Aspirin withdrawal in patients treated with ticagrelor presenting with non-ST elevation myocardial infarction.

Essentials Strong P2Y12 blockade may cause platelet inhibition that is only minimally enhanced by aspirin. We evaluated aspirin withdrawal on platelet reactivity in ticagrelor treated patients. Aspirin withdrawal resulted in increased platelet reactivity to arachidonic acid. Aspirin withdrawal caused little difference in adenosine diphosphate-induced platelet aggregation. SUMMARY: Background Recent studies have shown that the thromboxane A2 -dependent pathway is dependent on the ADP-P2Y12 pathway, and that strong P2Y12 receptor blockade alone causes inhibition of platelet aggregation that is minimally enhanced by aspirin. Data from the PLATO trial suggested that, among ticagrelor-treated patients, high-dose versus low-dose (< 100 mg day-1 ) aspirin is associated with an increased risk fof ischemic events. Objectives To evaluate the impact of aspirin withdrawal on platelet reactivity in acute coronary syndrome (ACS) patients treated with a potent P2Y12 blocker. Patients/Methods This was a current prospective, randomized, placebo-controlled, double-blind, cross-over study. The study population comprised 22 consecutive ACS patients who underwent percutaneous coronary intervention and were treated with aspirin (100 mg day-1 ) and ticagrelor. Thirty days post-ACS, open-label aspirin was stopped, and patients were randomized to either blinded aspirin or placebo for 2 weeks, with each patient crossing over to the other arm for an additional 2 weeks. Platelet reactivity to arachidonic acid and ADP determined with light-transmission aggregometry (LTA) and VerifyNow was evaluated at baseline, and 2 weeks and 4 weeks later. Results Aspirin withdrawal resulted in an increase in arachidonic-acid induced platelet reactivity as determined with both LTA (77.0% ± 11.3% versus 20.8% ± 4.4%) and VerifyNow (607.7 ± 10.6 aspirin reaction units [ARU] versus 408.5 ± 14.4 ARU). Platelet response to ADP, as determined with both LTA and VerifyNow, did not differ with either aspirin or placebo (32.9% ± 2.6% versus 35.8% ± 3.6%, and 33.5 ± 6.4 P2Y12 reaction units (PRU) versus 29.6 ± 5.7 PRU, respectively). Conclusions Aspirin withdrawal early post-ACS results in increased platelet reactivity in response to arachidonic acid, despite concomitant treatment with the potent P2Y12 blocker ticagrelor.

Bromelain-based enzymatic debridement and minimal invasive modality (mim) care of deeply burned hands.

The objective was to critically review the data and assess the implications of NexoBrid [NexoBrid-NXB formerly Debrase Gel Dressing-DGD]a in the special field of deep hand burns. Detailed analysis of endpoints in the treatment of hand burn patients was conducted as part of a multi-center, open label, randomized, controlled two-arm study to evaluate the safety and efficacy of NXB enzymatic debridement, comparing it to the current standard of care (SOC). These results were compared to a large cohort of patients treated with NXB in a previous, single arm study. Thirty-one burned hands were treated with NXB and 41 hand burns were in the SOC group. In the NXB group, 4 out of 31 hand burns (12.9%) required some excisional debridement compared to 29 out of the 41 (70.7%) in the SOC group (p<0.0001). Mean percentage of burn wound area excised in the NXB group was 4.4 ± 13.1% compared to 52.0 ± 41.4% in the SOC group (p<0.0001). None of the NXB-treated hands required escharotomy compared to 4 out of the 41 (9.7%) in the SOC group. NXB enzymatic debridement demonstrated a statistically significant reduction in burn wound excision and auto-grafting compared to SOC, and seems to prevent the need for emergency escharotomy. a DGD is produced by MediWound and distributed under the name NexoBrid®.

Le but était de réaliser une révision attentive des données et d'évaluer la place de Nexobrid (Nexobrid-NXB, précédemment Debrase Gel Dressing-DGD) dans l'indication particulière des brûlures profondes de la main. Une analyse détaillée des objectifs dans le traitement des brûlures de la main a été conduite en partie par une étude multicentrique, ouverte, randomisée, contrôlée avec 2 groupes pour évaluer la sécurité et l'efficacité de ce débridement enzymatique par rapport aux soins habituels (Standard of Care ou SOC). Ces résultats ont été comparés à une vaste cohorte de patients traités par NXB dans une étude précédente sur un seul groupe. 31 mains brûlées furent traitées par NXB et 41 dans le groupe SOC. Dans le groupe NXB, 4 sur 31 mains brûlées soit 12,9 % nécessitèrent une excision partielle, alors que 29 sur 41 dans le groupe SOC (70,7 %) (p < 0,0001). La moyenne des zones brûlées excisées dans le groupe NXB était de 4,4 (+ ou - 13,1 %) comparée aux 52,0 (+ ou - 41,4 % du groupe SOC) (p <0,0001). Aucune des mains traitées par NXB ont nécessité une excision totale, comparée à 4 sur 41 du groupe SOC (9,7 % du groupe). Le débridement enzymatique NXB montre une réduction statistiquement significative de l'indication d'excision avec autogreffe par rapport au groupe traité classiquement et semble prévenir la nécessité d'une escarrotomie en urgence.

Three quantitative approaches to the diagnosis of abdominal pain in children: practical applications of decision theory.

BACKGROUND/PURPOSE: The authors compared 3 quantitative methods for assisting clinicians in the differential diagnosis of abdominal pain in children, where the most common important endpoint is whether the patient has appendicitis. Pretest probability in different age and sex groups were determined to perform Bayesian analysis, binary logistic regression was used to determine which variables were statistically significantly likely to contribute to a diagnosis, and recursive partitioning was used to build decision trees with quantitative endpoints. METHODS: The records of all children (1,208) seen at a large urban emergency department (ED) with a chief complaint of abdominal pain were immediately reviewed retrospectively (24 to 72 hours after the encounter). Attempts were made to contact all the patients' families to determine an accurate final diagnosis. A total of 1,008 (83%) families were contacted. Data were analyzed by calculation of the posttest probability, recursive partitioning, and binary logistic regression. RESULTS: In all groups the most common diagnosis was abdominal pain (ICD-9 Code 789). After this, however, the order of the most common final diagnoses for abdominal pain varied significantly. The entire group had a pretest probability of appendicitis of 0.06. This varied with age and sex from 0.02 in boys 2 to 5 years old to 0.16 in boys older than 12 years. In boys age 5 to 12, recursive partitioning and binary logistic regression agreed on guarding and anorexia as important variables. Guarding and tenderness were important in girls age 5 to 12. In boys age greater than 12, both agreed on guarding and anorexia. Using sensitivities and specificities from the literature, computed tomography improved the posttest probability for the group from.06 to.33; ultrasound improved it from.06 to.48; and barium enema improved it from.06 to.58. CONCLUSIONS: Knowing the pretest probabilities in a specific population allows the physician to evaluate the likely diagnoses first. Other quantitative methods can help judge how much importance a certain criterion should have in the decision making and how much a particular test is likely to influence the probability of a correct diagnosis. It now should be possible to make these sophisticated quantitative methods readily available to clinicians via the computer.

The neuromythology of silicone breast implants.

OBJECTIVE: To define neurologic problems that may occur in women with silicone breast implants. BACKGROUND: The association between silicone breast implants (SBIs) and certain rheumatologic disorders has been discussed since the 1980s. Recent uncontrolled case series have reported neurologic problems believed to be associated with SBIs. DESIGN: Case series based on a retrospective data analysis of medical records from 131 women diagnosed as having a neurologic problem related to SBIs. METHODS: Data extracted from the medical records and analyzed included neurologic symptoms, neurologic examination findings, and a variety of laboratory studies. Symptoms, examination findings, and laboratory studies were analyzed using methods that would purposely overreport false-positive results in order to negate possible bias accusations. Finally, prior diagnoses made by evaluating physicians and thought to be related to SBIs were also recorded. An independent assessment was also made for alternative diagnoses using standards accepted by the medical and neurologic communities which did not necessarily accept a causative link between SBIs and their alleged complications. RESULTS: Neurologic symptoms were frequently endorsed, including fatigue (82%), memory loss and other cognitive impairment (76%), and generalized myalgias (66%). Despite multiple complaints, most patients (66%) had normal neurological examinations. Findings reported as abnormal were mild and usually subjective, including sensory abnormalities in 23%, mental status abnormalities in 13%, and reflex changes in 8%. No pattern of laboratory abnormalities was seen, either in combination or in attempts to correlate them with the clinical situation. Laboratory studies appeared to be random without an attempt to confirm or correlate with a particular diagnosis. Diagnoses by physicians endorsing the concept that SBIs cause illness included "human adjuvant disease" in all cases, memory loss and other cognitive impairment ("silicone encephalopathy") and/or "atypical neurologic disease syndrome" in 73%, "atypical neurologic multiple sclerosis-like syndrome" in 8%, chronic inflammatory demyelinating polyneuropathy in 23%, and some other type of peripheral neuropathy in 18%. There was no coherence in making these diagnoses; the presence of any symptoms in these women was sufficient to make these diagnoses. Alternatively, after review of the data, no neurologic diagnosis could be made in 82%. Neurologic symptoms could be explained in some cases by depression (n=16), fibromyalgia (n=9), radiculopathy (n=7), anxiety disorders (n=4), multiple sclerosis (n=4), multifocal motor neuropathy (n=1), carpal tunnel syndrome (n=1), dermatomyositis (n=1), and other psychiatric disorders (n=3). CONCLUSIONS: There is no evidence that SBIs are causally related to the development of any neurologic diseases. Methods of diagnosis that have been used to make the diagnosis of neurologic disease in these patients are contrary to standards accepted by the neurologic community. Several possible explanations exist for the neurologic and other symptoms in women with breast implants.

Transcriptional activation of a ras-like gene (kir) by oncogenic tyrosine kinases.

We report the characterization of a member of the ras gene family that is overexpressed in cells transformed by abl tyrosine kinase oncogenes. The gene, named kir (for kinase-inducible ras-like), is induced at the transcriptional level. kir mRNA has a rapid turnover and encodes a protein of 33 kDa with guanine nucleotide-binding activity but undetectable intrinsic GTPase activity. kir was cloned by differential screening of genes present in fully malignant versus growth factor-independent cell lines expressing wild-type or mutant forms of BCR/ABL. BCR/ABL and v-Abl induce transcription of the kir gene via specific signaling pathway(s), but kir overexpression alone is not sufficient to mediate transformation.

Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia.

Because studies of the treatment of children with occult bacteremia have yielded conflicting results, we compared ceftriaxone with amoxicillin for therapy. Inclusion criteria were age 3 to 36 months, temperature > or = 39 degrees C, an acute febrile illness with no focal findings or with otitis media (6/10 centers), and culture of blood. Subjects were randomly assigned to receive either ceftriaxone, 50 mg/kg intramuscularly, or amoxicillin, 20 mg/kg/dose orally for six doses. Of 6733 patients enrolled, 195 had bacteremia and 192 were evaluable: 164 Streptococcus pneumoniae, 9 Haemophilus influenzae type b, 7 Salmonella, 2 Neisseria meningitidis, and 10 other. After treatment, three patients receiving amoxicillin had the same organism isolated from their blood (two H. influenzae type b, one Salmonella) and two from the spinal fluid (two H. influenzae type b), compared with none given ceftriaxone. Probable or definite infections occurred in three children treated with ceftriaxone and six given amoxicillin (adjusted odds ratio 0.43, 95% confidence interval 0.08 to 1.82, p = 0.31). The five children with definite bacterial infections (three meningitis, one pneumonia, one sepsis) received amoxicillin (adjusted odds ratio 0.00, 95% confidence interval 0.00 to 0.52, p = 0.02). Fever persisted less often with ceftriaxone (adjusted odds ratio 0.52, 95% confidence interval 0.28 to 0.94, p = 0.04). Although the difference in total infections was not significant, ceftriaxone eradicated bacteremia, prevented significantly more definite focal bacterial complications, and was associated with less persistent fever.

[The initiating role of several respiratory and skin contaminants in food allergies]. / Le rôle initiateur de certains contaminants respiratoires et cutanés dans les allergies alimentaires.

The authors present data which suggest that mustard hypersensitivity can result from Isocyanates induced occupational asthma. Isothiocyanates present in mustard spice is probably responsible for this cross-sensitivity. Frequently, food allergies result from skin or respiratory primary contact and sensitization. Some examples are proposed. Distinctive structures and functions of immunological system in cutaneous, respiratory and digestive apparatus, give an explanation for the predominance of skin and respiratory immunological systems to promote hypersensitivity. For the prevention of food allergies, it is very important to avoid excessive skin and respiratory contaminations by allergens in the work and home environments.

[An underestimated prevalence: the association food allergy-occupational asthma]. / Une fréquence sous-estimée: l'association allergie alimentaire-asthme professionnel.

Two cases of asthma induced by isocyanates and complicated by food allergy to cruciferae (plants of the mustard family) are reported. Cross-allergy is suggested as a pathophysiological mechanism of this complication. Food allergy being difficult to diagnose and therefore often missed in a context of occupational asthma, the frequency of this association is probably underestimated.

Mezlocillin prophylaxis against infection after cesarean section: a comparison of techniques.

We studied 212 patients undergoing emergency cesarean section at an urban hospital. Four techniques of antibiotic prophylaxis were used, including single-dose and triple-dose parenteral therapy, parenteral and lavage therapy, and lavage therapy alone. One agent, mezlocillin, was used for all patients. There was no significant difference in surgically related infectious morbidity among the groups. This antibiotic proved efficacious when related to historical controls, and was the most economical of the modalities of administration studied.

Computerized tomography and pure sensory stroke.

We studied three patients fitting the clinical syndrome of "pure sensory" stroke. The abnormalities on computerized tomography (CT) scan differed and included posterior cerebral artery occlusion, lacunar infarct in the thalamocortical pathway, and hemorrhage in the thalamus. These cases were unique in that CT scan abnormalities were found in patients with pure sensory stroke.

Acute allergic reaction after composite pollen ingestion.

Three patients are presented who ingested a health food known as "bee pollen" and who experienced an immediate allergic reaction. Examination revealed that the bee pollen contained dandelion pollen, which belongs to the Compositae family as does ragweed. In vivo and in vitro studies demonstrated that the patients were sensitive to several Compositae family members, rather than to insect-derived antigens. In addition, radioallergosorbent inhibition studies confirmed the suspected cross-reactivity between the health food and Compositae pollens. This study indicates that atopic individuals may experience anaphylaxis from ingestion of antigens in certain food stuffs that cross-react with pollens to which they are sensitive.