Opioid analgesia in necrotizing pancreatitis: Incidence and timing of a hidden crisis.

BACKGROUND: Rates of opioid usage during necrotizing pancreatitis (NP) disease course are unknown. We hypothesized that a significant number of NP patients were prescribed opioid analgesics chronically. METHODS: Single institution IRB-approved retrospective study of 230 NP patients treated between 2015 and 2019. RESULTS: Data were available for 198/230 (86%) patients. 166/198 (84%) were discharged from their index hospitalization with a prescription for an opioid. At the first clinic visit following hospitalization, 110/182 (60%) were using opioids. Six months after disease onset, 72/163 (44%) continued to require opioids. At disease resolution, 38/144 (26%) patients remained on opioid medications. The rate of active opioid prescriptions at six months after disease onset declined throughout the period studied from 68% in 2015 to 39% in 2019. CONCLUSIONS: Opioid prescriptions are common in NP. Despite decline over time, 1 in 4 patients remain on opioids at disease resolution. These data identify an opportunity to adjust analgesic prescription practice in NP patients.

Apoptosis-modulatory miR-361-3p as a novel treatment target in endocrine-responsive and endocrine-resistant breast cancer.

Breast cancer (BC) is the most diagnosed cancer in women worldwide. In estrogen receptor (ER)-positive disease, anti-estrogens and aromatase inhibitors (AI) improve patient survival; however, many patients develop resistance. Dysregulation of apoptosis is a common resistance mechanism; thus, agents that can reinstate the activity of apoptotic pathways represent promising therapeutics for advanced drug-resistant disease. Emerging targets in this scenario include microRNAs (miRs). To identify miRs modulating apoptosis in drug-responsive and -resistant BC, a high-throughput miR inhibitor screen was performed, followed by high-content screening microscopy for apoptotic markers. Validation demonstrated that miR-361-3p inhibitor significantly increases early apoptosis and reduces proliferation of drug-responsive (MCF7), plus AI-/antiestrogen-resistant derivatives (LTED, TamR, FulvR), and ER- cells (MDA-MB-231). Importantly, proliferation-inhibitory effects were observed in vivo in a xenograft model, indicating the potential clinical application of miR-361-3p inhibition. RNA-seq of tumour xenografts identified FANCA as a direct miR-361-3p target, and validation suggested miR-361-3p inhibitor effects might be mediated in part through FANCA modulation. Moreover, miR-361-3p inhibition resulted in p53-mediated G1 cell cycle arrest through activation of p21 and reduced BC invasion. Analysis of publicly available datasets showed miR-361-3p expression is significantly higher in primary breast tumours vspaired normal tissue and is associated with decreased overall survival. In addition, miR-361-3p inhibitor treatment of BC patient explants decreased levels of miR-361-3p and proliferation marker, Ki67. Finally, miR-361-3p inhibitor showed synergistic effects on BC growth when combined with PARP inhibitor, Olaparib. Together, these studies identify miR-361-3p inhibitor as a potential new treatment for drug-responsive and -resistant advanced BC.

Cardiopulmonary and metabolic physiology during hemodialysis and inter/intradialytic exercise.

Hemodialysis is associated with numerous symptoms and side effects that, in part, may be due to subclinical hypoxia. However, acute cardiopulmonary and metabolic physiology during hemodialysis is not well defined. Intradialytic and interdialytic exercise appear to be beneficial and may alleviate these side effects. To better understand these potential benefits, the acute physiological response to exercise should be evaluated. The aim of this study was to compare and characterize the acute physiological response during hemodialysis, intradialytic exercise, and interdialytic exercise. Cardiopulmonary physiology was evaluated during three conditions: 1) hemodialysis without exercise (HD), 2) intradialytic exercise (IDEx), and 3) interdialytic exercise (Ex). Exercise consisted of 30-min constant load cycle ergometry at 90% V̇O2AT (anaerobic threshold). Central hemodynamics (via noninvasive bioreactance) and ventilatory gas exchange were recorded during each experimental condition. Twenty participants (59 ± 12 yr, 16/20 male) completed the protocol. Cardiac output (Δ = -0.7 L/min), O2 uptake (Δ = -1.4 mL/kg/min), and arterial-venous O2 difference (Δ = -2.0 mL/O2/100 mL) decreased significantly during HD. Respiratory exchange ratio exceeded 1.0 throughout HD and IDEx. Minute ventilation was lower (P = 0.001) during IDEx (16.5 ± 1.1 L/min) compared with Ex (19.8 ± 1.0 L/min). Arterial-venous O2 difference was partially restored further to IDEx (4.6 ± 1.9 mL/O2/100 mL) compared with HD (3.5 ± 1.2 mL/O2/100 mL). Hemodialysis altered cardiopulmonary and metabolic physiology, suggestive of hypoxia. This dysregulated physiology contributed to a greater physiological demand during intradialytic exercise compared with interdialytic exercise. Despite this, intradialytic exercise partly normalized cardiopulmonary physiology during treatment, which may translate to a reduction in the symptoms and side effects of hemodialysis.NEW & NOTEWORTHY This study is the first, to our knowledge, to directly compare cardiopulmonary and metabolic physiology during hemodialysis, intradialytic exercise, and interdialytic exercise. Hemodialysis was associated with increased respiratory exchange ratio, blunted minute ventilation, and impaired O2 uptake and extraction. We also identified a reduced ventilatory response during intradialytic exercise compared with interdialytic exercise. Impaired arterial-venous O2 difference during hemodialysis was partly restored by intradialytic exercise. Despite dysregulated cardiopulmonary and metabolic physiology during hemodialysis, intradialytic exercise was well tolerated.

Ventilatory and chronotropic incompetence during incremental and constant load exercise in end-stage renal disease: a comparative physiology study.

Maximal O2 uptake is impaired in end-stage renal disease (ESRD), reducing quality of life and longevity. While determinants of maximal exercise intolerance are well defined, little is known of limitation during submaximal constant load exercise. By comparing individuals with ESRD and healthy controls, the aim of this exploratory study was to characterize mechanisms of exercise intolerance in participants with ESRD by assessing cardiopulmonary physiology at rest and during exercise. Resting spirometry and echocardiography were performed in 20 dialysis-dependent participants with ESRD (age: 59 ± 12 yr, 14 men and 6 women) and 20 healthy age- and sex-matched controls. Exercise tolerance was assessed with ventilatory gas exchange and central hemodynamics during a maximal cardiopulmonary exercise test and 30 min of submaximal constant load exercise. Left ventricular mass (292 ± 102 vs. 185 ± 83 g, P = 0.01) and filling pressure (E/e': 6.48 ± 3.57 vs. 12.09 ± 6.50 m/s, P = 0.02) were higher in participants with ESRD; forced vital capacity (3.44 ± 1 vs. 4.29 ± 0.95 L/min, P = 0.03) and peak O2 uptake (13.3 ± 2.7 vs. 24.6 ± 7.3 mL·kg-1·min-1, P < 0.001) were lower. During constant load exercise, the relative increase in the arterial-venous O2 difference (13 ± 18% vs. 74 ± 18%) and heart rate (32 ± 18 vs. 75 ± 29%) were less in participants with ESRD despite exercise being performed at a higher percentage of maximum minute ventilation (48 ± 3% vs. 39 ± 3%) and heart rate (82 ± 2 vs. 64 ± 2%). Ventilatory and chronotropic incompetence contribute to exercise intolerance in individuals with ESRD. Both are potential targets for medical and lifestyle interventions.

The high-pressure, high-temperature phase diagram of cerium.

We present an experimental study of the high-pressure, high-temperature behaviour of cerium up to ∼22 GPa and 820 K using angle-dispersive x-ray diffraction and external resistive heating. Studies above 820 K were prevented by chemical reactions between the samples and the diamond anvils of the pressure cells. We unambiguously measure the stability region of the orthorhombic oC4 phase and find it reaches its apex at 7.1 GPa and 650 K. We locate the α-cF4-oC4-tI2 triple point at 6.1 GPa and 640 K, 1 GPa below the location of the apex of the oC4 phase, and 1-2 GPa lower than previously reported. We find the α-cF4 → tI2 phase boundary to have a positive gradient of 280 K (GPa)-1, less steep than the 670 K (GPa)-1 reported previously, and find the oC4 → tI2 phase boundary to lie at higher temperatures than previously found. We also find variations as large as 2-3 GPa in the transition pressures at which the oC4 → tI2 transition takes place at a given temperature, the reasons for which remain unclear. Finally, we find no evidence that the α-cF4 → tI2 is not second order at all temperatures up to 820 K.

Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy.

BACKGROUND: Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy. METHODS: We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT. RESULTS: Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8-18.1) ADT). Median SRT dose was 70 Gy (IQR 70-70), and median follow-up after SRT was 6.7 years (IQR 4.5-10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42-0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971). CONCLUSIONS: The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.

The role of a bus network in access to primary health care in Metropolitan Auckland, New Zealand.

UNLABELLED: Background: This study examined the spatial accessibility of the population of metropolitan Auckland, New Zealand to the bus network, to connect them to primary health providers, in this case doctors (GP) and dentists. Analysis of accessibility by ethnic identity and socio-economic status were also carried out, because of existing health inequalities along these dimensions. The underlying hypothesis was that most people would live within easy reach of primary health providers, or easy bus transport to such providers. METHODS: An integrated geographic model of bus transport routes and stops, with population and primary health providers (medical. and dental practices) was developed and analysed. RESULTS: Although the network of buses in metropolitan Auckland is substantial and robust it was evident that many people live more than 150 metres from a stop. CONCLUSION: Improving the access to bus stops, particularly in areas of high primary health care need (doctors and dentists), would certainly be an opportunity to enhance spatial access in a growing metropolitan area.

The Incorporation of an Advanced Donation Program Into Kidney Paired Exchange: Initial Experience of the National Kidney Registry.

The continued growth of kidney paired donation (KPD) to facilitate transplantation for otherwise incompatible or suboptimal living kidney donors and recipients has depended on a balance between the logistics required for patients and the collaborating transplant centers. The formation of chains for KPD and the shipping of kidneys have permitted networks such as the National Kidney Registry (NKR) to offer KPD to patients over a transcontinental area. However, over the last 3 years, we have encountered patient requests for a more flexible experience in KPD to meet their individual needs often due to rigid time constraints. To accommodate these requests, we have developed an Advanced Donation Program (ADP) in which the donor desires to donate by a specific date, but their paired recipient has not yet been matched to a specific donor or scheduled for surgery. After obtaining careful informed consent from both the donor and paired recipient, 10 KPD chains were constructed using an ADP donor. These 10 ADP donors have facilitated 47 transplants, and thus far eight of their paired recipients have received a kidney within a mean of 178 (range 10-562) days. The ADP is a viable method to support time limited donors in a KPD network.

Consensus conference on best practices in live kidney donation: recommendations to optimize education, access, and care.

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

Multiple-aetiology enteric infections involving non-O157 Shiga toxin-producing Escherichia coli--FoodNet, 2001-2010.

We describe multiple-aetiology infections involving non-O157 Shiga toxin-producing Escherichia coli (STEC) identified through laboratory-based surveillance in nine FoodNet sites from 2001 to 2010. A multiple-aetiology infection (MEI) was defined as isolation of non-O157 STEC and laboratory evidence of any of the other nine pathogens under surveillance or isolation of >1 non-O157 STEC serogroup from the same person within a 7-day period. We compared exposures of patients with MEI during 2001-2010 with those of patients with single-aetiology non-O157 STEC infections (SEI) during 2008-2009 and with those of the FoodNet population from a survey conducted during 2006-2007. In total, 1870 non-O157 STEC infections were reported; 68 (3.6%) were MEI; 60 included pathogens other than non-O157 STEC; and eight involved >1 serogroup of non-O157 STEC. Of the 68 MEI, 21 (31%) were part of six outbreaks. STEC O111 was isolated in 44% of all MEI. Of patients with MEI, 50% had contact with farm animals compared with 29% (P < 0.01) of persons with SEI; this difference was driven by infections involving STEC O111. More patients with non-outbreak-associated MEI reported drinking well water (62%) than respondents in a population survey (19%) (P < 0.01). Drinking well water and having contact with animals may be important exposures for MEI, especially those involving STEC O111.

Collision induced ultraviolet structure in nitrogen radar REMPI spectra.

We present 2 + 2 radar REMPI measurements in molecular nitrogen under atmospheric conditions and observe a strong interference in the (1,0) vibrational band of the a(1)Πg ← X(1)Σg(+) electronic manifold. The interference is suppressed by using circularly polarized light, permitting rotational analysis of the 2 + 2 radar REMPI spectrum. It is observed in pure nitrogen, though the structure varies with gas composition. The structure also varies with temperature and pressure. These results indicate that it is collision induced. We hypothesize that the source of the interference is a 3 + 1 REMPI process through the a(″1)Σg(+) electronic state.

The geographic distribution of patients seeking emergency dental care at the Royal Dental Hospital of Melbourne, Australia.

BACKGROUND: Little detail is known about the geographical catchment areas covered by dental hospitals, with no previous Australian studies of this kind. The aim of this study was to assess the geographical distribution of public dental emergency patients and their socioeconomic status to define catchment zones for a dental hospital. METHODS: All patients requesting emergency dental care at the Royal Dental Hospital Melbourne, meeting the inclusion criteria, in calendar years 2006 and 2010 were included in the sample. Geographic information systems tools were used to locate and link each patient address to the socioeconomic data. RESULTS: For both 2006 and 2010 95% of the patients were living within 50km of the hospital. In 2006, most of the patients seeking care lived within a 15km radius of the dental hospital whilst in 2010 that distance increased somewhat. Patients from areas with similar socioeconomic status living more than 10km away from the hospital had poorer access to dental emergency treatment. CONCLUSIONS: The hospital had a surprisingly large catchment zone that overlapped those of smaller community-based clinics.

Factors associated with improved biochemical response to neoadjuvant androgen deprivation therapy before definitive radiation therapy in prostate cancer patients.

BACKGROUND: In prostate cancer patients treated with androgen deprivation therapy (ADT) and radiation therapy (RT), a pre-RT PSA level 0.5 ng ml(-1), determined after neoadjuvant ADT and before RT, predicts for worse survival measures. The present study sought to identify patient, tumor and treatment characteristics associated with the pre-RT PSA in prostate cancer patients. METHODS: We reviewed the charts of all patients diagnosed with intermediate- and high-risk prostate cancer and treated with a combination of neoadjuvant (median, 2.2 and 2.5 months, respectively), concurrent, and adjuvant ADT and RT between 1990 and 2011. RESULTS: A total of 170 intermediate- and 283 high-risk patients met inclusion criteria. On multivariate analysis, both intermediate- and high-risk patients with higher pre-treatment PSA (iPSA) were significantly less likely to achieve a pre-RT PSA <0.5 ng ml(-1) (iPSA 10.1-20 ng ml(-1): P=0.005 for intermediate risk; iPSA 10.1-20 ng ml(-1): P=0.005, iPSA >20 ng ml(-1): P<0.001 for high risk). High-risk patients undergoing total androgen blockade were more likely to achieve a pre-RT PSA <0.5 ng ml(-1) (P=0.031). We observed an interaction between race and type of neoadjuvant ADT (P=0.074); whereas African-American men on total androgen blockade reached pre-RT PSA <0.5 ng ml(-1) as frequently as other men on total androgen blockade (P=0.999), African-American men on luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy/orchiectomy were significantly less likely to reach pre-RT PSA <0.5 ng ml(-1) compared with other men on LH-RH monotherapy/orchiectomy (P=0.001). CONCLUSIONS: Our findings suggest that total androgen blockade in the neoadjuvant period may be beneficial compared with LH-RH monotherapy for achieving a pre-RT PSA <0.5 ng ml(-1) in African-American men with high-risk prostate cancer. In addition, men with higher iPSA are more likely to have a pre-RT PSA greater than 0.5 ng ml(-1) in response to neoadjuvant ADT and are therefore candidates for clinical trials testing newer, more aggressive hormone-ablative therapies.

Relationship between fractional anisotropy of cerebral white matter and metabolite concentrations measured using (1)H magnetic resonance spectroscopy in healthy adults.

Fractional anisotropy (FA) of water diffusion in cerebral white matter (WM), derived from diffusion tensor imaging (DTI), is a sensitive index of microscopic WM integrity. Physiological and metabolic factors that explain intersubject variability in FA values were evaluated in two cohorts of healthy adults of different age spans (N=65, range: 28-50years; and N=25, age=66.6±6.2, range: 57-80years). Single voxel magnetic resonance spectroscopy (MRS) was used to measure N-acetylaspartate (NAA), total choline-containing compounds, and total creatine, bilaterally in an associative WM tract: anterior corona radiata (ACR). FA values were calculated for the underlying, proximal and two distal WM regions. Two-stage regression analysis was used to calculate the proportion of variability in FA values explained by spectroscopy measurements, at the first stage, and subject's age, at the second stage. WM NAA concentration explained 23% and 66% of intersubject variability (p<0.001) in the FA of the underlying WM in the younger and older cohorts, respectively. WM NAA concentration also explained a significant proportion of variability in FA of the genu of corpus callosum (CC), a proximal WM tract where some of the fibers contained within the spectroscopic voxel decussate. NAA concentrations also explained a significant proportion of variability in the FA values in the splenium of CC, a distal WM tract that also carries associative fibers, in both cohorts. These results suggest that MRS measurements explained a significant proportion of variability in FA values in both proximal and distal WM tracts that carry similar fiber-types.

Addition of short-term androgen deprivation therapy to dose-escalated radiation therapy improves failure-free survival for select men with intermediate-risk prostate cancer.

BACKGROUND: Dose-escalated (DE) radiation therapy (RT) and androgen deprivation therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa) is uncertain. PATIENTS AND METHODS: We identified 636 men treated for IR-PrCa with DE-RT (>75Gy). The adult comorbidity evaluation-27 index classifed comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. RESULTS: Forty-five percent received DE-RT and 55% DE-RT with ADT (median 6 months). On Cox proportional hazard regression that adjusted for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT classified Gleason 4 + 3 = 7 or ≥50% positive cores as unfavorable disease. The addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (P = 0.006) but did not improve FFS for men with unfavorable disease and moderate or severe comorbidity (P = 0.380). CONCLUSION: The addition of ADT to DE-RT improves FFS for men with unfavorable IR-PrCa, especially those with no or minimal comorbidity.

A SNP in steroid receptor coactivator-1 disrupts a GSK3ß phosphorylation site and is associated with altered tamoxifen response in bone.

The coregulator steroid receptor coactivator (SRC)-1 increases transcriptional activity of the estrogen receptor (ER) in a number of tissues including bone. Mice deficient in SRC-1 are osteopenic and display skeletal resistance to estrogen treatment. SRC-1 is also known to modulate effects of selective ER modulators like tamoxifen. We hypothesized that single nucleotide polymorphisms (SNP) in SRC-1 may impact estrogen and/or tamoxifen action. Because the only nonsynonymous SNP in SRC-1 (rs1804645; P1272S) is located in an activation domain, it was examined for effects on estrogen and tamoxifen action. SRC-1 P1272S showed a decreased ability to coactivate ER compared with wild-type SRC-1 in multiple cell lines. Paradoxically, SRC-1 P1272S had an increased protein half-life. The Pro to Ser change disrupts a putative glycogen synthase 3 (GSK3)ß phosphorylation site that was confirmed by in vitro kinase assays. Finally, knockdown of GSK3ß increased SRC-1 protein levels, mimicking the loss of phosphorylation at P1272S. These findings are similar to the GSK3ß-mediated phospho-ubiquitin clock previously described for the related coregulator SRC-3. To assess the potential clinical significance of this SNP, we examined whether there was an association between SRC-1 P1272S and selective ER modulators response in bone. SRC-1 P1272S was associated with a decrease in hip and lumbar bone mineral density in women receiving tamoxifen treatment, supporting our in vitro findings for decreased ER coactivation. In summary, we have identified a functional genetic variant of SRC-1 with decreased activity, resulting, at least in part, from the loss of a GSK3ß phosphorylation site, which was also associated with decreased bone mineral density in tamoxifen-treated women.

Travel patterns for government emergency dental care in Australia: a new approach using GIS tools.

BACKGROUND: Government subsidized dental care is provided as a community safety-net to complement the private dental sector. The aim of this study was to detail the geographic catchment characteristics of three outer metropolitan government dental clinics. METHODS: Three outer metropolitan dental clinics with the greatest number of geocoded triage patients were selected for the study. In total these three facilities had 5742 patients over the 12-week period with 2010 at clinic A, 1278 at clinic B and 2454 at clinic C. Cumulative proportions of patients' residential address locations at distances were calculated; there was close correlation between the three clinics. A best fit curve with a correlation coefficient of 0.998 was developed. RESULTS: In summary, approximately 50% of patients were within 6 km of the clinic and 75% were within 10 km. CONCLUSIONS: This study has critical outcomes for the planning of future services in developing a network model for care. The data presented will assist in the development of more evidence-based approaches to planning new service network structures.

A methodology for selecting the beam arrangement to reduce the intensity-modulated radiation therapy (IMRT) dose to the SPECT-defined functioning lung.

Macroaggregated albumin single-photon emission computed tomography (MAA-SPECT) provides a map of the spatial distribution of lung perfusion. Our previous work developed a methodology to use SPECT guidance to reduce the dose to the functional lung in IMRT planning. This study aims to investigate the role of beam arrangement on both low and high doses in the functional lung. In our previous work, nine-beam IMRT plans were generated with and without SPECT guidance and compared for five patients. For the current study, the dose-function histogram (DFH) contribution for each of the nine beams for each patient was calculated. Four beams were chosen based on orientation and DFH contributions to create a SPECT-guided plan that spared the functional lung and maintained target coverage. Four-beam SPECT-guided IMRT plans reduced the F(20) and F(30) values by (16.5 +/- 6.8)% and (6.1 +/- 9.2)%, respectively, when compared to nine-beam conventional IMRT plans. Moreover, the SPECT-4F Plan reduces F(5) and F(13) for all patients by (11.0 +/- 8.2)% and (6.1 +/- 3.6)%, respectively, compared to the SPECT Plan. Using fewer beams in IMRT planning may reduce the amount of functional lung that receives 5 and 13 Gy, a factor that has recently been associated with radiation pneumonitis.

Asynchronous, out-of-sequence, transcontinental chain kidney transplantation: a novel concept.

The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage.