Search

Background Although interest in frailty has expanded among cardiology experts over the past 2 decades, its integration, as part of cardiovascular disease management, is still lacking, above all in the acute cardiac care setting. The Clinical Frailty Scale (CFS) is a brief guided tool to assess frailty in hospital settings without specialist equipment. Purpose Our objective was to test the performance of the CFS in an older, unselected population, admitted to an Intensive Cardiac Care Unit (ICCU) during the year 2019. Methods The study sample included 431 patients ≥65 years old, admitted to an ICCU of a tertiary cardiac center in Italy. The CFS ranged from “very fit: 1” to “terminally ill: 9”, but it was considered present at a score ≥5. Our primary endpoint was defined by a combination of severe complications requiring critical care and in-hospital death. The data were collected from the hospital discharge summary and the electronic chart records. Results 158 patients (36.7%) were frail. These individuals had greater comorbidity and higher in-hospital mortality (Table 1). After a multivariable logistic regression analysis, 4 predictors were identified: signs of congestive heart failure (OR: 8.51, 95% Confidence Interval-CI: 4.63–14.6; p Conclusions The CFS is a simple guided frailty tool that may enhance outcome prediction in the acute cardiac care setting. These findings merit evaluation in larger cohorts of unselected patients. Funding Acknowledgement Type of funding sources: None.

Background: In late 2012, Hurricane Sandy struck the eastern United States. Healthcare infrastructure in New York City—including long-term care facilities (LTCFs)—was affected significantly. The authors examined the impact of the storm on LTCFs 2 years after the event, using a qualitative approach consisting of a semistructured interview focused on preparedness and response. Important insights regarding preparedness and response may be lost by quantitative analysis or outcome measurement alone. During Sandy, individuals at LTCFs experienced the event in important subjective ways that, in aggregate, could lead to valuable insights about how facilities might mitigate future risks. The authors used data from a semistructured interview to generate hypotheses regarding the preparation and response of LTCFs. The interview tool was designed to help develop theories to explain why LTCF staff and administrators experienced the event in the way they did, and to use that data to inform future policy and research. Methods: Representatives from LTCFs located in a heavily affected area of New York City were approached for participation in a semistructured interview. Interviews were digitally recorded and transcribed. Recurrent themes were coded based on time period (before, during, or after the storm) and content. A grounded theory approach was used to identify important themes related to the participants’ experiences.Results: A total of 21 interviews were conducted. Several overarching themes were identified, including a perception that facilities had not prepared for an event of such magnitude, of inefficient communication and logistics during evacuation, and of lack of easily identifiable or appropriate resources after the event. Access to electrical power emerged as a key identifier of recovery for most facilities. The experience had a substantial psychological impact on LTCF staff regardless of whether they evacuated or sheltered in place during the storm.Conclusion: Representatives from LTCFs affected by Sandy experienced the preparation, response, and recovery phases of the event with a unique perspective. Their insights offer evidence which can be used to generate testable hypothesis regarding similar events in the future, and can inform policy makers and facility administrators alike as they prepare for extreme weather events in similar settings. Results specifically suggest that LTCFs develop plans which carefully address the unique qualities of extreme weather events, including communication with local officials, evacuation and transfer needs in geographic areas with multiple facilities, and plans for the safe transfer of residents. Emergency managers at LTCFs should consider electrical power needs with the understanding that in extreme weather events, power failures can be more protracted than in other types of emergencies.

Background The relevance of laparoscopic resection of intrahepatic cholangiocarcinoma (ICC) remains debated. The aim of this study was to compare laparoscopic (LLR) and open (OLR) liver resection for ICC, with specific focus on textbook outcome and lymph node dissection (LND). Methods Patients undergoing LLR or OLR for ICC were included from two French, nationwide hepatopancreatobiliary surveys undertaken between 2000 and 2017. Patients with negative margins, and without transfusion, severe complications, prolonged hospital stay, readmission or death were considered to have a textbook outcome. Patients who achieved both a textbook outcome and LND were deemed to have an adjusted textbook outcome. OLR and LLR were compared after propensity score matching. Results In total, 548 patients with ICC (127 LLR, 421 OLR) were included. Textbook-outcome and LND completion rates were 22.1 and 48.2 per cent respectively. LLR was independently associated with a decreased rate of LND (odds ratio 0.37, 95 per cent c.i. 0.20 to 0.69). After matching, 109 patients remained in each group. LLR was associated with a decreased rate of transfusion (7.3 versus 21.1 per cent; P = 0.001) and shorter hospital stay (median 7 versus 14 days; P = 0.001), but lower rate of LND (33.9 versus 73.4 per cent; P = 0.001). Patients who underwent LLR had lower rate of adjusted TO completion than patients who had OLR (6.5 versus 17.4 per cent; P = 0.012). Conclusion The laparoscopic approach did not substantially improve quality of care of patients with resectable ICC.

Background & Aims Herein, we aimed to establish benchmark values – based on a composite indicator of healthcare quality – for the performance of laparoscopic left lateral sectionectomy (LLLS) and laparoscopic right hepatectomy (LRH) using data from expert centers. Methods Data from a nationwide multicenter survey including all patients undergoing LLLS and LRH between 2000 and 2017 were analyzed. Textbook outcome (TO) completion was considered in patients fulfilling all 6 of the following characteristics: negative margins, no transfusion, no complication, no prolonged hospital stay, no readmission and no mortality. For each procedure, a cut-off laparoscopic liver resection (LLR) volume by center was associated with TO on multivariable analysis. These cut-offs defined the expert centers. The benchmark values were set at the 75th percentile of median outcomes among these expert centers. Results Among 4,400 LLRs performed in 29 centers, 855 patients who underwent LLLS and 488 who underwent LRH were identified. The overall incidences of TO after LLLS and LRH were 43.7% and 23.8%, respectively. LLR volume cut-offs of 25 LLR/year (odds ratio [OR] 2.45; bootstrap 95% CI 1.65–3.69; p = 0.001) and 35 LLR/year (OR 2.55; bootstrap 95% CI 1.34–5.63; p = 0.003) were independently associated with completion of TO after LLLS and LRH, respectively. Eight centers for LLLS and 6 centers for LRH, including 516 and 346 patients undergoing LLLS/LRH respectively, reached these cut-offs and were identified as expert centers. After LLLS, benchmark values of severe complication, mortality and TO completion were defined as ≤5.3%, ≤1.2% and ≥46.6%, respectively. After LRH, benchmark values of severe complication, mortality and TO completion were ≤20.4%, ≤2.8% and ≥24.2%, respectively. Conclusions This study provides an up-to-date reference on the benchmark performance of LLLS and LRH in expert centers. Lay summary In a nationwide French survey of laparoscopic liver resection, expert centers were defined according to the completion of a textbook outcome, which is a composite indicator of healthcare quality. Benchmark values regarding intra-operative details and outcomes were established using data from 516 patients with laparoscopic left lateral sectionectiomy and 346 patients with laparoscopic right hepatectomy from expert centers. These values should be used as a reference point to improve the quality of laparoscopic resections.

The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study.This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection.Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010).Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección.Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), has debilitating long-term effects on infants and children with this condition. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to improve nutritional independence. Here we report a robust protocol for reconstruction of autologous intestinal mucosal grafts using primary IF patient materials. Human jejunal intestinal organoids derived from paediatric IF patients can be expanded efficiently in vitro with region-specific markers preserved after long-term culture. Decellularized human intestinal matrix with intact ultrastructure is used as biological scaffolds. Proteomic and Raman spectroscopic analyses reveal highly analogous biochemical composition of decellularized human SI and colon matrix, implying that they can both be utilised as scaffolds for jejunal graft reconstruction. Indeed, seeding of primary human jejunal organoids to either SI or colonic scaffolds in vitro can efficiently reconstruct functional jejunal grafts with persistent disaccharidase activity as early as 4 days after seeding, which can further survive and mature after transplantation in vivo. Our findings pave the way towards regenerative medicine for IF patients.

Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children1. The priority of patient care is to increase the length of functional intestine, particularly the jejunum, to promote nutritional independence2. Here we construct autologous jejunal mucosal grafts using biomaterials from pediatric patients and show that patient-derived organoids can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which forms biological scaffolds. Proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human small intestine and colon scaffolds, indicating that they can be used interchangeably as platforms for intestinal engineering. Indeed, seeding of jejunal organoids onto either type of scaffold reliably reconstructs grafts that exhibit several aspects of physiological jejunal function and that survive to form luminal structures after transplantation into the kidney capsule or subcutaneous pockets of mice for up to 2 weeks. Our findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with intestinal failure, ultimately aiding in the restoration of nutritional autonomy.

Liver transplantation remains the treatment of choice for patients with end-stage liver disease. However, allograft availability continues to be a problem, and extending the criteria for organ acceptance is key. Deceased donors after electrical accidents, as well as electricity-traumatized allografts, are not common but should be considered suitable. This study describes 2 cases of heart-beating organ donors with electrical injury to the liver. In 1 case, the electric shock was the cause of death; in the second case, the injury was caused by defibrillation at organ procurement. Both allografts had sustained sizeable electrical injury, and both resulted in excellent early posttransplant outcomes. These cases demonstrate that electrocution is not a contraindication to donation and that electricity-traumatized allografts may remain transplantable after careful assessment. Education of all staff in the management of such donors can optimize utility of such allografts.

Summary Background Effects of frequent nocturnal symptoms of gastro-oesophageal reflux disease (GERD-FNS) on health-related quality of life (HRQOL) and work productivity are not well documented. Aim To assess symptom severity, production loss, and HRQOL among employed adults with and without GERD-FNS. Methods Using several validated outcome measures in a web survey design, GERD was pre-specified as GERD Symptom and Medication Questionnaire score >9, and ≥1 episode of heartburn or acid regurgitation during the preceding week. GERD-FNS patients were those reporting ≥2 symptom-nights during the previous week; their outcomes were compared with those of patients having minimal or no nocturnal symptoms (GERD-NNS) and vs. non-GERD controls. Results Data were collected from 1002 GERD patients (476 GERD-FNS, 526 GERD-NNS) and 513 controls. Severe symptoms were more common, sleep abnormalities were more frequent (P

Introduction Postoperative delirium can be a serious consequence of major surgery, associated with longer hospital stays, readmission, cognitive and functional deterioration and mortality. Delirium is an acute, reversible disorder characterised by fluctuating course, inattention, disorganised thinking and altered level of consciousness. Delirium occurring in the hours immediately following anaesthesia and delirium occurring in the postoperative period of 1–5 days have been described as distinct clinical entities. This protocol describes an observational study with the aim of determining if delirium in the first hour following tracheal tube removal is a predictor of delirium in the 5 subsequent postoperative days. Improved understanding regarding the development of postoperative delirium would improve patient care and allow more effective implementation of delirium prevention measures. Methods and analysis Patients enrolled to the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomised controlled trial will be eligible for this substudy. A validated delirium assessment method, the 3-min Diagnostic Confusion Assessment Method and the Richmond Agitation and Sedation Scale will be used to assess 100 patients for delirium at 30 min and 60 min following tracheal tube removal. Patients will also be assessed for delirium over postoperative days 1–5 using three validated methods, the Confusion Assessment Method (CAM), CAM for the Intensive Care Unit and structured chart review. Logistic regression analysis will then be performed to test whether immediately postoperative delirium independently predicts subsequent postoperative delirium. Ethics and dissemination This observational substudy of ENGAGES has been approved by the ethics board of Washington University School of Medicine. Enrolment began in June 2016 and will continue until June 2017. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration number NCT02241655.

We report an unusual case of an isolated, large, thrombosed hypogastric artery aneurysm presenting as a voluminous pelvic mass with bilateral hydroureteronephrosis. The patient underwent successful surgical removal of the mass. Histology confirmed an aneurysm of the left hypogastric artery.

6Boehnnger Mannheim, Italv Summary Background: Early clinical trials have suggested that glutathione (GSH) offers protection from the toxic effects of cisplatin. Patients and methods: One hundred fifty-one patients with ovarian cancer (stage I-IV) were evaluated in a clinical trial of cisplatin (CDDP) ± glutathione (GSH). The objective was to determine whether GSH would enhance the feasibility of giving six cycles of CDDP at 100 mg/m2 without dose reduction due to toxicity. Results: When considering the proportion of patients receiving six courses of CDDP at any dose, GSH produced a significant advantage over control - 58% versus 39%, (P = 0.04). For these patients there was a significant difference between the reduction in creatinine clearance for GSH treated patients compared with control - 74% versus 62% (P = 0.006). Quality of life scores demonstrated that for patients receiving GSH there was a statistically significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As an indication of overall activity, these patients were statistically significantly more able to undertake housekeeping and shopping. Clinically assessed response to treatment demonstrated a trend towards a better outcome in the GSH group (73% versus 62%) but this was not statistically significant (P = 0.25). Conclusions: The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient's quality of life is improved.

Introduction Human hematopoietic stem cell transplantation (HSCT) has been used to treat a range of hematological and immunological disorders. As a result, the demand for hematopoietic stem cells (HSC) in clinical applications is increasing. Amniotic fluid stem cells (AFSC) serve as a potential alternative cell source for therapy. Amniotic fluid can be derived by amniocentesis or therapeutic amniodrainage. AFSC are multi-potent, have low risk of tumorigenicity, can be expanded and do not have legal or ethical limitations. The significant hematopoietic activity of murine AFSC led us to explore the potential of human AFSC (CD117/c-Kit+) towards hematopoietic differentiation and to reconstitution in vivo. Methods Human AFSC (2nd and 3rd trimester) and cord blood HSC (CB-HSC; control) were selected for CD117 and CD34 respectively using a MoFlo XDP sorter. Sorted cells (104 in 200μl PBS) were injected intravenously into sub-lethally irradiated NOD-SCID/IL2rγnull (NSG) mice (n=6/group). Hematopoietic engraftment of human cells (% of human CD45+ within total CD45+) and multi-lineage reconstitution (myeloid: CD13, CD14, CD15 and lymphoid: CD3, CD4 and CD8) were assessed at 16 weeks in blood, bone marrow (BM) and spleen by flow cytometry. For subsequent secondary transplants, BM mononuclear cells (MNC) derived from BM harvested from primary recipients of mice were intravenously injected into secondary recipients (1.5x107 MNC in 200μl PBS). Hematopoietic engraftment was assessed at 16 weeks post-transplantation (n=6/group). For further analysis of human donor cell engraftment, Q-PCR was performed on spleen samples harvested from primary and secondary recipients using oligonucleotide primers specific for human ALU repeat sequences; Immunohistochemistry was carried out using anti-human CD45 antibody and detected with a commercially available kit (Dako EnVision Plus, Dako). Results are expressed as mean±SEM, and statistical analysis was performed using 1-way ANOVA with Bonferroni post-hoc tests. Results Human AFSC engrafted the hematopoietic system of NSG mice at levels similar to the ones achieved with CB-HSC (blood: AFSC 7.5±1.3% vs. CB-HSC 6.1±2.2%, p=0.6; BM: AFSC 46.3±7.9% vs. CB-HSC 38.3±8.2%, p=0.6; spleen: AFSC 39.6±9.3% vs. CB-HSC 34.7±10.5%, p=0.7). Similarly, at 16 weeks following secondary transplantation, human donor cell engraftment was comparable between groups in blood (AFSC 11.5 ± 3.9% vs. CB-HSC 16.9 ± 3.9%, p=0.3) and other hematopoietic tissues. Q-PCR and immunohistochemistry confirmed donor cell engraftment in AFSC and CB-HSC groups. Importantly, there were no differences between groups in multi-lineage differentiation at 16 weeks post primary and secondary transplantation. Conclusion Human CD117/c-Kit+ AFSC have functional, multi-lineage hematopoietic potential that is similar to the current "gold-standard" stem cell source for hematopoietic transplantation. The ease of isolation during early gestation, as well as their gene-engineering and expansion potential make human AFSC a novel autologous fetal cell source for pre- and post-natal therapy of inherited hematological disorders. Disclosures No relevant conflicts of interest to declare.

Introduction Castleman's disease (CD) is a rare benign disorder that may grow in any area where lymphoid tissue is normally present but the most frequent site is mediastinum (67%); the abdomen is rarely affected by this pathology. In the pathogenesis of CD an important role could be played by HHV-8. Diagnosis is difficult and the diagnostic certainty is obtained only by histological examination. For this disease there is no gold-standard treatment. Case report We report the case of a woman of 33 years of age affected by a rare form of abdominal nodal localization of Castleman's Disease for which the patient underwent surgery. Conclusion CD must be included in the differential diagnosis of retroperitoneal tumors even though the definitive diagnosis can only be achieved by histological and immunohistochemical examination. In the case of single location, the treatment of choice is surgical removal.

A low-IF very compact low power quadrature receiver for ZigBee applications is presented. The receiver saves area and power with a quadrature self oscillating mixer based on high Q bond-wire inductors. The prototype, integrated in CMOS 90 nm, provides 76 dB of maximum voltage gain, with a 10 dB noise figure, an IIP3 of -13 dBm and a phase noise of -124 dBc/Hz @ 3.5 MHz with an active area of only 0.23 mm2 and a power consumption of 3.6 mW (including the baseband complex filter).

In the design of a single chip for wireless-sensor-network and WPAN applications (e.g., IEEE 802.15.4), the receiver sensitivity is generally sacrificed in favor of a vanishing power consumption and a low-cost solution. There is a trade off between these two requirements, as the use of resonant loads offers high power efficiency while an inductor-free approach saves die area resulting in a cheaper design. Since an LC-oscillator topology is mandatory to achieve a minimal current draw, the reduction of the number of coils has to be done in the LNA, the mixer and the quadrature generator. In this work, starting from the LNA-Mixer and VCO (LMV) cell topology, a single-coil low-power receiver shares the bias current among all the RF blocks of the analog front-end. The receiver prototype chip consumes 3.6mW and has an active die area of 0.35mm2. It is based on a low-IF architecture and includes a baseband variable-gain complex filter for channel selection.

Pralatrexate is a second generation antifolate that targets dihydrofolate reductase. It was found to have a higher affinity to reduced folate carrier type 1 (RFC-1), the primary folate transporter, and has high intracellular retention via enhanced polyglutamylation. Mucositis, rather than bone marrow toxicity, is the dose limiting toxicity (DLT) in patients. In this study, we examine whether the use of leucovorin (folinic acid) can reduce pralatrexate DLT when used in mouse xenografts, and possibly enable high dose pralatrexate treatment. Nude mice bearing H2052 mesothelioma xenografts were treated with pralatrexate at normal and toxic doses with or without leucovorin administration 24 hours later. Tumors were measured three times weekly and toxicity monitored through weight loss. Leucovorin was found to abrogate pralatrexate toxicities at high doses without sacrificing efficacy. These results demonstrate that high dose pralatrexate with subsequent leucovorin rescue may be a viable treatment strategy in mesothelioma and other cancers. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A266. Citation Format: Philip M. Tedeschi, Iqra Farooqi, Yamini Kathari, Joseph R. Bertino. Leucovorin rescue of high dose pralatrexate in mesothelioma xenografts. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A266.

As the debate about research on foetal tissue transplantation progressed, medical scientists learned more about the procedure and its potential for helping persons with degenerative brain disorders such as Parkinson's disease. Increased scientific knowledge significantly influenced the political process, yet it did not by any means resolve the debate. Rather, increased medical evidence served as a lens which focused discourse on particular issues related to foetal research, such as the details of obtaining informed consent, as well as technical matters related to tissue transplantation, for example, that the creation of a tissue bank was unreasonable, and that foetuses of certain ages were required for the procedure. This increased focus changed the character of the debate on foetal tissue transplantation research, and convinced some law-makers that they should encourage financial support for the research despite their anti-abortion political views.

The bioequivalence of two megestrol acetate formulations, 160-mg "tablets" and 160-mg "sachets," was investigated in a single-dose, open-label, balanced-for-sequence cross-over study involving 12 advanced-cancer patients. The observed plasma megestrol-acetate time course obtained with both formulations was consistent with the literature data. The main source of variability in the pharmacokinetic parameters was intersubject variability; drug formulation played only a minor (and nonsignificant) role. The width of the 90% confidence interval of the area-under-the-curve (AUC) ratio (sachets: tablets) computed according to Schuirmann (0.9-1.4) was mainly due to the presence of a single outlier, showing an AUC ratio of 2.7. The trend to higher bioavailability of the new formulation was not significant, especially as compared with the dose-response data reported in the literature.

Megestrol acetate (MA) was reported to induce weight gain and increase of appetite in cancer patients. Methods Out-patients of the “Divisione Terapia del Dolore” of the “Istituto Nazionale per la Cura dei Tumori” (Milano) with advanced non hormone-responsive tumors and loss or absence of appetite, who didn’t assume any corticosteroid were randomized for a Phase III trial, that consisted of two consecutive phases: a double-blind placebo controlled phase of 14 days (phase A) and an open phase of 76 days (phase B). During phase A patients were treated with MA 2 tablets × 160 mg/day (a low dose for this indication) or placebo. In phase B all patients received different dosages of MA according to the response to treatment. A patient was considered responsive if his appetite, evaluated by means of a categoric-numeric scale, increased by 2 or more points. Other parameters investigated were: food intake, body weight, Perfonnance Status (Karnofsky), mood state (POMS) and pain. Results Forty-two patients were enrolled in this trial. Thirty-three patients were evaluable for efficacy: 13/16 MA patients were responsive for appetite vs 5/17 placebo patients. This result is clinically and statistically significant ( P Conclusions MA showed a remarkable effect on appetite with a low dose (2 tablets × 160 mg/die) already after 14 days, without side-effects of relief. This result is of great importance considering the relevance of the quality of life and the low life expectancy of these patients and the low daily therapy costs of this treatment.

Carotid angiography showed a lesion in more than two-thirds of this series of ischaemic carotid strokes; two-thirds of the lesions shown were in the neck vessels. Carotid narrowing (incomplete occlusion) in the neck was much commoner after the age of 50 years and was frequently associated wth a temporary stroke. Complete carotid occlusion in the neck did not become commoner with increasing age as did carotid narrowing; nor was it associated with previous temporary strokes (as was carotid narrowing). It is therefore doubtful whether complete occlusion is usually the end-result of narrowing. Persisting strokes were frequently preceded by one or more temporary strokes; these ‘warning strokes’ were more frequent in patients with carotid narrowing. Middle cerebral artery lesions accounted for two-thirds of all intracranial lesions; they were particularly common in association with pregnancy and rarely caused temporary strokes.

Purpose To investigate the ability of leucovorin (LV) to abrogate dose-limiting toxicities of pralatrexate (PDX) while maintaining efficacy, in vivo. Methods H2052 mesothelioma cells were treated with the antifolates methotrexate (MTX), PDX and pemetrexed, with and without LV rescue 24 h later. Cell killing was evaluated 48 h later. Female nude mice bearing H2052 xenografts were treated with varying doses and schedules of the antifolate PDX and LV. Results In vitro, H2052 cells were more sensitive to PDX as compared to MTX and pemetrexed. Administration of LV 24 h after antifolate treatment reduced efficacy of antifolates MTX and pemetrexed, but not PDX. In vivo, LV was found to reduce toxicity of PDX at the maximum tolerated dose without sacrificing efficacy. Lethal doses of PDX were rescued by LV, and mice bearing the H2052 tumor demonstrated prolonged and enhanced tumor regression. Conclusions High-dose PDX with subsequent LV rescue may be a viable treatment strategy in mesothelioma and other cancers. The inclusion of LV rescue into new and existing PDX treatment protocols should be explored as a way to expand the tolerability and effectiveness of PDX in the clinic.

Clinical and biochemical hormonal changes observed in a 27-year-old man with Cushing's syndrome treated by implantation of the pituitary with yttrium90 are reported. Eight months after implantation a complete clinical regression of the syndrome was obtained. Hormonal determinations indicated relative adrenal insufficiency, whereas thyroidal and gonadal functions werenormal.

The mode circulation time was measured using intravenously injected technetium 99(m) and a collimation system devised to discriminate between the right and left sides of the head. The results in 21 normal men were used as a basis of assessing the findings in 205 patients, made up of five diagnostic groups (ischaemia, haematoma, subarachnoid haemorrhage, intracranial tumour, and head injury). The average mode circulation time in the affected hemisphere for the three groups with vascular disease was increased, but even in these groups half the patients had a mode circulation time within 1 SD of normal mean; similar results were found for asymmetry between the hemispheres. In serial measurements in 45 patients no correlation was found between change in mode circulation time and the clinical state. That so many results are within the normal range limits the value of this method.

e11073 Background: NCT has been shown to improve disease-free and overall survival in BC patients. Predictive markers of therapeutic response need to be carefully studied in order to distinguish sp...