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1.
Transpl Infect Dis ; 25(6): e14172, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37937964

RESUMEN

Donor-derived infections in solid organ transplantation can be prevented by risk stratification of donors based on available information, and inquiries surrounding possible or diagnosed infection are common questions posed to transplant infectious disease subspecialists. This article outlines the five key steps in addressing a donor call from a transplant team in a systematic approach, focusing on donor and recipient-specific factors, transmissibility and treatment of possible infections, and the likelihood of a patient's future organ offers and mortality remaining on the waitlist. These principles are then applied to five donor call cases, in which we review the key takeaway points and supporting literature. These cases can be used as a resource for teaching with trainees.


Asunto(s)
Enfermedades Transmisibles , Trasplante de Órganos , Trasplantes , Humanos , Donantes de Tejidos , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes
2.
Int J Mol Sci ; 24(17)2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37686064

RESUMEN

In this report, we establish a straightforward method for estimating the equilibrium constant for the creatine kinase reaction (CK Keq″) over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq″ is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we were able to obtain improved estimates of ΔGATP, necessitating the reinvestigation of previously reported ADP- and ΔGATP-dependent processes. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies and pH is not altered, the maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis around the role of submicromolar ADP in force generation.


Asunto(s)
Creatina Quinasa , Músculos , Transducción de Señal , Citoesqueleto de Actina , Adenosina Trifosfato
3.
Shoulder Elbow ; 15(1): 61-64, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36895604

RESUMEN

Background: Glomus tumors, also known as benign acral tumors are extremely rare. Previous glomus tumors from other regions of the body have been linked to neurological compression symptoms, however axillary compression at the scapular neck has never been described. Case presentation: Here, we report a case of axillary nerve compression in a 47-year-old man, secondary to a glomus tumor of the neck of the right scapula, initially misdiagnosed with biceps tenodesis performed and no pain improvement. The magnetic resonance imaging demonstrated a well-contoured, 12 mm tumefaction at the inferior pole of the scapular neck T2-hyperintense and T1-isointense and interpreted as a neuroma. An axillary approach allowed the dissection of the axillary nerve, and the tumor was completely removed. The pathological anatomical analysis resulted in a nodular red lesion measuring 14 × 10 mm, delimited and encapsulated with a definitive diagnostic of glomus tumor. The neurologic symptoms and pain disappeared 3 weeks after surgery and the patient reported satisfaction with the surgical procedure. After 3 months, the results remain stable with a complete resolution of the symptoms. Conclusions: In cases of unexplained and atypical pain in the axillary area, and to avoid potential misdiagnoses and inappropriate treatments, an in-depth exploration for a compressive tumor should be performed as a differential diagnosis.

4.
Colorectal Dis ; 25(2): 253-260, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36222737

RESUMEN

AIM: The impact of surgeon volume on 18-month unclosed ileostomy rates after rectal cancer surgery has not been fully explored. The aim of this study was to describe the effect of surgeon volume and evaluate factors predictive of an unclosed ileostomy. METHOD: Patients undergoing anterior resection with a diverting ileostomy for rectal cancer from March 2004 to October 2018 were identified from a prospectively maintained database. The unclosed ileostomy rate was determined by those with an unclosed ileostomy at 18 months. High- and low-volume surgeons (HVS and LVS, respectively) were classed as those performing five or more or fewer than five rectal cancer resections per year, respectively. Data on sex, age, American Society of Anesthesiologists grade, neoadjuvant chemoradiotherapy (CRT), tumour height, T-stage, anastomotic leak, surgical approach and adjuvant chemotherapy were also collected. Factors predictive of an unclosed ileostomy at 18 months were explored using a multivariate binary logistic regression analysis. RESULTS: A total of 415 patients (62.4% male) with a median age of 67 were eligible for analysis. Of these, 115 (27.7%) had an unclosed ileostomy at 18 months. HVS had an unclosed ileostomy rate of 24.6% (72/292) compared with 34.9% (43/123) for LVS. Volume was associated with an unclosed ileostomy in univariable analysis (p = 0.032) but not in multivariate analysis (OR 1.75, 95% CI 0.92-3.32, p = 0.08). Independent factors predictive of an unclosed ileostomy were anastomotic leak (OR 10.41, 3.95-27.0, p < 0.01), adjuvant chemotherapy (OR 2.23, 1.24-3.96, p < 0.01) and neoadjuvant CRT (OR 2.16, 1.15-5.75, p = 0.01). CONCLUSION: LVS were associated with a higher unclosed ileostomy at 18 months compared with HVS. This study adds further weight to the call for adoption of a minimum annual case threshold in rectal cancer surgery.


Asunto(s)
Neoplasias del Recto , Cirujanos , Humanos , Masculino , Femenino , Fuga Anastomótica , Ileostomía , Recto/cirugía , Neoplasias del Recto/cirugía , Anastomosis Quirúrgica , Estudios Retrospectivos
6.
Front Oncol ; 12: 920444, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35860583

RESUMEN

Objectives: Partial or total resistance to preoperative chemoradiotherapy occurs in more than half of locally advanced rectal cancer patients. Several novel or repurposed drugs have been trialled to improve cancer cell sensitivity to radiotherapy, with limited success. We aimed to understand the mechanisms of resistance to chemoradiotherapy in rectal cancer using patient derived organoid models. Design: To understand the mechanisms underlying this resistance, we compared the pre-treatment transcriptomes of patient-derived organoids (PDO) with measured radiotherapy sensitivity to identify biological pathways involved in radiation resistance coupled with single cell sequencing, genome wide CRISPR-Cas9 and targeted drug screens. Results: RNA sequencing enrichment analysis revealed upregulation of PI3K/AKT/mTOR and epithelial mesenchymal transition pathway genes in radioresistant PDOs. Single-cell sequencing of pre & post-irradiation PDOs showed mTORC1 and PI3K/AKT upregulation, which was confirmed by a genome-wide CRSIPR-Cas9 knockout screen using irradiated colorectal cancer (CRC) cell lines. We then tested the efficiency of dual PI3K/mTOR inhibitors in improving cancer cell sensitivity to radiotherapy. After irradiation, significant AKT phosphorylation was detected (p=0.027) which was abrogated with dual PI3K/mTOR inhibitors and lead to significant radiosensitisation of the HCT116 cell line and radiation resistant PDO lines. Conclusions: The PI3K/AKT/mTOR pathway upregulation contributes to radioresistance and its targeted pharmacological inhibition leads to significant radiosensitisation in CRC organoids, making it a potential target for clinical trials.

7.
Mo Med ; 118(5): 422-425, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34658433

RESUMEN

The need to augment standardized learner outcomes related to performance and clinical competency led to creating curricular elements that would provide instruction and assessment from multiple perspectives. The COVID-19 pandemic brought about needs for re-imagination of standardized simulated clinical experiences given the need for increased distance-learning and asynchronous formats. Our goal was to identify activities that would engage pre-clinical simulation through asynchronous virtual reality (VR) case scenarios. The intent was to provide additional resources whereby competencies could be more defined through performance metrics and standardized assessments additive to our established simulation-based curriculum throughout all curricular phases. Student reflection and metacognition identified gaps to guide future performance improvement through the VR activities. Learner outcomes encompassing history-taking, physical assessment, evidence-based clinical reasoning, and medical decision-making guided the instructional objectives. The composite data showed progressive improvements over five scenarios delivered in our second-year clinical medicine curriculum.


Asunto(s)
COVID-19 , Realidad Virtual , Simulación por Computador , Humanos , Pandemias , SARS-CoV-2
8.
Int Orthop ; 45(10): 2653-2661, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34383105

RESUMEN

AIM: To demonstrate how reverse shoulder arthroplasty (RSA) planning software could be used to improve how the trainees position glenoid and humeral implants and obtain optimal simulated range of motion (ROM). METHODS: We selected four groups of five various level participants: medical student (MS), junior resident (JR), senior resident (SR), and shoulder expert (SE). Thereafter, the 20 participants planned five cases of arthritic shoulders for a RSA on a validated planning software following three phases: (1) no guidelines and no ROM feedback, (2) guidelines but no ROM feedback, and (3) guidelines and ROM feedback. We evaluated the final simulated impingement-free ROM, the choice of the implant (baseplate size, graft, glenosphere), and the glenoid implant positioning. RESULTS: MS planning were significantly improved by the ROM feedback only. JR took the best advantage of both guidelines and ROM in final results. SR planning were less performant than SE into phase 1 regarding flexion, external rotation, and adduction (respectively - 10°, p = 0.03; - 11°, p = 0.003; and - 3°, p = 0,03), but reached similar results into phase 3 (respectively - 2°, p = 0.329; - 4°, p = 0.44; - 2°, p = 0.319). For MS, JR, and SR, we observed a systematic improvement in the agreement over the study course. The glenoid diameter remained highly variable even for SE. Comparing glenoid implant position to SE, the distance error decreased with advancing phases. CONCLUSION: Planning software can be used as a simulation training tool to improve implant positioning in shoulder arthroplasty procedures.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Cavidad Glenoidea , Articulación del Hombro , Cavidad Glenoidea/diagnóstico por imagen , Cavidad Glenoidea/cirugía , Humanos , Rango del Movimiento Articular , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/cirugía , Programas Informáticos
9.
J Pathol ; 255(2): 132-140, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34156092

RESUMEN

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with fewer than 50 cases occurring per year in the UK. These tumours are both chemotherapy- and radiotherapy-resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA sequencing, and methylation array analysis. A recurrent mutation within exon 1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p.Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair, and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31, and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumourigenesis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.


Asunto(s)
Factores de Transcripción Forkhead/genética , Liposarcoma/genética , Neoplasias Retroperitoneales/genética , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación
10.
Bone Joint J ; 103-B(4): 718-724, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33789477

RESUMEN

AIMS: The aim of this study was to identify risk factors for recurrent instability of the shoulder and assess the ability to return to sport in patients with engaging Hill-Sachs lesions treated with arthroscopic Bankart repair and Hill-Sachs remplissage (ABR-HSR). METHODS: This retrospective study included 133 consecutive patients with a mean age of 30 years (14 to 69) who underwent ABR-HSR; 103 (77%) practiced sports before the instability of the shoulder. All had large/deep, engaging Hill-Sachs lesions (Calandra III). Patients were divided into two groups: A (n = 102) with minimal or no (< 10%) glenoid bone loss, and B (n = 31) with subcritical (10% to 20%) glenoid loss. A total of 19 patients (14%) had undergone a previous stabilization, which failed. The primary endpoint was recurrent instability, with a secondary outcome of the ability to return to sport. RESULTS: At a mean follow-up of four years (1.0 to 8.25), ten patients (7.5%) had recurrent instability. Patients in group B had a significantly higher recurrence rate than those in group A (p = 0.001). Using a multivariate logistic regression, the presence of glenoid erosion of > 10% (odds ratio (OR) = 35.13 (95% confidence interval (CI) 8 to 149); p = 0.001) and age < 23 years (OR = 0.89 (0.79 to 0.99); p = 0.038) were associated with a higher risk of recurrent instability. A total of 80 patients (78%) could return to sport, but only 11 athletes (65%) who practiced high-risk (collision or contact-overhead) sports. All seven shoulders which were revised using a Latarjet procedure were stable at a mean final follow-up of 36 months (11 to 57) and returned to sports at the same level. CONCLUSION: Patients with subcritical glenoid bone loss (> 10%) and younger age (≤ 23 years) are at risk of failure and reoperation after ABR-HSR. Furthermore, following this procedure, one-third of athletes practicing high-risk sports are unable to return at their pre-instability level, despite having a stable shoulder. Cite this article: Bone Joint J 2021;103-B(4):718-724.


Asunto(s)
Artroscopía/métodos , Lesiones de Bankart/patología , Lesiones de Bankart/cirugía , Adolescente , Adulto , Anciano , Traumatismos en Atletas/patología , Traumatismos en Atletas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo
11.
Science ; 371(6524): 86-90, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33384377

RESUMEN

Metamorphic proteins switch between different folds, defying the protein folding paradigm. It is unclear how fold switching arises during evolution. With ancestral reconstruction and nuclear magnetic resonance, we studied the evolution of the metamorphic human protein XCL1, which has two distinct folds with different functions, making it an unusual member of the chemokine family, whose members generally adopt one conserved fold. XCL1 evolved from an ancestor with the chemokine fold. Evolution of a dimer interface, changes in structural constraints and molecular strain, and alteration of intramolecular protein contacts drove the evolution of metamorphosis. Then, XCL1 likely evolved to preferentially populate the noncanonical fold before reaching its modern-day near-equal population of folds. These discoveries illuminate how one sequence has evolved to encode multiple structures, revealing principles for protein design and engineering.


Asunto(s)
Quimiocinas C/química , Evolución Molecular , Ingeniería de Proteínas , Pliegue de Proteína , Humanos , Multimerización de Proteína
12.
J Surg Oncol ; 123(2): 432-438, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33169386

RESUMEN

BACKGROUND OBJECTIVES: The impact of tumor necrosis as a prognostic factor in gastrointestinal stromal tumor (GISTs) is still debated. The objective was to determine whether tumor necrosis is an independent risk factor for survival in patients with GISTs. METHODS: Patients undergoing surgery for primary GIST from March 2003 to October 2018 at two sarcoma referral centers were retrospectively identified. Patients who received neoadjuvant imatinib were excluded. Multivariable Cox regression models were produced, to assess whether tumor necrosis was an independent predictor of either overall or recurrence-free survival. RESULTS: Forty-one out of 195 (21.0%) patients had tumor necrosis. Tumor necrosis was associated with a significantly higher modified National Institute of Health risk score, with 29 out of 41 (70.7%) patients with necrosis classified as high risk, compared to 52 out of 153 (34.0%) without (p < .001). Tumor necrosis was found to be independently predictive of recurrence-free survival (hazard ratio: 5.26, 95% CI: 2.62-10.56, p < .001) on multivariable analysis. At 5 years, 44.3% of patients with necrosis had either died or developed recurrence, compared to 9.9% of those without. CONCLUSION: Tumor necrosis is an independent predictor of recurrence-free survival in patients with operable GISTs. It should be routinely reported by pathologists, and used by clinicians when counseling patients and deciding on adjuvant therapy.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Neoplasias Gastrointestinales/mortalidad , Tumores del Estroma Gastrointestinal/mortalidad , Necrosis , Recurrencia Local de Neoplasia/mortalidad , Anciano , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
13.
Arthrosc Tech ; 9(8): e1121-e1131, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32874892

RESUMEN

Significant controversy exists regarding the optimal surgical technique for anterior cruciate ligament (ACL) reconstruction in adolescents with 1 to 3 years of skeletal growth remaining. Graft choice and physeal injury remain primary concerns given significantly elevated rates of failure of hamstring autograft reconstructions in this population, as well as risks of leg-length discrepancy and growth axis deviation. Traditional (more vertical) transtibial drilling of the femoral tunnel can reduce risks of physeal injury but has been shown to have less accuracy restoring the native femoral ACL footprint and associated incomplete knee stabilization. On the other hand, anteromedial and outside-in drilling yields improvements in the tunnel location and biomechanics but at the cost of a more oblique trajectory and greater risk of physeal injury. A hybrid transtibial pin technique using a Pathfinder guide facilitates femoral drilling with the "best of both worlds," allowing for reproduction of the native ACL footprint and a more physeal-respecting femoral tunnel. When combined with an all-soft tissue quadriceps tendon autograft and suspensory fixation, the hybrid transtibial method yields a reliable, safe, and robust construct with promising results for the young athlete. We describe our preferred graft harvest, tunnel drilling, and fixation techniques to minimize physeal risks and optimize outcomes.

14.
Am J Sports Med ; 48(12): 3021-3027, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32909820

RESUMEN

BACKGROUND: Open physes and trochlear/notch geometries in pediatric patients limit the safe corridor for femoral interference screw graft fixation during medial patellofemoral ligament (MPFL) reconstruction. Accordingly, interest is increasing in anchor-based fixation, but biomechanical validation is deficient. PURPOSE: To compare anchor-based and tenodesis screw femoral fixation of MPFL grafts in a time-zero biomechanical model. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-seven fresh-frozen porcine distal femurs were potted for testing in an electromechanical load frame, while bovine tendons were used for MPFL grafts. Reconstructions were performed with 1 of 3 femoral fixation strategies: 4.5-mm biocomposite double-loaded threaded anchor (DLA group), 3.9-mm biocomposite knotless threaded anchor (KA group), or traditional 7 × 23-mm biocomposite tenodesis screw (TS group). For testing, femoral specimens were oriented and secured in the mechanical testing apparatus such that actuator tensile pull re-created the normal MPFL trajectory. Specimens underwent 10 cycles of 5- to 15-N loading at 1-Hz preconditioning, followed by 1000 cycles of 10- to 50 N-loading at 1 Hz. After cyclic loading, all specimens were loaded to failure at 305 mm/min. The average cyclic construct stiffness, displacement, and load-to-failure data between the 3 groups were compared using analysis of variance (ANOVA) with the significance level set at P < .05. RESULTS: Average cyclic construct stiffnesses were comparable across groups per repeated-measures ANOVA analysis: 68.3 ± 6.3, 71.4 ± 6.4, and 74.3 ± 7.9 N/mm for TS, DLA, and KA groups, respectively (at cycle 1000). Average construct displacements at cycles 100 and 1000 were significantly less in the anchor versus tenodesis screw groups per ANOVA and Tukey post hoc analysis: 7.7 ± 4.2 mm for the TS group versus 3.7 ± 0.4 and 4.3 ± 0.6 mm for the DLA and KA groups, respectively (at cycle 1000). There was no significant difference in ultimate failure loads between the anchor and tenodesis screw groups, but 3 of 9 TS constructs failed at loads below the average failure load of the native MPFL. CONCLUSION: Compared with the tenodesis group, anchor-based fixation produced constructs with equivalent cyclic stiffnesses, improved load-displacement characteristics, and had less failure load variability in the porcine cadaveric model. CLINICAL RELEVANCE: Femoral fixation of the MPFL graft with a single anchor (4.5 or 3.9 mm threaded) is a viable alternative to traditional tenodesis screw fixation.


Asunto(s)
Tornillos Óseos , Tendones/trasplante , Tenodesis , Animales , Fenómenos Biomecánicos , Cadáver , Bovinos , Fémur/cirugía , Porcinos
15.
Food Sci Nutr ; 8(8): 4340-4351, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32884714

RESUMEN

In contrast to other pulses, chickpea has a relatively high fat content (3%-10%). This study was designed to investigate direct-expanded chickpea-sorghum extruded snacks (50:50, 60:40, and 70:30 chickpea:sorghum, w/w) with respect to: their oxidative stability and sensory properties during accelerated (55°C) and room temperature (25°C) storage; correlations between chemical markers (peroxide value and p-anisidine value) and sensory data during accelerated storage; and the shelf-life of snacks extruded at the optimal expansion point as determined by a rotatable central composite design. Peroxide values and p-anisidine values were in the range of 0-2.5 mEq/Kg and 5-30, respectively, for both accelerated and room temperature storage, and increased during storage (p < .05). 70:30 and 60:40 (w/w) chickpea-sorghum snacks had higher peroxide and p-anisidine values compared to the 50:50 snack during storage at either temperature (p < .05). Rancid aroma and off-flavor of 60:40 and 70:30 chickpea-sorghum snacks (slightly intense = 6) also were higher than that of the 50:50 snack (moderately weak = 3) (p < .05). Significant correlations (p < .05) were found between chemical markers and sensory attributes (p < .05). The study illustrated that shelf-life decreased as the percentage of chickpea in the blend increased. Therefore, in terms of shelf-life, a 50:50 chickpea-sorghum blend is preferable.

16.
Cancers (Basel) ; 12(5)2020 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-32443649

RESUMEN

Radiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in vivo tumour xenografts and a few Phase I/II clinical trials. Most of the current evidence in this area comes from glioblastoma multiforme, non-small cell lung cancer, head and neck cancer, colorectal cancer, and prostate cancer. The biological basis for radiosensitivity following pathway inhibition was through inhibited DNA double strand break repair, inhibited cell proliferation, enhanced apoptosis and autophagy as well as tumour microenvironment changes. Dual PI3K/mTOR inhibition consistently demonstrated radiosensitisation of all types of cancer cells. Single pathway component inhibitors and other inhibitor combinations yielded variable outcomes especially within early clinical trials. There is ample evidence from preclinical studies to suggest that direct pharmacological inhibition of the PI3K/AKT/mTOR pathway components can radiosensitise different types of cancer cells. We recommend that future in vitro and in vivo research in this field should focus on dual PI3K/mTOR inhibitors. Early clinical trials are needed to assess the feasibility and efficacy of these dual inhibitors in combination with radiotherapy in brain, lung, head and neck, breast, prostate and rectal cancer patients.

17.
Cancer Treat Rev ; 86: 102013, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32278233

RESUMEN

Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) - they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting.


Asunto(s)
Liposarcoma/genética , Neoplasias Retroperitoneales/genética , Animales , Antineoplásicos Alquilantes/uso terapéutico , Aberraciones Cromosómicas , Genómica/métodos , Humanos , Liposarcoma/tratamiento farmacológico , Liposarcoma/metabolismo , Proteínas de Fusión Oncogénica/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Retroperitoneales/metabolismo , Trabectedina/uso terapéutico
19.
World J Gastrointest Surg ; 11(11): 407-413, 2019 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-31798790

RESUMEN

BACKGROUND: Benign oesophageal strictures carry a significant level of morbidity, causing burdensome symptoms impacting on quality of life. Post-oesophagectomy anastomotic stricture rates as high as 41% have been reported in the literature. These can require endoscopic dilatation, often multiple times to relieve dysphagia. The aim of the present study was to determine a single surgeons stricture rate in a series of 2-stage Ivor-Lewis procedures, and to identify any independent risk factors in their development. AIM: To determine a single surgeons stricture rate in a series of 2-stage Ivor-Lewis procedures, and to identify any independent risk factors in their development. METHODS: We performed a retrospective analysis of a prospectively collected database of Ivor-Lewis oesophagectomy performed from 2004-2018 to determine the stricture rate. The database comprised a single-surgeon series of open, two-stage oesophagectomies with a circular stapled intra-thoracic anastomosis. Tumour location, histology, neoadjuvant chemotherapy, stapler size, T-stage and R-status were analysed to see if they could predict stricture formation. Stricture was defined as dysphagia requiring endoscopic dilatation. Patients with anastomotic leaks were excluded on the basis they would develop an anastomotic stricture. RESULTS: One hundred and seventy patients were collected in the database. Nineteen were excluded on the basis of anastomotic leak, perioperative death and early recurrence. One hundred and fifty-four patients (119 males, 35 females) with a mean age of 64 ± 10 years were eligible for analysis. A total of 15 patients developed strictures a median of 99 d (interquartile range: 84-133) after surgery, giving a Kaplan-Meier estimated stricture rate of 10% at one year. None of the factors considered were found to be significantly associated with strictures. CONCLUSION: In this study the stricture rate was 10%, with the majority occurring in the first 100 d after surgery. No significant independent factors were found in the development of strictures.

20.
Nutrients ; 11(9)2019 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-31540391

RESUMEN

Iron (Fe) deficiency is one of the most common nutritional disorders, and is mainly due to insufficient intake of bioavailable Fe. Chickpea (Cicer arietinum L.) was examined as a potential vehicle for Fe fortification. Fortificants (FeSO4·7H2O (ferrous sulfate hepta-hydrate), FeSO4·H2O (ferrous sulfate mono-hydrate) and NaFeEDTA (ethylenediaminetetraacetic acid iron (iii) sodium salt)) were applied by a spraying and drying method. At 2000 µg g-1 iron fortificant, the fortified split desi seeds (dal), desi flour and kabuli flour supplied 18-19 mg, 16-20 mg and 11-19 mg Fe per 100 g, respectively. The overall consumer acceptability using a nine-point hedonic scale for sensory evaluation demonstrated that NaFeEDTA-fortified cooked chickpea (soup and chapatti) scored the highest among the three fortificants. Lightness (L*), redness (a*) and yellowness (b*) of Fe-fortified products changed over time. However, no organoleptic changes occurred. Fe bioavailability was increased by 5.8-10.5, 15.3-25.0 and 4.8-9.0 ng ferritin mg-1 protein for cooked split desi seeds (soup), desi chapatti and kabuli chapatti, respectively, when prepared using Fe-fortified chickpea. Desi chapatti showed significantly higher Fe bioavailability than the other two. The increase in Fe concentration and bioavailability in fortified chickpea products demonstrated that these products could provide a significant proportion of the recommended daily Fe requirement.


Asunto(s)
Cicer/química , Harina/análisis , Alimentos Fortificados/análisis , Hierro , Semillas/química , Adulto , Disponibilidad Biológica , Culinaria , Ácido Edético , Compuestos Férricos , Compuestos Ferrosos , Preferencias Alimentarias , Humanos , Hierro/análisis , Hierro/farmacocinética , Persona de Mediana Edad , Adulto Joven
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