Outcome of neoadjuvant treatment for pancreatic cancer in elderly patients: comparative, observational cohort study.

BACKGROUND: Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly. METHODS: This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70-74, 75 or more years) and respective treatment outcomes were compared. RESULTS: The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70-74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70-74 years, and 12 of 34 aged 75 years or more; P < 0.001). Resectability was similar among the three groups (60.0, 58.3, and 55.9 per cent respectively; P = 0.919). Trends towards shorter survival were observed in the elderly (median overall survival time 23.6, 18.0, and 17.6 months for patients aged less than 70, 70-74, and 75 or more years respectively; P = 0.090). After adjusting for co-variables, age was not a significant predictive factor. CONCLUSION: The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years.

Guiding the rational design of patient-centred drug trials in Cystic Fibrosis: A Delphi study.

BACKGROUND: Making trials more patient-centred improves recruitment and retention, patient satisfaction and makes research accessible to a more representative population. We aimed to understand the factors that influence participation and engagement in clinical trials in cystic fibrosis (CF) trials to guide the rational design and delivery of patient-centred trials. METHODS: We used a Delphi process, supported by extensive literature review and 3 workshops, to determine which factors stakeholders think exert significant influence in participation and engagement in CF trials. Panellists were recruited from across the UK and the study was administered online. RESULTS: We had representation from 19 CF centres; 28 people with CF (pwCF), 26 parents and 30 healthcare professionals (HCPs). Panels were presented with a shortlist of 104 factors and asked which they thought influence participation and engagement in CF trials. After 3 iterations, 43 statements met consensus for pwCF, 48 for the parents and 69 for the HCPs. CONCLUSIONS: We identified many targets to make trials more patient-centred. Whilst some require an overhaul of trial delivery, many are relatively easy to implement. We outline a list of 'dos and don'ts' for sponsors and research teams including: focus on good communication; recognise that lack of time is the greatest barrier to trial participation so minimise the frequency and length of visits; help participants fit trials around busy lives; remember trial participation can be a major life-event and support participants accordingly; and don't underestimate the impact of simple strategies e.g. on-site access to Wifi and cups of tea.

Photooxidation of hydrocarbons in the presence of aliphatic aldehydes.

A new group of gas-phase reactions have been shown to contribute to the photooxidation of hydrocarbons. The phtotooxidation of aliphatic aldehydes at wavelengths below 3400 angstroms produces intermediates that react with olefinic and aromatic hydrocarbons. Although the photooxidation rates are slower than those induced by nitrogen oxide, the rates are significant, considering the interest in urban atmospheric reactions. These results may indicate that the contro of nitrogen oxides alone may not effectively reduce photochemical air pollution.

Perceptual and physiological responses to the visual complexity of fractal patterns.

Fractals have experienced considerable success in quantifying the complex structure exhibited by many natural patterns and have captured the imagination of scientists and artists alike. With ever widening appeal, they have been referred to both as "fingerprints of nature" and "the new aesthetics." Our research has shown that the drip patterns of the American abstract painter Jackson Pollock are fractal. In this paper, we consider the implications of this discovery. We first present an overview of our research from the past five years to establish a context for our current investigations of human response to fractals. We discuss results showing that fractal images generated by mathematical, natural and human processes possess a shared aesthetic quality based on visual complexity. In particular, participants in visual perception tests display a preference for fractals with mid-range fractal dimensions. We also present recent preliminary work based on skin conductance measurements that indicate that these mid-range fractals also affect the observer's physiological condition and discuss future directions based on these results.

Symptoms are a poor indication of severity of reflux in Barrett's oesophagus

AIMS: Patients with Barrett's oesophagus have increased acid and duodenogastric reflux and impaired motility compared with non-Barrett's patients with reflux disease. Impaired sensitivity to acid infusion and distension have also been described, but the relationship of this visceral response to symptoms is unclear. A symptom index was used to compare Barrett's and non-Barrett's patients with reflux. METHODS: Patients with reflux (DeMeester score above 14) were studied with 24-h pH monitoring and manometry. An event marker recorded symptom events. An event was positive if it corresponded to a period greater than 10 s within 2 min either side of the drop in pH. The symptom index was calculated as the number of symptoms with pH less than 4/total number of symptoms x 100. RESULTS: Eighteen patients with Barrett's oesophagus were compared with 58 non-Barrett's patients with significant reflux. CONCLUSIONS: Patients with Barrett's oesophagus have a low symptom index compared with non-Barrett's patients with reflux disease. This occurs despite a near 100 per cent increase in acid exposure in the Barrett's group. Symptoms are thus no guide to the severity of reflux in patients with Barrett's oesophagus. Proof of efficacy of therapeutic modalities may need physiological rather than symptom-based confirmation.

Ocular findings associated with encephalomyelitis caused by Herpesvirus simiae.

A 29-year-old monkey handler developed acute encephalomyelitis with serological evidence of Herpesvirus simiae infection. He had sudden unilateral loss of vision on the 32nd day of illness caused by vitreous hemorrhage. This cleared gradually, revealing chorioretinal scarring and a gliovascular vitreous band which eventually caused local tractional retinal detachment.

In vitro studies on 6-fluoronoradrenaline at several peripheral sympathetic neuroeffector junctions.

A comparison of the effects of noradrenaline and 6-fluoronoradrenaline has been made at several peripheral sympathetic neuroeffector junctions. In the rat vas deferens preparation in the presence of 1 microM cocaine, 6-fluoronoradrenaline was found to be about 9 times more potent than noradrenaline as an agonist at presynaptic inhibitory alpha 2- adrenoceptors. In the rabbit aorta, 6-fluoronoradrenaline had approximately one tenth of the potency of noradrenaline in stimulating the postsynaptic alpha 1-adrenoceptors. Furthermore 6-fluoronoradrenaline, in contrast to previous reports, appears to be a substrate for the neuronal uptake process since exposure to cocaine potentiated the inhibition of the twitch response of the vas deferens by 6-fluoronoradrenaline. In addition, 6-fluoronoradrenaline increased the spontaneous outflow of radioactivity from rabbit pulmonary artery strips prelabelled with 3H-noradrenaline and this increase was blocked by cocaine (30 microM). These results demonstrate that 6-fluoronoradrenaline is a preferential alpha 2-adrenoceptor agonist which is a substrate for the neuronal uptake process in peripheral sympathetically innervated smooth muscle preparations.

Nuclear magnetic resonance analysis of methotrimeprazine (levomepromazine) hydroxylation in humans.

Two monohydroxylated metabolites of methotrimeprazine (levomepromazine), which previously have been identified in plasma and urine from psychiatric patients, were synthesized by nonenzymatic, FeCl2-catalyzed oxidation, isolated, and purified by preparative reversed-phase HPLC. Mass spectrometric analysis gave identical spectra for the two compounds, but did not reveal the positions of the OH groups. However, 1H NMR spectroscopy at 200 MHz demonstrated that one of the compounds, which had the shortest GC retention time on an OV-17 column, was hydroxylated in the 3-position on the phenothiazine nucleus, and that the other derivative was hydroxylated in the 7-position. The metabolism of methotrimeprazine differs, therefore, from that of its congener chlorpromazine, which is hydroxylated mainly in the 7-position in humans.

The somatic patient.

A significant proportion of patients seen in the Emergency Department will present with somatic complaints for which there is no apparent physiologic cause. Such patients may be divided into two broad categories: (1) those with symptoms and signs consciously synthesized by the patient, either for obvious secondary gain (malingering) or as a result of more subtle and complex motivations (factitious disorders); and (2) those patients with symptoms that are the unconscious expression of psychological stress (somatoform disorders). The somatoform disorders include (1) somatization disorder (characterized by a chronic history of numerous and widely divergent somatic complaints), (2) psychogenic pain disorder (somatization expressed in terms of persistent pain), (3) hypochondriasis (a conviction that one is diseased and disabled in conjunction with a well-focused constellation of supporting symptoms), and (4) conversion disorder (a single, usually nonpainful neurologic symptom, often with identifiable coping value for the patient). The first three disorders have been aggregately termed the "common somatization syndrome." Management of the somatically focused patient includes the communication of a caring attitude to the patient in conjunction with a cautious and diligent search for treatable medical or psychiatric illness. Resocialization and development of patient links with ongoing, nurturing nonmedical as well as medical support systems is of benefit.

Nonsurgical and extraperitoneal causes of abdominal pain.

Most patients presenting to the emergency department with acute abdominal pain suffer from disorders requiring other than surgical intervention. Unnecessary morbidity may be avoided through understanding the anatomic and physiologic variables involved in producing abdominal pain. Table 1 lists conditions that may simulate an acute surgical abdomen. Selected disorders were discussed.

Accuracy of the tongue blade test in patients with suspected mandibular fracture.

The inter-observer reliability and accuracy of the tongue blade test (TBT) for the identification of patients with mandibular fracture was prospectively evaluated using radiographic diagnosis as the gold standard. A consecutive sample of 110 patients presenting to the emergency department of a teaching county hospital was studied. Patients with uninterpretable x-rays, known diagnosis of mandibular fracture, or inability to cooperate for the test were excluded. Bilateral ability to crack a wooden tongue blade held between the teeth was scored as a negative test. Fifty-three patients had mandibular fractures. In the study group, the TBT had a sensitivity of 95.7%; a specificity of 63.5%; a positive predictive value of 66.2%; a negative predictive value of 95.2%; and an accuracy of 77.3%. The TBT provided contributory evidence useful in screening patients for mandibular fracture.

Necrotizing fasciitis in the pediatric age group: report of a case.

Necrotizing fasciitis is a rapidly progressive invasive soft tissue infection that is rarely seen in the pediatric population. In the majority of cases described in the medical literature, there has been an identifiable initiating event such as instrumentation or other trauma to the skin. Because of the rapid progression of the infection, the key to a successful outcome is early recognition and rapid initiation of definitive surgical management. A case is presented in which necrotizing fasciitis was seen in a child with no precipitating skin trauma.

Static splinting of extensor tendon repairs.

In a prospective review we assessed the results of extensor tendon injuries managed postoperatively with a static splint. Thirty-three patients with 44 injured digits were assessed 4 months after primary tendon repair, using the Strickland-Glogovac criteria. Patients were managed in a static splint, the duration of which was guided by the zone of injury. Four months after repair, excellent or good results were obtained in 95%. Overall it was found that static splinting was an effective and safe method of management after extensor tendon repair.

Production of a recombinant bovine enterokinase catalytic subunit in the methylotrophic yeast Pichia pastoris.

We describe the heterologous expression of a 26.3 kD protein containing the catalytic domain of bovine enterokinase (EKL) in the methylotrophic yeast Pichia pastoris. A highly active protein is secreted and glycosylated, and it has the native amino-terminus of EKL. The cDNA encoding EKL was cloned with the KEX2 protease cleavage site following the alpha mating factor prepro secretion signal from Saccharomyces cerevisiae. The secreted EKL was easily purified from the few native proteins found in the P. pastoris fermentation supernatant, using ion exchange and affinity chromatography. The yield of the purified EKL was 6.3 mg per liter of fermentation culture. This is significantly higher than previous reports of expressions in E. coli and COS cells. The ability of this highly specific protease to cleave immediately after the carboxyl-terminal residue of the (Asp)4-Lys recognition sequence allows regeneration of native amino-terminal residues of recombinant proteins. Its application is demonstrated by the removal of thioredoxin (TrxA), and polyhistidine fusion partners from proteins of interest.

Comparison of bursting pressure after scleral tunnel incision sealed with sutures or an adherent ocular bandage in human globes.

OBJECTIVE: To evaluate the efficiency of a hydrogel adherent ocular bandage for sealing of scleral tunnel incisions in human eye globes. METHODS: A 4-mm scleral tunnel incision was made in each of 10 globes and bursting pressure was measured using the Seidel test to check for wound leakage. Globes were sealed using either two interrupted 10-0 nylon sutures (n = 5) or an adherent ocular bandage in the form of polyethylene glycol hydrogel (n = 5). Bursting pressure was then measured for a second time. RESULTS: Bursting pressure was significantly higher after wound sealing in both groups. There were no statistically significant differences in bursting pressure between the two groups before or after sealing. CONCLUSIONS: The adherent ocular bandage successfully protected the incision in ex vivo human globes immediately after surgery, with a sealing efficiency comparable to two nylon sutures, suggesting that it is a safe and effective alternative to conventional suturing.