Management of patients with hereditary hemorrhagic telangiectasia undergoing general anesthesia: a cohort from a single academic center’s experience

Purpose

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant disease characterized by capillary malformation leading to multisite cutaneomucosal telangiectasias and multiorgan arteriovenous malformations, which can present challenges to anesthetic care. The primary aim of this report is to present a large cohort of patients with hereditary hemorrhagic telangiectasia undergoing general anesthesia at our institution in regard to comorbid conditions and complications of surgical and anesthetic management.

Methods

A computerized search from January 1, 2002 through December 31, 2011 of the Mayo Clinic medical records database was performed for patients with hereditary hemorrhagic telangiectasia who underwent general anesthesia. Medical records were reviewed. Eligibility criteria included patients with definite or suspected hereditary hemorrhagic telangiectasia based on the Curacao diagnostic criteria who underwent general anesthesia during the study period.

Results

We identified 74 patients with hereditary hemorrhagic telangiectasia who underwent 163 surgeries. The majority had pulmonary arteriovenous malformations (56.7 %) and iron deficiency anemia (64.7 %), and high levels of disease burden with a median American Society of Anesthesiologist Physical Status score of 3. Most surgeries were related to treating conditions associated with hereditary hemorrhagic telangiectasia, with the majority being procedures to the nasal mucosa for recurrent epistaxis (47.2 %). A sizeable proportion of procedures to the nasal mucosa required transfusion of blood (12/77). One case of epistaxis required 11 units of blood until it was successfully controlled. Another notable complication included migration of a coil to pulmonary arteriovenous malformations into the cerebral circulation.

Conclusion

Surgical patients with hereditary hemorrhagic telangiectasia often present with multiorgan involvement. The anesthesia provider needs to be aware of the high prevalence of pulmonary arteriovenous malformations, which may be asymptomatic but can lead to embolic complications. Hemorrhage from epistaxis can be severe, and relatively focal procedures to the nasal mucosa can require blood transfusions.     

Gender Differences in the Heritability of Musculoskeletal and Body Composition Parameters in Mother-Daughter and Mother-Son Pairs

Bone mass and body composition traits are genetically programmed, but the timing and gender and site specificities of their heritability are unclear. Mother-child correlations of bone mineral density (BMD) and bone mineral content, lean mass, and fat mass were studied in 169 premenopausal mothers and their 239 children. Heritability estimates of lean mass, fat mass, BMD, and area were derived for each gender and pubertal stage. There were significant correlations for most densitometry-derived variables at the spine, hip, femoral neck (FN), and total body (r = 0.192–0.388) in mother-postmenarcheal daughter pairs, for bone areas at all sites in early puberty (r = 0.229–0.508) and for volumetric-derived density at FN and spine (r = 0.238–0.368) in mother-son pairs. Fat mass correlations were significant in both genders after puberty (r = 0.299–0.324) and lean mass in postmenarcheal girls only (r = 0.299). Heritability estimates varied between 21% and 37% for mother-daughter and 18% and 35% for mother-son pairs for density-derived variables and between 26% and 40% for body composition variables. Maternal inheritance of bone traits is expressed in early-pubertal boys for several skeletal site traits but consistently involves most site traits in girls and boys by late puberty. Body composition inheritance is more variable.     

Substituted adamantylphthalimides: Synthesis,antiviral and antiproliferative activity

In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N-(4′-R²)phthalimidoadamantanes ( 1 – 7 ), 3-[N-(4′-R²)phthalimido]-1-adamantanols ( 8 – 10 ), and 3-[N-(4′-R²)phthalimido]adamantane-1-carboxylic acids ( 11 – 15 ), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH₂ substituent at the phthalimide (compounds 3 and 5 ). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. A minor antiviral activity against cytomegalovirus and varicella-zoster virus was found for compounds 3 and 5 , but these compounds lacked selectivity. The results presented are important for the rational design of the next-generation compounds with anticancer and antiviral activities.     

评估应用术前PLR、NLR及AGR预测乳腺癌患者预后的价值

目的探究术前血小板淋巴细胞比值（PLR）、中性粒细胞淋巴细胞比值（NLR）及白蛋白球蛋白比值（AGR）在评估乳腺癌患者预后中的价值。 方法选取2013年1月至2017年12月收治的1184例浸润性乳腺癌女性患者为浸润性乳腺癌组,随机选取仅患乳腺纤维腺瘤的患者279例为乳腺纤维腺瘤组。收集患者一般资料、术后病理资料、血型、术前外周血血小板、中性粒细胞、淋巴细胞数量以及血清白蛋白和球蛋白水平,并计算得出PLR、NLR及AGR。应用受试者功能特征曲线下面积来评估三者预测乳腺癌患者预后的能力。本研究使用SPSS 20.0及MedCalc软件进行统计学分析和绘图,P<0.05代表差异具有统计学意义。 结果浸润性乳腺癌患者的术前PLR及NLR均值显著高于乳腺纤维腺瘤患者（P<0.05）,而AGR低于乳腺纤维腺瘤患者（P<0.05）。Cox比例回归风险分析显示,患者的诊断年龄、PLR、NLR、AGR、肿瘤直径、组织学分级、阳性淋巴结个数和分子分型均为乳腺癌的预后危险因素（P<0.05）。ROC曲线分析结果得出,PLR、NLR及AGR的最佳诊断临界值分别为147.4、2.9及1.7。应用术前PLR（AUC=0.796,P<0.001）、NLR（AUC=0.716,P<0.001）及AGR（AUC=0.748,P<0.001）预测乳腺癌患者预后均有价值,且PLR价值更高。 结论术前PLR、NLR及AGR对乳腺癌患者预后的判断均具价值,三者相比,PLR价值更高,有望成为判断乳腺癌患者预后的补充指标。     

Therapeutic vaccination for HPV induced cervical cancers

Cervical Cancer is the second leading cause of cancer-related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.     

Two-stage vertical flow multi-soil-layering (MSL) technology for efficient removal of coliforms and human pathogens from domestic wastewater in rural areas under arid climate

This paper investigates the removal efficiency of organic matter, nitrogen, phosphorus, coliforms and pathogens from rural domestic wastewater in a two-stage vertical flow multi-soil-layering (MSL) system. The effects of wastewater quality, season and arid climate conditions on pollutants removal efficiency by the system were examined for one year. The experimental setup included two similar MSL systems composed of two layers: soil-mixture-layers (SML) and gravel permeable layers (PL) that are arranged in a brick like pattern. The applied hydraulic loading rate was 1000 L m^?2 day^?1. Results showed that most of the physicochemical contaminants elimination occurred while the wastewater percolated through the first MSL stage. The second stage demonstrated an improvement in the reduction of all pollutants, especially fecal bacteria indicators and pathogens. The mean overall removal rates performed by the two-stage MSL system were 97% for TSS, 96% for BOD₅, 91% for COD, 96% for TN and 95% for TP. For bacterial indicators, the combination of two-stage MSL system achieved high log removals between 2.21 and 3.15 log units. Contaminants reduction processes in MSL technology are more dependent on internal than external environmental factors. The effectiveness of the two-stage MSL system to treat domestic wastewater was strongly influenced by wastewater quality. Significant relationships between influent contaminants level and their removal efficiency were found. The efficiency of MSL technology to reduce contaminants is not sensitive to season and air temperature fluctuations. This is due to the capacity of MSL system materials to withstand the air temperature variation, which highlights one of the advantages of MSL’s technology. Wastewater quality is the most important factor affecting the removal of contaminants in the MSL, which could be a critical parameter to considered when designing MSL system. Two-stage MSL system achieved a high treated wastewater quality amenable for treated wastewater reuse in agriculture recommended by Moroccan code of practice. Therefore, the combination of two-stage vertical flow MSL system could be considered an efficient and promising domestic wastewater treatment solution in arid countries to promote environmental protection and wastewater reuse.     

Synthesis,biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles

The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin.     

The dynamic fetal brain

PURPOSE: To evaluate fetuses with normal intracranial anatomy in the second trimester that became abnormal in the third trimester. METHODS: We sonographically examined 6 fetuses with a normal second-trimester head sonogram that presented later in pregnancy with an abnormal head sonogram. RESULTS: Four categories of intracranial pathology were depicted: obstructive hydrocephalus, intraventricular intracranial hemorrhage, non-intraventricular intracranial hemorrhage, and porencephaly. CONCLUSIONS: Despite a normal midtrimester intracranial examination, evaluation of the fetal intracranial contents should be undertaken in subsequent sonographic examinations, because significant pathology can develop spontaneously.