A Woman with Leukocytosis

Posted by • December 8th, 2016

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Primary causes of neutrophilia encompass benign, congenital, and familial syndromes. Another category of primary neutrophilias includes those associated with clonal bone marrow diseases. An 86-year-old woman was seen at the hospital because of fatigue, night sweats, leukocytosis, and splenomegaly. Review of the peripheral-blood smear revealed neutrophilia without dysplastic features, immature forms, or monocytosis. A diagnostic procedure was performed in a new Case Record.

Clinical Pearl

• Is chronic neutrophilic leukemia (CNL) common?

CNL, which was first described approximately a century ago, is rare, with only a few hundred cases reported in the literature. The diagnosis is often made incidentally, but constitutional symptoms such as sweats, fatigue, weight loss, and abdominal symptoms related to splenomegaly, can be present.

Clinical Pearl

• What are the World Health Organization (WHO) diagnostic criteria for CNL?

The diagnosis of CNL, a condition that was first recognized as a distinct entity in the 2001 WHO classification guidelines, requires the presence of unexplained peripheral-blood leukocytosis (≥25×109 white cells per liter), with neutrophils and bands comprising at least 80% of white cells, immature granulocytes comprising less than 10% of white cells, myeloblasts comprising less than 1% of white cells, an absolute monocyte count of less than 1×109 cells per liter, and absence of granulocytic dysplasia; a hypercellular bone marrow with increased granulocytic forms, less than 5% myeloblasts, and normal neutrophil maturation; splenomegaly; exclusion of BCR-ABL1, PDGFRA, PDGFRB, and FGFR1 genetic abnormalities; and exclusion of the diagnoses of polycythemia vera, primary myelofibrosis, and essential thrombocythemia.

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Morning Report Questions

Q: What mutations are associated with CNL?

A: In the past several years, it has been shown that up to 90% of patients with CNL harbor a CSF3R (colony-stimulating factor 3 receptor) mutation; the presence of this mutation has been added to the revised 2016 WHO list of diagnostic criteria for CNL. The genetic profile of CNL may include other abnormalities, such as SETBP1, ASXL1, and TET2 mutations. Whether these abnormalities affect the pathogenesis, evolution, or prognosis of CNL is currently not clear. One study suggested that concurrent ASXL1 mutations may be prognostically detrimental.

Q: How is CNL treated, and how does the location of a CSF3R mutation influence the choice of therapy?

A: The most effective therapeutic approach to CNL has not been well defined. Oral agents, including hydroxyurea and busulfan, have been used to control leukocytosis and splenomegaly and improve quality of life. CSF3R mutations occur at two distinct regions: the membrane proximal region and the cytoplasmic tail, which can be truncated by nonsense and missense mutations. Mutations occurring at the former region result in dysregulation of JAK family kinases, whereas mutations occurring at the latter region result in dysregulation of SRC family–TNK2 kinases. Membrane proximal mutations may confer sensitivity to JAK kinase inhibitors such as ruxolitinib, whereas truncation mutations confer sensitivity to the multikinase inhibitor dasatinib but not to JAK kinase inhibitors.

Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery

Posted by • December 7th, 2016

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On the first day of my second year of residency, I showed up to the cardiac surgery intensive care unit (CSICU) terrified for what awaited me.  It wasn’t uncommon for patients recovering from cardiac surgery to be on three different vasopressors while intubated with four chest tubes and pacing wires. Even after a year of general surgery residency, the CSICU was a bit of a foreign land to me.   One thing I learned quickly, though, was that bleeding after cardiac surgery was relatively common.

Many patients required blood transfusions and occasionally had to return to the operating room due to ongoing bleeding.  In an effort to reduce postoperative bleeding, transfusion, and reoperation, most cardiac surgery units administer antifibrinolytic agents such as tranexamic acid, a lysine analogue. Although studies have shown that tranexamic acid can reduce the risk of blood loss and transfusion after cardiac surgery, it also has a prothrombotic effect, and the risk of myocardial infarction, stroke, or other complications is unclear. Further, some studies have shown an increased risk of seizures with tranexamic acid, potentially due to cerebral infarction.

A recent multicenter, double-blind, randomized-controlled study by Myles et al. published in NEJM investigates the risks and benefits of intra-operative tranexamic acid infusion in cardiac surgery. According to the trial’s 2-by-2 factorial design, patients at increased surgical risk undergoing coronary-artery surgery (either on- or off-pump and with or without concomitant valve procedures) were randomized to receive aspirin or placebo (results reported in a separate study) and tranexamic acid or placebo. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Secondary outcomes included all components of the composite primary outcome as well as reoperation due to major hemorrhage or cardiac tamponade, transfusion, and seizures (which was added later in the study and was based on clinical diagnosis).

Among the 2311 patients randomized to receive tranexamic acid and the 2320 patients who received placebo, baseline characteristics and comorbidities were evenly distributed between groups. The composite primary outcome was reported in 17% of patients in the tranexamic acid group and 18% of patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.81 to 1.05; P = 0.22). This result was not affected by whether or not patients received aspirin. Rates of the individual components of the composite outcome were similar between groups.

Tranexamic acid was associated with lower rates of bleeding, blood loss, number of patients transfused, number of blood products transfused (4331 vs. 7994, P<0.001), and major hemorrhage or cardiac tamponade requiring reoperation (1.4% vs. 2.8%, P=0.001). However, postoperative seizures were more common in the tranexamic acid group (15 vs. 2 patients; relative risk, 7.62; 95% CI, 1.77 to 68.71; P = 0.002 by Fisher’s exact test). In a post-hoc analysis, seizure was associated with poorer outcomes such as stroke (relative risk, 21.88; 95% CI, 10.06 to 47.58; P<0.001) and death (relative risk, 9.52; 95% CI, 2.53 to 35.90; P = 0.02). Several years into the study, the dose of tranexamic acid administered was halved after some studies showed a possible dose-related risk of seizure.  The dose reduction did not affect the risk of seizure (although the study was underpowered for this analysis).

Overall, tranexamic acid seems to reduce bleeding complications after cardiac surgery, most impressively by reducing the number of transfusions required by 47%. In addition, tranexamic acid did not increase the risk of death, myocardial infarction, or stroke. However, this study corroborates data linking tranexamic acid to higher risk of seizure.

How will this study change current practice in cardiac surgery? Will cardiac surgery units that do not currently use tranexamic acid change their practice? NEJM Deputy Editor John Jarcho comments, “Surgeons really don’t like bleeding, for good reasons. I think they will see these findings as a good reason to use antifibrinolytic therapy, if they weren’t using it previously.”

Resident Burnout

Posted by • December 1st, 2016

This podcast is the second in a series that reflects medicine’s most pressing issues through the eyes of residents. “The House” provides residents with a forum to share their stories from the bedside, where they are learning far more than the lessons of clinical medicine.

Lisa Rosenbaum is a cardiologist at Brigham and Women’s Hospital in Boston, an instructor at Harvard Medical School, and National Correspondent for the New England Journal of Medicine.
Dan Weisberg is a resident in Internal Medicine and Primary Care at Brigham and Women’s Hospital and Harvard Medical School.

Postpartum Depression

Posted by • December 1st, 2016

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Untreated postpartum depression is common affects the health of the woman, infant, and family. Pregnant women should receive information about the signs and symptoms of postpartum depression and its effects. Treatment depends on the severity of symptoms and the level of functional impairment and can include social support, psychological therapy, and pharmacotherapy (generally an SSRI as first-line treatment). A new Clinical Practice article explains further.

Clinical Pearl

What are some of the risk factors for postpartum depression?

The strongest risk factor for postpartum depression is a history of mood and anxiety problems and, in particular, untreated depression and anxiety during pregnancy. The rapid decline in the level of reproductive hormones after childbirth probably contributes to the development of depression in susceptible women, although the specific pathogenesis of postpartum depression is unknown; in addition to hormonal changes, proposed contributors include genetic factors and social factors including low social support, marital difficulties, violence involving the intimate partner, previous abuse, and negative life events.

Clinical Pearl

What is the natural course of postpartum depression?

The natural course of postpartum depression is variable. Although it may resolve spontaneously within weeks after its onset, approximately 20% of women with postpartum depression still have depression beyond the first year after delivery, and 13% after 2 years; approximately 40% of women will have a relapse either during subsequent pregnancies or on other occasions unrelated to pregnancy.

Morning Report Questions

Q: How would you evaluate a woman for possible postpartum depression? 

A: The best method for detecting postpartum depression remains controversial. Administration of the 10-item Edinburgh Postnatal Depression Scale (EPDS) is recommended by both the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics as a method of identifying possible postpartum depression. The U.S. Agency for Healthcare Research and Quality suggests that serial testing, beginning with the use of a sensitive, two-question screening tool relating to feelings of depression or hopelessness and of a lack of interest or pleasure in activities, followed by the use of a second, more specific instrument for women who give a positive answer to either screening question, may be a reasonable strategy to reduce both false positive and false negative results. The evaluation of women with possible postpartum depression requires careful history taking to ascertain the diagnosis, identify coexisting psychiatric disorders, and manage contributing medical and psychosocial issues. During the process of history taking, special attention should be given to a personal or family history of depression, postpartum psychosis, or bipolar disorder, especially if depression or bipolar disorder had been associated with pregnancy. Coexisting anxiety and obsessive–compulsive symptoms are common among women with postpartum depression and should be investigated further. Women should be asked about social support as well as substance abuse and violence involving an intimate partner. An examination to assess mental status should be conducted, as well as a physical examination if symptoms suggest a medical cause. Laboratory investigations should be performed as indicated; measurement of hemoglobin and thyroid-stimulating hormone levels are generally recommended.

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Q: What are some of the antidepressants that are used in women with postpartum depression who are breast-feeding?

A: Although data on long-term child development are limited, in most cases breast-feeding need not be discouraged among women who are taking an antidepressant medication. Selective serotonin reuptake inhibitors (SSRIs) pass into breast milk at a dose that is less than 10% of the maternal dose, and drugs in this class are generally considered to be compatible with breast-feeding of healthy, full-term infants. Despite some variability among SSRIs in terms of their passage into breast milk, switching the antidepressant medication because of lactation is not usually recommended for women who had previously been receiving effective treatment with a given agent, owing to the risk of a relapse of depression. Serotonin norepinephrine reuptake inhibitors (SNRIs) or mirtazapine are commonly used either when SSRIs are ineffective or when a woman has previously had a positive response to these agents since available data also suggest minimal passage into breast milk. Data on safety for these agents remain limited, however, since fewer than 50 cases have been reported in which women who were breast-feeding were taking either SNRIs or mirtazapine.

Niraparib Maintenance Therapy in Ovarian Cancer

Posted by • December 1st, 2016

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Ovarian cancer is a leading cause of death from gynecologic cancers worldwide. A randomized, placebo-controlled, phase 3 trial conducted by Mirza et al. evaluated the efficacy and safety of niraparib versus placebo as maintenance treatment in a broad population of patients with platinum-sensitive, recurrent ovarian cancer. Among these patients, the use of niraparib, a PARP inhibitor, was associated with a significantly longer duration of progression-free survival than placebo, with moderate bone marrow toxicity. A new Original Article summarizes.

Clinical Pearl

• What is the usual pattern of response to platinum and taxane treatment in patients with advanced ovarian cancer?

Despite a high initial response rate to platinum and taxane treatment in patients with advanced cancer, the effectiveness of the treatments diminishes over time, and most patients have a relapse. Platinum retreatment is used in patients in whom there is an assumed platinum sensitivity, with diminishing effectiveness and a cumulative increase in toxicity.

Clinical Pearl

• To what class of drugs does niraparib belong?

Niraparib is a highly selective inhibitor of poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) 1/2, nuclear proteins that detect DNA damage and promote its repair. Clinical studies have evaluated PARP inhibitors in patients with recurrent ovarian cancer, including those with germline BRCA mutations, platinum-sensitive disease, or both.

Morning Report Questions

Q: Does niraparib maintenance therapy prolong progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer?

A: The trial by Mirza et al. enrolled two independent cohorts on the basis of the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort). Before the database lock, tumor testing of archived tissue samples was performed with the use of a central laboratory DNA-based test to define the population of patients in the non-gBRCA cohort in whom tumors were found to have homologous recombination deficiency (HRD). Such patients were included in the non-gBRCA HRD-positive subgroup. (Decreased rates of homologous recombination have been found to cause inefficient DNA repair.) The three predefined primary efficacy populations were the gBRCA cohort, the HRD-positive subgroup of the non-gBRCA cohort, and the overall non-gBRCA cohort. The authors found that niraparib had a positive effect among patients with platinum-sensitive recurrent ovarian cancer. The duration of progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer was significantly longer in the niraparib group than in the placebo group, regardless of the presence or absence of gBRCA mutations or HRD status.

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Q: What adverse events were associated with niraparib in the trial by Mirza et al.?

A: In the trial by Mirza et al., Grade 3 or 4 hematologic events that were observed in at least 10% of patients receiving niraparib were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%). Treatment discontinuations because of these events were infrequent. Most of the hematologic laboratory abnormalities occurred within the first three treatment cycles; after dose adjustment on the basis of an individual adverse-event profile, the incidence of grade 3 or 4 thrombocytopenia, neutropenia, or fatigue was infrequent beyond cycle 3.

Reduction in HIV Transmission with Dapivirine Vaginal Ring – Is it Enough?

Posted by • November 30th, 2016

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While you are working for one month in a health center in South Africa, a 19-year-old woman comes to the clinic and asks for your advice: She is HIV-negative, and is unsure of her partner’s HIV status. Is there anything she can do to prevent her from acquiring HIV?

Preexposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is an emerging approach to prevent HIV transmission, with some data in men who have sex with men suggesting effectiveness. However, the efficacy of PrEP in women has been inconsistent, especially in young women in sub-Saharan Africa. Studies of vaginal tenofovir gel and oral tenofovir-emtricitamine in women have failed to consistently demonstrate a reduction in the risk of HIV acquisition. The limited efficacy was thought to be attributed to poor adherence and possibly a lower concentration of tenofovir in the female genital tract.

Two studies appearing in this week’s NEJM highlight a new approach to prophylaxis against HIV. Both the Ring study and the Aspire study were randomized, double-blind, placebo-controlled trials conducted in sub-Saharan Africa. These trials examined the effectiveness of a monthly self-inserted vaginal ring that contains sustained-release dapivirine, a non-nucleotide reverse transcriptase inhibitor, in healthy, nonpregnant, HIV-uninfected women aged 18-45 years who were engaged in regular sexual activity. All participants received treatment for sexually transmitted infections and a standard HIV prevention package (including regular HIV testing, counseling, and condoms).

The primary outcome in both studies was new HIV infections. In both studies, the HIV incidence rate was lower in the dapivirine group than in the placebo group. In the Ring study, incidence rates were 4.1 vs. 6.1 per 100 person-years (relative reduction, 31%) and in the Aspire study, the rates were 3.3 vs. 4.5 per 100 person-years (relative reduction, 27%). In the Aspire study, the ring did not significantly reduce HIV incidence in women ≤21 years old, but was associated with a 61% relative reduction in women >21. Adherence to treatment was good in both studies, based on pre-specified levels of plasma dapivirine concentrations and remaining dapivirine levels in returned rings.

In prior studies, poor adherence to PrEP therapies was hypothesized as the primary reason for treatment failure. The finding from these two studies that the dapivirine ring only reduced HIV acquisition by approximately 30% suggests that the ring itself had limited efficacy or that the thresholds for adherence selected by the investigators were insufficient to identify poor adherence. “Preventing HIV transmission is an important individual and public health goal and new approaches are needed. What to do with this modest effect is a challenging question for the field” says Dr. Lindsey Baden, Deputy Editor at the NEJM. Additionally, the reduced efficacy in younger women complicates the benefits.  In an accompanying editorial, Dr. Adaora A. Adimora from the Institute for Global Health and Infectious Diseases at the University of North Carolina School of Medicine concludes, “The past few years have yielded substantial progress in strategies for the prevention of HIV infection. Nevertheless, considerable work will be required to achieve safe, effective, affordable HIV prevention for all women at risk.”

Von Willebrand’s Disease

Posted by • November 24th, 2016

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Von Willebrand’s disease is an inherited bleeding disorder characterized by defective platelet adhesion and aggregation. It is the most common inherited bleeding disorder and is generally transmitted as an autosomal dominant trait. It is mainly associated with mucosal bleeding and excessive bleeding after trauma or surgery. A variety of effective treatments are available and research is summarized in a new Review Article.

Clinical Pearl

What are the different types of von Willebrand’s disease?

Von Willebrand’s disease is subdivided into types 1, 2, and 3. Type 1, which accounts for 70 to 80% of cases, is characterized by a quantitative deficiency of von Willebrand factor. Type 2, accounting for approximately 20% of cases, is caused by dysfunctional von Willebrand factor, resulting in a normal or reduced von Willebrand factor antigen concentration but a large reduction in von Willebrand factor function. Type 2 is further subdivided on the basis of specific phenotypic characteristics. Type 3 von Willebrand’s disease is rare (accounting for <5% of cases), is the most severe form, and is caused by the absence of circulating von Willebrand factor.

Clinical Pearl

What are some of the clinical features of von Willebrand’s disease?

The symptoms of von Willebrand’s disease vary among patients, depending on the level of residual von Willebrand factor activity, the disease subtype, and to some extent, age and sex. In children with von Willebrand’s disease, the most frequent presenting symptoms are bruising and epistaxis. In adults, the most common symptoms are hematomas, menorrhagia, and bleeding from minor wounds. The majority of patients (60 to 80%) have bleeding after surgery or dental extractions. A well-known, serious, and possibly life-threatening bleeding complication is gastrointestinal bleeding from angiodysplasia. It is most common in elderly patients with type 2 or 3 von Willebrand’s disease. Intraarticular (joint) bleeding is a frequent complication in patients with hemophilia but has not been reported as a major problem in patients with von Willebrand’s disease, although it may be a presenting symptom in those with type 2N (type 2 subtype Normandy) or type 3 disease. It is now known that joint bleeding occurs in a considerable number of severely affected patients, potentially leading to arthropathy and reduced joint function.

Morning Report Questions

Q: Does the progressive physiological rise in von Willebrand factor levels throughout life reduce bleeding episodes in older patients with von Willebrand’s disease?

A: As a result of the physiologic rise in von Willebrand factor levels throughout life, patients with type 1 von Willebrand’s disease may have levels within the normal range when they become older. It is still not known whether this rise results in fewer bleeding episodes. A recent study showed that among patients with type 1 disease, bleeding symptoms occurred as frequently in patients who were older than 65 years of age as in those who were 18 to 65 years of age, which suggests that the age-dependent rise in von Willebrand factor levels does not lead to a mitigation of bleeding symptoms. Even though von Willebrand factor antigen levels also rise with age in patients with type 2 disease, von Willebrand factor activity remains low because of the functional defect in the protein. In these patients, an increase in bleeding symptoms is observed with increasing age. These observations should be confirmed in larger prospective studies.

Q: What are some of the factors other than mutations in the VWF gene that may play a role in reducing von Willebrand factor levels? 

A: Even though many mutations causing type 1 von Willebrand’s disease have been identified, no mutations are found in approximately 30% of patients. Genetic modifiers outside the VWF gene and physiological factors probably play a role in reducing von Willebrand factor levels. One of the major genetic determinants of von Willebrand factor levels outside the VWF gene is the ABO blood group, with 25% lower von Willebrand factor levels in persons with type O blood than in those with other types. Genomewide association studies have identified several other genetic loci that are associated with von Willebrand factor levels in healthy persons. Studies have confirmed that these genetic loci lead to variability in von Willebrand factor levels in patients with von Willebrand’s disease, as well as in healthy persons. The newly recognized genetic loci may contribute to the variability in the von Willebrand’s disease phenotype and may explain low levels of von Willebrand factor in affected patients who do not have a mutation in the VWF gene. Apart from genetic modifiers, physiological factors such as age and the response to exercise and the acute-phase response, as well as the menstrual cycle and pregnancy in women, also play a role in the variability of von Willebrand factor levels.

A Man with Acute Liver Injury

Posted by • November 24th, 2016

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HEV infection is uncommon in the United States, although 20% of the population has antibodies to HEV. The diagnosis should be considered in patients who present with acute hepatitis after returning from a trip to an area in which HEV is endemic. In a new Case Record article, a 50-year-old man from India with a remote history of alcohol use was admitted to the hospital because of abnormal liver function test results, anemia, and acute kidney injury. A diagnosis was made.

Clinical Pearl

What are some of the features of HEV infection?

HEV is endemic throughout Central and Southeast Asia, India, the Middle East, North Africa, and Mexico. In these areas, HEV is a major cause of acute hepatitis and acute liver failure, with high attack rates among adults between 15 and 40 years of age. HEV is transmitted enterically and is responsible for waterborne outbreaks of hepatitis; person-to-person transmission is uncommon. The mean incubation period is 40 days. A high mortality rate (15 to 25%) occurs among pregnant women. The risk of hepatic decompensation is increased in patients with underlying chronic liver disease.

Clinical Pearl

What is the usual course of hepatitis E virus infection?

Illness is generally self-limited, but cases of chronic hepatitis attributed to HEV that have progressed rapidly to cirrhosis have been reported in transplant recipients and, rarely, in persons with human immunodeficiency virus infection or preexisting liver disease or in those undergoing chemotherapy for cancer.

Morning Report Questions

Q: Are there reliable serologic tests for diagnosing acute hepatitis E available in the United States? 

A: The diagnosis of acute hepatitis E is made most readily by testing for anti-HEV IgM antibodies in serum, although available tests may not be reliable and are not licensed for use in the United States. The diagnosis can also be made by detecting HEV in serum or stool with the use of a polymerase-chain-reaction (PCR) assay. A liver biopsy is generally unnecessary. However, serologic testing for HEV should be interpreted with caution, because the test has several limitations, including variability in the sensitivity and specificity of tests available in the United States.

Q: Is there an established role for antiviral therapy in cases of acute hepatitis E infection? 

A: Antiviral treatments for acute HEV infection have not been well studied; most of the literature on treatment involves reports of immunocompromised patients with chronic HEV infection. When decreasing the immunosuppression is not feasible or does not lead to viral clearance, antiviral therapy with pegylated interferon alone or in combination with ribavirin has been shown to be effective. Whether antiviral treatment with ribavirin improves outcomes in patients with severe acute HEV infection is unknown, but several case reports suggest a benefit. However, ribavirin is also associated with a substantial risk of hemolytic anemia. There is evidence that acute HEV infection can resolve without antiviral therapy.

Thresholds for Abdominal Aortic Aneurysm Repair in England and the United States

Posted by • November 23rd, 2016

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Imagine you are assessing a relatively healthy 85-year-old man who was brought to the hospital after a fall at home. Due to concern for spinal fractures, he underwent CT scans of his head, C-spine, chest, abdomen, and pelvis. Although no traumatic injuries were found, an incidental finding of a 5.5 cm infrarenal abdominal aortic aneurysm (AAA) was noted on the CT scan of the abdomen. The patient is asymptomatic from this aneurysm with no complaints of abdominal pain, back pain, or syncopal episodes. Should he undergo aneurysm repair? Can you watch and wait? Is he at risk for aneurysm rupture if you don’t intervene?

International guidelines recommend aneurysm repair once aneurysm diameter exceeds 5.5 cm for men and 5.0 cm for women. However, these guidelines are not applied universally and there is still uncertainty about the ideal diameter for intervention. In this week’s NEJM, Karthikesalingam et al. compared thresholds for AAA repair in the U.S. and England and differences in rates of aneurysm repair, in-hospital mortality, aneurysm rupture, long-term survival, aneurysm-related mortality, preoperative aneurysm diameter at time of repair, and prevalence of risk factors.  The authors used several unlinked databases and stratified the comparisons by age and gender. Survival comparisons also were adjusted for year of surgery and whether the repair was open or endovascular.

Rates of intact aneurysm repair increased in both countries from 2005–2012, but rates were significantly lower in England (odds ratio, 0.49; P<0.0001). The percentage of repairs that were endovascular was also lower in England (45% vs. 67%, P<0.001).  After controlling for multiple factors, in-hospital mortality and 3-year survival after elective repair were similar in the two countries.

Although rates of hospitalization for aneurysm rupture decreased in both countries from 2005–2012, hospitalization was significantly more common in England (OR, 2.23; P<0.001). Aneurysm –related mortality also declined in both countries, but again was significantly higher in England (OR, 3.60; P<0.001). The mean aneurysm diameter (weighted for age and gender) at intact AAA repair was significantly larger in England than in the U.S. (6.37 vs. 5.83 cm; P<0.001).

The study authors conclude that the rate of intact AAA repair in England is about half as high as in the U.S., likely because surgeons in England repair aneurysms when they are larger than surgeons in the U.S. The higher rate of intact aneurysm repair at a lower diameter in the U.S. did not appear to increase perioperative risk or mortality. In fact, the authors suggest that the higher rate of ruptured aneurysm hospitalization and mortality in England may be due to the higher-diameter aneurysm repair thresholds.

The major weakness of this study is that the authors cannot establish a causal relationship between the increased rates of aneurysm-rupture outcomes in England and the threshold at which they repair aneurysms. In addition, this study is limited by the retrospective design and the use of several unlinked databases during different time periods. Although this study is unlikely to change practice, it does provide more support for the existing international guidelines and may lead some countries to reconsider AAA repair thresholds.

Acute Pancreatitis

Posted by • November 17th, 2016

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Approximately 80% of patients admitted with acute pancreatitis have mild, self-limited disease and are discharged within several days. Mortality associated with acute pancreatitis has decreased over time, and the overall mortality is now approximately 2%. A new Review Article summarizes recent changes in the management of acute pancreatitis, encompassing fluid resuscitation, antibiotic use, nutritional support, and treatment of necrosis, and also addresses common misunderstandings and areas of controversy.

Clinical Pearl

What are some of the factors that might contribute to unexplained pancreatitis?

The cause of acute pancreatitis often cannot be established, and the proportion of persons who are considered to have idiopathic acute pancreatitis increases with age. A number of potential factors might contribute to unexplained pancreatitis, including unidentified genetic polymorphisms, exposure to smoking and other environmental toxins, and effects of coexisting diseases that are commonly associated with acute pancreatitis (e.g., obesity and diabetes).

Clinical Pearl

What is the role of prophylactic antibiotics in acute pancreatitis?

Although the development of infected pancreatic necrosis confers a significant risk of death, well-designed trials and meta-analyses have shown no benefit of prophylactic antibiotics. Prophylaxis with antibiotic therapy is not recommended for any type of acute pancreatitis unless infection is suspected or has been confirmed.

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Morning Report Questions

Q: Should patients with acute pancreatitis receive enteral or parenteral nutrition? 

A: Total parenteral nutrition is now known to be more expensive, riskier, and no more effective than enteral nutrition in patients with acute pancreatitis. In patients with mild acute pancreatitis who do not have organ failure or necrosis, there is no need for complete resolution of pain or normalization of pancreatic enzyme levels before oral feeding is started. A low-fat soft or solid diet is safe and associated with shorter hospital stays than is a clear-liquid diet with slow advancement to solid foods. Most patients with mild acute pancreatitis can be started on a low-fat diet soon after admission, in the absence of severe pain, nausea, vomiting, and ileus (all of which are unusual in mild cases of acute pancreatitis). A need for artificial enteral feeding may be predicted by day 5, on the basis of symptoms that continue to be severe or an inability to tolerate attempts at oral feeding. Although nasojejunal tube feeding is best for minimizing pancreatic secretion, randomized trials and a meta-analysis have shown that nasogastric or nasoduodenal feeding is clinically equivalent. Total parenteral nutrition should be reserved for the rare cases in which enteral nutrition is not tolerated or nutritional goals are not met. Unfortunately, total parenteral nutrition continues to be used frequently in patients with acute pancreatitis.

Q: What is the risk of recurrent gallstone pancreatitis if cholecystectomy is delayed?

A: Cholecystectomy prevents recurrent gallstone pancreatitis. A delay of cholecystectomy for more than a few weeks places the patient at a high (up to 30%) risk for relapse. Cholecystectomy performed during the initial hospitalization for mild pancreatitis due to gallstones reduces the rate of subsequent gallstone-related complications by almost 75%, as compared with cholecystectomy performed 25 to 30 days after discharge. For patients with severe or necrotizing pancreatitis, cholecystectomy may be delayed in order to address other clinically significant conditions or provide time for the pancreatic inflammation to diminish, allowing for better operative exposure.