The functional trajectories of older women having surgery for gynaeoncology cancer: A single site prospective observational study.

INTRODUCTION: Population aging longevity and advances in robotic surgery suggest that increasing numbers of older women having gynaeoncological surgery is likely. Postoperative morbidity and mortality are more common in older than younger women with the age-associated characteristics of multimorbidity and frailty being generally predictive of worse outcome. Priorities that inform treatment decisions change during the life course: older patients often place greater' value on quality-of-life-years gained than on life expectancy following cancer treatments. However, data on post-operative cognition, frailty, or functional independence is sparse and not routinely collected. This study aimed to describe the clinical characteristics and trajectory of functional change of older women in the 12 months following gynaeoncological surgery and to explore the associations between them. MATERIALS AND METHODS: The prospective observational cohort study recruited consecutive women aged 65 or over scheduled for major gynaeoncologic surgery between July 2017 and April 2019. Baseline data on cancer stage, multimorbidity, and geriatric syndromes including cognition, frailty, and functional abilities were collected using standardised tools. Delirium and post-operative morbidity were recorded. Post hospital assessments were collected at 3-, 6-, and 12-months. RESULTS: Overall, of 103 eligible participants assessed pre-operatively, most (77, 70%) remained independent in personal care at all assessments from discharge to 12 months. Functional trajectories varied widely over the 12 months but overall there was no significant decline or improvement for the 85 survivors. Eleven experienced a clinically significant decline in function at six months. This was associated with baseline low mood (P < 0.05), albeit with small numbers (6 of 11). Cognitive impairment and frailty were associated with lower baseline function but not with subsequent functional decline. DISCUSSION: There was no clear clinical profile to identify the minority of older adults who experienced a clinically significant decline six months after surgery and for most, the decline was transient. This may be helpful in enabling informed patient consent. Assessment for geriatric syndromes and frailty may improve individual care but our findings do not indicate criteria for segmenting the patient population for selective attention. Future work should focus on causal pathways to potentially avoidable decline in those patients where this is not determined by the cancer itself.

Elective Lung Resections in the Elderly: Where Do We Draw the Line?

INTRODUCTION: The increasing longevity of the Western population means patients with a more advanced age are being diagnosed with resectable disease. With improvements in imaging and diagnostic capabilities, this trend is likely to develop further. As a unit operating on a higher proportion of older patients and with limited literature regarding the population of older than 85 years, we retrospectively compared the outcomes of patients older than 85 years in our unit treated with elective lung resection for non-small cell lung cancer (NSCLC) with those between the age of 80 and 84 years inclusive. METHODS: All patients who underwent elective lung cancer resection between the years 2012 and 2015 were identified from the National Thoracic Surgical Database. RESULTS: A total of 701 elective lung resections were performed during this time frame; 76 patients between the ages of 80 and 84 years and 18 patients older than 85 years. The follow-up period was 3 to 7 years. There was a significant increase in the Thoracic Surgery Scoring System (2.04; 2.96%, p = 0.0015) and a significant reduction in the transfer factor (94.7; 69.5%, p = 0.0001) between the younger and older groups. There were three (3.9%) in-hospital deaths in the 80 to 84 years age group and no in-hospital deaths in the 85 years and older age group. CONCLUSION: This study demonstrates that surgery for early NSCLC can be safely performed in 85 years and older population. This is a higher risk population and parenchymal-sparing procedures should be considered.

Functional recovery in older women undergoing surgery for gynaecological malignancies: A systematic review and narrative synthesis.

OBJECTIVES: Older women are increasingly undergoing surgery for gynaecological malignancies. Although survival data is available other outcomes such as functional recovery are less well described. This systematic review and narrative synthesis describes functional recovery after gynaeoncology surgery with respect to baseline characteristics. MATERIALS AND METHODS: Systematic search of MEDLINE and EMBASE databases and Cochrane Library between 1974 to 2018. Two reviewers independently reviewed abstracts/papers for inclusion against the following criteria: Results analysed and presented using narrative synthesis. RESULTS: Fifteen studies identified (8 Endometrial, 2 Ovarian, 2 Vulval, 3 mixed cancer types). 1/15 used a standalone functional assessment tool, 14/15 used Health-Related Quality of Life tools (EORTC QLQ C30 (8), FACT-G (3), SF-36 (3)) comprising items describing function. More studies showed full recovery to baseline (n = 13) than incomplete recovery (n = 2). Four studies reported a negative association between older age and functional trajectory. Recovery was more likely and occurred faster in minimally-invasive surgery. Few studies reported baseline characteristics including cognition, frailty or comorbidities and none examined associations with functional recovery. CONCLUSION: There is inadequate data on functional recovery of older women following gynaeoncology surgery. Future studies are needed to identify factors associated with poorer/better outcomes. This may enable identification of opportunities for risk reduction, improve equity of access and better shared-decision making.

Retrospective Observational Study into the Early Causes of Death Following Surgery for NSCLC.

INTRODUCTION: Respiratory failure has historically been the major cause of mortality after elective lung resections. With improved intubation using fiber-optic scopes, better preoperative respiratory risk assessment, more advanced anesthetic single lung ventilation, and minimally invasive surgical technique, this may have changed. Our objective was to assess the main causes of mortality over the past 10 years in patients undergoing elective lung surgery in a major UK center. MATERIALS AND METHODS: A retrospective unit data search was made for all deaths during the 10-year period between January 2007 and December 2016 inclusive. All inpatient deaths within 30 days of an elective anatomical lung resection for lung malignancies were included. RESULTS: Three-thousand three-hundred sixteen lung resections for malignancy were performed in the 10-year period. There were 44 (1.3%) deaths during this period, 27 (61.4%) after open lobectomies, 8 (18.2%) after video-assisted thoracoscopic surgery lobectomies, 5 (11.4%) after sleeve lobectomies, and 4 (9%) after pneumonectomies. Causes of death included 24 (54.5%) respiratory failure, 10 (22.7%) ischemic bowel, 4 (9%) coronary events, 2 (4.5%) strokes, 2 (4.5%) on table hemorrhage, 1 (2.3%) massive pulmonary embolus, and 1 (2.3%) postoperative hemorrhage. CONCLUSION: Although respiratory failure is still a major cause of mortality in the postoperative patient, bowel ischemia has been found to be the second greatest cause of death. This study highlights the need to identify those at risk of this fatal complication during preoperative assessment and their postoperative management.

Preclinical pharmacology of FMPD [6-fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene]: a potential novel antipsychotic with lower histamine H1 receptor affinity than olanzapine.

FMPD [6-fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene] is a potential novel antipsychotic with high affinity for dopamine D2 (Ki= 6.3 nM), 5-HT(2A) (Ki= 7.3 nM), and 5-HT6 (Ki= 8.0 nM) human recombinant receptors and lower affinity for histamine H1 (Ki= 30 nM) and 5-HT2C (Ki= 102 nM) human recombinant receptors than olanzapine. Oral administration of FMPD increased rat nucleus accumbens 3,4-dihyroxyphenylacetic acid concentrations (ED200 = 6 mg/kg), blocked 5-HT2A agonist-induced increases in rat serum corticosterone levels (ED50= 1.8 mg/kg), and inhibited the ex vivo binding of [125I]SB-258585 [4-iodo-N-[4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-benzenesulfonamide] to striatal 5-HT6 receptors (ED50= 10 mg/kg) but failed to inhibit ex vivo binding of [3H]pyrilamine to hypothalamic histamine H1 receptors at doses of up to 30 mg/kg. In electrophysiology studies, acute administration of FMPD selectively elevated the number of spontaneously active A10 (versus A9) dopamine neurons and chronic administration selectively decreased the number of spontaneously active A10 (versus A9) dopamine neurons. FMPD did not produce catalepsy at doses lower than 25 mg/kg p.o. In Fos-induction studies, FMPD had an atypical antipsychotic profile in the striatum and nucleus accumbens and increased Fos expression in orexin-containing neurons of the hypothalamus. FMPD produced only a transient elevation of prolactin levels. These data indicate that FMPD is an orally available potent antagonist of dopamine D2, 5-HT2A, and 5-HT6 receptors and a weak antagonist of H1 and 5-HT2C receptors. FMPD has the potential to have efficacy in treating schizophrenia and bipolar mania with a low risk of treatment-emergent extrapyramidal symptoms, prolactin elevation, and weight gain. Clinical trials are needed to test these hypotheses.

Bicyclo[2.2.1]heptanes as novel triple re-uptake inhibitors for the treatment of depression.

A series of substituted naphthyl containing chiral [2.2.1] bicycloheptanes were prepared utilizing asymmetric Diels-Alder chemistry. This paper describes structure-activity relationships in this series. The N-methyl 2-naphthyl analogue (16d) and its des-methyl analogue (17d) are active triple re-uptake inhibitors both in vivo and in vitro.