Parenteral fish oil lipid emulsion use in adults: a case series and review from an intestinal failure referral center.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) is a complication of long-term PN use, attributed to the use of ω-6 injectable lipid emulsions (ILE). Fish oil (FO) ILE have been successful in reversing liver injury in neonates. Evidence for pure FO ILE use in adult patients is limited. METHODS: Case series of the use of FO lipid emulsions in adults with IFALD from the University of Chicago PN registry. Analysis of medical charts and PN formulations was performed. RESULTS: Three cases of IFALD treated with FO ILE were identified. The first case was a 30-year-old man with short bowel syndrome (SBS), hyperbilirubinemia, and biopsy-proven IFALD. Following a change from a soy lipid emulsion to FO lipid emulsion, his liver tests rapidly improved and remained stable over 202 weeks of use. The second case was a 76-year-old woman with intestinal failure (IF) due to a frozen bowel. A change from a soy ILE to a composite lipid and later to a pure FO ILE did not result in improvement in her liver tests. The third case was a 28-year-old man with SBS and biopsy-proven IFALD. Change to a composite ILE and subsequently FO lipid emulsion resulted in a gradual improvement in liver tests. No clinical essential fatty acid (EFA) deficiencies were identified during treatment. CONCLUSION: FO ILE may be effective in the treatment of adult patients with cholestatic IFALD. Use is safe with no EFA deficiencies detected in up to 4 years of use.

Weaker SARS-CoV-2 vaccine responses in nonalcoholic fatty liver disease with advanced liver fibrosis.

Background: SARS-CoV-2 vaccine responses that could harbor potential risks to chronic liver diseased patients. Aims: To assess immune response following Pfizer's SARS-CoV-2 vaccine in patients with different liver fibrosis severities of nonalcoholic fatty liver disease (NAFLD). Methods: Clinical and histological (NAS-score and fibrosis stage) characteristics of NAFLD patients before vaccine were correlated with serologic vaccine responses of two doses of the BNT162b2. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed on day seven following immunization (Liaison assay). Results: The mean-age of patients (n = 157) was 56.9 ± 13.2 years (46.5 % males). 94.8 % had a positive response (anti-S levels ≥ 19 AU/ml). The anti-S cutoff of 200 AU/ml used to separate strong vs. weak responses. A strong response (anti-S titers ≥ 200 AU/ml) was observed in 93/157 (59.2 %) patients with a mean-age of 53.1 ± 13.8 years (45.2 % males). A weak response (anti-S titers < 200 AU/ml) was observed in 64/157 (40.8 %) cases with a mean-age of 62.3 ± 10.2 years (p < 0.0001). The strong response subgroup had lower metabolic comorbidities, including glucose hemostasis, hypertension, and dyslipidemia (p < 0.04). Moreover, the strong response subgroup had fibrosis stages F0-F2 (75.3 % vs. 56.3 %) and lower rates of advanced stages F3-F4 (24.7 % vs. 43.8 %). The F0-F2 subgroups had significantly higher rates of strong responses than the F3-F4 stages. The anti-S ≥ 200 and anti-S ≥ 400 AU/ml response achieved in 66 % and 36.8 % of the F0-F2 population was significantly higher than the 45.1 % (p = 0.006) and 23.5 % (p = 0.05) in the F3-F4 population, respectively. The Fib-4 calculations and Fibroscan evaluations were consistent with histologic fibrosis assessment. Conclusion: Advanced liver fibrosis (assessed by histology, Fib-4, or Fibroscan) is a risk factor for lower response to Pfizer's BNT162b2 vaccine, and patients should be prioritized for the vaccine booster against SARS-CoV-2.

SARS-CoV-2 vaccine alleviates disease burden and severity in liver transplant recipients even with low antibody titers.

BACKGROUND AND AIMS: We retrospectively assessed the clinical Pfizer's mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients. PATIENTS AND METHODS: One hundred and sixty-seven LT cases followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay). RESULTS: In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19 AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100 AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection. CONCLUSION: Pfizer's BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.

Advanced Liver Fibrosis Correlates With Impaired Efficacy of Pfizer-BioNTech COVID-19 Vaccine in Medical Employees.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine has been offered to nonallergic ≥16-year-old Israeli adults since December 19, 2020. Data regarding factors associated with vaccine ineffectiveness are limited. The aim of this study is to assess the impact of hepatic fibrosis on the efficacy of the BioNTech vaccine. Serum severe acute respiratory syndrome coronavirus 2 spike immunoglobulins (S IgG) obtained at least 7 days following vaccination completion was correlated with the prevaccine calculated Fibrosis-4 (FIB-4) score among 719 employees in the Hadassah Medical Center, Jerusalem. Positive vaccine response (S IgG levels ≥ 19 AU/mL) was found in 708 of 719 individuals (98.5%). Vaccine failure (S IgG levels < 19) was found in 11 (1.5%); of these, 7 were immunosuppressed. Mean FIB-4 available in 501 of 708 vaccine responders was 1.13 ± 0.66, mean age 51.4 ± 12.4 years (29.3% males), and mean S IgG titers 239.7 ± 86.1 AU/mL. Similar to the general population, 70.5% had normal FIB-4 (<1.3), 26.8% undetermined FIB-4 (1.3-2.67), and 2.7% advanced FIB-4 (>2.67). When divided into response subgroups, 158 of 501 individuals (30.1%) with IgG titers 19-100 AU/mL had a mean FIB-4 of 1.48 ± 0.82; 198 (39.5%) with IgG titers 101-200 AU/mL had mean FIB-4 of 1.22 ± 0.76; 83 (16.6%) with titers 201-300 AU/mL had mean FIB-4 of 1.04 ± 0.48; 38 (7.6%) individuals with IgG titers 301-400 AU/ml had a mean FIB-4 of 1.08 ± 0.63; and 121 (24.2%) with IgG titers >400 AU/mL had mean FIB-4 of 1.18 ± 0.87. Increased FIB-4, age, and male gender significantly correlated with lower postvaccine IgG titers (P < 0.001). FIB-4 results were confirmed using FibroScan data displaying advanced fibrosis impact on weakened COVID-19 vaccine response. Conclusion: Immune suppression, older age, male gender, and advanced chronic liver disease are risk factors for lower vaccine response. The FIB-4 provides a simple tool to prioritize candidates for third-dose vaccine booster.

Uncommon side effects of common drugs in patients with familial dysautonomia.

PURPOSE: Patients with the autosomal recessive disorder of familial dysautonomia typically exhibit exacerbated adverse side effects to many common drugs. We aimed to catalog these adverse effects - with a focus on common drugs that are frequently administered to FD patients and compare their incidences to those within the general population. METHODS: We used data of 595 FD patients from an international database with information on drugs received and adverse effects. To investigate the molecular causes of reported differences in drug responses in FD patients, we used expression microarrays to compare the mRNA expression profiles in peripheral blood leukocytes of FD patients (n = 12) and healthy individuals (n = 10). RESULTS: Several drug classes, including cholinergics, anti-cholinergics, anti-convulsants, methylxanthines, SSRIs, and antibiotics caused either unreported symptoms or elevated rates of adverse events in FD patients. FD patients experienced different or more frequent adverse side effects than the general population in 31/123 drugs. These side effects included blood cell dyscrasias, amenorrhea, gastrointestinal bleeding, and bronchospasm. New findings include enhanced reaction of FD patients to H2 antagonist agents and to serotonin receptor agonists. We also detected eight genes differentially expressed between FD patients and healthy individuals that may underlie the differential drug responses of FD patients. CONCLUSION: We provide evidence that suggests the use of several common drugs should be discontinued or reduced in FD patients.

Randomised clinical trial: A phase 2 double-blind study of namodenoson in non-alcoholic fatty liver disease and steatohepatitis.

BACKGROUND: Namodenoson, an A3 adenosine receptor (A3AR) agonist, improved liver function/pathology in non-alcoholic steatohepatitis (NASH) preclinical models. AIM: To evaluate the efficacy and safety of namodenoson for the treatment of non-alcoholic fatty liver disease (NAFLD) with or without NASH METHODS: This phase 2 study included 60 patients with NAFLD (ALT ≥60 IU/L) who were randomised (1:1:1) to oral namodenoson 12.5 mg b.d. (n = 21), 25 mg b.d. (n = 19), or placebo (n = 20) for 12 weeks (total follow-up: 16 weeks). The main efficacy endpoint involved serum ALT after 12 weeks of treatment. RESULTS: Serum ALT decreased over time with namodenoson in a dose-dependent manner. The difference between change from baseline (CFB) for ALT in the namodenoson 25 mg b.d. arm vs placebo trended towards significance at 12 weeks (P = 0.066). Serum AST levels also decreased with namodenoson in a dose-dependent manner; at 12 weeks, the CFB for 25 mg b.d. vs placebo was significant (P = 0.03). At Week 12, 31.6% in the namodenoson 25 mg b.d. arm and 20.0% in the placebo arm achieved ALT normalisation (P = 0.405). At week 16, the respective rates were 36.8% and 10.0% (P = 0.038). A3AR expression levels were stable over time across study arms. Both doses of namodenoson were well tolerated with no drug-emergent severe adverse events, drug-drug interactions, hepatotoxicity, or deaths. Three adverse events were considered possibly related to study treatment: myalgia (12.5 mg b.d. arm), muscular weakness (25 mg b.d. arm), and headache (25 mg b.d. arm). CONCLUSION: A3AR is a valid target; namodenoson 25 mg b.d. was safe and demonstrated efficacy signals (ClinicalTrials.gov #NCT02927314).

Gastrointestinal manifestations of synthetic cannabinoids: a retrospective cohort study.

BACKGROUND: Synthetic cannabinoids (SC) are chemical substances which activate cannabinoid receptors similarly to tetrahydrocannabinol, but with a higher efficacy. These substances are used as illicit recreational drugs, often smoked as herbal mixtures. The continuing availability and rapid evolution of SC is an ongoing health risk. The adverse effects of SC are wide ranging, and span from mild behavioral changes to death. Knowledge regarding gastrointestinal (GI) manifestations of SC use is sparse. METHODS: Single tertiary-care referral medical center retrospective study. RESULTS: The medical records of patients presented to hospital emergency care due to SC use between January 2014 and February 2018 were retrieved from Hadassah Mount Scopus Hospital's computerized database. The records were reviewed for clinical outcomes and laboratory tests. Fifty-five (55) patients were identified with a hospital presentation due to SC use. Twenty-one (21) out of 55 patients (38%) reported gastrointestinal complaints. The most common complaints were abdominal pain and vomiting. Of those, 28% had recurrent emergency department presentations due to abdominal pain and 66% presented with leukocytosis. Serum lactate was elevated in 66% of patients with GI manifestations. One patient had an abnormal computerized tomography (CT) abdominal angiography scan, which was compatible with intestinal ischemia. CONCLUSIONS: The clinical spectrum of gastrointestinal manifestations in SC intoxication ranges from mild symptoms, such as abdominal pain and vomiting, to even more severe symptoms suggestive of intestinal ischemia. Clinicians should be aware that abdominal pain and other gastrointestinal complaints can be associated with SC use.

Effect of Enzyme-Inducing Antiseizure Medications on the Risk of Sub-Therapeutic Concentrations of Direct Oral Anticoagulants: A Retrospective Cohort Study.

BACKGROUND: Stroke and thromboembolic events occurring among patients taking direct oral anticoagulants (DOACs) have been associated with low concentrations of DOACs. Enzyme-inducing antiseizure medications (EI-ASMs) are associated with enhanced cytochrome-P450-mediated metabolism and enhanced P-glycoprotein-mediated transport. OBJECTIVE: The aim of this study was to evaluate the effect of concomitant EI-ASM use on DOAC peak concentrations in patients treated in clinical care. METHODS: We performed a retrospective cohort study of patients treated with DOACs for atrial fibrillation and venous thromboembolic disease in an academic general hospital. In total, 307 patients treated with DOACs between August 2015 and January 2020 were reviewed. Clinical characteristics and peak DOAC plasma concentrations of patients co-treated with an EI-ASM were compared with those of patients not treated with an EI-ASM. An apixaban dose score (ADS) was defined to account for apixaban dosage and the number of apixaban dose-reduction criteria. RESULTS: In total, 177 peak DOAC plasma concentrations (including apixaban, rivaroxaban, and dabigatran) from 131 patients were measured, including 24 patients co-treated with an EI-ASM and 107 controls not treated with an EI-ASM. The proportion of patients with DOAC concentrations below the expected range was significantly higher among EI-ASM users than among patients not taking an EI-ASM (37.5 vs. 9.3%, respectively; p = 0.0004; odds ratio 5.82; 95% confidence interval [CI] 2.03-16.66). Most of these patients were treated with apixaban (85%); however, sensitivity analysis results were also significant (p = 0.031) for patients with non-apixaban DOACs. In patients co-treated with apixaban and an EI-ASM, median apixaban peak concentration was 106 ng/mL (interquartile range [IQR] 71-181) compared with 150 ng/mL (IQR 94-222) in controls (p = 0.019). In multivariable analysis, EI-ASM use was associated with 6.26-fold increased odds for apixaban concentration below the expected range (95% CI 2.19-17.90; p = 0.001). Apixaban concentrations were significantly associated with EI-ASM use, moderate enzyme inhibitor use, and ADS. CONCLUSIONS: Concurrent EI-ASM and DOAC use presents a possible risk for DOAC concentrations below the expected range. The clinical significance of the interaction is currently unclear.

DA-REPOCH Versus R-CHOP for the Treatment of Activated B-Cell Subtype Diffuse Large B-Cell Lymphoma: A Community Center Experience.

Diffuse large B-cell lymphoma (DLBCL) represents around one quarter of non-Hodgkin lymphomas in both the United States and globally. The activated B-cell (ABC) subtype of DLBCL is associated with higher relapse rates and a worse prognosis when treated with standard regimens in comparison to other subtypes of DLBCL. Recent studies have demonstrated a potential benefit with combination of dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-REPOCH) in comparison to standard combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in ABC DLBCL patients. We aimed to see if there was any benefit on progression-free survival (PFS) and overall survival (OS) in a pooled patient population from a community oncology practice with the use of DA-REPOCH in ABC DLBCL. Our study did not reveal a statistically significant advantage in either PFS or OS with DA-REPOCH; however, a smaller percentage or patients progressed or relapsed when treated with DA-REPOCH. While the toxicity profile was similar, a higher percentage of patients receiving R-CHOP experienced grade 3 or higher toxicities. A prospective trial of R-CHOP versus DA-REPOCH in patients with the ABC subtype of DLBCL is warranted to further determine a potential benefit to DA-REPOCH in this patient population.

Lack of Correlation Between Serum Ferritin Levels and Patient Outcome in Israeli Adults with Hepatitis A Infection.

BACKGROUND: In developed countries, hepatitis A virus (HAV) infection occurs mainly in adults. It is usually symptomatic and may cause acute liver failure (ALF). In patients with chronic liver disease, serum ferritin levels (SFL) can predict short-term prognosis. OBJECTIVES: To determine whether admission SFL can serve as a prognostic marker in patients with HAV infection. METHODS: A retrospective analysis of 33 adults with HAV infection was conducted. Because none of our patients presented with ALF, the parameter "length of hospital stay," was used as a surrogate marker of disease severity. RESULTS: The mean (± SD) at admission SFL was 2529 ± 4336 ng/ml. SFL correlated with the levels of international normalized ratio (INR), liver enzymes, and degree of hemolysis that occurred during the disease course. SFL did not correlate with the levels of either albumin or bilirubin or with the length of the hospital stay. The mean length of hospital stay was 5.1 ± 2.0 days, which correlated with the levels of INR, albumin, and bilirubin as well as the degree of hemolysis. However, in multivariate analysis only albumin and bilirubin predicted the length of the hospital stay. Follow-up SFL, which were available only in eight patients, decreased during the hospital stay. CONCLUSIONS: In adults with acute HAV infection, SFL may be increased. SFL correlated with the degree of liver injury and hemolysis that occur during the disease. However, in our cohort of HAV patients, who had a relatively benign disease course, SFL were of no prognostic value.

A Validated Score Assessing the Risk of an Intra-Abdominal Abscess in Patients with Crohn's Disease Presenting at the Emergency Department.

BACKGROUND AND AIMS: A majority of acutely ill Crohn's disease [CD] patients who present to Emergency Department [ED] will undergo an abdominal CT to rule out disease complications. We aimed to generate a simple non-invasive scoring model to predict the presence of an intra-abdominal abscess in CD patients in the ED. METHODS: We performed a retrospective case-control study at four Israeli hospitals from January 1, 2010 to May 30, 2018. Inclusion criteria included patients with an established diagnosis of CD that had cross-sectional abdominal imaging performed. A total of 322 patients were included, and 81 [25%] were diagnosed with an intra-abdominal abscess. RESULTS: In univariate analysis, ileo-colonic location (odds ratio [OR] 1.88, p = 0.0148), perianal CD [OR 7.01, p = 0.0004], fever [OR 1.88, p = 0.0247], neutrophil-to-lymphocyte ratio [OR 1.12, p < 0.0001], and C-reactive protein [OR 1.10, p < 0.0001] were significantly associated with abscess formation, whereas current use of corticosteroids was negatively associated with abscess formation [OR 0.46, 95% CI, 0.2-0.88, p = 0.0192]. We developed a diagnostic score that included five parameters that were significant on multivariate regression analysis, with assignment of weights for each variable according to the coefficient estimate. A low cut-off score of ≤7 was associated with a negative predictive value [NPV] of 93% for abscess formation, whereas a high cut-off score of >9 was associated with a positive predictive value of 65%. We validated this score with an independent cohort [area under the curve of 0.881 and NPV of 98.5%]. CONCLUSION: We recommend incorporating this score as an aid for stratifying acutely ill CD patients in the ED with low or high probability of the presence of an intra-abdominal abscess.

Ascites and Gallbladder Abnormalities are Frequent Findings in Adults with Hepatitis A Virus Infection.

BACKGROUND: Since the implementation of a hepatitis A virus (HAV) immunization program for children, which began in 1999 in Israel, HAV infections in the country have occurred mostly in adults. HAV infection in adults is usually symptomatic and may present with hepatic, as well as extrahepatic, abdominal complications. OBJECTIVES: To estimate the prevalence of extrahepatic abdominal complications in patients diagnosed with HAV. METHODS: Most extrahepatic abdominal complications corresponding to HAV infection have ultrasonographic manifestations; therefore, we retrospectively collected findings from ultrasound examinations in addition to laboratory data from adult patients with HAV infection who were admitted to our medical center between 2004 and 2016. Associations between ultrasonographic findings and laboratory parameters that reflect disease severity were identified. RESULTS: A total of 43 consecutive adult patients were included in this study. None presented with fulminant hepatic failure. Thirty patients (70%) had at least one ultrasonographic finding. Ascites was noted in 8 patients, a thickened gallbladder wall was observed in 14, pericholecystic fluid was found in 8, and biliary sludge was observed in 4. Significant associations included the presence of any ultrasonographic finding and peak total bilirubin levels (P = 0.021), the presence of ascites with peak aspartate and alanine aminotransferase levels (P = 0.041 and P = 0.038, respectively), and the presence of biliary sludge and nadir albumin during the HAV disease course (P = 0.037). CONCLUSIONS: Abdominal ultrasonographic findings, such as ascites and gallbladder abnormalities, are frequently observed during acute HAV infection and are significantly associated with disease severity.

Acute Portal Vein Thrombosis Predicts Concomitant Diagnosis of Hepatocellular Carcinoma in Cirrhotic Patients.

PURPOSE: Portal vein thrombosis (PVT) is a common condition in cirrhotic patients and mostly attributed to portal hypertension. The objective of our study was to examine the association of PVT with hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: A retrospective study was performed to identify cirrhotic patients with thrombosis of the portal system. Clinical and laboratory characteristics were collected and analyzed. RESULTS: Thirty-nine patients were identified. Twenty-four out of 39 patients with PVT did not develop HCC (group A) after follow-up time of 38.5 months from the diagnosis of PVT. Eight patients (20.5%) were diagnosed with HCC within two weeks following diagnosis of PVT (group B). Seven patients (17.9%) were diagnosed with tumor thrombus (group C) at time of PVT diagnosis. The average age was 53.5, 66.5, and 69 years for groups A, B, and C respectively. Most patients (75 and 87.5% for groups B and C respectively) diagnosed with PVT and HCC were males. The most common cause of cirrhosis in groups B and C was chronic hepatitis B virus infection (HBV) in 62.5% and 50% respectively. The most common clinical presentation of PVT in group A was abdominal pain in 55.5% compared to new/worsening ascites in 43% and 37.5% for groups B and C respectively. The platelet count in groups B and C was higher as compared to that in group A (126 and 125 vs. 107 thousand, P = NS). CONCLUSION: In 38.4% of cases, new diagnosis of PVT was associated with concomitant diagnosis of HCC. Identifiable risk factors were chronic HBV infection and higher platelet count.

Radiographic markers for measuring tibial rotation based on CT-reconstructed radiographs: an accuracy and feasibility study.

OBJECTIVES: Malreduction in the axial plane (malrotation) following tibial fracture surgery is often undiagnosed. A few clinical and radiographic methods have been proposed for measuring tibial rotation intraoperatively, yet have failed to match the accuracy of computed tomography (CT). The aim of this study was to develop radiographic tools for future intraoperative assessment of the tibial shaft rotation profile. METHODS: The setting was a laboratory computerized analysis. Twenty lower limb CT scans were used to construct a three-dimensional (3D) model using AMIRA© software. A virtual 3D cylinder was implanted in the posterior condylar line and in the transmalleolar axis. The 3D models were used to simulate four standard knee and ankle plain radiographs. On each radiograph, four landmarks were depicted by two observers and their relation with the cylinder was measured and analyzed for accuracy and reproducibility. A cadaveric lower leg was implanted with two Kirschner wires. A CT scan was performed in addition to 2D fluoroscopy. The simulated radiographs and the fluoroscopy were compared for accuracy. RESULTS: Measurement of the landmarks showed reliability in most of the knee anteroposterior and ankle mortise radiographs (coefficients of variation < 0.01 and = 0.01) respectively. Cadaveric measurement of the landmarks using real fluoroscopy and simulated radiographs were similar. CONCLUSIONS: To date, no reliable and common methods have been reported for the evaluation of tibial axial rotation. We propose a model in which simple radiographic landmarks can be used to calculate a 3D coordinate system that accurately assesses the axial rotation angle of the tibial shaft.

Fatal Mesenteric Ischemia Induced by Synthetic Cannabinoids: A Case Report and Literature Review.

Worldwide use of synthetic cannabinoids (SCs) is rapidly increasing, in part due to the generation of numerous new compounds, sidestepping legal restrictions. Their detection using standard toxicology panels is difficult, due to their vast heterogeneity and lack of structural resemblance to cannabinoids. Sympathetic overactivity and arterial spasm play a role in some of the life-threatening reactions to SCs, such as coronary or cerebral vasoconstriction. Here we report a patient with repeated consumption of SCs that led to mesenteric ischemia and death. A 29-year-old man was frequently evaluated in the Emergency Medicine Department for recurrent transient crampy abdominal pain, associated with the use of the SCs colloquially known as "Mr. Nice Guy." He was finally hospitalized with a protracted attack, associated with diarrhea and leukocytosis. Initial evaluation including computed tomography was unremarkable. Diarrhea and leukocytosis gradually resolved, but bouts of hypertension and abdominal pain occurred in association with repeated consumption of the SCs. On the fifth hospital day, the patient developed abrupt abdominal pain, associated with profound shock and signs of peritoneal irritation and succumbed within an hour. Postmortem CT scan was consistent with intestinal perforation most probably due to a nonobstructive mesenteric infarction. There was no evidence of a single vessel infarction.

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience.

2-Chlorodeoxyadenosine (2-CdA), a purine analog, has become universally accepted as the agent of choice in treating hairy cell leukemia (HCL). However, few studies have reported long-term outcomes after 2-CdA treatment. Between January 1990 and June 2003, 86 consecutive patients with HCL were treated with a single 7-day course of 2-CdA by continuous infusion at a dose of 0.1 mg/kg per day. Of the 86 patients (mean age: 49 years), 67 patients (79%) achieved a complete remission (CR); 18 patients (21%) achieved a partial remission (PR); and 1 patient's response was unable to be assessed. The progression-free survival (PFS) for initial relapse after 12 years was 54%. At a median follow-up of 9.7 years (range, 0.3-13.8 years), 31 (36%) of 85 patients relapsed. There were 23 relapsed patients treated with a second cycle of 2-CdA; 2 patients were treated with alternative agents; and 6 patients were observed. Of the 23 relapsed patients retreated with 2-CdA, 12 (52%) achieved a CR and 7 (30%) patients achieved a PR (overall response rate: 83%). The overall survival (OS) rate after 12 years was 87%. There were 15 patients (17%) who developed other malignancies. Long-term follow-up of up to 14 years (median: 9.7 years) showed an excellent PFS and OS for HCL patients after 2-CdA treatment.