Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients.

Dysfunction of the central nervous system (CNS) is a prominent feature of the acquired immune deficiency syndrome (AIDS). Many of these patients have a subacute encephalitis consistent with a viral infection of the CNS. We studied the brains of 12 AIDS patients using in situ hybridization to identify human immunodeficiency virus [HIV, referred to by others as human T-cell lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), AIDS-associated retrovirus (ARV)] nucleic acid sequences and immunocytochemistry to identify viral and cellular proteins. Nine patients had significant HIV infection in the CNS. In all examined brains, the white matter was more severely involved than the grey matter. In most cases the infection was restricted to capillary endothelial cells, mononuclear inflammatory cells, and giant cells. In a single case with severe CNS involvement, a low-level infection was seen in some astrocytes and neurons. These results suggest that CNS dysfunction is due to indirect effects rather than neuronal or glial infection.     

Comparison of a Low,Fixed Dose and a High,Weight-Based Dose of Recombinant Factor VIIa in the Treatment of Warfarin-Associated Intracranial Hemorrhage

Background

Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established.

Methods

This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions.

Results

Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups.

Conclusions

A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.     

Coxsackievirus B4 myocarditis and meningoencephalitis in newborn twins

Coxsackievirus B4 (CB4) is a picornavirus associated with a variety of human diseases, including neonatal meningoencephalitis, myocarditis and type 1 diabetes. We report the pathological findings in twin newborns who died during an acute infection. The twins were born 1 month premature but were well and neurologically intact at birth. After a week they developed acute lethal neonatal sepsis and seizures. Histopathology demonstrated meningoencephalitis and severe myocarditis, as well as pancreatitis, adrenal medullitis and nephritis. Abundant CB4 sequences were identified in nucleic acid extracted from the brain and heart. In situ hybridization with probes to CB4 demonstrated infection of neurons, myocardiocytes, endocrine pancreas and adrenal medulla. The distribution of infected cells and immune response is consistent with reported clinical symptomatology where systemic and neurological diseases are the result of CB4 infection of select target cells.     

AMP-18,一种新发现的胃黏膜保护因子

AMP-18是一种新发现的由胃腺体上皮细胞合成的小分子蛋白质,独特表达于胃黏膜,机体其他部位少见,胃癌组织中表达缺失．AMP-18 由185个氨基酸组成,除去N端信号肽(20个氨基酸)后大小约18 ku,第54-150个氨基酸组成高度保守的结构域(BRICHOS区域)承担主要的生理功能．AMP-18由胃腺体上皮细胞以胞吐的方式分泌到胃黏液中,他的合成和分泌与个体生长发育有关,并受福斯高林、吲哚美辛、地塞米松等药物的影响．目前发现 AMP-18的生理功能主要有促进胃黏膜上皮细胞的有丝分裂,促进细胞的迁徙,促胃肠黏膜损伤的修复,保持胃肠黏膜的完整等．     

The provision of a time-critical elective surgical service during the COVID-19 Crisis: a UK experience

IntroductionWith the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic.Materials and methodsA protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 ‘clean’ site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff.ResultsA total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive.ConclusionThis study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.     

Neurocritical Care Resource Utilization in Pandemics: A Statement by the Neurocritical Care Society

Neurocritical Care -     

Effects of chronic cocaine abuse on memory and learning

Sixteen chronic (M = 5 years) weekly cocaine users who were at least 10 days (M = 20 days) abstinent were compared to age, education, race, and gender matched controls on the California Verbal Learning Test, Wechsler Adult Intelligence Scale-Revised (WAIS-R) Vocabulary, and Block Design. Subjects with developmental disorder, neurological, psychiatric, or other substance abuse history were excluded. Cocaine subjects learned and recalled fewer words than controls, but did not differ on IQ. Results suggested significant residual impairment in verbal learning efficiency subsequent to chronic cocaine use that results from memory storage difficulties rather than attentional impairment or general intellectual reduction. A dose-response relationship is suggested.