Background
There are concerns about the extent of impaired endocrine and exocrine pancreatic function and poor quality of life (QoL) after pancreatectomy, but there is little information from large ...prospective follow‐up studies.
Methods
Consecutive patients undergoing pancreaticoduodenectomy or distal pancreatectomy between 2007 and 2011 were included. Relative bodyweight (RBW), triceps skinfold thickness (TSFT), serum protein, albumin, transferrin, fasting blood glucose, postprandial 2‐h glucose (PP2), glycosylated haemoglobin A1c and stool elastase measurements, and European Organization for Research and Treatment of Cancer QLQ‐C30 questionnaires were collected serially for 1 year.
Results
Some 136 patients undergoing pancreatic resection completed the study. RBW and TSFT recovered to over 90 per cent of the preoperative value by 12 months, whereas transferrin, albumin and protein had returned to preoperative levels by 3 months. Diabetes mellitus, impaired fasting glucose or raised PP2 was present in 42 of 76 patients at 6 months and 36 of 76 at 12 months. Although steatorrhoea and diarrhoea had mainly resolved by 3 months, stool elastase level decreased after operation and showed no recovery. Nutritional status, pancreatic endocrine function and QoL returned to preoperative levels in 63 (46·3 per cent), 72 (52·9 per cent) and 77 (56·6 per cent) of 136 patients within 6 months of pancreatectomy. Multivariable analysis revealed that age 60 years or more, operation type, chronic pancreatitis and malignant disease had a significant impact on nutritional index, pancreatic function and QoL.
Conclusion
About half of all patients can expect recovery from pancreatectomy after 6 months, but those with risk factors need more careful follow‐up and supportive management.
Reasonable recovery takes at least 6 months
Tumour-infiltrating lymphocytes (TILs) are known to be associated with response to primary systemic therapy (PST) in breast cancer. This study was conducted to assess the association of TIL subsets ...with pathological complete response (pCR) after PST in breast cancer in relation to breast cancer subtype, breast cancer stem cell (BCSC) phenotype and epithelial-mesenchymal transition (EMT).
The pre-chemotherapeutic biopsy specimens of 153 breast cancer patients who underwent surgical resection after anthracycline- or anthracycline/taxane-based PST were analysed. TIL subsets (CD4+, CD8+, and FOXP3+ TILs), BCSC phenotype, and the expression of EMT markers were evaluated by immunohistochemistry and were correlated with pCR after PST.
Infiltration of CD4+ and CD8+ T lymphocytes was closely correlated with BCSC phenotype and EMT. High levels of CD4+, CD8+, and FOXP3+ TILs were associated with pCR, and CD8+ TILs were found to be an independent predictive factor for pCR. In addition, CD8+ TILs were associated with pCR irrespective of breast cancer subtype, CD44+/CD24- phenotype, EMT, and chemotherapeutic regimen in subgroup analyses.
These findings indicate that CD8+ cytotoxic T lymphocytes are a key component of TILs associated with chemo-response and can be used as a reliable predictor of response to anthracycline- or anthracycline/taxane-based PST in breast cancer.
To compare the diagnostic performance of PET with the amyloid ligand Pittsburgh compound B (PiB-PET) to fluorodeoxyglucose (FDG-PET) in discriminating between Alzheimer disease (AD) and ...frontotemporal lobar degeneration (FTLD).
Patients meeting clinical criteria for AD (n = 62) and FTLD (n = 45) underwent PiB and FDG-PET. PiB scans were classified as positive or negative by 2 visual raters blinded to clinical diagnosis, and using a quantitative threshold derived from controls (n = 25). FDG scans were visually rated as consistent with AD or FTLD, and quantitatively classified based on the region of lowest metabolism relative to controls.
PiB visual reads had a higher sensitivity for AD (89.5% average between raters) than FDG visual reads (77.5%) with similar specificity (PiB 83%, FDG 84%). When scans were classified quantitatively, PiB had higher sensitivity (89% vs 73%) while FDG had higher specificity (83% vs 98%). On receiver operating characteristic analysis, areas under the curve for PiB (0.888) and FDG (0.910) were similar. Interrater agreement was higher for PiB (κ = 0.96) than FDG (κ = 0.72), as was agreement between visual and quantitative classification (PiB κ = 0.88-0.92; FDG κ = 0.64-0.68). In patients with known histopathology, overall classification accuracy (2 visual and 1 quantitative classification per patient) was 97% for PiB (n = 12 patients) and 87% for FDG (n = 10).
PiB and FDG showed similar accuracy in discriminating AD and FTLD. PiB was more sensitive when interpreted qualitatively or quantitatively. FDG was more specific, but only when scans were classified quantitatively. PiB slightly outperformed FDG in patients with known histopathology.
Near infrared spectroscopy (NIRS) is a non-invasive method to measure brain activity via changes in the degree of hemoglobin oxygenation through the intact skull. As optically measured hemoglobin ...signals strongly correlate with BOLD signals, simultaneous measurement using NIRS and fMRI promises a significant mutual enhancement of temporal and spatial resolutions. Although there exists a powerful statistical parametric mapping tool in fMRI, current public domain statistical tools for NIRS have several limitations related to the quantitative analysis of simultaneous recording studies with fMRI. In this paper, a new public domain statistical toolbox known as NIRS-SPM is described. It enables the quantitative analysis of NIRS signal. More specifically, NIRS data are statistically analyzed based on the general linear model (GLM) and Sun's tube formula. The
p-values are calculated as the excursion probability of an
inhomogeneous random field on a representation manifold that is dependent on the structure of the error covariance matrix and the interpolating kernels. NIRS-SPM not only enables the calculation of activation maps of oxy-, deoxy-hemoglobin and total hemoglobin, but also allows for the super-resolution localization, which is not possible using conventional analysis tools. Extensive experimental results using finger tapping and memory tasks confirm the viability of the proposed method.
The multistep sequence leading to leukocyte migration is thought to be locally regulated at the inflammatory site. Here, we show that broad systemic programs involving long-range signals from the ...sympathetic nervous system (SNS) delivered by adrenergic nerves regulate rhythmic recruitment of leukocytes in tissues. Constitutive leukocyte adhesion and migration in murine bone marrow (BM) and skeletal-muscle microvasculature fluctuated with circadian peak values at night. Migratory oscillations, altered by experimental jet lag, were implemented by perivascular SNS fibers acting on β-adrenoreceptors expressed on nonhematopoietic cells and leading to tissue-specific, differential circadian oscillations in the expression of endothelial cell adhesion molecules and chemokines. We showed that these rhythms have physiological consequences through alteration of hematopoietic cell recruitment and overall survival in models of septic shock, sickle cell vaso-occlusion, and BM transplantation. These data provide unique insights in the leukocyte adhesion cascade and the potential for time-based therapeutics for transplantation and inflammatory diseases.
Display omitted
► Leukocyte recruitment in tissues exhibits a circadian rhythm peaking at night ► Absence of local innervation abolishes oscillations ► Diurnal expression of adhesion molecules mediates circadian leukocyte recruitment ► Circadian time influences leukocyte recruitment in inflammation
The aim of the present study was to assess the efficacy and safety of teneligliptin in combination with metformin in Korean patients with type 2 diabetes mellitus who were inadequately controlled ...with metformin monotherapy. Patients glycated haemoglobin (HbA1c) 7.0–10.0%, on stable metformin ≥1000 mg/day were randomized 2 : 1 to receive 20 mg teneligliptin plus metformin (n = 136) or placebo plus metformin (n = 68). The primary endpoint was the change in HbA1c levels from baseline to week 16. The mean baseline HbA1c was 7.9% in the teneligliptin group and 7.8% in the placebo group. The differences between the teneligliptin and placebo groups regarding changes in HbA1c and fasting plasma glucose levels were −0.78 % and −1.24 mmol/l (22.42 mg/dl), respectively, at week 16. The incidence of adverse events was similar between the groups. The addition of teneligliptin once daily to metformin was effective and generally well tolerated in Korean patients with type 2 diabetes.
A
bstract
We present measurements of the branching fractions for the decays
B
→
Kμ
+
μ
−
and
B
→
Ke
+
e
−
, and their ratio (
R
K
), using a data sample of 711 fb
−
1
that contains 772 × 10
6
B
B
¯
...events. The data were collected at the ϒ(4
S
) resonance with the Belle detector at the KEKB asymmetric-energy
e
+
e
−
collider. The ratio
R
K
is measured in five bins of dilepton invariant-mass-squared (
q
2
):
q
2
∈ (0
.
1
,
4
.
0)
,
(4
.
00
,
8
.
12)
,
(1
.
0
,
6
.
0), (10
.
2
,
12
.
8) and (
>
14
.
18) GeV
2
/c
4
, along with the whole
q
2
region. The
R
K
value for
q
2
∈ (1
.
0
,
6
.
0) GeV
2
/c
4
is
1.03
−
0.24
+
0.28
± 0
.
01. The first and second uncertainties listed are statistical and systematic, respectively. All results for
R
K
are consistent with Standard Model predictions. We also measure
CP
-averaged isospin asymmetries in the same
q
2
bins. The results are consistent with a null asymmetry, with the largest difference of 2.6 standard deviations occurring for the
q
2
∈ (1
.
0
,
6
.
0) GeV
2
/c
4
bin in the mode with muon final states. The measured differential branching fractions,
d
ℬ
/dq
2
, are consistent with theoretical predictions for charged
B
decays, while the corresponding values are below the expectations for neutral
B
decays. We have also searched for lepton-flavor-violating
B
→
Kμ
±
e
∓
decays and set 90% confidence-level upper limits on the branching fraction in the range of 10
−
8
for
B
+
→
K
+
μ
±
e
∓
, and
B
0
→
K
0
μ
±
e
∓
modes.
We report on the effects of carbon content on the martensitic transformation and its contribution to the work-hardening behavior of Fe–Mn–C steels during tensile deformation based on analysis by ...X-ray diffraction, electron backscatter diffraction and transmission electron microscopy. Austenite/ε-martensite dual-phase Fe–17Mn–C (wt.%) steels containing different carbon contents (0.01, 0.10, 0.20 wt.%) were investigated before, during and after tensile deformation. Before deformation, the transformation of austenite to thermally induced ε-martensite on cooling was suppressed as the carbon content increases. To precisely monitor microstructural changes during deformation, stepwise loading experiments were carried out in combination with electron backscatter diffraction analysis. This approach revealed that with increasing carbon content, the kinetics of transformation of γ phase to deformation stimulated ε-martensite became faster, while that of ε-martensite to α’-martensite was sluggish. We attribute this controversial effect to an increased γ grain size by the microstructural refinement of thermally induced ε-martensite and the reduction of solid solution strengthening effects by the redistribution of solute carbon. In addition, the dependence of deformation-induced ε-martensite on the loading direction differed from that of α’-martensite, and the evolution of α’ morphology was controlled by achieving appropriate levels of strain during stepwise loading. Based on the observations at the surface and inside the bulk after deformation, insights into various deformation-driven displacive phenomena, such as the formation of α’-martensite at the nonintersecting parts of two εinitial bands, the presence of nanotwinned bundles inside austenite, cementite precipitation inside α’-martensite, and the origin of the serrated flow in strain–stress curves, were obtained. Therefore, the present study is able assist in identifying whether the deformation-induced martensitic transformation varied as a function of carbon content and the resulting fracture behavior, thereby enabling us to understand the work-hardening behavior of these steels.