Variation in hospital mortality after pancreatoduodenectomy is related to failure to rescue rather than major complications: a nationwide audit

Background

In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low- and high-mortality hospitals are compared, and independent predictors for FTR investigated.

Impact of borderline personality disorder traits on the association between age and health-related quality of life: A cohort study in the general population

BackgroundIncreasing age as well as borderline personality pathology are associated with a lower level of health-related quality of life (HR-QoL). Our objective was to investigate whether the presence of borderline personality traits modifies the association between age and HR-QoL in the general population.MethodsCross-sectional data from 5,303 respondents (aged 21–72 years) of the Netherlands Mental Health Survey and Incidence Study-2 were analyzed. Borderline personality traits were assessed with the International Personality Disorder Examination questionnaire. Mental and physical HR-QoL were measured with the Medical Outcomes Study Short Form Health Survey. Multiple linear regression analysis was used to examine the association of borderline personality traits, age and their interaction on mental as well as physical HR-QoL, adjusted for demographic variables as well as somatic and mental disorders.ResultsA total of 1,520 (28.7%) respondents reported one or more borderline personality traits of which 58 (1.1%) reported five or more indicative of a borderline personality disorder. A higher age was associated with lower physical HR-QoL. This negative association became significantly stronger in the presence of borderline personality traits. The association between increasing age and mental HR-QoL was positive in the absence of borderline personality traits and negative in the presence of borderline personality traits.ConclusionBorderline personality traits negatively interfere with the association between age and HR-QoL irrespective of somatic and mental disorders. Attention of clinicians and researchers for subthreshold borderline personality pathology is needed in middle-aged and older persons.     

E-selectin and very late activation antigen-4 mediate adhesion of hematopoietic progenitor cells to bone marrow endothelium

 Adhesion of CD34⁺ hematopoietic progenitor cells (HPCs) to sinusoidal endothelium probably plays a key role in homing of transplanted CD34⁺ HPCs to the bone marrow (BM). We have investigated the role of various adhesion molecules in the interaction of purified CD34⁺ HPCs derived from BM or peripheral blood (PB) and a human BM-derived endothelial cell line. Adhesion of CD34⁺ HPCs to endothelial cells was measured with the use of a double-color flow microfluorimetric adhesion assay. In this assay, adhesion is measured under stirring conditions, simulating blood flow in sinusoidal marrow vessels. Adhesion of PB CD34⁺ cells to human BM endothelial cells (HBMECs) was observed only after interleukin (IL)-1β prestimulation of the endothelial cells. This adhesion was strongly increased after addition of phorbol-myristate acetate (PMA). Adhesion of PB CD34⁺ cells to IL-1β-prestimulated HBMECs was inhibited by blocking monoclonal antibodies (mAbs) against E-selectin and by neuraminidase treatment of the PB CD34⁺ cells. mAbs against very late activation antigen (VLA)-4 inhibited adhesion only when the E-selectin-mediated interaction was prevented. No clear inhibiting effect was found with blocking mAbs against β₂-integrins. Stimulation with the β₁-integrin-activating mAb, 8A2, induced adhesion of CD34⁺ cells to endothelial cells. In conclusion, stimulation of both endothelial cells and CD34⁺ HPCs is necessary for adhesion of CD34⁺ HPCs to endothelial cells. We furthermore demonstrated that E-selectin and VLA-4 mediated this adhesion. Received: 26 April 1999 / Accepted: 8 February 2000     

Islet and beta cell volumes in offspring of severely diabetic (ketotic) chinese hamsters

Summary Chinese hamsters bred at the Upjohn Laboratory were studied at varying ages from 15 days to 19 months. Diabetic animals three to six months and those 10 to 19 months of age were glycosuric and hyper glycemic; there was ketonuria and ketonemia but blood glycerol and fasting plasma insulin levels were low when these values were compared with normal control animals of comparable ages. Using quantitative technics developed in our laboratory, the volumes of islets, beta cells and beta granules were diminished. The increase in volume of nongranular cells is progressive with duration of diabetes. Glycogen infiltration was observed in beta cells of these diabetic animals. — Although offspring (fifteen-day-old weanlings) of the mating of two severely diabetic (ketotic) animals were normoglycemic and glycosurie, their plasma insulin levels were higher than those of their controls. The islet volume was somewhat higher than that of the controls but the beta cells were degranulated both by light and electron microscopy; the beta cells exhibited glycogen infiltration. These results are consistent with the thesis that the primary defect is in insulin biosynthesis.

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Insel- und B-Zell-Volumen im Pankreas von Nachkommen schwer diabetischer chinesischer Hamster

Zusammenfassung Mit von den Autoren entwickelten morphometrischen Methoden wurde das B-Zell-Volumen im Pankreas chinesischer Hamster der Upjohn Kolonie bestimmt. Das Alter der untersuchten Tiere schwankte zwischen 15 Tagen und 19 Monaten. Die diabetischen Tiere waren entweder 3 – 6 oder 10–19 Monate alt. Sie waren hyperglykämisch und glykosurisch, teilweise bestand Ketonurie. Die Plasmainsulin- und Glyzerin-Konzentrationen im Gesamtblut waren niedriger als diejenigen gleichaltriger Normaltieren erniedrigt. Bei diabetisehen Tieren waren B-Zell- und-Granula-Volumen vermindert. Mit zunehmender Dauer des Diabetes nahm der Anteil der nicht granulierten B-Zellen zu. Die B-Zellen diabetischer Tiere zeigten Glykogeninfiltration. 15 Tage alte Nachkommen zweier ketotisch-diabetischer Eltern waren normoglykämisch, hatten aber im Vergleich zu gleichaltrigen Kontrolltieren erhöhte Plasmainsulin-Konzentrationen. Das Inselzellvolumen war gegenüber der Norm erhöht, aber die B-Zellen waren degranuliert und zeigten Glykogeninfiltration. Diese Resultate stimmen mit der Hypothese überein, daß der primäre Defekt, der beim chinesischen Hamster die Entwicklung eines diabetischen Syndroms zur Folge hat, die Biosynthese des Insulins betrifft.

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Le, volume des îlots de Langerhans et des cellules B du pancréas de la progéniture de hamsters chinois sévèrement diabetiques

Résumé Des hamsters chinois provenant de la colonie des Laboratoires Upjohn ont été étudiés à différents âges allant de 15 jours à 19 mois. On trouve une glycosurie et une hyperglycémie chez les animaux diabétiques de 3 à 6 mois et chez ceux de 10 à 19 mois. On observe également une cétonurie et une cétonémie, mais les taux de glycérol sanguin et les taux d'insuline plasmatique à jeun sont bas par comparaison à ceux détectés chez des témoins d'âge comparable. Le volume des îlots, des cellules et des granules, mesuré par des méthodes quantitatives élaborées dans notre laboratoire, est diminué. Le volume des cellules non-granulées augmente progressivement avec la durée du diabète. On observe une infiltration de glycogène dans les cellules B des animaux diabétiques. Bien que la progéniture, âgée de 15 jours, de deux animaux sévèrement diabétiques (avec cétose) ait des taux normaux de glycémie et une glycosurie, leur insulinémie est plus élevée que celle mesurée chez les témoins. Le volume de leurs îlots est un peu plus grand que celui des contrôles, mais, en microscopie optique et électronique, les cellules sont dégranulées et montrent une infiltration de glycogène. Ces résultats confirment l'hypothèse que le défaut primaire est au niveau de la biosynthèse de l'insuline.

     

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Radiologic abnormalities and autonomic neuropathology in the digestive tract of the ketonuric diabetic Chinese hamster

Summary Barium x-ray patterns of ketonuric diabetic Chinese hamsters displayed marked dilatation of the stomach, small and large intestine. Hypomotility was manifested by flocculation of barium in the small and large bowel. Impaired transit time was further characterized by prolonged emptying of the stomach (mean 570 min diabetics; 200 min controls) and delayed stool formation (mean 230 min diabetics; and 100 min controls) and passage (mean 457 min diabetics; 210 min controls). Ultrastructural analysis of Auerbach's myenteric plexuses of the small intestine indicated acute degeneration in certain distal, unmyelinated axons. Swelling, deposition of glycogen, aggregation of neurofilaments and dense accumulation of lamellar bodies were observed. The severity and frequency of barium flocculation, glycogen deposition, aggregation of neurofilaments and lamellar inclusion bodies in axons were directly related to duration of ketonuria. The data strongly suggest that autonomic neuropathology in the plexuses of Auerbach may be a critical factor underlying gastrointestinal dysfunction in the ketonuric diabetic Chinese hamster.     

Early oral feeding after pancreatoduodenectomy enhances recovery without increasing morbidity

Objective

The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes.

Methods

An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake.

Results

The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien–Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods.

Conclusions

The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity.     

Macrolide-resistant Staphylococcus aureus colonization in cystic fibrosis patients: is there transmission to household contacts?

OBJECTIVES: Patients with cystic fibrosis (CF) are frequently colonized by macrolide-resistant Staphylococcus aureus, a result of maintenance macrolide therapy. As transmission of S. aureus between household contacts is common, we examined the prevalence of macrolide-resistant S. aureus colonization in CF patients on maintenance azithromycin therapy and their household contacts and compared this with the S. aureus macrolide resistance prevalence in the community. PATIENTS AND METHODS: Sixty-five CF patients on maintenance macrolide therapy and 194 household contacts were screened for S. aureus colonization by culturing sputa, cough swabs and nasal swabs. Resistance to macrolide, lincosamide and methicillin was determined by disc diffusion tests. The prevalence of macrolide-resistant S. aureus colonization in both groups was compared with figures from a nationwide study into S. aureus carriership and resistance. To assess possible transmission, genotyping of S. aureus was performed using the spa-typing method. RESULTS: Macrolide resistance among CF patients with S. aureus colonization was 69.6%; 75% of these isolates displayed lincosamide resistance too. Among household contacts, macrolide resistance prevalence did not differ significantly from resistance prevalence in the community (9.6% versus 6.3%; P = 0.358). No methicillin resistance was observed. No identical (macrolide-resistant and -susceptible) S. aureus genotypes were observed between CF patients and their household contacts except for one household, suggesting a probable transmission. CONCLUSIONS: No significant increase in macrolide-resistant S. aureus colonization was observed among household contacts of CF patients on long-term azithromycin therapy. Transmission of macrolide-resistant S. aureus could not be proved by genotyping in the majority of households.