急性缺血性卒中影像学检查的建议——美国心脏协会的科学声明（上）

卒中是一种常见、严重的疾病,仅美国每年的新发病例就高达795000例,并已成为全世界人类死亡和残疾的主要病因。10年前,重组型组织纤溶酶原激活剂（recombinant tissue plasminogen activator,rt—PA）被批准用于治疗急性缺血性卒中。rt—PA应用指南建议,应在卒中发病后3h内静脉给予rt—PA,给药前应行头部CT检查,排除颅内出血。     

Update Experience of Surgery for Acute Limb Ischaemia in a District General Hospital – Are We Getting Any Better?

INTRODUCTION

The aims of this study were to audit results of a 10-year experience of surgery for acute limb ischaemia (ALI) in terms of limb salvage and mortality rates, and to compare results with a historical published series from our unit.

PATIENTS AND METHODS

All emergency operations performed during the period 1993–2003 were identified from theatre registers and patient notes reviewed to determine indications for, and outcome of, surgery. Data were compared to a similar cohort who underwent surgery from 1980 to 1990.

RESULTS

There was a 33% increase in workload from 87 to 116 patients between the two time periods. The number of patients with idiopathic ALI reduced (24% versus 4%; P < 0.05), and there were fewer smokers (71% versus 39%; P < 0.05) and a greater number of claudicants (17% versus 35%; P < 0.05) in those treated from 1993–2003. Latterly, more patients underwent pre-operative heparinisation (33% versus 80%; P < 0.05), received prophylactic antibiotics (14% versus 63%; P < 0.05), and had anaesthetic presence in theatre (46% versus 88%; P < 0.05). There was also a reduction in local anaesthetic procedures (80% versus 41%; P < 0.05). Despite increased pre-operative (15% versus 47%; P < 0.05) and on-table imaging (0% versus 16%; P < 0.05) technical success did not improve. Whilst complication rates were identical at 62%, there were fewer cardiovascular complications in the recent cohort. The 30-day mortality rate for embolectomy fell from 45% to 33%. Multivariate analysis revealed age > 70 years, prolonged symptom duration, ASA score ≥ III, lack of prophylactic antibiotics, absence of an anaesthetist, and operations performed under local anaesthetic to be associated with increased risk of mortality. Factors adversely affecting limb salvage included prolonged duration from symptom onset to operation, and a history of claudication or smoking.

CONCLUSIONS

Despite improvements in pre- and peri-operative management, arterial embolectomy/thrombectomy remains a procedure with a high morbidity and mortality. Further attempts to improve outcome must be directed at early diagnosis and referral as delay from symptom onset to surgery is a major determinant of outcome.     

Choosing event‐driven and daily HIV pre‐exposure prophylaxis – data from two European PrEP demonstration projects among men who have sex with men

IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Acute generalized exanthematous pustulosis due to thallium

Acute generalized exanthematous pustulosis (AGEP) is characterized clinically by fever, pruritus and acute pustular eruption. Usually a drug is found to be the responsible agent. We present a patient who experienced an acute generalized exanthematous pustulosis due to radioactive thallium. The eruption cleared rapidly after discontinuation of the drug and systemic corticosteroid therapy.     

Degenerative lumbar spinal stenosis—results of expansive laminoplasty

Expansive laminoplasty, a procedure used more and more often for cervical myelopathy, was carried out in patients with lumbar spinal stenosis in the Department of Orthopaedics, Paraplegia, Physical Medicine and Rehabilitation of our institute. Twenty-five such clinico-radiologically proven cases were operated upon. For radiological evaluation, computed tomography (CT) was used. Expansive laminoplasty decompresses the nerve roots by osteoplastic enlargement of the lumbar spinal canal, with the maintenance of spinal stability. These advantages were confirmed during the follow-up of 3 to 5 years. Using CT, the spinal canal was found to be enlarged to a nearly rectangular shape and the average enlargement was 124%. The visual analogue scale (VAS) was used for subjective pain assessment before and after the surgery. The ultimate outcome was assessed by the Surin et al. criteria (Spine 17:1-8, 1992).     

A phase I study of sequential versus concurrent interleukin-3 and granulocyte-macrophage colony-stimulating factor in advanced breast cancer patients treated with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy

Cumulative thrombocytopenia is a dose-limiting toxicity of dose- intensive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential interleukin-3 (IL-3) and granulocyte-macrophage colony- stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to each cytokine administered alone. Ninety- three patients with advanced breast cancer were treated with five cycles of FLAC chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg) administered subcutaneously for each schedule of cytokine administration. The GM-CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM- CSF (schedule B) was associated with higher platelet nadirs, shorter durations of platelet counts less than 50,000/microL, and the need for fewer platelet transfusions over five cycles of FLAC chemotherapy compared with concurrent cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated with unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared with each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF with IL-3 administered for 9 days before beginning GM-CSF may be superior to shorter durations of IL- 3 administered sequentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematologic toxicity associated with multiple cycles of FLAC chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted.