Utility of a multidisciplinary tumor board in the management of pancreatic and upper gastrointestinal diseases: an observational study

Background & objectives

Multidisciplinary tumor boards (MDTBs) are frequently employed in cancer centers but their value has been debated. We reviewed the decision-making process and resource utilization of our MDTB to assess its utility in the management of pancreatic and upper gastrointestinal tract conditions.

Isoelectronic perturbations to f-d-electron hybridization and the enhancement of hidden order in URu2Si2

Electrical resistivity measurements were performed on single crystals of URu_2–xOs_xSi₂ up to x = 0.28 under hydrostatic pressure up to P = 2 GPa. As the Os concentration, x, is increased, 1) the lattice expands, creating an effective negative chemical pressure P_ch(x); 2) the hidden-order (HO) phase is enhanced and the system is driven toward a large-moment antiferromagnetic (LMAFM) phase; and 3) less external pressure P_c is required to induce the HO→LMAFM phase transition. We compare the behavior of the T(x, P) phase boundary reported here for the URu_2-xOs_xSi₂ system with previous reports of enhanced HO in URu₂Si₂ upon tuning with P or similarly in URu_2–xFe_xSi₂ upon tuning with positive P_ch(x). It is noteworthy that pressure, Fe substitution, and Os substitution are the only known perturbations that enhance the HO phase and induce the first-order transition to the LMAFM phase in URu₂Si₂. We present a scenario in which the application of pressure or the isoelectronic substitution of Fe and Os ions for Ru results in an increase in the hybridization of the U-5f-electron and transition metal d-electron states which leads to electronic instability in the paramagnetic phase and the concurrent formation of HO (and LMAFM) in URu₂Si₂. Calculations in the tight-binding approximation are included to determine the strength of hybridization between the U-5f-electron states and the d-electron states of Ru and its isoelectronic Fe and Os substituents in URu₂Si₂.

The heavy-fermion superconducting compound URu2Si2 is known for its second-order phase transition into the so-called “hidden-order” (HO) phase at a transition temperature T0 ≈17.5 K. Extensive investigation of the phase space in proximity to the HO phase transition has provided a detailed picture of the electronic and magnetic structure of this unique phase (1–42). However, more than three decades after the initial characterization of URu2Si2 (1–3), the order parameter for the HO phase is still unidentified.Most perturbations to the URu2Si2 compound have the effect of suppressing HO. The application of an external magnetic field (H) suppresses the HO phase (41, 43) and many of the chemical substitutions (x) at the U, Ru, or Si sites that have been explored significantly reduce T0, even at modest levels of substituent concentration (44–52). At present, only three perturbations are known to consistently enhance the HO phase in URu2Si2: 1) external pressure P, 2) isoelectronic substitution of Fe ions for Ru, and 3) isoelectronic substitution of Os ions for Ru. Upon applying pressure P, the HO phase in pure URu2Si2 is enhanced (6) and the system is driven toward a large-moment antiferromagnetic (LMAFM) phase (53). The HO→LMAFM phase transition is identified indirectly by a characteristic “kink” at a critical pressure Pc ≈1.5 GPa in the T0 (P) phase boundary (18, 53, 54) and also directly by neutron diffraction experiments, which reveal an increase in the magnetic moment from μ ∼ (0.03±0.02)μB/U in the HO phase to μ ∼ 0.4 μB/U in the LMAFM phase (13, 55, 56).Recent reports indicate that the isoelectronic substitution of Fe ions for Ru in URu2Si2 replicates the T0(P) behavior in URu2Si2 (57–59). An increase in x in URu2−xFexSi2 enhances the HO phase and drives the system toward the HO→LMAFM phase transition at a critical Fe concentration xc ≈0.15 (58, 60). The decrease in the volume of the unit cell due to substitution of smaller Fe ions for Ru may be interpreted as a chemical pressure, Pch, where the Fe concentration x can be converted to Pch (x) (57, 59). In addition, the induced HO→LMAFM phase transition in URu2−xFexSi2 occurs at combinations of x and P that consistently obey the additive relationship: Pch(x) + Pc ≈1.5 GPa (57, 59). These results have led to the suggestion that Pch is equivalent to P in affecting the HO and LMAFM phases (58, 59).Reports of the isoelectronic substitution of larger Os ions for Ru have shown that an increase in x in URu2−xOsxSi2 1) expands the volume of the unit cell, thus creating an effective negative chemical pressure (Pch ≤0); 2) enhances the HO phase; and 3) drives the system toward a similar HO→LMAFM phase transition at a critical Os concentration of xc ≈0.065 (60–62). These results are contrary to the expectation that a negative Pch would lead to a suppression of HO and complicate the view of chemical pressure as a mechanism affecting the evolution of phases in URu2Si2.In this paper, we report on the behavior of the T(x, P) boundary for the URu2−xOsxSi2 system based on ρ(T) measurements of single crystals of URu2−xOsxSi2 as a function of Os concentration x and applied pressure P. The T(x, P) phase boundary observed here for the URu2−xOsxSi2 system (57–59) is compared to that of the URu2−xFexSi2 system and also with the behavior of T(P) in pure URu2Si2. As an explanation for the enhancement of HO toward the HO→LMAFM phase transition, we suggest a scenario in which each of the perturbations of Os substitution, Fe substitution, and pressure P favors delocalization of the 5f electrons and increases the hybridization of the uranium 5f-electron and transition metal (Fe, Ru, Os) d-electron states. To avoid an ad hoc explanation of the effect of increasing the Os concentration x in URu2−xOsxSi2, compared to the effects of pressure P and Fe substitution, we explain how pressure P, Fe substitution, and Os substitution are three perturbative routes to enhancement of the U-5f- and d-electron hybridization. The importance of the 5f- and d-electron hybridization to the emergence of HO/LMAFM is presented in the context of the Fermi surface (FS) instability that leads to a reconstruction and partial gapping of the FS during the transition from the paramagnetic (PM) phase to the HO and LMAFM phases (2, 6, 20, 22, 24–26, 37, 38, 63).In an effort to further understand the effect of isoelectronic substitution on the 5f- and d-electron hybridization, calculations in the tight-binding approximation were made for compounds from the series UM2Si2 (M = Fe, Ru, and Os). The calculations indicate that the degree of hybridization is largely dependent on the magnitude of the difference between the binding energy of the localized U-5f electrons and that of the transition metal d electrons.     

Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors

BackgroundPancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP.MethodsPatients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP.ResultsAmong 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5 cm, IQR:1.0–1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n = 109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p = 0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23–71) versus PD/DP (37 months, 95% CI: 33–47, p = 0.480).ConclusionComparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN.     

Health conditions, health symptoms and driving difficulties in older adults

OBJECTIVES: Previous research has indicated that age-related medical or health conditions can affect driving performance in older adults but little, if any, research has examined the mechanisms through which health conditions affect driving difficulties in older adults. DESIGN: Cross-sectional, correlational study. SETTING: Random sample from the community. We examined the nature of the relations among health conditions, health-related symptoms, physical fitness levels and specific types of self-reported driving difficulties in a random sample of older adults. PARTICIPANTS: Three hundred eighteen adults 60 years of age or older. INTERVENTION: None. MEASUREMENTS: General health, health-related symptoms, driving-related difficulties and physical activity. RESULTS: Our findings support the position that health-related symptoms are more clearly associated with driving difficulties than are health conditions, and mediate the relations between health conditions and driving difficulties. Health-related symptoms involving the spine and lower body appeared to be particularly relevant to difficulties with driving experienced in those body areas (i.e. spine and lower body). CONCLUSION: These findings are encouraging, in that the most frequently reported symptoms are in areas highly amenable to modification and, in that most of our respondents indicated a willingness to engage in exercise if an association between fitness and driving was demonstrated.     

A moderately high fat diet promotes salt-sensitive hypertension in obese zucker rats by impairing nitric oxide production

The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NO(x)) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NO(x) excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NO(x) excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge.     

Prognostic value of circulating pregnancy-associated plasma protein levels in patients with chronic stable angina.

AIMS: Unstable coronary atherosclerotic plaque can be present in patients with chronic stable coronary artery disease (CAD). Our objective was to assess whether measurement of plasma pregnancy-associated plasma protein (PAPP-A) level, a reflection of plaque instability, in patients with chronic stable CAD had an independent prognostic value on the subsequent incidence of death, acute coronary syndrome (ACS), and revascularization. METHODS AND RESULTS: Patients referred for coronary angiography were recruited. A cohort of 103 patients with stable symptoms for at least 6 weeks and with a coronary angiogram showing at least a 50% luminal diameter narrowing formed our study population. Median follow-up was 4.9 years. Mean age was 65+/-10 years. In a multivariable model that included CAD traditional risk factors, ejection fraction, extent of coronary atherosclerosis, prior history of myocardial infarction, prior revascularization, discharge medications, and C-reactive protein, the plasma PAPP-A was found to be significantly associated with the endpoint of future death [adjusted hazard ratio (HR) 5.29; 95% CI 1.27-22.0; P=0.023] and with the endpoint of future death and ACS (adjusted HR 3.56; 95% CI 1.27-10.0; P=0.015), but not with the endpoint of future death and revascularization. CONCLUSION: Measurement of plasma PAPP-A level in patients with chronic stable CAD has an independent prognostic value on the occurrence of death and ACS.     

Chronic kidney disease prevalence and rate of diagnosis

Background

Chronic kidney disease is a major public health problem. However, no study to date has estimated the prevalence of chronic kidney disease based on the clinical guidelines established by the National Kidney Foundation and few studies have explored the rate of diagnoses by primary care providers.

Subjects and Methods

Cross-sectional study of ambulatory patients in Rochester, NY. The purpose of this study was to estimate the prevalence of chronic kidney disease and the rate of primary caregiver diagnosis in ambulatory patients with chronic kidney disease.

Results

Among the 24,492 outpatients that had at least 2 glomerular filtration rate estimates ≥3 months apart, 6895 had an estimated glomerular filtration rate <60 mL/min/1.73 m², indicating a 28.2% period prevalence of chronic kidney disease. The rate of clinical diagnosis among those with chronic kidney disease was 26.5% (95% confidence interval, 17.9 to 35.1), suggesting that 74% of patients with chronic kidney disease are undiagnosed.

Conclusions

We demonstrate that the prevalence of chronic kidney disease is substantially higher in health-seeking individuals than in the general population. Moreover, we demonstrate that laboratory reporting of estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation alone does not result in an optimal rate of clinical diagnosis.     

Metronidazole lacks antibacterial activity in guinea pigs infected with Mycobacterium tuberculosis

Metronidazole, which is used for the treatment of infections caused by anaerobic organisms, was evaluated in Mycobacterium tuberculosis-infected guinea pigs. M. tuberculosis can adapt to hypoxia, which is present in the primary lesions of infected guinea pigs. Metronidazole treatment (for 6 weeks at 100 mg/kg of body weight) resulted in no reduction in the bacillary burden and significantly worsened lesion inflammation.     

Enhanced factor H binding to sialylated Gonococci is restricted to the sialylated lacto-N-neotetraose lipooligosaccharide species: implications for serum resistance and evidence for a bifunctional lipooligosaccharide sialyltransferase in Gonococci

We isolated serologically identical (by serovar determination and porin variable region [VR] typing) strains of Neisseria gonorrhoeae from an infected male and two of his monogamous female sex partners. One strain (termed 398078) expressed the L1 (Galalpha1 --> 4 [corrected] Galbeta1 --> 4Glcbeta1 --> 4HepI) lipooligosaccharide (LOS) structure exclusively; the other (termed 398079) expressed the lacto-N-neotetraose (LNT; Galbeta1 --> 4GlcNAcbeta1 --> 3Galbeta1 --> 4Glcbeta1 --> 4HepI) LOS structure. The strain from the male index case expressed both glycoforms and exhibited both immunotypes. Nuclear magnetic resonance analysis revealed that sialic acid linked to the terminal Gal of L1 LOS via an alpha2 --> 6 linkage and, as expected, to the terminal Gal of LNT LOS via an alpha2--> 3 linkage. Insertional inactivation of the sialyltransferase gene (known to sialylate LNT LOS) abrogated both L1 LOS sialylation and LNT LOS sialylation, suggesting a bifunctional nature of this enzyme in gonococci. Akin to our previous observations, sialylation of the LNT LOS of strain 398079 enhanced the binding of the complement regulatory molecule, factor H. Rather surprisingly, factor H did not bind to sialylated strain 398078. LOS sialylation conferred the LNT LOS-bearing strain complete (100%) resistance to killing by even 50% nonimmune normal human serum (NHS), whereas sialylation of L1 LOS conferred resistance only to 10% NHS. The ability of gonococcal sialylated LNT to bind factor H confers high-level serum resistance, which is not seen with sialylated L1 LOS. Thus, serum resistance mediated by sialylation of gonococcal L1 and LNT LOS occurs by different mechanisms, and specificity of factor H binding to sialylated gonococci is restricted to the LNT LOS species.