Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.

Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods: Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated. Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04). Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

Clinical outcomes in elderly patients with advanced non-small cell lung cancer: results from ARIES, a bevacizumab observational cohort study.

AIMS: Retrospective analyses from first-line clinical studies in advanced non-small cell lung cancer (NSCLC) have reported conflicting results on progression-free survival (PFS) and overall survival benefits with the addition of bevacizumab to chemotherapy in elderly patients. Here we report effectiveness and safety outcomes by age subgroup for patients with NSCLC in the ARIES observational cohort study. MATERIALS AND METHODS: ARIES enrolled patients with advanced non-squamous NSCLC who received first-line bevacizumab-containing treatment per physician's choice. Kaplan-Meier estimates were used to calculate medians and 95% confidence intervals for PFS and overall survival for patients aged <65, ≥65, <75 and ≥75 years. RESULTS: In total, 1967 patients receiving first-line treatment with bevacizumab and chemotherapy were enrolled. The median PFS and overall survival values were 6.4 (95% confidence interval = 6.0-6.8) and 14.2 (95% confidence interval = 12.7-15.2) months for patients aged <65 years, respectively, and 6.8 (95% confidence interval = 6.3-7.0) and 12.1 (95% confidence interval = 11.4-13.1) months for patients ≥65 years, respectively. For patients <75 years, the median PFS and overall survival values were 6.6 (95% confidence interval = 6.3-6.9) and 13.5 (95% confidence interval = 12.6-14.5) months, respectively, and 6.6 (95% confidence interval = 5.9-7.1) and 11.6 (95% confidence interval = 10.0-12.5) months, respectively, for patients ≥75 years. Incidence proportions of bevacizumab-associated adverse events were generally similar across all age groups. CONCLUSIONS: Data from the ARIES study suggest that treatment with bevacizumab in combination with chemotherapy is a viable first-line treatment option for elderly bevacizumab-eligible patients with advanced non-squamous NSCLC.

Identification of a novel papillomavirus in a Northern Fulmar (Fulmarus glacialis) with viral production in cartilage.

We report the identification of a novel papillomavirus, Fulmarus glacialis papillomavirus 1 (FgPV1), present within an interdigital foot mass of a Northern Fulmar (Fulmarus glacialis). The mass of interest was composed of normal stratified and keratinized epithelium and dense mesenchymal cells with central cartilaginous islands. Within the nuclei of many chondrocytes were loose aggregates or paracrystalline arrays of virions approximately 50 nm in size. Degenerate polymerase chain reaction was used to identify the virus as a putative papillomavirus, and the entire viral genome of 8132 base pairs was subsequently amplified and sequenced. Analysis revealed canonical papillomavirus architecture, including the early open reading frames E6, E7, E1, and E2 and the 2 late proteins L1 and L2. FgPV1 is most closely related to a cluster of avian and reptilian papillomaviruses as visualized by phylogenetic trees. This observation suggests that papillomavirus virion production can occur in mesenchymal cells.

Safety and effectiveness of bevacizumab treatment for metastatic colorectal cancer: final results from the Avastin(®) Registry - Investigation of Effectiveness and Safety (ARIES) observational cohort study.

AIMS: The Avastin(®) Registry - Investigation of Effectiveness and Safety (ARIES) observational cohort study (OCS) was designed to prospectively examine outcomes associated with bevacizumab-containing treatment for metastatic colorectal cancer (mCRC) in a community-based setting, where patient populations are less restricted than those in randomised trials. MATERIALS AND METHODS: Patients with mCRC who were eligible for bevacizumab in combination with chemotherapy in first- or second-line treatment were enrolled from November 2006 to September 2008. There were no protocol-specified treatment regimens; the dose and schedule of bevacizumab and chemotherapy were at the treating physician's discretion. The objectives in the ARIES OCS included analyses of progression-free survival (PFS), overall survival, treatment patterns and safety in each of the first- and second-line treatment cohorts. RESULTS: ARIES enrolled 1550 patients with mCRC receiving first-line therapy with bevacizumab. The median follow-up time was 20.6 months. The median PFS in this cohort was 10.2 months (95% confidence interval 9.8-10.6) and the median overall survival was 23.2 months (95% confidence interval 21.2-24.8). In a separate cohort of 482 patients with second-line mCRC, the median follow-up time was 16.9 months, the median PFS and overall survival from the start of second-line treatment to the end of follow-up was 7.9 months (95% confidence interval 7.2-8.3) and 17.8 months (95% confidence interval 16.5-20.7), respectively. Incidences of known bevacizumab-associated adverse events in ARIES were generally consistent with those previously reported in OCSs and randomised trials. CONCLUSION: Results from the prospective ARIES OCS add further evidence to support the effectiveness and safety of bevacizumab when added to first- and second-line treatment regimens for patients with mCRC in community treatment settings.

Suspicious cervical lymph nodes detected after thyroidectomy for papillary thyroid cancer usually remain stable over years in properly selected patients.

CONTEXT: The risk of loco-regional recurrence in papillary thyroid cancer (PTC) patients ranges from 15-30%. However, the clinical significance of small-volume loco-regional recurrence detected by highly sensitive ultrasonography is unclear. OBJECTIVE: Our objective was to describe the natural history of abnormal cervical lymph nodes (LN) diagnosed after initial treatment. DESIGN: We conducted a retrospective cohort study. PATIENTS: 166 PTC with patients who had at least one abnormal LN outside the thyroid be on ultrasound and selected for active surveillance were included. MAIN OUTCOME MEASURE: LN growth during a period of active surveillance was the primary outcome. RESULTS: Most patients had classical PTC (85%) and an intermediate risk of recurrence (77%). The median LN size at the start of the observation period was 1.3 cm (range, 0.5-2.7 cm) in largest diameter, with all nodes having at least one abnormal sonographic characteristic (70% of patients had LN with at least two abnormal features). In almost all patients, the LN were in the lateral neck, primarily in levels 3 (43%) and 4 (58%). After a median follow-up of 3.5 yr, only 20% (33 of 166) grew at least 3 mm, 9% (15 of 166) grew at least 5 mm, and 14% (23 of 166) resolved. None of the clinical or sonographic features were predictive of LN growth (positive predictive value range = 0.21-0.57). There were no local complications (nerve damage or local invasion) related to the abnormal nodes and no disease-related mortality. CONCLUSIONS: Suspicious cervical LN in the lateral neck usually remain stable for long periods of time in properly selected PTC patients and can be safely followed with serial ultrasounds.

Initial therapy with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural disease recurrence in properly selected patients with differentiated thyroid cancer.

OBJECTIVE: To describe the risk of structural disease recurrence in a cohort of patients with differentiated thyroid cancer selected for treatment with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation (RRA). DESIGN: Retrospective review. PATIENTS: A total of 289 patients were selected for either thyroid lobectomy (n = 72) or total thyroidectomy (n = 217) without RRA and followed with modern disease detection tools in a tertiary referral centre. Most patients had papillary thyroid cancer (89%) without clinically evident lymph node metastases (91%). However, 55% (156/289) of patients had primary tumours that were >1 cm and 10% (28/289) had minor extrathyroidal extension. MEASUREMENTS: The primary endpoint was detection of recurrent/persistent structural disease. RESULTS: After a 5-year median follow-up, structural disease recurrence was detected in 2·3% (5/217) of patients treated with total thyroidectomy without RRA, and in 4·2% (3/72) of patients treated with thyroid lobectomy. Size of the primary tumour, the presence of cervical lymph node metastases and American Thyroid Association risk category were all statistically significant predictors of recurrence. Changes in serum thyroglobulin were not helpful in identifying the presence of persistent/recurrent structural disease. Importantly, 88% (7/8) of the patients that had recurrent disease were rendered clinically disease free with additional therapies. CONCLUSIONS: Initial risk stratification is able to identify a cohort of patients with differentiated thyroid cancer with a very low risk of structural disease recurrence following treatment with either thyroid lobectomy or total thyroidectomy without RRA. Our data strongly support a selective approach to the initial management of thyroid cancer.

Comparison of efficacy of 2220 MBq versus 3700 MBq I-131 for ablation of thyroid remnant in patients with differentiated thyroid cancer.

AIM: We evaluated the efficacy of two doses of I-131 (2220 MBq versus 3700 MBq) after thyroid hormone withdrawal for thyroid remnant ablation postoperatively in patients with differentiated thyroid cancer (DTC). METHODS: A total of 133 patients with DTC were studied retrospectively. Group 1 (N.=48) included patients with a primary tumor less than 4 cm in mean diameter and confined to the thyroid gland that received an average ablation dose of 2220 MBq. Group 2 (N.=81) included patients with a primary tumor equal to or greater than 4 cm in mean diameter and/or with vascular invasion and/or intrathyroidal lymphovascular invasion and/or microscopic extrathyroidal extension that received an average ablation dose of 3700 MBq. There was no significant difference between the two groups in terms of demographic characteristics or the radioiodine uptake in the neck (2.86+2.31% versus 2.84+1.21%, P=0.97). The success of the remnant ablation was judged by the standard institutional protocol: I-123 whole body scan (WBS) and serum Thyroglobulin (Tg) level after thyroid hormone withdrawal or preparation with recombinant human TSH (rhTSH) 6-12 months after ablation. RESULTS: Overall, remnant ablation was successful in 121/133 (91%) patients. There was no statistically significant difference in the success of ablation between Group 1 and Group 2 (87.5% versus 93%, P=0.273). CONCLUSION: Therefore, for thyroid remnant ablation after thyroid hormone withdrawal, an administered I-131 dose of 2220 MBq is just as effective as 3700 MBq and has the potential for fewer longterm side effects.

Skin-sparing mastectomy with immediate breast reconstruction: a critical analysis of local recurrence.

PURPOSE: The purpose of this study was to provide follow-up data regarding the incidence of local breast cancer recurrence in patients undergoing skin-sparing mastectomy versus conventional non-skin-sparing mastectomy methods. PATIENTS AND METHODS: A retrospective follow-up study and analysis were performed of patients who underwent mastectomies for invasive breast cancer at The New York Presbyterian Hospital, Cornell University Medical College and Strang-Cornell Breast Center between 1990 and 1998. RESULTS: A total of 198 patients were identified in this study, and the mean follow-up was 49 months. This group included 71 patients who underwent skin-sparing mastectomy and 127 who underwent non-skin-sparing mastectomy procedures. No statistical differences in local recurrence rates were demonstrated between patients treated with skin-sparing mastectomy and those who underwent non-skin-sparing mastectomy. Local recurrence was present in four of 71 (5.6%) patients undergoing skin-sparing mastectomy and in five of 127 (3.9%) of those undergoing non-skin-sparing mastectomy. CONCLUSIONS: The use of skin-sparing mastectomy does not lead to an increase in local recurrence rates when compared with conventional non-sparing mastectomies and provides for improved aesthetic results after immediate reconstruction.

Outcome of treatment for limb and limb girdle sarcomas at the Royal Marsden Hospital.

AIMS: In this study we aimed to determine local recurrence, mortality an d amputation rates in patients presenting with limb and limb girdle soft tissue sarcomas. METHOD: A review of all 439 patients presenting with p rimary or recurrent soft tissue sarcomas of limb and limb girdle to the Royal Marsden Hospital between 1989 and 1995 was carried out. RESULTS: The local recurrence rate was 15.5% and the mortality rate was 30%, with a median follow up of 3.2 years and an overall amputation rate of 4.8%. CONCLUSION: The outcome of limb and limb girdle sarcomas in this study i s comparable to those reported elsewhere.

Local and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies.

BACKGROUND: Skin-sparing mastectomies (SSMs) are being used more frequently to treat many cases of breast cancer. This type of surgery maximizes breast skin preservation and facilitates immediate reconstruction, resulting in a superior cosmetic appearance after mastectomy and a more satisfied patient. Although SSMs are becoming more common, there are few data regarding the local and distant recurrence rates. METHODS: A total of 231 patients treated with mastectomies from 1990 to 1998 were studied, including 77 SSM and 154 non-skin-sparing (NSSM) mastectomy patients. RESULTS: The local recurrence rates for SSM and NSSM were 3.90% (3 of 77 patients) and 3.25% (5 of 154 patients), respectively. The local recurrence-free survival at 5 years was 95.3% for SSM patients and 95.2% for NSSM patients (P = .28). The distant recurrence rates of SSM and NSSM were 3.9% (3 of 77 patients) and 3.9% (6 of 154 patients), respectively. The distant recurrence-free actuarial survival at 5 years was 90.2% for SSM patients and 92% for NSSM patients (P = .07). CONCLUSIONS: Mastectomies using the skin-sparing technique do not appear to result in any increase in local or distant recurrence and improve aesthetic results of the immediate reconstruction.

Synergistic effects of interferon gamma and tumour necrosis factor alpha on T84 cell function.

BACKGROUND: Inflammatory bowel disease (IBD) is characterised by chronic intestinal inflammation and increased epithelial permeability. Both tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been implicated in IBD. AIMS: To understand better the effects of these cytokines on epithelial cell function. METHODS: T84 cells were cultured with IFN-gamma and TNF-alpha and changes in transepithelial resistance (TER), fluorescein isothiocyanate (FITC) dextran flux, short circuit current (I(sc)), cystic fibrosis transmembrane conductance regulator (CFTR) protein levels, cell morphology, TNF receptor gene expression, and apoptosis were assayed. RESULTS: Relative to controls, significant changes (p<0.05) occurred in cells incubated with IFN-gamma for two days: TER was decreased to 20 (6.2)%, FITC-dextran flux was increased by 109 (19)-fold, cAMP and Ca dependent I(sc) were decreased to 51 (6.4)% and 24 (2.2)%, respectively, and CFTR levels were decreased to 47 (11)%. Cell morphology was altered but cell death was not induced. TNF receptor mRNA levels were increased. When added with IFN-gamma, TNF-alpha accelerated IFN-gamma dependent changes. Relative to controls, significant changes occurred after one day of culture with IFN-gamma plus TNF-alpha: TER was decreased to 27 (3.5)%, FITC-dextran flux was increased by 185 (45)-fold, and cAMP and Ca dependent I(sc) were decreased to 66 (12)% and 35 (6.8)%, respectively. TNF-alpha also enhanced IFN-gamma dependent changes in cell morphology but did not induce cell death. CONCLUSION: IFN-gamma alters T84 cell epithelial properties and TNF-alpha can enhance these effects, perhaps due to IFN-gamma dependent increases in TNF receptor gene expression. Overall, these studies suggest that in IBD, TNF-alpha may have synergistic effects on IFN-gamma mediated alterations of epithelial cell function.

The use and abuse of wound care materials in the treatment of diabetic ulcerations.

With the ever-increasing availability of wound care materials for use in diabetic foot ulcerations, a thorough understanding of the indications and applications of these materials is important for wound-management success. The coupling of a lack of understanding of the interaction of wound care materials and the dynamic nature of wound-healing physiology may lead to a protracted healing course that may constitute an abuse of an otherwise useful adjunct to wound healing protocols. This article provides an overview of wound care products, their indications, and possible complications of inappropriate use.

Dialysis membrane to prevent cadmium ion specific electrode fouling.

We present a simple method of protecting a Cd(II) ion-selective electrode from fouling using a dialysis membrane. Drift due to fouling is inevitable during continuous exposure of the electrode to the bulk solution. It presents a major problem in the case of automated titrations because recalibration is not possible. The drift is due to natural organic matter present in the sediment, and the membrane prevents its accumulation on the electrode surface. This was verified by calibrating a Cd electrode exposed to sediment for varying times, both with and without a membrane covering. There are two types of time dependent biases. A primary drift occurs without exposure to sediments and is probably caused by oxidation of the surface. A more important effect due to natural organic matter accumulation causes additional drift and deteriorates the Nernstian response of the electrode. From these results, it is possible to predict the uncertainty associated with measurements of binding constants and surface site densities for a Langmuir model. In general, the biased electrode overestimates the total metal concentration, reduces the value of the stability constants and increases estimates of maximum surface site densities.

Wound management in the diabetic foot.

The multiple opinions expressed in this Grand Rounds section make it clear that management of the diabetic patient with a foot wound is complex at best. Several significant points are repeated many times. The need for a detailed history and physical exam, accurate assessment of neurologic, vascular, metabolic status, and addressing the etiologic factor involved are all essential. All authors point to multispecialty integrated treatment protocols to produce the greatest success. Little mention is made of the use of topical agents to accelerate healing. This is due to the lack of unbiased studies, and the many available reports that demonstrate rapid healing when a complete and objective protocol is followed. The aims of this Grand Rounds are to stimulate interest in this important subject, and to provide the practitioner with a scaffold with which to build their own wound care management protocols.

Malignant epithelial parotid tumours: a rational treatment policy.

Formal parotidectomy was undertaken in 271 patients by one surgeon over 11 years. Forty patients were treated for malignant salivary tumours (nine were recurrent). Low-grade tumours (45 per cent) were treated by surgery alone, untreated high-grade tumours (55 per cent) by surgery and radiotherapy, before or after operation, depending on clinical findings. The aims of surgery were to obtain tumour clearance, to preserve the facial nerve if possible, and to perform radical neck dissection for palpable malignant lymphadenopathy proven cytologically and for high-grade tumours when intraoperative jugulodigastric lymph node biopsy confirmed metastasis. Four patients sustained facial weakness as a result of surgery. At a median of 46 months follow-up two patients had developed local recurrence. Eleven patients with high-grade but none with low-grade tumours died from metastases. Patients with high-grade lesions with facial weakness from malignant infiltration and those with lymphatic metastasis have a significantly worse prognosis than those without. Locoregional control of parotid cancers can be achieved by formal parotidectomy and selective irradiation without routine sacrifice of the facial nerve.

Development of GM-CSF antagonist peptides.

Granulocyte/macrophage colony stimulating factor (GM-CSF) is both a hematopoietic growth factor and a cytokine implicated in inflammatory disease. The development of GM-CSF antagonist peptides corresponding to the GM-CSF native sequence should allow their modification into higher affinity analogs, but this is hampered by the low affinity of linear peptides. To adequately evaluate such low affinity peptides, the use of several independent assays should allow specific versus nonspecific inhibitors to be distinguished. In this study, inhibition of GM-CSF-dependent cell growth, inhibition of GM-CSF binding and immunologic cross-reactivity between GM-CSF-derived peptides and native protein by neutralizing antibodies have been used to evaluate peptide analogs with potential bioactivity. The GM-CSF sequence was divided into 6 peptides ranging in size from 15-24 amino acids. Antisera were raised to these peptides in mice and assayed for immunologic cross-reactivity. 4/6 anti-peptide antisera bound GM-CSF on ELISA and 3/6 on immunoprecipitation. Antisera to two of the peptides (corresponding to residues 17-31 and 96-112) inhibited GM-CSF-dependent cellular proliferation in two cell lines, with one peptide derived from residues 17-31 demonstrating inhibition of GM-CSF binding and direct biological inhibitory activity. A peptide that did not elicit native GM-CSF reactive antibodies, corresponding to residues 54-78, was recognized by two neutralizing monoclonal antibodies. It exhibited inhibition of GM-CSF binding and direct biological antagonist activity. These studies implicate two sites in mediating GM-CSF biological activity, and indicate that biological antagonists can be developed based on these sites.

Management of soft tissue sarcoma.

A total of 485 patients with a proven or suspected diagnosis of soft tissue sarcoma were referred over a 3-year period. Of these, 61 were referred for opinion only and 424 for definitive treatment. Overall there were 223 patients with primary soft tissue sarcoma and 84 with recurrent sarcoma, 84 with benign soft tissue tumours and 22 with non-soft tissue sarcoma malignancy; 11 patients were referred with known metastatic disease. The commonest benign tumours mimicking soft tissue sarcoma were fibromatosis and benign intermuscular or intramuscular lipoma. The malignant tumours suspected clinically of being soft tissue sarcoma were bone tumours, lymphoma and metastatic carcinoma. Of the 172 patients with primary soft tissue sarcoma referred with a proven diagnosis this had been established by excision biopsy in 94 and open incision biopsy in 48. By contrast, of those undiagnosed at referral, 44 of 51 patients with soft tissue sarcoma had the diagnosis made by Tru-cut core biopsy. Amputation was performed in four of 165 patients with primary extremity soft tissue sarcoma and in five of 54 with recurrent extremity sarcoma, giving an overall amputation rate of 4 per cent. It is proposed that the amputation rate for extremity soft tissue sarcoma can be reduced by the use of reconstructive procedures, particularly myocutaneous flaps to the proximal limbs and limb girdles, and free vascularized flaps to sites distal to the midthigh and midarm.

Carboxyhemoglobin levels in patients with cocaine-related chest pain.

Carboxyhemoglobin (COHb) levels were measured in patients who came to an emergency department complaining of acute chest pain. For subjects not receiving prior oxygen therapy, those with cocaine-related chest pain (n = 10) had a higher mean COHb level than a comparison group (n = 28) with nonischemic chest pain (4.50 +/- 2.40 vs 2.73 +/- 0.66; p < 0.05). Four of the seven (57 percent) who smoked crack had COHb levels greater than 4.5 percent, while only one of six (17 percent) smokers of only tobacco had such a level. These findings suggest an additional mechanism, the formation of COHb, which could aggravate cocaine-induced cardiotoxicity.

Prospective multicenter evaluation of cocaine-associated chest pain. Cocaine Associated Chest Pain (COCHPA) Study Group.

OBJECTIVE: To describe a large cohort of patients who had chest pain following cocaine use, and to determine the incidence of and clinical characteristics predictive for myocardial infarction in this group of patients. METHODS: A prospective observational cohort study of consecutive patients with cocaine-associated chest pain was conducted in six municipal hospital emergency departments (EDs). Demographic variables, drug abuse patterns, medical histories, chest pain characteristics, ECG results, and laboratory data were recorded. Myocardial infarction was the primary endpoint. RESULTS: Fourteen of 246 patients (5.7%; 95% confidence interval [CI], 2.7-8.7%) had myocardial infarction, as diagnosed by elevated CK-MB isoenzyme levels. There were two deaths (0.8%). The patients had a median age of 33 years. The majority were male (71.5%), non-white (83.3%), cigarette smokers (83.3%) who used cocaine regularly. Chest pain began a median of 60 minutes after cocaine use and persisted for a median of 120 minutes. Chest pain was most frequently described as substernal (71.3%) and pressure-like (46.7%). Shortness of breath (59.3%) and diaphoresis (38.6%) were common. There was no clinical difference between patients who had myocardial infarctions and those who did not. Twelve patients had arrhythmias and four had congestive heart failure. All cases requiring intervention were evident upon presentation. An ECG revealing ischemia or infarction had a sensitivity of 35.7% for predicting a myocardial infarction. The specificity, positive predictive value, and negative predictive value of the ECGs were 89.9%, 17.9%, and 95.8%, respectively. CONCLUSIONS: Myocardial infarction in patients who have cocaine-associated chest pain is not uncommon. No clinical parameter available to the physician can adequately identify patients at very low risk for myocardial infarction. Therefore, all patients with cocaine-associated chest pain should be evaluated for myocardial infarction.