A clinical classification system for grading platinum hypersensitivity reactions.

OBJECTIVES: Current grading systems for platinum hypersensitivities (pHSR) rely on subjective features rather than objective clinical signs leading to inconsistencies in grading. To standardize classification of pHSR, a clinical grading system was developed at our institution. We report the clinical outcomes our classification system and evaluate its correlation with the classification systems currently published and used in practice. METHODS: This was a retrospective review of patients with pHSR from 2011 to 2017. Demographics, chemotherapeutic histories (CT), and details of their initial HSR were collected. Mild reactions were defined as local skin manifestations only. Moderate-low reactions included widespread skin, respiratory or GI findings. Moderate-standard reactions were defined as transient cardiovascular compromise (CVC), hypoxia or neurologic changes whereas sustained changes (>10 min) were used to define severe reaction. Fischer Exact Tests (p < .05) and binary logistic regression analyses were performed. Spearman correlation were used to assess relationships between our grading system and the NCCN and CTCAEv4.0 criteria. RESULTS: 87 patients were identified with most having ovarian cancer (n = 55, 63.2%), receiving carboplatin (n = 62, 71.3%), and on second-line CT (n = 34, 42.5%). Chest pain was associated with transient CVC (OR 10.0, 95% CI 1.148-87.133) while nausea/vomiting (OR 8.420, 95% CI 1.263-55.275) was associated with transient hypoxia albeit less closely than transient hypotension (OR 17.010, 95% CI 2.026-142.825). Only presyncope/syncope remained associated with sustained CVC (OR 38.0, 95% CI 2.815-512.912) on logistic regression. The classification system was most strongly correlated with the NCCN grading system (ρ 0.761, p < .001). CONCLUSIONS: This classification system offers an objective means of grading pHSR severity and correlates with currently-used grading systems.

A case of ANCA associated vasculitis in a patient presenting with chest pain.

Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a group of multisystem autoimmune small vessel diseases. We report here a case of a 68-year-old woman who initially presented with 29-day history of chest pain, malaise and anorexia. Cardiac problems were ruled out and she was considered to have pneumonia. Her symptoms persisted and blood tests showed renal impairment and evidence of an inflammatory response. A kidney biopsy, chest computed tomography (CT) scan and ANCA testing confirmed a diagnosis of AAV renal injury. She was treated with glucocorticoids and cyclophosphamide (CTX) for six months at which time her kidney function had improved and she avoided the need for dialysis. This case study illustrates that the clinical manifestations of AVV are complex, varied, and prone to misdiagnosis.

Bronchial biopsy and reactivity in patients with chest tightness relieved with bronchodilator.

OBJECTIVE: It has been hypothesized that some patients with chest tightness of unknown origin can be successfully treated with a bronchodilator and that they should be diagnosed with chest pain variant asthma. We conducted a prospective study to characterize newly diagnosed patients with chest tightness relieved with bronchodilator use and without characteristic bronchial asthma attacks. METHODS: Eleven patients were registered following recurrent positive responses of chest tightness to inhalation of a ß2-agonist. These patients underwent assessments of airway responsiveness to methacholine, bronchial biopsy and bronchial lavage under fiber-optic bronchoscopy before receiving treatment. RESULTS: For the patients with chest tightness relieved with bronchodilator use, the bronchial biopsy specimens exhibited significant increases in lymphocyte and macrophage infiltration (p < 0.05) and no significant increase in eosinophils (p = 0.2918) compared with the control subjects. The bronchial responsiveness to methacholine was increased in two of the patients with chest tightness, and it was not increased in seven; in addition, increased percentages of eosinophils were detected in bronchial lavage fluid (5% or more) from two patients, but no increase was detected in eight patients. CONCLUSIONS: We suspect that the chest tightness was induced by airway constriction in these patients, but further study is necessary to validate this hypothesis. We propose that the chest tightness relieved with bronchodilator use was attributed to airway constriction resulting from inflammation with lymphocytes and macrophages and/or that the chest tightness was directly attributed to airway inflammation. This clinical trial is registered at www.umin.ac.jp (UMIN13994 and UMIN 16741).

[Periodic fever with increased IgD]. / Fièvre périodique avec élévation des immunoglobulines D.

Periodic fever or hereditary inflammatory fevers are characterized by intermittent inflammatory attacks. Many entities are well recognized today such as familial mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS). We report on the case of a 6-year-old boy referred for evaluation of a recurrent fever associated with chest pain, pneumonitis, or pleuritis since the age of 5 years. Laboratory data showed leukocytosis, a high erythrocyte sedimentation rate, and C-reactive protein; however, a permanent high serum level IgD was noted. Stereotypical episodes of fever appeared every 4-6 weeks, while infectious, malignant, and auto-immune causes were eliminated. A search for the most common mutations of the FMF gene in Tunisian patients (M694V, M680I, V726A, E148Q, M694I, and A744S) were negative. Likewise, urinary leukotriene E(4), which may be increased in HIDS, was normal in this patient. Mevalonate kinase activity in lymphocytes was not assayed. Ethnic origin and clinical presentation suggest FMF with an increased IgD rather than authentic HIDS, in spite of the lack of improvement under colchicine treatment and the negativity of the main mutations involved in FMF.

Smoking is associated with epicardial coronary endothelial dysfunction and elevated white blood cell count in patients with chest pain and early coronary artery disease.

BACKGROUND: Smoking is a major risk factor for cardiovascular events. One of the potential mechanisms may be related to both coronary endothelial dysfunction and increased inflammatory response. The present study was designed to test the hypothesis that smoking is associated with epicardial coronary endothelial dysfunction and inflammation. METHODS AND RESULTS: Coronary endothelial function in response to acetylcholine was assessed in 881 patients (115 current smokers and 766 nonsmokers, including 314 previous smokers). Smokers were significantly younger than nonsmokers (43+/-1 versus 51+/-1 years, P<0.0001), had more epicardial vasoconstriction in response to intracoronary acetylcholine (-19+/-2% versus -14+/-1% change in coronary artery diameter, P=0.03), and were more likely than nonsmokers to have epicardial endothelial dysfunction (46% versus 35%, P=0.005), but their microvascular endothelial function was intact. Smokers had higher white blood cell counts than nonsmokers (7.7+/-0.2 versus 6.6+/-0.1x10(9)/L, P<0.0001), higher myeloperoxidase (156+/-19 versus 89+/-8 ng/mL), higher lipoprotein-associated phospholipase A2 (242+/-12 versus 215+/-5 ng/mL), and higher levels of intracellular adhesion molecule (283+/-14 versus 252+/-5 ng/mL). There were no differences in the levels of C-reactive protein, fibrinogen, or vascular cell adhesion molecule between the groups. CONCLUSIONS: Young smokers are characterized by epicardial coronary endothelial dysfunction, preserved microvascular endothelial function, and increased levels of inflammatory biomarkers and oxidative stress. The present study provides further information regarding the potential mechanisms by which smoking contributes to cardiovascular events.

Inflammation, endothelial cell activation, and coronary microvascular dysfunction in women with chest pain and no obstructive coronary artery disease.

BACKGROUND: Coronary artery microvascular dysfunction is prevalent in women with chest pain in the absence of obstructive coronary artery disease (CAD) and is manifested by attenuated coronary flow reserve (CFR). Markers of inflammation and endothelial cell activation have been found to be elevated in patients with chest pain but without CAD. The relationship between inflammation, endothelial activation, and CFR is not known. METHODS: Ninety-four women with chest pain in the absence of obstructive angiographic CAD underwent catheterization-based assessment of CFR and measurement of levels of inflammatory markers (n = 78) and endothelial cell activation in the NHLBI WISE study. RESULTS: Coronary flow reserve did not correlate with levels of C-reactive protein (high-sensitivity C-reactive protein) (rs = -0.07, P = .53), interleukin (IL)-6 (rs = -0.12, P = .31), IL-18 (rs = 0.14, P = .23), tumor necrosis factor alpha (rs = -0.09, P = .43), transforming growth factor beta1 (rs = 0.02, P = .84), and soluble intracellular adhesion molecule-1 (rs = 0.04, P = .68). Median levels of markers of inflammation and endothelial cell activation did not differ between the 57 women with abnormal CFR (< 2.5) and the 37 women with normal coronary microvascular function (high-sensitivity C-reactive protein 0.32 vs 0.25 mg/dL, P = .80; IL-6 2.89 vs 2.39 pg/mL, P = .63; IL-18 218 vs 227 pg/mL, P = .59; tumor necrosis factor alpha 2.7 vs 2.4 pg/mL, P = .43; transforming growth factor beta1 9928 vs 12436 pg/mL, P = .76; soluble intracellular adhesion molecule-1 286 vs 287 pg/mL, P = .95). Multivariable models demonstrated no evidence of associations between markers of inflammation and of endothelial cell activation and CFR. CONCLUSIONS: Coronary microvascular dysfunction is not associated with markers of inflammation and endothelial cell activation in women with chest pain in the absence of obstructive CAD. These results suggest that inflammation and endothelial cell activation may not play a pathophysiological role in coronary microvascular dysfunction.

[Influence of Helicobacter pylori infection on the results of 24-hour gastric pH-metry in patients diagnosed because of atypical chest pain]. / Wplyw zakazenia Helicobacter pylori na wyniki 24-godzinnej pH-metrii zoladkowej u pacjentów diagnozowanych z powodu nietypowego bólu w klatce piersiowej.

UNLABELLED: Changes in gastric acidity induced by Helicobacter pylori (Hp) infection, may influence intensity of symptoms in patients diagnosed because of chest pain. The aim of this study was to compare the results of 24-hours gastric pH-metry in patients suffering from atypical chest pain infected and not-infected by Hp. PATIENTS AND METHODS: In 99 men diagnosed because of atypical chest pain performed were: interview, physical examination, gastroduodenoscopy with musoca biopsy from gastric corpus and antrum, as well as 24-hour gastric pH-metry. Hp infection was diagnosed on the basis of positive urease test or/and histologic examination. RESULTS: 78% of subjects were infected by Hp. Hp positive patients had lower total and night-time percentage of monitoring time with gastric pH<4 and greater with pH > 6. Patients with isolated antral Hp colonization and subjects with pangastritis didn't differ in respect to gastric pH-metry parameters values. However in patients, with Hp colonization only in gastric corpus the time with gastric pH < 4 was shorter and with pH > 6 longer than in other groups. CONCLUSIONS: Hp-positive patients with atypical chest pain had lower gastric acidity than Hp-negative subjects. In patients with corporal Hp gastric mucosa colonization higher intra-gastric pH was observed than in the rest of patients.

Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony-stimulating factor associated with the acute chest syndrome in patients with sickle cell disease.

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.