A Critical Assessment of the Golden Hour and the Impact of Procedural Timing in Stroke Thrombectomy.

BACKGROUND AND PURPOSE: Previous studies in acute ischemic stroke have demonstrated the importance of minimizing delays to endovascular treatment and keeping thrombectomy procedural times at <30-60 minutes. The purpose of this study was to investigate the impact of thrombectomy procedural times on clinical outcomes. MATERIALS AND METHODS: We retrospectively compared 319 patients having undergone thrombectomy according to procedural time (<30 minutes, 30-60 minutes, and >60 minutes) and time from stroke onset to endovascular therapy (≤6 or >6 hours). Clinical characteristics of patients with postprocedural intracranial hemorrhage were also assessed. Logistic regression was used to determine independent predictors of poor outcome at 90 days (mRS ≥3). RESULTS: Greater age (OR, 1.03; 95% CI, 1.01-1.06; P = .016), higher admission NIHSS score (OR, 1.10; 95% CI, 1.04-1.16; P = .001), history of diabetes mellitus (OR, 1.96; 95% CI, 1.05-3.65; P = .034), and postprocedural intracranial hemorrhage were independently associated with greater odds of poor outcome. Modified TICI scale scores of 2c (OR, 0.11; 95% CI, 0.04-0.28; P < .001) and 3 (OR, 0.15; 95% CI, 0.06-0.38; P < .001) were associated with reduced odds of poor outcome. Although not statistically significant on univariate analysis, onset to endovascular therapy of >6 hours was independently associated with increased odds of poor outcome (OR, 2.20; 95% CI, 1.11-4.36; P = .024) in the final multivariate model (area under the curve = 0.820). Procedural time was not independently associated with clinical outcome in the final multivariate model (P > .05). CONCLUSIONS: Thrombectomy procedural times beyond 60 minutes are associated with lower revascularization rates and worse 90-day outcomes. Procedural time itself was not an independent predictor of outcome. While stroke thrombectomy procedures should be performed rapidly, our study emphasizes the significance of achieving revascularization despite the requisite procedural time. However, the potential for revascularization must be weighed against the risks associated with multiple thrombectomy attempts.

A randomized trial of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon.

BACKGROUND: Conventional interferon monotherapy fails to achieve virological clearance in most hepatitis C-infected patients. The use of high-dose induction regimens may improve the initial clearance of virus, while the addition of ribavirin appears to improve the rates of sustained response once clearance is achieved. AIM: To compare the efficacy and safety of re-treatment with an induction regimen of high-dose interferon alpha-2b, with or without ribavirin, in chronic hepatitis C patients who have not responded to standard dose interferon monotherapy. METHODS: Previous virological non-responders to standard dose interferon (3-5 MU three times weekly for > or = 12 weeks) were randomized to receive, unblind, either 10 MU interferon alpha-2b daily for 10 days, then 5 MU daily for 74 days, then 5 MU three times weekly for 24 weeks (total 36 weeks) (group A), or the above regimen with the addition of ribavirin, 1000-1200 mg/day, at day 11 (group B). All patients were followed up for 24 weeks after completion of therapy. RESULTS: End of treatment virological response was noted in one of 10 (10%) patients in group A and in eight of 15 (54%) patients in group B (P=0.04). The sole end treatment responder in group A and three in group B relapsed on follow-up. The apparent improvement in response in group B compared to group A nearly reached statistical significance (group B 5/15 vs. group A 0/10; P=0.06). CONCLUSIONS: In this small pilot study, a 36-week high-dose induction interferon monotherapy protocol did not yield sustained responses in previous non-responders to standard dose interferon. However, the same regimen with ribavirin yielded a 33% sustained response rate, nearly reaching statistical significance. The therapy was well tolerated, despite the higher doses of interferon used and the addition of ribavirin. High-dose interferon with ribavirin appears to be a therapeutic option for non-responders to conventional interferon monotherapy.

Multicenter study of noninvasive monitoring systems as alternatives to invasive monitoring of acutely ill emergency patients.

BACKGROUND: Recent reports showed lack of effectiveness of pulmonary artery catheterization in critically ill medical patients and relatively late-stage surgical patients with organ failure. Since invasive monitoring requires critical care environments, the early hemodynamic patterns may have been missed. Ideally, early noninvasive hemodynamic monitoring systems, if reliable, could be used as the "front end" of invasive monitoring to supply more complete descriptions of circulatory pathophysiology. OBJECTIVES: To evaluate the accuracy and reliability of noninvasive hemodynamic monitoring consisting of a new bioimpedance method for estimating cardiac output combined with arterial BP, pulse oximetry, and transcutaneous PO2 and PCO2; we compared this system of noninvasive monitoring with simultaneous invasive measurements to evaluate circulatory deficiencies in acutely ill patients shortly after hospital admission where invasive monitoring was not readily available. We also preliminarily explored early differences in temporal hemodynamic patterns of survivors and nonsurvivors. DESIGN AND SETTING: Prospective comparison of simultaneous invasive and noninvasive measurements of circulatory function with retrospective analysis of data in university-run county hospitals, university hospitals and affiliated teaching hospitals, and a community private hospital. PATIENTS: We studied 680 patients, including 139 severely injured or hemorrhaging patients in the emergency department (ED), 129 medical (nontrauma) patients on admission to the ED, 274 high-risk surgical patients intraoperatively, and 138 patients recently admitted to the ICU. RESULTS: A new noninvasive impedance device provided cardiac output estimations under conditions in which invasive thermodilution measurements were not usually applied. There were 2,192 simultaneous bioimpedance and thermodilution cardiac index measurements; the correlation coefficient, r = 0.85, r2 = 0.73, p < 0.001. The precision and bias was -0.124+/-0.75 L/min/m2. Both invasive and noninvasive monitoring systems provide similar information and identified episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous O2, high transcutaneous CO2, and low oxygen consumption before and during initial resuscitation. The limitations of noninvasive systems were described. CONCLUSIONS: Noninvasive monitoring systems gave continuous displays of physiologic data that provided information allowing early recognition of low flow and poor tissue perfusion that were more pronounced in the nonsurvivors. Noninvasive systems may be acceptable alternatives where invasive monitoring is not available.

Pyridoxal 5'-phosphate as an antidote for cyanide, spermine, gentamicin, and dopamine toxicity: an in vivo rat study.

Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, readily forms complexes with a wide variety of potentially toxic substances, including cyanide (KCN), spermine (SPM), gentamicin (GM), and dopamine (DOP). The role of PLP as an antidote for these toxicants in vivo was studied. Rats were given intraperitoneal injections of the toxicant, followed by injections of either saline or PLP. For KCN, PLP increased the LD50 from 0.088 to 0.188 mmol/kg and extended the survival time at the highest dose employed from a median of 3 min to a median of 60 min. For SPM, PLP increased the LD50 from 0.162 to 0.262 mmol/kg and prevented death from renal failure at all doses employed except the highest. PLP protected against GM-induced neuromuscular paralysis and death. In the case of DOP, results were equivocal, but no deaths were seen in the PLP-treated rats. The combination of individually nontoxic doses of GM, DOP, and SPM caused death with renal tubular necrosis, pulmonary edema and hemorrhages, congestion of the viscera, and a diffuse coagulopathy. Because many seriously ill patients have elevated SPM levels and are given GM and/or DOP, we suggest that further investigation of the potential protective role of PLP in serious illness be undertaken.

Focal loss of pigment in the Belgian Tervuren dog.

Hypopigmentation most commonly affecting the face and mouth of the Belgian Tervuren dog was characterized by an absence of melanocytes in the epidermis. Pigment loss usually occurred during young adulthood, and although there was partial repigmentation in some dogs, complete repigmentation did not occur. Treatment with vitamin and mineral supplements was unrewarding. The condition appeared to have some degree of heritability and to be similar to vitiligo in man.

Partial trisomy of chromosome 15.

Chromosome analysis of a moderately mentally retarded female revealed a 47,XX,+G? karyotype. Giemsa-trypsin banding showed the extra chromosome to be a deleted chromosome 15 (47,XX,+15q-). This case points out the importance of cytogenetic studies in moderately retarded individuals without significant physical anomalies.

Translocation of 9q/13q resulting in duplication (trisomy 9pter leads to 9q22) and deficiency (monosomy 13pter leads to 13q12).

A profoundly retarded, 12-year-old female is described. Her phenotype is compatible with the clinical features of the trisomy 9p syndrome. Cytogenetic analyses showed her to be trisomic for 9pter leads to 9q22 and monosomic for 13pter leads to 13q12, as the result of adjacent-2 segregation during meiosis in her mother. The family pedigree shows this (9;13) translocation to be present in at least three generations.

X-linked nonspecific mental retardation. Report of a large kindred.

A seven-generation pedigree of apparent X-linked, nonspecific mental retardation is reported. There are 19 known affected males who appear to have received the gene through normal mothers. Retardation, lack of fine motor coordination, hyperactivity and a speech defect are the characteristics of affected individuals studied.