Association of HLA types A1-B8-DR3 and B27 with rapid and slow progression of HIV disease

We examined how HLA types A1-B8-DR3 and B27 were related to progression of clinical disease and rate of loss of CD4 lymphocytes in the Edinburgh City Hospital cohort of HIV-positive patients, mainly injection drug users. Patients (n = 692) were prospectively followed from 1985 through March 1994. Accurately estimated seroconversion times were determined retrospectively for a subgroup of 313 (45%). Of 262 patients (39%) who were fully or partially HLA typed, 155 (50%) had known seroconversions. Of 34 patients typed positive for A1-B8-DR3, 29 progressed to CDC stage IV, 22 to AIDS and 20 died. Twelve patients were typed positive for B27; six of these progressed to CDC stage IV, one to AIDS and none died. In a proportional hazards analysis of the 313 patients with known seroconversions, A1-B8-DR3 was significantly associated with covariate-adjusted relative risks of 3.7 (95% CI 1.9- 7.2), 3.1 (1.6-6.0) and 1.9 (1.1-3.2) for progression from seroconversion to death, AIDS and CDC stage IV, respectively. Events for B27 were too rare to include B27 in analyses to death and AIDS, but B27 was significantly associated with slower progression to CDC stage IV (0.3, CI 0.1-0.9). Random effects growth curve models were used to estimate individual rates of loss of square root CD4 count and loss of CD4 percentage, for 603 and 617 patients, respectively. A1-B8-DR3 was associated with rapid loss of both markers (p = 0.02 and p = 0.01, respectively); B27 was associated with slow loss of both markers (p = 0.04 and p < 0.005).      

End-stage renal disease and outcome in a surgical intensive care unit

Introduction

End-stage renal disease (ESRD) is associated with an increased propensity for critical illness, but whether ESRD is independently associated with a greater risk of death after major surgical procedures is unclear.

Methods

This was a retrospective analysis of prospectively collected data from all adult (>18 years) patients admitted to a 50-bed surgical intensive care unit (ICU) between January 2004 and January 2009. ESRD was defined as the need for chronic peritoneal dialysis or hemodialysis for at least 6 weeks prior to ICU admission. We used multivariable logistic regression analysis and propensity-score matching to adjust for possible confounders.

Results

In total, 12,938 adult patients were admitted during the study period; 199 patients had ESRD at ICU admission, giving a prevalence of 1.5%. Patients with ESRD were more likely to be male (72.9% versus 63.0%, P = 0.004) and had higher severity scores, a higher incidence of diabetes mellitus and cirrhosis, and a lower incidence of cancer at ICU admission than those without ESRD. Patients with ESRD were more likely to have any type of organ failure at ICU admission and during the ICU stay. Patients with ESRD had higher ICU and hospital mortality rates (23.1% and 31.2% versus 5.5% and 10.0%, respectively, P <0.001 pairwise) and longer ICU length of stay (2 (1 to 7) versus 1 (1 to 3) days, P <0.001). In multivariable logistic regression analysis, ESRD was independently associated with a greater risk of in-hospital death (odds ratio = 3.84, 95% confidence interval 2.68 to 5.5, P <0.001). In 199 pairs of patients, hematologic and hepatic failures were more prevalent, ICU and hospital mortality rates were higher (23.1% versus 15.1% and 31.2% versus 19.1%, P <0.05 pairwise), and ICU length of stay was longer (2 (1 to 7) versus 1 (1 to 7) days, P <0.001) in patients with ESRD.

Conclusions

In this large cohort of surgical ICU patients, presence of ESRD at ICU admission was associated with greater morbidity and mortality and independently associated with a greater risk of in-hospital death. Our data can be useful in preoperative risk stratification.     

Stabilization of HIV incidence in women of reproductive age in southern Mozambique

Introduction

The collection of incidence data on HIV infection is necessary to evaluate the status and dynamics of the epidemic and the effectiveness of intervention strategies. However, this is usually difficult in low‐income countries.

Methods

Five yearly point HIV prevalence estimations (in 1999, 2003, 2004, 2005 and 2008) were obtained for women between 15 and 45 years of age participating in three studies carried out for other purposes at the Antenatal Clinic (ANC) in Manhiça, Mozambique. HIV incidence was estimated between prevalence points using a previously validated methodology. Two methods were used, one based on mortality rates for three HIV epidemic scenarios, and the other based on survival information after infection. The pattern over time was captured by fitting a log‐regression model.

Results

The prevalence of HIV infection ranged from 12% in 1999 to 49% in 2008. The HIV incidence increased from approximately 3.5 cases per 100 person‐years in 2001 to 14 per 100 person‐years in 2004, with stabilization thereafter to levels of around 12 cases per 100 person‐years. The incidence estimates were comparable for the two methods used.

Conclusion

These findings indicate an increase in the prevalence and incidence of HIV infection among women of reproductive age over the 9 years of the analysis, with a plateau in the incidence of infection since 2005. However, the very high figures for both prevalence and incidence highlight the importance of the continuation of the prevention and treatment programmes that already exist, and suggest that implementation of preventive measures is needed in this area.     

Non-invasive molecular imaging for preclinical cancer therapeutic development

Molecular and non-invasive imaging are rapidly emerging fields in preclinical cancer drug discovery. This is driven by the need to develop more efficacious and safer treatments, the advent of molecular-targeted therapeutics, and the requirements to reduce and refine current preclinical in vivo models. Such bioimaging strategies include MRI, PET, single positron emission computed tomography, ultrasound, and optical approaches such as bioluminescence and fluorescence imaging. These molecular imaging modalities have several advantages over traditional screening methods, not least the ability to quantitatively monitor pharmacodynamic changes at the cellular and molecular level in living animals non-invasively in real time. This review aims to provide an overview of non-invasive molecular imaging techniques, highlighting the strengths, limitations and versatility of these approaches in preclinical cancer drug discovery and development.     

Use of I-131 labeled, murine Fab against a high molecular weight antigen of human melanoma: preliminary experience

High molecular weight antigen (HMWA) is a tumor-associated proteoglycan of human malignant melanoma. I-131 labeled Fab fragments of these specific antibodies were used for preliminary feasibility studies for radioimmunodetection and therapy of human subjects who had inoperable metastatic melanoma. Ten patients received tracer doses of 5-13 mCi (185-481 MBq) of I-131 (anti-HMWA) Fab. All patients (8/8) who had melanoma lesions greater than 1 cm by correlative diagnostic methods had one or more lesions that had localization to tumor of the radiolabeled Fab. In all, 17 of 23 (74%) documented metastases were seen. There were no false positives in this series. Two patients who had avid uptake received potentially radiotherapeutic doses of 142 mCi (5,254 MBq) (one patient) and 181 mCi (6,697 MBq) and 193 (7,141 MBq) (total: 374 mCi or 13,838 MBq) (one patient). For both of these patients, whole body imaging studies showed that the localization of the high dose I-131 Fab was predominantly in tumor. The patient who received the larger dose showed a greater than 50% reduction in the size of pelvic and pericaval nodes, with stabilization of disease at the smaller nodal size for a period of three months. On whole body images, the anti-Fab HMWA appears to be more tumor selective than Fab preparations that target the p97 antigen for melanoma, and there is less uptake in liver.     

Clinical utilities and biological characteristics of melanoma sentinel lymph nodes

An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient’s nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN.     

常见医院感染多重耐药革兰阴性杆菌Ⅰ类整合子标志物检测

目的了解浙江省湖州解放军第98医院从临床分离的常见医院感染多重耐药革兰阴性杆菌Ⅰ类整合子存在状况。方法从临床分离鲍曼不动杆菌60株、铜绿假单胞菌30株、阴沟肠杆菌20株、嗜麦芽窄食单胞菌19株和黄杆菌属15株(脑膜败血性黄杆菌12株、产吲哚金黄杆菌3株),采用聚合酶链反应及序列分析的方法检测Ⅰ类整合子标志物 int Ⅰ 1及qacE△1 基因。结果鲍曼不动杆菌、铜绿似单胞菌、阴沟肠杆菌、嗜麦芽窄食单胞菌和黄杆菌属中 int Ⅰ 1基因阳性率分别为58.3%、0、95.0%、0和0,qacE△1基因阳性率分别为83.3%、83.3%、85.0%、10.5%和0。合计144株中 int Ⅰ 1和 qacE△1阳性株数(%)分别为54株(37.5%)、94株(65.3%),Ⅰ类整合子标志物总阳性率为68.1%(98/144)。结论解放军第98医院从临床分离的常见医院感染多重耐药革兰阴性杆菌Ⅰ类整合子携带率相当高。     

Vocal cord dysfunction following esophageal atresia and tracheoesophageal fistula (EA/TEF) repair

BackgroundThe purpose of this study was to determine risk factors and long-term outcomes in patients with esophageal atresia +/?tracheoesophageal fistula (EA/TEF) with vocal cord dysfunction (VCD) owing to recurrent laryngeal nerve (RLN) injury.MethodA retrospective chart review was performed for EA/TEF patients repaired at our institution from 1999 to 2014 (REB #1000032265).ResultsOf 197 patients, 22 (11.2%) were diagnosed with VCD by indirect laryngoscopy following EA/TEF repair. Aspiration was documented on video swallow study for 21 patients, and as a result, 13 required thickened feeds and 8 required gastrostomy tube feeds. Of the 16 H-type TEF patients, 8 (50%) had VCD. Following discharge, 20 (90.9%) patients with VCD eventually tolerated full feeds orally without aspiration but only 8 (36.4%) had documented recovery of vocal cord movement at long-term follow up (mean 452 days). Overall, patients with VCD were more likely to have feeding modifications, increased exposure to radiological studies, and increased frequency of Otolaryngology follow-up compared to EA/TEF patients without VCD.ConclusionEA/TEF patients are at risk for VCD. Clinical improvement did not always correlate with recovery of VC motion. Strategies to minimize RLN damage will improve outcomes and quality of life for EA/TEF patients.Level of evidenceLevel III.     

Intracranial Artery Calcium Burden Predicts Recurrent Cerebrovascular Events in Transient Ischaemic Attack Patients

Background: Patients with initial transient ischaemic attack (TIA) subsequently have a higher risk of recurrent TIA or acute ischemic stroke (AIS). The role of scoring intracranial arterial calcification (IAC) in predicting the prevalence of stroke remains unclear. We aim to evaluate if radiological CT calcium score measuring IAC burden could predict future ischemic events in a cohort of TIA patients. Methods: We studied consecutive patients from July 2014 to December 2015 who presented with first episode of TIA. All patients had noncontrasted CT or CT-angiogram of the brain on admission. CT calcium score (cm3) was quantified by measuring calcium deposition in the bilateral internal carotid arteries, middle cerebral arteries, and vertebrobasilar system. Patients were followed up for 2 years and ischemic events for either recurrent TIA or AIS were recorded. We compared patients in terms of clinical profile at presentation and CT calcium score using appropriate univariate and multivariable analyses. Results: Of 156 TIA patients studied, 22% (n = 35) had recurrent TIA or AIS within 2 years of follow-up. On univariate analyses, recurrent TIA/AIS was associated with gender (OR 0.61; 95%CI 0.40-0.95; P = .038), hypertension (mean difference 2.49; 95%CI 1.08-5.75; P = .030) and higher CT calcium score (mean difference 0.84 95%CI 0.16-1.52 P = .016). On multivariable logistic regression, a higher CT calcium score was significantly associated with recurrent TIA/AIS (adjusted OR 1.25 95%CI 1.01-1.55 P = .042). Conclusions: In TIA patients, higher IAC burden by measurement of a quantitative CT calcium score may be associated with recurrent ischemic events.     

云南红豆杉中四个新紫杉烷类二萜化合物的分离和结构鉴定

自云南红豆杉(Taxus yunnanensis ChengetL.K.Fu)树皮的二氯甲烷提取部分又分离得到7个紫杉烷类二萜和生物碱,经光谱(IR,MS,¹HNMR,¹H-¹H’COSY,¹³C-¹HCOSY)解析推定4个新的紫杉烷类二萜涨化合物的结构为5-decinnamoyl-11-acetyl-19-hydroxyl taxagifine(I),2-deacetoxy-5.decinnamoyl taxinineJ(II),1-hydroxy-2,7,9-trideacetyl baccatinI(IV)和7-xyIosyl-10-deacetyl baccatinIII(VII),3个已知的紫杉烷类二苑和生物碱是5-decinnamoyI taxinineJ(III),7-xylosyl taxol(V)和7-xylosyl cephalomannine(VI),它们是首次从该植物中得到。