The liver is the commonest site of metastatic disease for patients with colorectal cancer,with at least 25%developing colorectal liver metastases(CRLM)during the course of their illness.The management of CRLM has evol...The liver is the commonest site of metastatic disease for patients with colorectal cancer,with at least 25%developing colorectal liver metastases(CRLM)during the course of their illness.The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology(cross sectional,nuclear medicine and interventional),Oncology,Liver surgery,Colorectal surgery,and Histopathology.Patient management is based on assessment of sophisticated clinical,radiological and biomarker information.Despite incomplete evidence in this very heterogeneous patient group,maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure.To this end,liver resection is maximised by the use of downsizing chemotherapy,optimisation of liver remnant by portal vein embolization,associating liver partition and portal vein ligation for staged hepatectomy,and combining resection with ablation,in the context of improvements in the functional assessment of the future remnant liver.Liver resection may safely be carried out laparoscopically or open,and synchronously with,or before,colorectal surgery in selected patients.For unresectable patients,treatment options including systemic chemotherapy,targeted biological agents,intraarterial infusion or bead delivered chemotherapy,tumour ablation,stereotactic radiotherapy,and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability.Currently evolving areas include biomarker characterisation of tumours,the development of novel systemic agents targeting specific oncogenic pathways,and the potential reemergence of radical surgical options such as liver transplantation.展开更多
We aimed to determine short-term patient-reported outcomes in men having general anesthetic transperineal （TP） prostate biopsies. A prospective cohort study was performed in men having a diagnostic TP biopsy. This w...We aimed to determine short-term patient-reported outcomes in men having general anesthetic transperineal （TP） prostate biopsies. A prospective cohort study was performed in men having a diagnostic TP biopsy. This was done using a validated and adapted questionnaire immediately post-biopsy and at follow-up of between 7 and 14 days across three tertiary referral hospitals with a response rate of 51.6%. Immediately after biopsy 43/201 （21.4%） of men felt light-headed, syncopal, or suffered syncope. Fifty-three percent of men felt discomfort after biopsy （with 95% scoring 〈5 in a 0-10 scale）. Twelve out of 196 men （6.1%） felt pain immediately after the procedure. Despite a high incidence of symptoms （e.g., up to 75% had some hematuria, 47% suffered some pain）, it was not a moderate or serious problem for most, apart from hemoejaculate which 31 men suffered. Eleven men needed catheterization （5.5%）. There were no inpatient admissions due to complications （hematuria, sepsis）. On repeat questioning at a later time point, only 25/199 （12.6%） of men said repeat biopsy would be a significant problem despite a significant and marked reduction in erectile function after the procedure. From this study, we conclude that TP biopsy is well tolerated with similar side effect profiles and attitudes of men to repeat biopsy to men having TRUS biopsies. These data allow informed counseling of men prior to TP biopsy and a benchmark for tolerability with local anesthetic TP biopsies being developed for clinical use.展开更多
Objective Embryonic movements （EM） and angiogenesis pathways are evolutionarily conserved mechanisms which are essential for proper embryonic development. Deviations in these processes by exposure to cigarette smoke...Objective Embryonic movements （EM） and angiogenesis pathways are evolutionarily conserved mechanisms which are essential for proper embryonic development. Deviations in these processes by exposure to cigarette smoke condensate （CSC） may cause vascular and morphogenetic disorders. Methods Using chicken and mouse embryos, we have demonstrated the in vivo effects of CSC on EM, vascular development, and organogenesis. Results Examination of the CSC exposed chicken embryos revealed a significant reduction in EM, stunted growth, deviated pattern of blood vessels, hemorrhages, and localized necrosis. Likewise, mouse embryos that were exposed to CSC at E8.5 and E9.5 died between E11.5 and E12.5, respectively. These mouse embryos showed defects in morphogenesis and remodeling of the embryonic vasculature, while littermate controls showed normal development. Conclusion Cigarette smoking during pregnancy is fatal for growing embryos. CSC may induce the remodeling of embryonic vasculature, leading to various pathologies.展开更多
The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks sti...The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks still need to be overcome and this form of organ support remains a long way from clinical practice.While hepatocyte transplantation may be effectively correct metabolic defects,it is far less effective in restoring liver function than liver transplantation.Tissue engineering,using extracellular matrix scaffolds with an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells,holds great promise for the treatment of failure of organs within gastrointestinal tract,such as endstage liver disease,pancreatic insufficiency,bowel failure and type 1 diabetes.Particularly in the liver field,where there is a significant mortality of patients awaiting transplant,human bioengineering may offer a source of readily available organs for transplantation.The use of autologous cells will mitigate the need for long term immunosuppression thus removing a major hurdle in transplantation.展开更多
The liver has remarkable regenerative potential,with the capacity to regenerate after 75%hepatectomy in humans and up to 90%hepatectomy in some rodent models,enabling it to meet the challenge of diverse injury types,i...The liver has remarkable regenerative potential,with the capacity to regenerate after 75%hepatectomy in humans and up to 90%hepatectomy in some rodent models,enabling it to meet the challenge of diverse injury types,including physical trauma,infection,inflammatory processes,direct toxicity,and immunological insults.Current understanding of liver regeneration is based largely on animal research,historically in large animals,and more recently in rodents and zebrafish,which provide powerful genetic manipulation experimental tools.Whilst immensely valuable,these models have limitations in extrapolation to the human situation.In vitro models have evolved from 2-dimensional culture to complex 3 dimensional organoids,but also have shortcomings in replicating the complex hepatic micro-anatomical and physiological milieu.The process of liver regeneration is only partially understood and characterized by layers of complexity.Liver regeneration is triggered and controlled by a multitude of mitogens acting in autocrine,paracrine,and endocrine ways,with much redundancy and cross-talk between biochemical pathways.The regenerative response is variable,involving both hypertrophy and true proliferative hyperplasia,which is itself variable,including both cellular phenotypic fidelity and cellular trans-differentiation,according to the type of injury.Complex interactions occur between parenchymal and non-parenchymal cells,and regeneration is affected by the status of the liver parenchyma,with differences between healthy and diseased liver.Finally,the process of termination of liver regeneration is even less well understood than its triggers.The complexity of liver regeneration biology combined with limited understanding has restricted specific clinical interventions to enhance liver regeneration.Moreover,manipulating the fundamental biochemical pathways involved would require cautious assessment,for fear of unintended consequences.Nevertheless,current knowledge provides guiding principles for strategies to optimise liver regeneration potential.展开更多
Proximal symphalangism(SYM1B)(OMIM 615298) is an autosomal dominant developmental disorder affecting joint fusion. It is characterized by variable fusions of the proximal interphalangeal joints of the hands,typically ...Proximal symphalangism(SYM1B)(OMIM 615298) is an autosomal dominant developmental disorder affecting joint fusion. It is characterized by variable fusions of the proximal interphalangeal joints of the hands,typically of the ring and little finger,with the thumb typically being spared. SYM1 is frequently associated with coalition of tarsal bones and conductive hearing loss. Molecular studies have identified two possible genetic aetiologies for this syndrome,NOG and GDF5. We herein present a British caucasian family with SYM1 B caused by a mutation of the GDF5 gene. A mother and her three children presented to the orthopaedic outpatient department predominantly for feet related problems. All patients had multiple tarsal coalitions and hand involvement in the form of either brachydactyly or symphalangism of the proximal and middle phalanx of the little fingers. Genetic testing in the eldest child and his mother identified a heterozygous missense mutation in GDF5 c.1313G>T(p.R438L),thereby establishing SYM1 B as the cause of the orthopaedic problems in this family. There were no mutations identified in the NOG gene. This report highlights the importance of thorough history taking,including a three generation family history,and detailed clinical examination of children with fixed planovalgus feet and other family members to detect rare skeletal dysplasia conditions causing pain and deformity,and provides details of the spectrum of problems associated with SYM1 B.展开更多
AIM To systematically review the results of studies looking at autologous matrix-induced chondrogenesis(AMIC) in humans. METHODS A literature search was performed, adhering to the PRISMA guidelines, to review any stud...AIM To systematically review the results of studies looking at autologous matrix-induced chondrogenesis(AMIC) in humans. METHODS A literature search was performed, adhering to the PRISMA guidelines, to review any studies using such techniques in humans. Our initial search retrieved 297 articles listed on MEDLINE, Google Scholar, CINHal and EMBASE. From these studies, 15 studies meeting the eligibility criteria were selected and formed the basis of our systematic review.RESULTS The study designs, surgical techniques and outcome measures varied between the studies. Although all studies reported improvements in patient outcome measures, this was not necessarily correlated with magnetic resonance imaging findings. Although there were many additional procedures performed, when AMIC was performed in isolation, the results tended to peak at 24 mo before declining. CONCLUSION Although short-term studies suggest improved patient reported outcomes with a variety of scaffolds, surgical techniques and rehabilitation regimes, the literature remains equivocal on whether the defect size and location, and patient factors affect the outcome. Patientbenefit appears to be maintained in the short-tomedium term but more high level studies with extensive and robust validated outcome measures should be conducted to evaluate the medium-and long-term effect of the AMIC procedure.展开更多
Reperfusion is the key strategy in acute ST-segment elevation myocardial infarction(STEMI) care,and it is time-dependent.Shortening the time from symptom to reperfusion and choosing the optimal reperfusion strategy fo...Reperfusion is the key strategy in acute ST-segment elevation myocardial infarction(STEMI) care,and it is time-dependent.Shortening the time from symptom to reperfusion and choosing the optimal reperfusion strategy for STEMI patients are great challenges in practice.We need to improve upon the problems of low reperfusion rate,non-standardized treatment,and economic burden in STEMI care.This article briefly reviews the current status of reperfusion strategy in STEMI care,and also introduces what we will do to bridge the gap between the guidelines and implementation in the clinical setting through the upcoming China STEMI early reperfusion program.展开更多
PURPOSE:To describe a case of orbital cellulitis arising in a patient treated with an anti-TNFα agent.DESIGN:Single interventional case report.METHODS:A 42-year-old man developed severe unilateral orbital cellulitis ...PURPOSE:To describe a case of orbital cellulitis arising in a patient treated with an anti-TNFα agent.DESIGN:Single interventional case report.METHODS:A 42-year-old man developed severe unilateral orbital cellulitis while receiving infliximab(Remicade,Centocor)treatment for Ankylosing spondylitis(AS)as part of the open-label phase of a trial conducted at our tertiary referral center.Cultures grew Staphylococcus aureus.RESULTS:Infliximab treatment was stopped and the patient made a full recovery after receiving appropriate antibiotic therapy.Infliximab therapy was resumed after three weeks.CONCLUSIONS:Clinical vigilance is warranted when treating patients with anti-TNFα agents as these are associated with a diverse and growing number of ophthalmic complications.Resolved infection does not preclude the use of such agents.展开更多
Objectives Wound healing in the skin is a multifarious orchestration of cellular processes and cigarette smoking may be a cause for delayed wound healing. The aim of this study was to investigate the plausible associa...Objectives Wound healing in the skin is a multifarious orchestration of cellular processes and cigarette smoking may be a cause for delayed wound healing. The aim of this study was to investigate the plausible association between exposures of cigarette total particulate matter （TPM） and wound healing. Methods An in vivo wound healing model of mice was established for determination of assorted events of wound healing, dermal matrix regeneration, re-epithelialization, and neovascularization. A total of 72 adult mice, separated in eight groups, were exposed to TPM for 12 days. Results A highly considerable diminution in wound closure （P〈0.001） was pragmatic among all TPM-treated mice from day 6 to day 8 post-wounding. Histological investigations unveiled a noteworthy impede in the outcome of re-epithelialization, dermal matrix regeneration and maturation of collagen bundles among all TPM-exposed wounds. Delayed commencement of neovascularization was pragmatic among all TPM-treated mice, on day 12 post wounding. Abbot curve, angular spectrum, and other different parameters of 3D surface behavior of wounds revealed a very highly significant reduction （P〈0.001） in angiogenesis on days 6 and 8 post-wounding, which points that application of TPM instigates extensive delay in trigging the progression of angiogenesis, resulting in delayed onset of wound healing. Conclusion Our annotations validate the damaging effects of TPM on wound healing and excessive use of TPM may lead to the production of chronic wounds and oral ulcers.展开更多
Liver transplantation is the only curative therapy for end stage liver disease,but is limited by the organ shortage,and is associated with the adverse consequences of immunosuppression.Repopulation of decellularised w...Liver transplantation is the only curative therapy for end stage liver disease,but is limited by the organ shortage,and is associated with the adverse consequences of immunosuppression.Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution,allowing reliable and timely organ sourcing without the need for immunosuppression.Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact,as well as retaining the instructive cell fate determining biochemicals contained therein.Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models,using a wide range of cell types including primary cells,cell lines,foetal stem cells,and induced pluripotent stem cells.Within these models,a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo.Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes,though advances in organoid culture may help address this.Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo,but with cell types that would limit clinical applications,and which have not been shown to have the specific functions of liver sinusoidal endothelial cells.Minority cell groups such as Kupffer cells and stellate cells have not been repopulated.Bioengineering by repopulation of decellularised scaffolds has significantly progressed,but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.展开更多
The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment.As the lesion itself,as ...The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment.As the lesion itself,as well as each treatment,can cause specific neural damage,the long-term neurocognitive outcomes are highly complex and challenging to assess.The number of neurocognitive studies in this population grows exponentially worldwide,motivating modern neuroscience to provide guidance in follow-up before,during and after treatment.In this review,we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types.Based on this information,we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.展开更多
BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of t...BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.AIM To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.METHODS A systematic search of available literature was performed in November 2022.Data extracted included study characteristics,method of assessment of pancreas stump perfusion,POPF and other post-pancreatic surgery specific complications.RESULTS Five eligible studies comprised two prospective non-randomised studies and three case reports,total 156 patients.Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump,with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump.There was significant heterogeneity in the definition of POPF.Studies had a combined POPF rate of 12%;intraoperative perfusion assessment revealed hypoperfusion was present in 39%of patients who developed POPF.The rate of POPF was 11%in patients with no evidence of hypoperfusion and 13%in those with evidence of hypoperfusion,suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off.Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.CONCLUSION The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality.It does not support a causative link between hypoperfusion and POPF.Further well-designed prospective studies are required to investigate this.展开更多
Background: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and the oretical toxicity of iNO, and a relative lack of information about appropriate doses...Background: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and the oretical toxicity of iNO, and a relative lack of information about appropriate doses. Aim: To determine whether adose-response relationship existed for iNO in preterm infants.Design: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, bloodgas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. Subjects: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. Outcome measure: A clinically significant dose-response was defined as a rise in the post-ductalarterial oxygen tension (PaO2) of at least 3 kPa. Results:Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified(likelihood ratio test, p = 0.34). Conclusion: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.展开更多
Aim: To compare diagnostic accuracy of procalcitonin for early diagnosis of s erious bacterial infection (SBI) in children presenting with fever and no focus of infection. Methods: Prospective, observational study inv...Aim: To compare diagnostic accuracy of procalcitonin for early diagnosis of s erious bacterial infection (SBI) in children presenting with fever and no focus of infection. Methods: Prospective, observational study involving 72 children (1 - 36 mo) presenting to the paediatric units of two university hospitals. All ch ildren had blood cultures, urine cultures, white blood cell counts (WBC), chest X- ray, C- reactive protein (CRP)- and procalcitonin (PCT) done at presentati on. Results: Eight (11.1% ) children had SBI (1 pneumonia, 2 meningitis, 4 sept icaemia/ occult bacteraemia, 2 pyelonephritis), 19 (26.4% ) had possible bacter ial infection (received antibiotic treatment, but no organism grown) and 45 (62. 5% ) had viral or possible viral infection (virus isolated and/or uneventful re covery without antibiotics). PCT (> 2 ng/l), CRP(>50 mg/l) and McCarthy’s scor e ( < 9) had sensitivities and specificities of 50% /85.9% , 75% /68.7% and 87.5% /67.2% , respectively. Negative and positive likelihood ratios for CRP ( > 5 0 mg/l), PCT ( > 2 ng/l), white blood cells ( > 15 × 109/l) and McCarthy’s score ( < 9)were 0.36/2.4, 0.58/ 3.5, 0.94/1.1 and 0.19/2.7, respectively. A com bination of PCT, CRP and WBC generated a positive likelihood ratio of 10.6, chan ging the post- test probability to 54% . Conclusion: For early diagnosis of SB I in children presenting with fever and no focus of infection, the diagnostic ut ility of procalcitonin is similar to the traditional markers infection and clini cal scoring. While a low procalcitonin level cannot be used to exclude SBI in th is population, a combination of PCT, CRP and WBC may be more useful in predictin g SBI.展开更多
Aims: To determine risk factors for development of microa-lbuminuria (MA) in relation to detection of limited joint mobility (LJM+ ) of the interphalangeal joints in a longitudinal cohort of type 1 diabetic (T1DM) sub...Aims: To determine risk factors for development of microa-lbuminuria (MA) in relation to detection of limited joint mobility (LJM+ ) of the interphalangeal joints in a longitudinal cohort of type 1 diabetic (T1DM) subjects. Methods: A total of 479 T1DM subjects diagnosed <16 years were followed from diagnosis of diabetes with annual assessments consisting of assessment of LJM, measurement of HbA1c and insulin-like growth factor 1 (IGF-1), and three urine samples for albumin: creatinine ratio (ACR). Results: After a median follow up of 10.9 years, 162 subjects (35.1% ) developed LJM at median age 13.0 years and duration 5.2 years. More subjects developed LJM after compared to before puberty (67.6 v 32.4% ). In LJM+ compared to LJM-subjects, HbA1c (mean 10.1 (SD 1.6) v 9.6 (1.4) % )) and ACR levels (median 1.1 (range 0.2-242.9) v 0.9 (0.4-70.7) mg/mmol) were higher, and in a Cox model probability of developing LJM was related to puberty and higher HbA1c levels. ACR levels were higher after detection of LJM compared to before (median 1.2 (range 0.4-102.6) v 0.8 (0.2-181.9) mg/mmol). Probability of developing MA was related to puberty,HbA1c, female sex, and presence of LJM(a 1.9-fold increased risk). Both LJM and MA were associated with lower height SDS (LJM: mean 0.0 (SD 1.0) v 0.2 (1.1); MA: 0.0 (1.0) v 0.2 (SD 1.0)) and lower IGF-1 levels. Conclusion: The development of LJM was associated with an increased risk of microalbuminuria, independent of glycaemic control. Risk for both microalbuminuria and LJM was associated with puberty, reduced growth, and reduced IGF-1 levels, and may indicate underlying shared pathogenic mechanisms.展开更多
荧光原位杂交（fluorescence in situ hybridisation，FISH）是在石蜡包埋组织中检测细胞染色体变化及基因异常的一种敏感性强、特异性高的分子生物学方法。对石蜡包埋组织进行FISH染色所采用的方法有两种，在提取的细胞核上进行和直接...荧光原位杂交（fluorescence in situ hybridisation，FISH）是在石蜡包埋组织中检测细胞染色体变化及基因异常的一种敏感性强、特异性高的分子生物学方法。对石蜡包埋组织进行FISH染色所采用的方法有两种，在提取的细胞核上进行和直接在石蜡包埋组织切片上进行。然而，从石蜡包埋组织中提取细胞核进行FISH的方法复杂、耗时，而且所需组织较多，展开更多
文摘The liver is the commonest site of metastatic disease for patients with colorectal cancer,with at least 25%developing colorectal liver metastases(CRLM)during the course of their illness.The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology(cross sectional,nuclear medicine and interventional),Oncology,Liver surgery,Colorectal surgery,and Histopathology.Patient management is based on assessment of sophisticated clinical,radiological and biomarker information.Despite incomplete evidence in this very heterogeneous patient group,maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure.To this end,liver resection is maximised by the use of downsizing chemotherapy,optimisation of liver remnant by portal vein embolization,associating liver partition and portal vein ligation for staged hepatectomy,and combining resection with ablation,in the context of improvements in the functional assessment of the future remnant liver.Liver resection may safely be carried out laparoscopically or open,and synchronously with,or before,colorectal surgery in selected patients.For unresectable patients,treatment options including systemic chemotherapy,targeted biological agents,intraarterial infusion or bead delivered chemotherapy,tumour ablation,stereotactic radiotherapy,and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability.Currently evolving areas include biomarker characterisation of tumours,the development of novel systemic agents targeting specific oncogenic pathways,and the potential reemergence of radical surgical options such as liver transplantation.
文摘We aimed to determine short-term patient-reported outcomes in men having general anesthetic transperineal （TP） prostate biopsies. A prospective cohort study was performed in men having a diagnostic TP biopsy. This was done using a validated and adapted questionnaire immediately post-biopsy and at follow-up of between 7 and 14 days across three tertiary referral hospitals with a response rate of 51.6%. Immediately after biopsy 43/201 （21.4%） of men felt light-headed, syncopal, or suffered syncope. Fifty-three percent of men felt discomfort after biopsy （with 95% scoring 〈5 in a 0-10 scale）. Twelve out of 196 men （6.1%） felt pain immediately after the procedure. Despite a high incidence of symptoms （e.g., up to 75% had some hematuria, 47% suffered some pain）, it was not a moderate or serious problem for most, apart from hemoejaculate which 31 men suffered. Eleven men needed catheterization （5.5%）. There were no inpatient admissions due to complications （hematuria, sepsis）. On repeat questioning at a later time point, only 25/199 （12.6%） of men said repeat biopsy would be a significant problem despite a significant and marked reduction in erectile function after the procedure. From this study, we conclude that TP biopsy is well tolerated with similar side effect profiles and attitudes of men to repeat biopsy to men having TRUS biopsies. These data allow informed counseling of men prior to TP biopsy and a benchmark for tolerability with local anesthetic TP biopsies being developed for clinical use.
基金supported by the grant from Post Doctor Program, Chonbuk National University (2008)
文摘Objective Embryonic movements （EM） and angiogenesis pathways are evolutionarily conserved mechanisms which are essential for proper embryonic development. Deviations in these processes by exposure to cigarette smoke condensate （CSC） may cause vascular and morphogenetic disorders. Methods Using chicken and mouse embryos, we have demonstrated the in vivo effects of CSC on EM, vascular development, and organogenesis. Results Examination of the CSC exposed chicken embryos revealed a significant reduction in EM, stunted growth, deviated pattern of blood vessels, hemorrhages, and localized necrosis. Likewise, mouse embryos that were exposed to CSC at E8.5 and E9.5 died between E11.5 and E12.5, respectively. These mouse embryos showed defects in morphogenesis and remodeling of the embryonic vasculature, while littermate controls showed normal development. Conclusion Cigarette smoking during pregnancy is fatal for growing embryos. CSC may induce the remodeling of embryonic vasculature, leading to various pathologies.
文摘The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation.Despite the initial promising developments in xenotransplantation,roadblocks still need to be overcome and this form of organ support remains a long way from clinical practice.While hepatocyte transplantation may be effectively correct metabolic defects,it is far less effective in restoring liver function than liver transplantation.Tissue engineering,using extracellular matrix scaffolds with an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells,holds great promise for the treatment of failure of organs within gastrointestinal tract,such as endstage liver disease,pancreatic insufficiency,bowel failure and type 1 diabetes.Particularly in the liver field,where there is a significant mortality of patients awaiting transplant,human bioengineering may offer a source of readily available organs for transplantation.The use of autologous cells will mitigate the need for long term immunosuppression thus removing a major hurdle in transplantation.
文摘The liver has remarkable regenerative potential,with the capacity to regenerate after 75%hepatectomy in humans and up to 90%hepatectomy in some rodent models,enabling it to meet the challenge of diverse injury types,including physical trauma,infection,inflammatory processes,direct toxicity,and immunological insults.Current understanding of liver regeneration is based largely on animal research,historically in large animals,and more recently in rodents and zebrafish,which provide powerful genetic manipulation experimental tools.Whilst immensely valuable,these models have limitations in extrapolation to the human situation.In vitro models have evolved from 2-dimensional culture to complex 3 dimensional organoids,but also have shortcomings in replicating the complex hepatic micro-anatomical and physiological milieu.The process of liver regeneration is only partially understood and characterized by layers of complexity.Liver regeneration is triggered and controlled by a multitude of mitogens acting in autocrine,paracrine,and endocrine ways,with much redundancy and cross-talk between biochemical pathways.The regenerative response is variable,involving both hypertrophy and true proliferative hyperplasia,which is itself variable,including both cellular phenotypic fidelity and cellular trans-differentiation,according to the type of injury.Complex interactions occur between parenchymal and non-parenchymal cells,and regeneration is affected by the status of the liver parenchyma,with differences between healthy and diseased liver.Finally,the process of termination of liver regeneration is even less well understood than its triggers.The complexity of liver regeneration biology combined with limited understanding has restricted specific clinical interventions to enhance liver regeneration.Moreover,manipulating the fundamental biochemical pathways involved would require cautious assessment,for fear of unintended consequences.Nevertheless,current knowledge provides guiding principles for strategies to optimise liver regeneration potential.
文摘Proximal symphalangism(SYM1B)(OMIM 615298) is an autosomal dominant developmental disorder affecting joint fusion. It is characterized by variable fusions of the proximal interphalangeal joints of the hands,typically of the ring and little finger,with the thumb typically being spared. SYM1 is frequently associated with coalition of tarsal bones and conductive hearing loss. Molecular studies have identified two possible genetic aetiologies for this syndrome,NOG and GDF5. We herein present a British caucasian family with SYM1 B caused by a mutation of the GDF5 gene. A mother and her three children presented to the orthopaedic outpatient department predominantly for feet related problems. All patients had multiple tarsal coalitions and hand involvement in the form of either brachydactyly or symphalangism of the proximal and middle phalanx of the little fingers. Genetic testing in the eldest child and his mother identified a heterozygous missense mutation in GDF5 c.1313G>T(p.R438L),thereby establishing SYM1 B as the cause of the orthopaedic problems in this family. There were no mutations identified in the NOG gene. This report highlights the importance of thorough history taking,including a three generation family history,and detailed clinical examination of children with fixed planovalgus feet and other family members to detect rare skeletal dysplasia conditions causing pain and deformity,and provides details of the spectrum of problems associated with SYM1 B.
文摘AIM To systematically review the results of studies looking at autologous matrix-induced chondrogenesis(AMIC) in humans. METHODS A literature search was performed, adhering to the PRISMA guidelines, to review any studies using such techniques in humans. Our initial search retrieved 297 articles listed on MEDLINE, Google Scholar, CINHal and EMBASE. From these studies, 15 studies meeting the eligibility criteria were selected and formed the basis of our systematic review.RESULTS The study designs, surgical techniques and outcome measures varied between the studies. Although all studies reported improvements in patient outcome measures, this was not necessarily correlated with magnetic resonance imaging findings. Although there were many additional procedures performed, when AMIC was performed in isolation, the results tended to peak at 24 mo before declining. CONCLUSION Although short-term studies suggest improved patient reported outcomes with a variety of scaffolds, surgical techniques and rehabilitation regimes, the literature remains equivocal on whether the defect size and location, and patient factors affect the outcome. Patientbenefit appears to be maintained in the short-tomedium term but more high level studies with extensive and robust validated outcome measures should be conducted to evaluate the medium-and long-term effect of the AMIC procedure.
基金Project (No.2003CB5500) supported by the National Natural Science Foundation of China
文摘Reperfusion is the key strategy in acute ST-segment elevation myocardial infarction(STEMI) care,and it is time-dependent.Shortening the time from symptom to reperfusion and choosing the optimal reperfusion strategy for STEMI patients are great challenges in practice.We need to improve upon the problems of low reperfusion rate,non-standardized treatment,and economic burden in STEMI care.This article briefly reviews the current status of reperfusion strategy in STEMI care,and also introduces what we will do to bridge the gap between the guidelines and implementation in the clinical setting through the upcoming China STEMI early reperfusion program.
文摘PURPOSE:To describe a case of orbital cellulitis arising in a patient treated with an anti-TNFα agent.DESIGN:Single interventional case report.METHODS:A 42-year-old man developed severe unilateral orbital cellulitis while receiving infliximab(Remicade,Centocor)treatment for Ankylosing spondylitis(AS)as part of the open-label phase of a trial conducted at our tertiary referral center.Cultures grew Staphylococcus aureus.RESULTS:Infliximab treatment was stopped and the patient made a full recovery after receiving appropriate antibiotic therapy.Infliximab therapy was resumed after three weeks.CONCLUSIONS:Clinical vigilance is warranted when treating patients with anti-TNFα agents as these are associated with a diverse and growing number of ophthalmic complications.Resolved infection does not preclude the use of such agents.
基金supported by the grant from Post Doctor Program, Chonbuk National University (2008)
文摘Objectives Wound healing in the skin is a multifarious orchestration of cellular processes and cigarette smoking may be a cause for delayed wound healing. The aim of this study was to investigate the plausible association between exposures of cigarette total particulate matter （TPM） and wound healing. Methods An in vivo wound healing model of mice was established for determination of assorted events of wound healing, dermal matrix regeneration, re-epithelialization, and neovascularization. A total of 72 adult mice, separated in eight groups, were exposed to TPM for 12 days. Results A highly considerable diminution in wound closure （P〈0.001） was pragmatic among all TPM-treated mice from day 6 to day 8 post-wounding. Histological investigations unveiled a noteworthy impede in the outcome of re-epithelialization, dermal matrix regeneration and maturation of collagen bundles among all TPM-exposed wounds. Delayed commencement of neovascularization was pragmatic among all TPM-treated mice, on day 12 post wounding. Abbot curve, angular spectrum, and other different parameters of 3D surface behavior of wounds revealed a very highly significant reduction （P〈0.001） in angiogenesis on days 6 and 8 post-wounding, which points that application of TPM instigates extensive delay in trigging the progression of angiogenesis, resulting in delayed onset of wound healing. Conclusion Our annotations validate the damaging effects of TPM on wound healing and excessive use of TPM may lead to the production of chronic wounds and oral ulcers.
文摘Liver transplantation is the only curative therapy for end stage liver disease,but is limited by the organ shortage,and is associated with the adverse consequences of immunosuppression.Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution,allowing reliable and timely organ sourcing without the need for immunosuppression.Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact,as well as retaining the instructive cell fate determining biochemicals contained therein.Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models,using a wide range of cell types including primary cells,cell lines,foetal stem cells,and induced pluripotent stem cells.Within these models,a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo.Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes,though advances in organoid culture may help address this.Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo,but with cell types that would limit clinical applications,and which have not been shown to have the specific functions of liver sinusoidal endothelial cells.Minority cell groups such as Kupffer cells and stellate cells have not been repopulated.Bioengineering by repopulation of decellularised scaffolds has significantly progressed,but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.
基金funded by the Fonds voor Wetenschappelijk Onderzoek for a senior post-doctoral fellowship.PCF is supported by funding from the Bernard Wolfe Health Neuroscience Fund(206368/Z/17/Z)His research is also supported by the NIHR Cambridge Biomedical Research Centre(BRC-1215-20014).
文摘The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment.As the lesion itself,as well as each treatment,can cause specific neural damage,the long-term neurocognitive outcomes are highly complex and challenging to assess.The number of neurocognitive studies in this population grows exponentially worldwide,motivating modern neuroscience to provide guidance in follow-up before,during and after treatment.In this review,we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types.Based on this information,we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.
文摘BACKGROUND Post-operative pancreatic fistula(POPF)is the primary cause of morbidity following pancreaticoduodenectomy.Rates of POPF have remained high despite well known risk factors.The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest.AIM To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF.METHODS A systematic search of available literature was performed in November 2022.Data extracted included study characteristics,method of assessment of pancreas stump perfusion,POPF and other post-pancreatic surgery specific complications.RESULTS Five eligible studies comprised two prospective non-randomised studies and three case reports,total 156 patients.Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump,with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump.There was significant heterogeneity in the definition of POPF.Studies had a combined POPF rate of 12%;intraoperative perfusion assessment revealed hypoperfusion was present in 39%of patients who developed POPF.The rate of POPF was 11%in patients with no evidence of hypoperfusion and 13%in those with evidence of hypoperfusion,suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off.Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified.CONCLUSION The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality.It does not support a causative link between hypoperfusion and POPF.Further well-designed prospective studies are required to investigate this.
文摘Background: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and the oretical toxicity of iNO, and a relative lack of information about appropriate doses. Aim: To determine whether adose-response relationship existed for iNO in preterm infants.Design: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, bloodgas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. Subjects: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. Outcome measure: A clinically significant dose-response was defined as a rise in the post-ductalarterial oxygen tension (PaO2) of at least 3 kPa. Results:Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified(likelihood ratio test, p = 0.34). Conclusion: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.
文摘Aim: To compare diagnostic accuracy of procalcitonin for early diagnosis of s erious bacterial infection (SBI) in children presenting with fever and no focus of infection. Methods: Prospective, observational study involving 72 children (1 - 36 mo) presenting to the paediatric units of two university hospitals. All ch ildren had blood cultures, urine cultures, white blood cell counts (WBC), chest X- ray, C- reactive protein (CRP)- and procalcitonin (PCT) done at presentati on. Results: Eight (11.1% ) children had SBI (1 pneumonia, 2 meningitis, 4 sept icaemia/ occult bacteraemia, 2 pyelonephritis), 19 (26.4% ) had possible bacter ial infection (received antibiotic treatment, but no organism grown) and 45 (62. 5% ) had viral or possible viral infection (virus isolated and/or uneventful re covery without antibiotics). PCT (> 2 ng/l), CRP(>50 mg/l) and McCarthy’s scor e ( < 9) had sensitivities and specificities of 50% /85.9% , 75% /68.7% and 87.5% /67.2% , respectively. Negative and positive likelihood ratios for CRP ( > 5 0 mg/l), PCT ( > 2 ng/l), white blood cells ( > 15 × 109/l) and McCarthy’s score ( < 9)were 0.36/2.4, 0.58/ 3.5, 0.94/1.1 and 0.19/2.7, respectively. A com bination of PCT, CRP and WBC generated a positive likelihood ratio of 10.6, chan ging the post- test probability to 54% . Conclusion: For early diagnosis of SB I in children presenting with fever and no focus of infection, the diagnostic ut ility of procalcitonin is similar to the traditional markers infection and clini cal scoring. While a low procalcitonin level cannot be used to exclude SBI in th is population, a combination of PCT, CRP and WBC may be more useful in predictin g SBI.
文摘Aims: To determine risk factors for development of microa-lbuminuria (MA) in relation to detection of limited joint mobility (LJM+ ) of the interphalangeal joints in a longitudinal cohort of type 1 diabetic (T1DM) subjects. Methods: A total of 479 T1DM subjects diagnosed <16 years were followed from diagnosis of diabetes with annual assessments consisting of assessment of LJM, measurement of HbA1c and insulin-like growth factor 1 (IGF-1), and three urine samples for albumin: creatinine ratio (ACR). Results: After a median follow up of 10.9 years, 162 subjects (35.1% ) developed LJM at median age 13.0 years and duration 5.2 years. More subjects developed LJM after compared to before puberty (67.6 v 32.4% ). In LJM+ compared to LJM-subjects, HbA1c (mean 10.1 (SD 1.6) v 9.6 (1.4) % )) and ACR levels (median 1.1 (range 0.2-242.9) v 0.9 (0.4-70.7) mg/mmol) were higher, and in a Cox model probability of developing LJM was related to puberty and higher HbA1c levels. ACR levels were higher after detection of LJM compared to before (median 1.2 (range 0.4-102.6) v 0.8 (0.2-181.9) mg/mmol). Probability of developing MA was related to puberty,HbA1c, female sex, and presence of LJM(a 1.9-fold increased risk). Both LJM and MA were associated with lower height SDS (LJM: mean 0.0 (SD 1.0) v 0.2 (1.1); MA: 0.0 (1.0) v 0.2 (SD 1.0)) and lower IGF-1 levels. Conclusion: The development of LJM was associated with an increased risk of microalbuminuria, independent of glycaemic control. Risk for both microalbuminuria and LJM was associated with puberty, reduced growth, and reduced IGF-1 levels, and may indicate underlying shared pathogenic mechanisms.
文摘荧光原位杂交（fluorescence in situ hybridisation，FISH）是在石蜡包埋组织中检测细胞染色体变化及基因异常的一种敏感性强、特异性高的分子生物学方法。对石蜡包埋组织进行FISH染色所采用的方法有两种，在提取的细胞核上进行和直接在石蜡包埋组织切片上进行。然而，从石蜡包埋组织中提取细胞核进行FISH的方法复杂、耗时，而且所需组织较多，
