Arterial Complications following Total Knee Arthroplasty (TKA): A Systematic Review and Proposal for Improved Monitoring.

Introduction: Total knee arthroplasty (TKA) is a common operation and is becoming more common due to population aging and increasing BMI. TKA provides excellent improvement in quality of life but carries risk of arterial complications in the perioperative period. This systematic review aims to provide a greater understanding of the incidence of such complications, and time taken to diagnose arterial injury. Materials and methods: PubMed, Medline, Ovid SP and EMBASE databases were searched with the following MeSH keywords: 'complication', 'vascular injury', 'ischaemia', 'spasm', 'thrombosis', 'pseudoaneurysm', 'transection', 'pulse', 'ABPI OR ABI', 'Doppler', 'amputation'. All arterial vascular events in the perioperative state of the total knee replacement were included. Records were independently screened by two reviewers, and data was extracted according to a pre-determined proforma. Overall incidence and time to diagnosis was calculated for complications. Systematic review registration PROSPERO: CRD42018086643. No funding was received. Results: Twelve studies were selected for inclusion. A total of 3325 cases of arterial complications were recorded across all studies, and were divided into three categories, pseudoaneurysms (0.06%); ischaemia and thrombosis (0.17%); haemorrhage and arterial transections (0.07%). Time taken to reach the diagnosis for each complication was longest in the ischaemia and thrombosis group (6.8 days), followed by pseudoaneurysm (3.5 days) and haemorrhage and transections (3.0 days). Conclusion: TKA post-operative vascular complications are rare, but when they do occur they lead to limb and life threatening complications. This should be discussed with patients during the consent process. Current times to diagnosis represent missed opportunities to recognise arterial injury and facilitate rapid treatment of the complication. A very low threshold for seeking specialist input should be adopted, and any concern for vascular injury, such as unexplained perioperative bleeding, absent lower limb pulses in the post-operative period or unexplained severe pain should warrant immediate review by a vascular surgeon, and in centres where this is not possible, immediate blue-light transfer to the closest vascular centre.

Current landscape of ESMO/ASCO Global Curriculum adoption and medical oncology recognition: a global survey.

BACKGROUND: With the implementation of multidisciplinary treatment and development of multiple novel anticancer drugs in parallel with expanding knowledge of supportive and palliative care, a need for separate training and specialisation in medical oncology emerged. A Global Curriculum (GC) in medical oncology, developed and updated by a joint European Society for Medical Oncology/American Society of Clinical Oncology (ESMO/ASCO) GC Task Force/Working Group (GC WG), greatly contributed to the recognition of medical oncology worldwide. MATERIAL AND METHODS: ESMO/ASCO GC WG carried out a global survey on medical oncology recognition and GC adoption in 2019. RESULTS: Based on our survey, medical oncology is recognised as a separate specialty or sub-specialty in 47/62 (75%) countries participating in the survey; with a great majority of them (39/47, 83%) recognising medical oncology as a standalone specialty. Additionally, in 9 of 62 (15%) countries, medical oncology is trained together with haematology as a specialty in haemato-oncology or together with radiotherapy as a specialty in clinical oncology. As many as two-thirds of the responding countries reported that the ESMO/ASCO GC has been either fully or partially adopted or adapted in their curriculum. It has been adopted in a vast majority of countries with established training in medical oncology (28/41; 68%) and adapted in 12 countries with mixed training in haemato-oncology, clinical oncology or other specialty responsible for training on systemic anticancer treatment. CONCLUSIONS: With 75% of participating countries reporting medical oncology as a separate specialty or sub-specialty and as high as 68% of them reporting on GC adoption, the results of our survey on global landscape are reassuring. Despite a lack of data for some regions, this survey represents the most comprehensive and up-to-date information about recognition of medical oncology and GC adoption worldwide and will allow both societies to further improve the dissemination of the GC and global recognition of medical oncology, thus contributing to better cancer care worldwide.

Research needs in breast cancer.

New research questions emerge as medical needs continue to evolve and as we improve our understanding of cancer biology and treatment of malignancies. Although significant advances have been made in some areas of breast cancer research resulting in improvements in therapies and outcomes over the last few decades, other areas have not benefited to the same degree and we continue to have many gaps in our knowledge. This article summarizes the 12 short and medium-term clinical research needs in breast cancer deemed as priorities in 2016 by a panel of experts, in an attempt to focus and accelerate future research in the most needed areas: (i) de-escalate breast cancer therapies in early breast cancer without sacrificing outcomes; (ii) explore optimal adjuvant treatment durations; (iii) develop better tools and strategies to identify patients with genetic predisposition; (iv) improve care in young patients with breast cancer; (v) develop tools to speed up drug development in biomarker-defined populations; (vi) identify and validate targets that mediate resistance to chemotherapy, endocrine therapy and anti-HER2 therapies; (vii) evaluate the efficacy of local-regional treatments for metastatic disease; (viii) better define the optimal sequence of treatments in the metastatic setting; (ix) evaluate the clinical impact of intra-patient heterogeneity (intra-tumor, inter-tumor and inter-lesion heterogeneity); (x) better understand the biology and identify new targets in triple-negative breast cancer; (xi) better understand immune surveillance in breast cancer and further develop immunotherapies; and (xii) increase survivorship research efforts including supportive care and quality of life.

Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.

PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.

1st International consensus guidelines for advanced breast cancer (ABC 1).

The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines.

Sensitive indirect spectrophotometric determination of isoniazid.

A simple, rapid, sensitive and accurate indirect spectrophotometric method for the microdetermination of isoniazid (INH) in pure form and pharmaceutical formulations is developed. The procedure is based on the reaction of copper(II) with isoniazid in the presence of neocuproine (NC). In the presence of neocuproine, copper(II) is reduced easily by isoniazid to a Cu(I)-neocuproine complex, which shows an absorption maximum at 454 nm. By measuring the absorbance of the complex at this wavelength, isoniazid can be determined in the range 0.3-3.5 microgml-1. This method was applied to the determination of isoniazid in pharmaceutical formulation and enabled the determination of the isoniazid in microgram quantities (0.3-3.5 microgml-1). The results obtained for the assay of pharmaceutical preparations compared well with those obtained by the official method and demonstrated good accuracy and precision.

Tamoxifen and ovarian cysts: a prospective study.

PURPOSE: To prospectively follow a group of women with breast cancer on tamoxifen for the development of ovarian cysts. METHODS: 72 women were followed every 6 months with pelvic examination and vaginal ultrasound. Chi square and Student's t-test were used for statistical analysis. RESULTS: The duration of treatment was 31.5+/-20 months. The mean age was 51.2+/-9.8 years. 55.6% were post-menopausal. Out of 72 women, 18 (25%) developed ovarian cysts. The mean age of women who developed ovarian cysts was significantly lower than in those who did not (47.0+/-7.0 and 52.5+/-10.2 years, respectively, P=0.03), however, the mean duration of treatment was not significantly different (33.3+/-17.4 and 29.3+/-20 months, respectively, P=0.45). Out of 32, 14 (43.8%) pre-menopausal and out of 40, 4 (10%) post-menopausal women developed ovarian cysts (P=0.003). They developed the cysts after an average duration of 33.3+/-18 and 50.7+/-6.2 months, respectively (P=0.7). The average diameter of the cysts was 2.8+/-1.2 cm. All cysts were simple except for one pre-menopausal women. All the cysts in post-menopausal women resolved spontaneously. One pre-menopausal patient had a multi-loculated cyst, was operated and had a serious cystadenoma. In nine patients, the cysts resolved spontaneously and in three after discontinuation of tamoxifen, and one patient was lost to follow-up. All cysts were asymptomatic. CONCLUSION: Ovarian cysts frequently develop in women with breast cancer on tamoxifen. The majority of the cysts resolve spontaneously, therefore an expectant management with follow-up ultrasonography is recommended.

Biochemical characterisation of a hydrophobic ligand binding protein from the tapeworm Hymenolepis diminuta.

The cestode Hymenolepis diminuta contains an abundant, cytoplasmic, hydrophobic ligand, binding protein (H-HLBP). Studies with polarity sensitive probes suggest a single hydrophobic binding site, the results also indicate that the single tryptophan in the molecule (Trp41) is involved in ligand binding. Of the possible physiological ligands tested, only haematin and retinoids (retinol and retinoic acid) show appreciable binding in addition to fatty acids. H-HLBP also binds a range of anthelmintics, again with K(D) values in the nM range. The interaction of anthelmintics with hydrophobic binding proteins may be important in determining drug specificity and site of action and could have a role in the development of drug resistance.

Ocular findings in aplastic anemia.

OBJECTIVE: To analyze the ocular findings in aplastic anemia. DESIGN: Eighteen patients with aplastic anemia were examined. RESULTS: Ocular findings included cotton wool spots (38%), nerve fiber layer or preretinal hemorrhages (67%), vitreous hemorrhages (13%), a picture resembling central retinal vein occlusion (13%) and optic disk edema (6%). Preretinal hemorrhages were the presenting sign of aplastic anemia in 2 patients (13%). CONCLUSIONS: A blood profile is needed in patients with unexplained retinal hemorrhages. Patients with aplastic anemia need to avoid ocular massage and Valsalva maneuvers to decrease ocular morbidity.