RESUMEN

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer (BTC), published in late 2022 were adapted in December 2023, according to established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with BTC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with BTC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Taiwan Oncology Society (TOS). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. Drug access and reimbursement in the different regions of Asia are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with BTC across the different countries and regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices and molecular profiling, as well as age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different countries.

Asunto(s)

RESUMEN

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Asunto(s)

RESUMEN

AIM: To determine the efficacy of preoperative chemoradiotherapy as per the CROSS protocol for oesophageal/gastroesophageal junction cancer (OEGEJC), when expanded to patients outside of the inclusion/exclusion criteria defined in the original clinical trial. MATERIALS AND METHODS: Data were collected retrospectively on 229 OEGEJC patients referred for curative-intent preoperative chemoradiotherapy. Outcomes including pathological complete response (pCR), overall survival (OS), cancer-specific survival and recurrence-free survival (RFS) of patients who met CROSS inclusion criteria (MIC) versus those who failed to meet criteria (FMIC) were determined. RESULTS: In total, 42.8% of patients MIC, whereas 57.2% FMIC; 16.6% of patients did not complete definitive surgery. The MIC cohort had higher rates of pCR, when compared with the FMIC cohort (33.3% versus 20.6%, P = 0.039). The MIC cohort had a better RFS, cancer-specific survival and OS compared with the FMIC cohort (P = 0.006, P = 0.004 and P = 0.009, respectively). Age >75 years and pretreatment weight loss >10% were not associated with a poorer RFS (P = 0.541 and 0.458, respectively). Compared with stage I-III patients, stage IVa was associated with a poorer RFS (hazard ratio (HR) = 2.158; 95% confidence interval (CI) = 1.339-3.480, P = 0.001). Tumours >8 cm in length or >5 cm in width had a trend towards worse RFS (HR = 2.060; 95% CI = 0.993-4.274, P = 0.052). CONCLUSION: Our study showed that the robust requirements of the CROSS trial may limit treatment for patients with potentially curable OEGEJC and can be adapted to include patients with a good performance status who are older than 75 years or have >10% pretreatment weight loss. However, the inclusion of patients with celiac nodal metastases or tumours >8 cm in length or >5 cm in width may be associated with poor outcomes.

Asunto(s)

RESUMEN

China's initial participation in the global monitoring of auroras for scientific and space weather investigations has been enabled by the successful launch of the Chinese Fengyun-3D satellite, which carries a wide-field auroral imager.

RESUMEN

The ability of dipolarizing flux bundles (DFBs) in transporting magnetic flux from the mid-tail reconnection site for near-Earth dipolarization is evaluated by two methods: the generalized Ohm's law and the concept of flux preserving and line preserving. From the generalized Ohm's law, the breakdown of the frozen-in condition (FIC) for ions is shown to be intimately related to that for electrons. When FIC is not satisfied for the ion fluid associated with energy conversion, it also implies the same for the electron fluid. When FIC holds, the plasma has the flux preserving property. It further guarantees that charged particles on a given magnetic field line will stay together on a magnetic field line at later times, i.e., line preserving. Conversely, when line preserving does not hold, flux preserving does not hold also. Previous detailed examination on the FIC for DFBs revealed that the majority of DFBs associated with energy conversion violate the FIC for the ion fluid. This implies that FIC does not hold for the electron fluid also. Furthermore, plasmas in substorm injections come from vastly different locations, violating the line preserving property and implying that FIC is broken for the magnetic flux tubes associated with substorm injection and dipolarization. These observations indicate that DFBs are not an effective agent to transport magnetic flux within the magnetosphere and further imply that mid-tail magnetic reconnection is rather ineffective in transporting magnetic flux for near-Earth dipolarization.

RESUMEN

3D printing is used extensively in product prototyping and continues to emerge as a viable option for the direct manufacture of final parts. It is known that dielectric materials with relatively high real permittivity-which are required in important technology sectors such as electronics and communications-may be 3D printed using a variety of techniques. Among these, the fused deposition of polymer composites is particularly straightforward but the range of dielectric permittivities available through commercial feedstock materials is limited. Here we report on the fabrication of a series of composites composed of various loadings of BaTiO3 microparticles in the polymer acrylonitrile butadiene styrene (ABS), which may be used with a commercial desktop 3D printer to produce printed parts containing user-defined regions with high permittivity. The microwave dielectric properties of printed parts with BaTiO3 loadings up to 70 wt% were characterised using a 15 GHz split post dielectric resonator and had real relative permittivities in the range 2.6-8.7 and loss tangents in the range 0.005-0.027. Permittivities were reproducible over the entire process, and matched those of bulk unprinted materials, to within ~1%, suggesting that the technique may be employed as a viable manufacturing process for dielectric composites.

RESUMEN

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.(AU)

Asunto(s)

RESUMEN

A new synchrotron-based technique for elemental imaging that combines radiography and fluorescence spectroscopy has been developed and applied to study the spatial distribution of Ag, Zr and Mo in an Al alloy during heating and melting to 700, and then re-soldification. For the first time, multi-element distributions have been mapped independently and simultaneously, showing the dissolution of Ag- and Zr-rich particles during melting and the inter-dendritic segregation of Ag during re-solidification. The new technique is shown to have wide potential for metallurgical and materials science applications where the dynamics of elemental re-distribution and segregation in complex alloys is of importance.

RESUMEN

Histopathological and ultrastructural investigations were conducted on 36 tench, Tinca tinca (L.), from Lake Trasimeno (Italy). The gills, intestine, liver, spleen, kidney and heart of 21 individuals were found to harbour an extensive infection of larvae of an unidentified digenean trematode. The eyes, gonads, swim bladder and muscles were uninfected. The parasites in each tissue type were embedded in a granulomatous proliferation of tissue, forming a reactive fibroconnective capsule around each larva. Most of the encysted larvae were metacercariae, in a degenerative state, but on occasion some cercariae were found. Many of the granulomas were either necrotic or had a calcified core. Within the granuloma of each, the occurrence of granulocytes, macrophages, rodlet cells and pigment-bearing macrophage aggregates was observed. Hearts bore the highest parasitic infection. Whilst the presence of metacercariae within the intestine was found positioned between the submucosa and muscle layers, metacercariae in the liver were commonly found encysted on its surface where the hepatocytes in close contact with the granuloma were observed to have electron-lucent vesicles within their cytoplasm. Metacercariae encysting adjacent to the cartilaginous rods of gill filaments were seen to elicit a proliferation of the cartilage from the perichondrium. Rodlet cells, neutrophils and mast cells were frequently observed in close proximity to, and within, infected gill capillaries. Given the degenerated state of most granulomas, a morphology-based identification of the enclosed digeneans was not possible.

Asunto(s)

RESUMEN

A histochemical and ultrastructural investigation of the cellular inflammatory response within the intestines of tench Tinca tinca L. naturally infected with the caryophyllidean cestode Monobothrium wageneri was conducted and the data obtained compared to those in uninfected counterparts. Cestode infections within the intestines were evident through the appearance of raised inflammatory swellings induced by the deep penetration of their scolices into the intestinal wall. Cestodes typically attached in tight clusters, inducing a massive hyperplastic granulocyte response of mast cells and neutrophils, which were significantly more numerous (P < 0·01) in the intestines of infected (n = 14) than of uninfected (n = 9) tench. Neutrophils were more abundant than mast cells (P < 0·01) in host tissues in close proximity to the parasite tegument. In transmission electron microscopy sections, mast cells and neutrophils were frequently observed in contact with or inside capillaries, and in close proximity to the cestode. Degranulation of both cell types was seen in the submucosa and lamina muscularis, notably in the immediate tissues surrounding the scolex of M. wageneri. No tegumental secretions were seen at the host-parasite interface. Occasional rodlet cells were encountered in the submucosa of infected fish.

Asunto(s)

RESUMEN

Light, ultrastructural and immunocytochemical investigations were carried out on the skin of gilthead seabream, Sparus aurata L., naturally infected with lymphocystis iridovirus, to assess pathology and host cellular responses. Of 220,000 young seabream examined, 32,400 (14.7%) had clinical signs of lymphocystis and within 6 months of disease appearance, 45% of clinically affected fish had died. A subsample of 20 S. aurata (80.0 ± 12.5mm total length, mean ± S.D.), including 10 with lymphocystis on the skin and 10 clinically normal, were examined via immunohistochemistry. Affected skin displayed macroscopic, wart-like clusters of hypertrophic fibroblasts which arose from the dermis and were covered by the epithelium. Clusters were encountered on the head, trunk and fins, but there was no evidence of visceral lymphocystis. The lymphocysts were surrounded by numerous granular cells that were positive for the antimicrobial peptide (AMP) piscidin 3 and underwent intense degranulation. To identify the type of granular cells involved in this viral disease, a double immunohistochemical staining with the monoclonal antibody G7 (mAb G7), which is specific for seabream acidophilic granulocytes (AGs), and with anti-histamine (as a marker for mast cells, MCs) was applied to the skin sections of the 10 clinically normal fish and 10 fish with lymphocystis. In infected skin, the number of G7-positive cells (i.e., AGs) (18.5 ± 10.5, mean number of cells per 20,000 µm(2) ± S.D.) was significantly higher compared to their density in uninfected skin (1.4 ± 2.2) (t test, p<0.01). Notably, the AGs that infiltrated the skin lesions of infected animals were found to be degranulated and to produce the pro-inflammatory cytokine interleukin-1ß. No histamine-positive granular cells (i.e., MCs) were encountered in the lymphocystis lesions. The present study shows the response of skin to lymphocystis disease virus (LCDV) and provides evidence that AGs, but not MCs, are recruited and activated in response to this skin infection.

Asunto(s)

RESUMEN

A total of 37 European eels, Anguilla anguilla, collected from Lake Piediluco, Central Italy, and measuring 35 to 75.5 cm in total length (mean±1 SD, 56.41 ± 10.89 cm) were examined, and their acanthocephalan infections assessed. Thirty-two (86.49%) eels were infected with Acanthocephalus rhinensis (mean±1 SD, 67.38 ± 65.16; range, 1-350), a species that, purportedly, can be discriminated on the basis of a characteristic band of orange-brown pigmentation encircling the anterior end of the trunk. This feature, however, was not seen on any of the A. rhinensis specimens that were removed, either attached to the gut wall or free within the gut lumen, from infected eels. Approximately 40% of the eels were coinfected with the dracunculid swimbladder nematode Anguillicoloides crassus, while a single eel was also coinfected with eight specimens of a second acanthocephalan, Dentitruncus truttae. From the stomachs of two eels, 109 intact and partially digested specimens of amphipod Echinogammarus tibaldii (Pinkster & Stock 1970) were recovered, 16 (14.6%) of these were infected with one to two cystacanths of A. rhinensis per host. From a sample of 850 E. tibaldii taken from the peripheral lakeside vegetation, 102 (12%; sex ratio, 1:1) gammarids were infected with one to two A. rhinensis cystacanths. Unparasitised ovigerous female E. tibaldii specimens had significantly higher numbers of eggs in their brood pouches compared with their infected counterparts (t-test, P < 0.01).

Asunto(s)

RESUMEN

The method, which allows shape reconstruction by reading the intensity from the scanning electron microscopy image, is presented and discussed in details. The method is applied to read the morphology of etch-pits, which were formed on the GaN surface by etching in molten KOH-NaOH eutectic mixture to delineate dislocations. The etch-pit depth distributions are obtained and used to determine densities of pits related to screw, mixed or edge-type dislocations. The results are compared with atomic force microscopy.

RESUMEN

Angelopoulos et al. (Research Articles, 15 August 2008, p. 931) reported that magnetic reconnection in Earth's magnetotail triggered the onset of a magnetospheric substorm. We provide evidence that (i) near-Earth current disruption, occurring before the conventional tail reconnection signatures, triggered the onset; (ii) the observed auroral intensification and tail reconnection are not causally linked; and (iii) the onset they identified is a continuation of earlier substorm activities.

RESUMEN

Immunopathological and ultrastructural studies were carried out on the gut of 30 specimens of powan Coregonus lavaretus (L.) from Lake Piediluco, Italy. The digestive tracts of 10 (33.3%) of the powan were found to harbour an acanthocephalan Dentitruncus truttae (Sinzar 1955). The numerous trunk spines of D. truttae reduced the number of mucosal folds near the parasite site of infection. The acanthocephalan induced hyperplasia and hypertrophy of the intestinal mucous cells and many worms were surrounded with an adherent mucous gel. Near the site of acanthocephalan attachment, the number of mucous cells was significantly higher (P<0.01) in comparison to those found in uninfected intestines. Rodlet cells (RCs) were present in the epithelial layer in both infected and uninfected fish, with no significant difference in the numbers observed (P>0.05). In infected intestine, mast cells were more abundant than in uninfected gut (P<0.01). Migration of the mast cells and their intense degranulation at the site of infection were suggested. Immunohistochemical tests applied to sections of intestinal tissue of both infected and uninfected powan revealed that the parasitized C. lavaretus had a larger number of mast cells positive for met-enkephalin and serotonin antisera.

Asunto(s)

RESUMEN

OBJECTIVES: While lower socioeconomic status is associated with lower level of education and increased incidence of cardiovascular diseases, the impact of socioeconomic status on out-of-hospital cardiac arrest outcomes is unclear. We used residential property values as a proxy for socioeconomic status to determine if there was an association with: (1) bystander CPR rates and (2) survival to hospital discharge for out-of-hospital cardiac arrest. METHODS: We performed a secondary data analysis of cardiac arrest cases prospectively collected as part of the Ontario Prehospital Advanced Life Support study, conducted in 20 cities with ALS and BLS-D paramedics. We measured patient and system characteristics for cardiac arrests of cardiac origin, not witnessed by EMS, occurring in a single residential dwelling. We obtained property values from the Municipal Property Assessment Corporation. Analyses included descriptive statistics with 95% CIs and stepwise logistic regression. RESULTS: Three thousand six hundred cardiac arrest cases met our inclusion criteria between 1 January 1995 and 31 December 1999. Patient characteristics were: mean age 69.2, male 67.8%, witnessed 44.7%, bystander CPR 13.2%, VF/VT 33.8%, time to vehicle stop 5:36min:s, return of spontaneous circulation 12.7%, and survival 2.7%. Median property value was $184,000 (range $25,500-2,494,000). For each $100,000 increment in property value, the likelihood of receiving bystander CPR increased (OR=1.07; 95% CI 1.01-1.14; p=0.03) and survival decreased (OR=0.77; 95% CI 0.61-0.97; p=0.03). CONCLUSIONS: This is the largest study showing an association between socioeconomic status and survival, and the first study showing an association with bystander CPR. Our findings suggest targeting CPR training among lower socioeconomic groups.

Asunto(s)

RESUMEN

Fish serve as a good model for studying vertebrate immune systems because they have a relatively simple system. Descriptions of histopathological effects of helminth parasites on fish are few and far between with limited observations made on the identification of the inflammatory cells involved in the host reaction. Recently, two cell types found within teleosts received a great deal of attention, namely mast cells and rodlet cells. Fish most cells also known as eosinophilic granule cells, are morphologically and functionally similar to their mammalian counterparts. Acute tissue damage causes mast cells degranulation and the release of mediators of inflammation, whereas, an increase in the number of these cells is usually found in chronically inflamed tissues. Rodlet cells, however, are exclusive to fish and are characterized by a distinct cell cortex and conspicuous inclusions, called rodlets, which accounts for their name. Piscidin has also been encountered within rodlet cells. As important cell types within the immune system of fish, both mast cells and rodlet cells have been seen to increase in number in infected fish, notably at the sites of pathogen attachment or infection. The present survey will provide data from studies with the light microscope on the response of mast cells and rodlet cells in a range of fish species (Anguilla anguilla, Oncorhynchus mykiss, Salmo trutta, Coregonus lavoretus) infected with a range of different parasite genera including representatives from the Digenea, Cestoda, Nematoda and Acanthocephala.

Asunto(s)

RESUMEN

BACKGROUND: Docetaxel induces an anti-tumor response in men with advanced prostate cancer (PCa); however, the side effects associated with docetaxel treatment can be severe, resulting in discontinuation of therapy. Thus, identification of an effective adjuvant therapy to allow lower doses of docetaxel is needed. Advanced PCa is typically accompanied by skeletal metastasis. Receptor activator of NFkB ligand (RANKL) is a key pro-osteoclastic factor. Targeting RANKL decreases establishment and progression of PCa growth in bone in murine models. METHODS: The efficacy of inhibiting RANKL, using a recombinant soluble RANK extracellular domain fused with the immunoglobulin Fc domain (RANK-Fc), was tested as an adjuvant therapy with docetaxel for PCa bone metastasis in a murine intra-tibial model. RESULT: The combination of RANK-Fc and docetaxel reduced tumor burden in bone greater than either treatment alone. CONCLUSION: The combination of docetaxel with a RANKL-inhibiting agent merits further investigation for treatment of advance PCa.

Asunto(s)

RESUMEN

LBH589 is a novel cinnamic hydroxamic acid analog (HAA) pan-histone deacetylase inhibitor (HDACi) currently in early phase clinical development.

Asunto(s)

RESUMEN

The effect of a naturally acquired infection by three acanthocephalan parasites Dentitruncus truttae, Echinorhynchus truttae, and Polymorphus minutus on the reproductive potential of their intermediate host, Echinogammarus tibaldii (Amphipoda) from Lake Piediluco (Centre of Italy) was assessed. During May 2007, 1135 amphipods were collected from two different samplings and examined for larval helminths. Forty-five amphipods were infected and of those, 16 were infected with D. truttae (intensity=1-3 larvae), 15 with E. truttae (intensity=1-2 larvae), and 14 with P. minutus (intensity=1 larva). The sex ratio was nearly 1:1 in all examined amphipods. One female infected with D. truttae contained six eggs in the brood pouch and another female infected with E. truttae contained five eggs. However, none of the eight female amphipods harbouring P. minutus larva contained eggs in their brood pouch. Uninfected females of the same size and body length as that of the infected females contained between 20 and 32 eggs. No acanthocephalan species were found to co-occur.

Asunto(s)