted by Sara Fazio • June 13th, 2014

In the latest Case Record of the Massachusetts General Hospital, a 32-year-old man was admitted to this hospital because of a violaceous eruption that was followed by muscle pain and weakness, leading to respiratory failure. New papules with white centers developed. A diagnostic procedure was performed.

Malignant atrophic papulosis can occur in association with autoimmune diseases, most often SLE [systemic lupus erythematosus], but it has also been reported in patients with progressive systemic sclerosis, rheumatoid arthritis, discoid lupus, and dermatomyositis.

Clinical Pearls

What are dermatologic findings seen in patients with dermatomyositis?

Gottron’s papules are erythematous papules that overlie interphalangeal and metacarpophalangeal joints, elbows, and knees. They are pathognomonic for dermatomyositis. A heliotrope rash is seen in 30 to 60% of patients with dermatomyositis. Periungual erythema and edema are less specific signs that may be seen in dermatomyositis and other connective-tissue diseases, such as SLE.

What is malignant atrophic papulosis?

Malignant atrophic papulosis, or Degos’s disease, is a rare small-vessel vasculopathy, in which crops of erythematous cutaneous papules progress to depressed, porcelain-white scars with a varicelliform or varioliform appearance and a violaceous rim (consisting of fine telangiectasias) and then to inactive, atrophic white scars. Lesions are small, measuring between 0.5 and 1 cm in diameter. New papules typically occur in crops, and lesions at differing stages are usually seen. Tens to hundreds of lesions may be seen at any given time. Classic sites of involvement are the trunk and proximal extremities; however, cases involving the face, scalp, and genitalia have been reported.

Morning Report Questions

Q: What are associated multi-system features of malignant atrophic papulosis?

A: In the majority of reported cases, malignant atrophic papulosis is a multisystem disease in which skin findings precede gastrointestinal and central nervous system involvement or, on rare occasions, other organ involvement by weeks to years. Abdominal pain, nausea, diarrhea, and melena signal the onset of gastrointestinal tract infarcts occurring anywhere from the mouth to the anus. Bowel perforation resulting in peritonitis is a common cause of death in these patients. Involvement of the central nervous system is seen in approximately 20% of patients, heralded by hemiparesis, monoplegia, sensory abnormalities, or visual changes. A chronic, benign, skin-limited form of malignant atrophic papulosis has been recognized, and malignant atrophic papulosis also has been reported in families with an autosomal-dominant mode of inheritance, with variable expressivity.

Q: What is the pathogenesis of malignant atrophic papulosis?

A: The pathogenesis of malignant atrophic papulosis has yet to be fully elucidated. A study of four patients showed increased expression of MxA (a type I interferon-inducible protein), signifying dysregulated interferon-(alpha), and C5b-C9 (membrane-attack complex) in endothelial cells, vessel walls, perivascular interstitium, inflammatory cells, and keratinocytes in involved skin, suggesting that complement-mediated injury to endothelial cells may be involved in the pathogenesis of malignant atrophic papulosis.

Take the Critical Care Challenge

Posted by Karen Buckley • June 12th, 2014

It is not uncommon for patients to have an expected death in an ICU. The final Critical Care Challenge is now open for your votes and comments:

Twelve days after his subdural hematoma, it has become increasingly obvious that the patient is unlikely to make a functional recovery. What steps should be taken at this time?

Look for poll results and the answer with the final review in the Critical Care series on June 26, which covers issues related to the end of life in the absence of discordance between the patient’s family and caregivers. You may also wish to view past articles in the series, including Traumatic Intracranial Hypertension, ICU Acquired Weakness and Recovery from Critical Illness, and Nutrition in the Acute Phase of Critical Illness.

Pharmacology and the Treatment of Complicated Skin and Skin-Structure Infections

Posted by Daniela Lamas • June 11th, 2014

Treating skin and soft tissue infections isn’t the most glamorous job in medicine. But as these infections – ranging from cellulitis to abscess and often accompanied by fever and other signs of systemic illness – lead to nearly 900,000 hospital admissions annually, it’s an essential one. And with the emergence of strains of methicillin-resistant Staphylococcus aureus (MRSA) in the community in recent years, coupled with toxicity and inconvenience of existing antibiotic options – many of which require twice-daily intravenous dosing, such as with vancomycin – there’s a real need for new therapies.

Two recent articles in NEJM offer hopeful news about a potentially less burdensome course of treatment for the estimated 15 million skin and soft tissue infections that occur yearly in the US.

Both studies test drugs whose mechanism of action is similar to vancomyin – the current go-to in our therapeutic armamentarium for skin and soft tissue infection. These semisynthetic antibiotics, called dalbavancin and oritavancin, do their job by blocking steps in how gram-positive bacteria like staph create their cell walls. Because the drugs have a longer half-life allowing  for weekly+ dosing, they could be a desirable option for patients and providers who would no longer be saddled with twice daily dosing of an intravenous antibiotic.

But do they work as well as our mainstays of treatment? To address that question, Dr. Boucher and colleagues enrolled more than 1200 patients with cellulitis, a major abscess or wound infection associated with erythema and drainage or swelling, along with at least one systemic sign of infection such as a fever or elevated white blood cell count. These patients received either three days of intravenous vancomycin followed by oral linezolid for 10 to 14 days, or the study drug – dalbavancin – given as one IV infusion on day one and then again on day eight. Overall, patients randomly assigned to dalbavancin were just as likely to see a response in their cellulitis to those who received the daily intravenous dosing of vancomycin and a week of daily pills.

An accompanying paper describes similar results with the drug oritavancin. In this study, led by Dr. Corey and colleagues, nearly 1,000 patients with cellulitis, abscess or wound infection received either oritavancin in a single dose, or 7 to 10 days of IV vancomycin given twice daily. Once again, those who received the single dose drug were just as likely for their infection to decrease in size in the first few days and to regress fully after the course of treatment.

While these results are promising, it’s not time to say goodbye to vancomycin for skin and soft tissue infections just yet, writes Dr. Henry Chambers, who heads the Division of Infectious Diseases at University of California in San Francisco, in an accompanying editorial.  He notes that both studies were non-inferiority trials, which allow us to conclude that the drugs aren’t significantly worse than vancomycin, but don’t prove that they are more effective. While no safety concerns were identified during the period of study monitoring, the studies assessed only a small number of patients and the medication effects may linger so we don’t know whether they could cause unforeseen reactions weeks or months after administration. Furthermore, the studies do not address how these drugs might work for patients with more severe staph infections such as pneumonia, infections of bones or joints, or infections of the heart valve.

These are key questions to answer, he writes, as these long-acting antibiotics could “profoundly impact how these infections are managed by reducing or in some cases eliminating costs and risks of hospitalization.”

Antibiotic Prophylaxis for Vesicoureteral Reflux

Posted by Joann Schulte • June 6th, 2014

Are Charlie’s kidneys backed up?  Does he need antibiotics?  His parents want to know if 2-year-old Charlie is going to be on long-term antibiotics to prevent any new bladder infections.  He’s just finished treatment for a urinary tract infection (UTI).    You explain that a voiding cystourethrogram will need to be done first to categorize the grade of reflux and then you’ll talk.  Original research published recently in NEJM describes the uncertainty of the value of antibiotic prophylaxis in altering vesicoureteral reflux (VUR).

Randomized clinical trials are the currency by which medical treatments are evaluated, but the trials don’t always produce definitive results.  That’s the case with the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial.

About a third of febrile children with UTIs may experience VUR, which can lead to renal scarring.   Some individuals with VUR are at an increased risk for pyelonephritis, hypertension, and progressive renal failure. However, the severity of VUR greatly varies and thus may affect patients differently.

The trial, which enrolled 607 children at 19 sites, was designed to evaluate the effectiveness of long-term antimicrobial prophylaxis in preventing febrile or symptomatic recurrence of UTIs.  Secondary outcomes evaluated the likelihood of renal scarring and treatment failure and antimicrobial resistance.  Enrolled children received either trimethoprim sulfamethoxazole or placebo and were tracked for two years.

Fewer recurrent UTIs were documented in the prophylaxis group than in the placebo group (RR 0.55, 95% CI 0.38-0.78).  However, antibiotic resistance was more common in the group getting antibiotic prophylaxis than in the placebo group (63% vs. 19%). No significant difference in renal scarring was noted between the two groups at the 2-year observation.

In an accompanying editorial, NEJM Deputy Editor Dr. Julie Ingelfinger and Dr. Bruder Stapleton noted that the decision to use antibiotic prophylaxis “remains a clinical dilemma” because the RIVUR study demonstrated that antibiotic resistance occurred more often in the arm assigned to prophylaxis and because no difference in renal scarring was found between the two groups.  The editorialists wrote that the RIVUR study results suggest that a general recommendation of antibiotic prophylaxis for children with VUR needs more evidence before it can universally adopted.

Adverse Health Effects of Marijuana Use

Posted by Sara Fazio • June 5th, 2014

As marijuana use becomes legal in some states, the dominant public opinion is that marijuana is a harmless source of mood alteration. Although the harms associated with marijuana use have not been well studied, enough information is available to cause concern.  A new review on this topic comes from Drs. Nora Volkow, Ruben Baler, Wilson Compton and Susan Weiss at the National Institute on Drug Abuse in Bethesda.

In light of the rapidly shifting landscape regarding the legalization of marijuana for medical and recreational purposes, patients may be more likely to ask physicians about its potential adverse and beneficial effects on health.

Clinical Pearls

• What is the addictive potential of marijuana?

Despite some contentious discussions regarding the addictiveness of marijuana, the evidence clearly indicates that long-term marijuana use can lead to addiction. Indeed, approximately 9% of those who experiment with marijuana will become addicted (according to the criteria for dependence in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV]). The number goes up to about 1 in 6 among those who start using marijuana as teenagers and to 25 to 50% among those who smoke marijuana daily. According to the 2012 National Survey on Drug Use and Health, an estimated 2.7 million people 12 years of age and older met the DSM-IV criteria for dependence on marijuana. Indeed, early and regular marijuana use predicts an increased risk of marijuana addiction, which in turn predicts an increased risk of the use of other illicit drugs.

• What is the effect of marijuana on brain development in young persons?

As compared with unexposed controls, adults who smoked marijuana regularly during adolescence have impaired neural connectivity (fewer fibers) in specific brain regions. These include the precuneus, a key node that is involved in functions that require a high degree of integration (e.g., alertness and self-conscious awareness), and the fimbria, an area of the hippocampus that is important in learning and memory. In addition, imaging studies in persons who use cannabis have revealed decreased activity in prefrontal regions and reduced volumes in the hippocampus. The negative effect of marijuana use on the functional connectivity of the brain is particularly prominent if use starts in adolescence or young adulthood, which may help to explain the finding of an association between frequent use of marijuana from adolescence into adulthood and significant declines in IQ.

Morning Report Questions

Q: How does exposure to marijuana affect driving ability?

A: Both immediate exposure and long-term exposure to marijuana impair driving ability; marijuana is the illicit drug most frequently reported in connection with impaired driving and accidents, including fatal accidents. There is a relationship between the blood THC concentration and performance in controlled driving-simulation studies, which are a good predictor of real-world driving ability. Recent marijuana smoking and blood THC levels of 2 to 5 ng per milliliter are associated with substantial driving impairment. According to a meta-analysis, the risk of involvement in an accident increases by a factor of about 2 when a person drives directly after use of marijuana.

Q: What are the known effects of marijuana smoking on the pulmonary and cardiovascular systems?

A: The effects of long-term marijuana smoking on the risk of lung cancer are unclear. Marijuana smoking is also associated with inflammation of the large airways, increased airway resistance, and lung hyperinflation, associations that are consistent with the fact that regular marijuana smokers are more likely to report symptoms of chronic bronchitis than are nonsmokers; however, the long-term effect of low levels of marijuana exposure does not appear to be significant. The immunologic competence of the respiratory system in marijuana smokers may also be compromised, as indicated by increased rates of respiratory infections and pneumonia. Marijuana use has also been associated with vascular conditions that increase the risks of  myocardial infarction, stroke, and transient ischemic attacks during marijuana intoxication.

Table 1. Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana.

Pregnancy and Infection

Posted by Sara Fazio • June 5th, 2014

Pregnant women have an increased severity of infections with some organisms, including influenza virus, hepatitis E virus, herpes simplex virus, and malaria parasites. A new review on this topic includes an update on immunologic alterations during pregnancy.

Pregnant women are more severely affected by infections with some organisms, including influenza virus, hepatitis E virus, and herpes simplex virus, and malaria parasites. The evidence is more limited for organisms that cause coccidioidomycosis, measles, smallpox, and varicella. The threshold for diagnostic evaluation, as well as hospitalization and treatment, may be lower for pregnant women than for other patients, and this factor may bias some of the reports of increased disease severity.

Clinical Pearls

How does pregnancy impact the severity of influenza infection?

Pregnant women are at increased risk for severe illness from influenza virus infection. Cardiopulmonary adaptive changes occurring during pregnancy, such as increased heart rate and stroke volume and reduced pulmonary residual capacity, may increase the risk of hypoxemia and contribute to the increased severity. During the pandemic of 1918, maternal mortality was 27% (50% when influenza was complicated by pneumonia), and during the pandemic of 1957, 50% of deaths among reproductive-age women occurred among those who were pregnant. During the 2009 H1N1 influenza A pandemic, pregnant women were generally at increased risk for severe disease, including disease leading to hospitalization, admission to an intensive care unit, or death, as compared with nonpregnant women and the general population. In the United States, 5% of all deaths from pandemic influenza were among pregnant women, although pregnant women represent only about 1% of the U.S. population.

What impacts the risk of malaria infection in pregnancy and what are the harmful effects?

In areas of high transmission, most women harboring parasites do not present with symptoms. Of pregnant women who are symptomatic, the majority are women having their first pregnancy; women who have been pregnant more than once and who live in areas where malaria is highly endemic are less likely to present with clinical signs or symptoms of malaria, even if they have high parasite loads. Pregnant women have a risk of severe malaria that is three times as high as that among nonpregnant women; a median maternal mortality of 39% has been reported in studies in the Asia-Pacific region. Maternal death also has been reported in association with P. vivax infection. The harmful effects of malaria (mainly due to P. falciparum) during pregnancy — maternal anemia, low birth weight, and preterm birth — have long been recognized. In areas of stable endemic transmission (e.g., sub-Saharan Africa), up to 25% of pregnant women have acute infection, leading to placental malaria. P. falciparum is the only species associated with placental sequestration, which is believed to be the cause of many of the manifestations of P. falciparum disease during pregnancy.

Morning Report Questions

Q: What is the impact of listeria infection during pregnancy?

A: Primarily a foodborne pathogen, listeria can contaminate a variety of raw foods, such as uncooked meats and vegetables, unpasteurized milk, and soft cheeses. Infection may be asymptomatic or may be manifested as an influenza-like illness; severe infection is rare during pregnancy, and no maternal deaths due to listeriosis have been reported among pregnant hospitalized women. L. monocytogenes infections most commonly occur during the third trimester and seem to be rare earlier in pregnancy. However, listeria has a predilection for the placenta and fetus, and, depending on the stage of pregnancy, listeriosis can lead to pregnancy loss, stillbirth, preterm birth, or serious neonatal disease.

Q: What changes in the immune system occur during pregnancy?   

A: There is evidence that aspects of innate immunity (phagocytic activity, (alpha)-defensin expression, and numbers of neutrophils, monocytes, and dendritic cells) are maintained or enhanced during pregnancy, particularly during the second and third trimesters. Conversely, the number of CD3+ T lymphocytes (both CD4+ and CD8+) decrease during pregnancy as do Th1 and Th2 responses to mitogenic or antigenic lymphocyte stimulation. However, there is limited information on the longitudinal trends of such alterations during pregnancy. Levels of several cytokines are altered: levels of interferon-(gamma), monocyte chemoattractant protein 1, and eotaxin are decreased in most pregnant women, whereas tumor necrosis factor (alpha), interleukin-10, and granulocyte colony-stimulating factor levels rise. Data indicating that fetus-specific cytotoxic T-cell responses can be generated during pregnancy without loss of the fetus, as well as data from studies of pregnant mice showing normal memory T-cell development after lymphocytic choriomeningitis virus infection, contradict the idea of systemic immunosuppression during pregnancy. A more recent theory proposed a shift from Th1 to Th2 immunity during pregnancy. Th2 cells stimulate B lymphocytes, increase antibody production, and suppress the cytotoxic T-lymphocyte response, decreasing the robustness of cell-mediated immunity.

Traumatic Intracranial Hypertension

Posted by Sara Fazio • May 30th, 2014

The latest article in the Critical Care series reviews the methods of monitoring and treating traumatic intracranial hypertension in intensive care settings.

An elevation in intracranial pressure can be a medical or surgical emergency. There are many possible conditions that can lead to elevated intracranial pressure on either an acute or a chronic basis.

Clinical Pearls

How is the epidemiology of traumatic brain injury changing?

Traumatic brain injury is a medical and social problem worldwide, with an estimated 10 million cases leading to hospitalization or death each year. In low- and medium-income countries, in which the use of motor-powered transportation is increasing, the incidence of this condition is rising and involves predominantly young men. In contrast, in richer countries, the epidemiology of traumatic brain injury is changing because of two main factors: the rate of traffic incidents is decreasing owing to successful enforcement of safety laws and preventive measures, whereas the aging of the population makes such injury in the elderly more frequent.

What is the relationship between intracranial volume and pressure?

Under normal conditions, the total volume within the skull remains constant and is determined by the sum of the cerebrospinal fluid, blood, and brain-tissue compartments. The volume of these compartments is tightly regulated, and cerebral blood flow is kept constant by autoregulation. When additional volume is added to the system, compensatory mechanisms (e.g., displacement of cerebrospinal fluid to the spinal subarachnoid space and compression of the cerebral venous bed) operate to keep intracranial pressure constant. The relationship between intracranial volume and intracranial pressure is exponential. Initially, pressure increases only slightly with increasing volume, but when the buffering capabilities of the system are exceeded, intracranial pressure rises steeply. This explains the rapid deterioration that is frequently seen in patients with a traumatic intracranial hematoma.

Morning Report Questions

Q: What are current guidelines for the monitoring of intracranial pressure in patients with traumatic brain injury, and what are associated risks?

A: International guidelines recommend the monitoring of intracranial pressure in all patients with survivable severe traumatic brain injury and abnormalities on computed tomography (CT) obtained at the time of admission, as well as in selected patients (e.g., those who are over the age of 40 years with motor posturing or hypotension) with a normal CT scan. The insertion of intracranial catheters carries risks of hemorrhage and infection. Ventricular catheters, with deeper brain penetration, are more risky. Reported rates of hemorrhage are variable (1 to 7% for ventricular catheters; less than that for intraparenchymal probes), and only rarely do such hemorrhages require surgical evacuation. Placement of an intracerebral catheter is relatively contraindicated in patients with coagulopathy (i.e., increased prothrombin time, partial thromboplastin time, or international normalized ratio or a platelet count of <100,000 per microliter). The risk of infection is higher with ventricular catheters than with parenchymal probes, with reported rates of infection ranging from 1 to 27%.

Q: What medical therapies are available for increased intracranial pressure?

A: During the past 10 years, management of increased intracranial pressure has evolved toward standardized strategies that use a “staircase” approach with an escalating treatment intensity. Sedation and analgesia are used to treat pain and agitation and to prevent arterial hypertension and patient-ventilator dyssynchrony. Hyperosmolar agents reduce brain volume and intracranial pressure through multiple mechanisms. In the first minutes of infusion, mannitol and hypertonic saline expand the plasma volume, decrease blood viscosity, and reduce the cerebral blood volume. Once plasma osmolarity increases, a gradient across the blood-brain barrier is established, and water is extracted from the brain. Induced arterial blood hypocarbia (hyperventilation) reduces intracranial pressure at the expense of decreasing cerebral blood flow as a result of vasoconstriction. Hyperventilation carries a serious risk of cerebral ischemia. For this reason, current guidelines recommend additional monitoring for cerebral ischemia. Barbiturates depress the cerebral metabolism and reduce cerebral blood flow, causing a proportional decrease in cerebral blood volume and a decrease in intracranial pressure. Initial enthusiasm for barbiturate therapy has been tempered by the recognition of serious side effects, including cardiac depression, arterial hypotension, and an increased risk of infection. Mild hypothermia (32 to 34 degrees C) is effective in decreasing intracranial pressure, but studies on the clinical benefit are contradictory, and current evidence does not support its general use in patients with traumatic brain injury.

Figure 3. Staircase Approach to the Treatment of Increased Intracranial Pressure.

Chest Pain and a Pleural Effusion

Posted by Sara Fazio • May 30th, 2014

In the latest Case Record of the Massachusetts General Hospital, a 64-year-old man was admitted to the hospital with recurrent pleuritic chest pain. Imaging showed a loculated left pleural effusion and underlying consolidation in the left lower lobe. Treatment with antibiotics brought some improvement, but pain recurred and worsened.

The differential diagnosis of a persistent pleuropulmonary process includes infection, aspiration of either gastric or oropharyngeal contents, thromboembolic disease, collagen vascular disease, and malignant tumors.

Clinical Pearls

What are infectious causes of pleuropulmonary disease?

Viral infections can cause pleural effusions; they are generally associated with a prodrome, fever, and increased white-cell counts. Community-acquired bacterial pneumonias with parapneumonic effusions commonly cause localized pleuropulmonary disease; they are generally accompanied by fever, leukocytosis, cough, and increased sputum production. Tuberculosis is a recognized cause of both parenchymal disease and pleural disease. Primary tuberculosis is classically manifested by lymphadenopathy, infiltrates, and pleural effusions. Aspiration of gastric contents tends to involve the dependent portions of the lung and can cause pulmonary infiltrates with effusions. One infection that can account for a complex pleuropulmonary process with chest-wall pain is actinomycosis. When actinomycosis goes untreated, it can cause sinus formation and drainage at the skin surface.

What is the epidemiology of malignant mesothelioma?

Malignant mesothelioma is a rare tumor, with an incidence of 2 to 20 cases per 1 million patients in the United States and Canada. It was vanishingly rare until asbestos was introduced in the construction industry and other industries. The most common cause of diffuse malignant mesothelioma in the United States is exposure to and inhalation of asbestos. The latency from the time of exposure to the development of malignant mesothelioma is generally several decades. Low-level exposures, as well as bystander and secondary exposures, can cause this disease, and no threshold of asbestos exposure has been established for the development of malignant mesothelioma.

Morning Report Questions

Q: How is the diagnosis of malignant mesothelioma established?

A: Establishing the diagnosis of mesothelioma can be difficult. Cytologic examination of pleural fluid is unlikely to yield a diagnosis. When nodular pleural thickening is present, a fine-needle biopsy can be performed to establish the diagnosis, but there is only a 25% chance that the biopsy will yield a diagnosis in the presence of a nondiagnostic effusion. Video-assisted thoracoscopic surgery (VATS) is the diagnostic procedure of choice; it yields a diagnosis in more than 90% of cases.

Q: What is the clinical treatment and prognosis of malignant mesothelioma?

A: In the management of localized cases of mesothelioma, the option of radical surgery, such as an extrapleural pneumonectomy, should be considered. This procedure entails en bloc resection of the visceral and parietal pleurae, the whole lung, the ipsilateral diaphragm, and a portion of the pericardium, as well as mediastinal lymph-node dissection. Retrospective analyses show that the median survival among patients who undergo surgery is longer than the median survival among patients who do not undergo surgery (11 months vs. 7 months), but these studies have a strong selection bias for patients who are eligible for surgery. It is clear that the combination of aggressive surgery and chemotherapy, with or without radiation therapy, can afford a median survival time of approximately 20 months and a chance for remission. In one series, there was a 5-year survival rate of 46% among patients with epithelioid mesothelioma who did not have malignant cells in the epithelial tissue, resection margins, or extrapleural lymph nodes after treatment. Clinical trials comparing single-agent cisplatin with a combination of cisplatin and a novel multitargeted antifolate (pemetrexed or raltitrexed) show a statistically significant prolongation in survival among patients in the combination groups.