OPTN/SRTR 2018 Annual Data Report: Pancreas

The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.     

Geriatric-based versus general wards for older acute medical patients: a randomized comparison of outcomes and use of resources

BACKGROUND: The effects of residence in an acute geriatrics-based ward (AGW) with emphasis on early rehabilitation and discharge planning for older patients with acute medical illnesses were assessed. Outcome and use of resources were compared with those of patients treated in general medical wards (MWs). A per-protocol rather than intention-to-treat analysis was performed. METHODS: A randomized trial with 3-months follow-up. A total of 190 patients aged 70 years and older were randomized to an acute geriatrics-based ward, and 223 patients were randomized to general medical wards. RESULTS: The two groups were comparable at inclusion. However, after care in the AGW, 71% of patients could be discharged directly home compared with 64% of those treated in MWs (relative risk 1.17; 95% CI, 0.93-1.49). The length of stay was shorter in the AGW (mean 5.9 vs 7.3 days; P = .002). The proportion of patients in geriatric or other hospital wards or in nursing homes did not differ, but the proportion of AGW patients in sheltered living tended to be lower (P = .085). At the follow-up, case fatality, ADL function, psychological well-being, need for daily personal assistance, drug consumption, need for readmission to hospital, and total health care costs after discharge did not differ between the two groups. Poor global outcome was observed in 37% of AGW and 34% of MW patients. CONCLUSIONS: A geriatric approach with greater emphasis on early rehabilitation and discharge planning in the AGW shortened the length of hospital stay and may have reduced the need for long-term institutional living. This occurred despite patients in an acute geriatric ward not having better medical or functional outcome than older acute patients treated in general medical wards.     

Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.     

Phospholipase C from Clostridium perfringens stimulates formation and release of platelet-activating factor (PAF-acether) in cultured intestinal epithelial cells (INT 407)

This study demonstrates the ability of phospholipase C from Clostridium perfringens to stimulate the generation of platelet-activating factor (PAF-acether) in cultured intestinal epithelial cells (INT 407). Cells were exposed to phospholipase C for up to 60 min, and the content of PAF-acether within the cells and in the extracellular medium was determined. Phospholipase C caused a time-dependent formation of PAF-acether within the cells and also release of PAF-acether to the medium. In contrast, phospholipase C did not affect the cellular acetylhydrolase activity or the ability of the cells to metabolize extracellularly added 14C-PAF-acether. These findings suggest the possibility that intestinal epithelial cells, when stimulated with a naturally occurring intestinal bacterial toxin, generate and release PAF-acether. The possibility that this might contribute to the pathophysiology of inflammatory bowel disease is discussed.     

Failure of electric shock treatment for rattlesnake envenomation

The use of high-voltage electric shock therapy for the treatment of snake venom poisoning has recently gained popularity in the United States. We present a case that documents the dangerous, ineffective application of electric shock to the face of a patient envenomated by a Great Basin rattlesnake (Crotalus viridis lutosus). The successful use of antivenin in this critically ill, antivenin-allergic patient is described.     

Lecithin : cholesterol acyl transfer (LACT) and fatty acid composition of lecithin and cholesterol esters in young male myocardial infarction survivors.

Lecithin : cholesterol acyl transfer (LCAT) and relative fatty acid composition of serum lecithin and cholesterol esters were studied in 20 young male survivors of myocardial infarction (MI). Comparisons were made with controls matched for serum cholesterol. There was no difference in LCAT rate between MI patients and controls. The relative content of arachidonic acid in cholesterol esters was higher in MI patients. The fatty acid composition of lecithin and cholesterol esters suggests an equal transfer of linoleic and oleic acids from lecithin to cholesterol. Furthermore negative correlations were found between LCAT and linoleic acid content of lecithin (r = --0.43, P less than 0.01) and cholesterol esters (r = --0.45, P less than 0.01). This inverse relationship does not seem to be linked to substrate specificity, but rather to be mediated by influences in common on serum lipid content and turnover.     

Radial diffusion effects in a finite extravascular space surrounding a single capillary

An analysis is presented for transcapillary exchange as applied to the indicator-dilution technique. A single capillary is considered surrounded by a finite extravascular space in which the diffusion rate is finite in the radial direction. The outer boundary of the extravascular space is a semipermeable membrane representing a cell wall. The problem is solved for an arbitrary time, varying capillary input function by means of an eigenfunction expansion in the outer annulus, and a Laplace transformation in the capillary. The results indicate that the finite size of the extravascular space coupled with the finite diffusion rate have an appreciable effect on extraction. Comparisons with related theoretical work are indicated.     

Effects of a fall prevention program including exercise on mobility and falls in frail older people living in residential care facilities

BACKGROUND AND AIMS: Impaired mobility is one of the strongest predictors for falls in older people. We hypothesized that exercise as part of a fall prevention program would have positive effects, both short- and long-term, on gait, balance and strength in older people at high risk of falling and with varying levels of cognition, residing in residential care facilities. A secondary hypothesis was that these effects would be associated with a reduced risk of falling. METHODS: 187 out of all residents living in 9 facilities, > or =65 years of age were at high risk of falling. The facilities were cluster-randomized to fall intervention or usual care. The intervention program comprised: education, environment, individually designed exercise, drug review, post-fall assessments, aids, and hip protectors. Data were adjusted for baseline performance and clustering. RESULTS: At 11 weeks, positive intervention effects were found on independent ambulation (FAC, p=0.026), maximum gait speed (p=0.002), and step height (> or =10 cm, p<0.001), but not significantly on the Berg Balance Scale. At 9 months (long-term outcome), 3 intervention and 15 control residents had lost the ability to walk (p=0.001). Independent ambulation and maximum gait speed were maintained in the intervention group but deteriorated in the control group (p=0.001). Residents with both higher and lower cognition benefited in most outcome measures. No association was found between improved mobility and reduced risk of falling. CONCLUSIONS: Exercise, as part of a fall prevention program, appears to preserve the ability to walk, maintain gait speed, ambulate independently, and improve step height. Benefits were found in residents with both lower and higher cognitive impairment, but were not found to be associated with a reduced risk of falling.     

Evidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin-responsive glucose transporter (GLUT4) translocation.

Interaction of the activated insulin receptor (IR) with its substrate, insulin receptor substrate 1 (IRS-1), via the phosphotyrosine binding domain of IRS-1 and the NPXY motif centered at phosphotyrosine 960 of the IR, is important for IRS-1 phosphorylation. We investigated the role of this interaction in the insulin signaling pathway that stimulates glucose transport. Utilizing microinjection of competitive inhibitory reagents in 3T3-L1 adipocytes, we have found that disruption of the IR/IRS-1 interaction has no effect upon translocation of the insulin-responsive glucose transporter (GLUT4). The activity of these reagents was demonstrated by their ability to block insulin stimulation of two distinct insulin bioeffects, membrane ruffling and mitogenesis, in 3T3-L1 adipocytes and insulin-responsive rat 1 fibroblasts. These data suggest that phosphorylated IRS-1 is not an essential component of the metabolic insulin signaling pathway that leads to GLUT4 translocation, yet it appears to be required for other insulin bioeffects.